How would degranulation limit inflammation? The MCs are releasing pro-inflammatory cytokines, as you pointed out.

Consider including a quantification of the increase reported by Esaulova et al? It's always difficult to evaluate the importance of a finding like this without some appreciation of the magnitude of the change.

Is there another experiment you think could answer this question?

Another reader left a similar comment above, but I wonder if you've considered trying other pruritogens besides chloroquine? Chloroquine is often used to model non-histaminergic itch, but (of course) histaminergic itch is also important, and accounts for a large proportion of itch signaling.

Wow, is this reaction typical for mechanical stress at the level of the skin?

Hi there! Looks like the figure images/links are broken

Did you consider using structure as a search parameter, in addition to sequence?

Interesting and important inference! Have you considered using your setup to do dose response tests for morphine?

Fantastic! I'd love to see some specific comparisons

Your analysis of the behavioral syllables is fascinating! In regard to the freezing, have you considered whether the mole rats were responding to specific stimuli in the room? Was an experimenter present during filming?

Did you notice any inflammatory or adjuvant effect from the olive oil?

5.7% vs. 5% does not seem like strong evidence of an association... is this a significant difference?

Are these symptoms associated with AD in Lyme disease patients?

Interesting paper so far! I'm not sure what this phrase means, though... Do you mean AD in older patients is more severe?

Beautifully written paper!

Regarding the EVs' regulation of DETCs: how long does the effect last? If you allowed the ticks to feed for 3 days, then removed them and waited another 48 hours before taking the biopsies... do you expect the DETCs would still show impaired rounding?

The docking models are interesting, but do you have any empirical data that indicate SC binds TRPA1/TRPV1?

Very interesting work! Wondering if you could explain the rationale for including DEM and CPZ groups in this experiment. I assume these are typical treatments for ACD?

Have you considered testing an algogen alongside pruritogens to confirm that these neurons are specific to itch?

Hi there! Just wondering why you specifically conducted this test in the morning? Have you noticed changes at other times of day?

This sounds like an incredible setup! Is it possible to collect longer videos?

Wow, the results look profound. Just curious about the onset of the scratching behavior. I'm looking at the time course data in Sup Fig 1b... why did you start measuring scratching at 7 weeks? Is that when you started to notice scratching?

Wow, what an intense response! I'm a little confused about the pain response data, though. Swipes are often considered an indication of pain, so I would interpret the behavioral data as evidence of increased pain in the Ddx3x(BRN3A) mice. But if I'm understanding correctly, the same mice showed a reduction in pain responses according to your hot plate and capsaicin injection experiments. Did I get that right? What's your thinking on this?

Looks like less of an effect (or maybe a slower effect?) in DRGs... wondering what you make of that?

I'm confused about the labels in the figure. What does "IgE+Ag" refer to?

I would be curious to hear more about your reasoning, here. Why do you think BMMCs are more sensitive to stimulation than MC cell lines?

Maybe I missed it elsewhere in the text, but could you provide detail about the cameras and capture settings?

Did you validate these behavioral data with manual analysis of the videos?

Wow, great! Did DLC reliably call all of these positions in most frames?

Agree! Seems like these are critical steps for establishing Csm-mediated RNA KD as robust and specific technique. Do you have plans for further characterization?

You measured GFP fluorescence, but did you also measure RNA levels directly? I'm curious how KD efficiency of targets like MALAT1, NEAT1 or TARDBP would change with spacer length.

Interesting! Is it possible to say anything about binding affinity for these ligands, or how they compare in activity assays?

Interesting! Is it possible to say anything about binding affinity for these ligands, or how they compare in activity assays?

You measured GFP fluorescence, but did you also measure RNA levels directly? I'm curious how KD efficiency of targets like MALAT1, NEAT1 or TARDBP would change with spacer length.

Agree! Seems like these are critical steps for establishing Csm-mediated RNA KD as robust and specific technique. Do you have plans for further characterization?