AAMC SB B/B #76, please help.

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sapientnarwhal

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PLEASE CAREFULLY CONSIDER MY EXPLANATION, I UNDERSTAND THE REASONING, YET I DISAGREE WITH THE CORRECT ANSWER.

I was split between B and D. Initially I chose D, yet I changed my answer to B.

The question stem asks specifically for the effects of overexpressing PRR. The passage indicates (or at least strongly implies) that this experiment is conducted in vitro. Because these cells are derived from neurons (likely hypothalamic neurons), we can infer that endogenous prorenin (renin precursor) expression is little to non-existent. Without endogenous and exogenous prorenin (control and losartan), we do not expect PRR OE and/or PRR WT (control with empty vector) to activate the angiotensin II dependent pathway (RAAS) leading to hypertension. Thus PRR overexpression has the direct effect of participating in some other angiotensin II independent pathway leading to hypertension.

Of course we expect PRR OE to increase hypertension in the presence of prorenin as we are adding its natural substrate which then participates in the angiontensin II dependent pathway (RAAS). However, this is not a direct result of PRR OE, but instead a result of adding prorenin. (we see that prorenin + empty vector results in increased ROS levels relative to the control condition with empty vector => we can infer that prorenin is binding endogenous PRR, leading to activation of the angiotensin II dependent pathway for hypertension. It is apparent that introduced PRR in the presence of prorenin increases BP through both pathways. Again, only in the presence of prorenin.)

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PRR OE will only increase BP in an angiontensin II dependent manner in the presence of prorenin.
Again, we can confidently assert that PRR OE increases BP in an ATII independent manner, because ROS levels increased in the absence of prorenin.

We cannot confidently state that PRR OE increases BP in an ATII dependent manner. We can say that prorenin is necessary for PRR OE to participate in the ATII dependent pathway.
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Relevant to this dilemma, I certainly understood each passage and experiment in the SB (86% for both C/P and B/B, many incorrects were due to second guessing on questions like these). Maybe don't second guess?

@NextStepTutor_1




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Hi @sapientnarwhal -

That's a really interesting point. That said, note that in the empty vector group, adding losartin to prorenin doesn't significantly reverse the effects of prorenin, whereas that reversal takes place in the WT-PRR cells and is the sign of AT-II dependence. This would seem to suggest that the PRR overexpression itself induces the AT-II dependence. It may still be the case that prorenin must be present for that difference to manifest, but that's a separate issue -- partial AT-II dependence is an underlying feature that only shows up when you know how to probe for it. It's like UV visualization of compounds in TLC -- just b/c you have to shine a UV light on the plate to see a trace left by a compound doesn't mean that it's only there in the presence of UV.

That said, a more realistic caveat might be that the answer choices state "in part", and "in part" could potentially refer to some degree of substrate-dependence (i.e. the idea that you need prorenin to be present for the AT-II dependent effects to emerge). It took me a little while to reason through the point I sketched out above -- far longer than the amount of time you have to make a decision under test-like circumstances.

So, also, BTW, congrats on your Section Bank performance! That's phenomenal, and very promising. As w/ Q74, it sounds like the name of the game is to align your thinking with that of the AAMC. In the context of the MCAT as a whole, the cognitive steps of (1) making the figure tell a story about losartin moderating the effects of prorenin in WT-PRR cells and (2) understanding what an AT-II antagonist is and linking that to the question stem are by themselves more than enough to make this a difficult question in its own right, without getting into an additional issue of possible substrate-dependence. It's not a 100% guarantee, but raising a third non-obvious point in a data interpretation question might be a warning sign of getting too far into the weeds, at which point the best option might be sticking w/ your first answer.

Hope this helps & good luck -- almost there!!
 
did anyone else notice that the figure and the figure description have conflicting labels?

It says that empty vectors=white bars in the figure description and on the figure, the legend says that the empty vector is in black (which they are).
 
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