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 +0  (nbme19#13)

This is essentially a formal logic question. Logically speaking, the question asks us to identify a mechanism that tumor suppressors have which proto-oncogenes do not. In other words, what is a mechanism shared by all known tumor suppressors but not shared by any known proto-oncogenes? For that reason, it can’t be phosphorylation; sure, phosphorylation is a mechanism of tumor suppressors but it’s also a mechanism of many known proto-oncogenes.


 +0  (nbme20#15)

The more general principle: endothelia vasodilate in the presence of high CO2; you gotta get rid of that acid somehow! Can’t let it accumulate, as lower pH within a “micro-environment” affects structure/efficiency of enzymes, proteins, etc. The more acidic a local environment, the more you expect nearby vasculature to dilate (as a means of increasing flow rate, thereby ferrying off accumulate acid).

The anesthesiologist can exploit this mechanism. By hyperventilating (blowing off CO2), the brain vasculature senses a low CO2 / “hunky-dory state,” which requires no vasodilation. In other words, the vasculature does not need to continue the ATP-consuming practice of synthesizing Nitric Oxide (NO).


 +0  (nbme20#11)

As described in the question stem, this mutation occurs within an intron (a gene segment which is transcribed [DNA->RNA] but not translated). RNA splicing enzyme(s) grab RNA and “loop it”; an intron is cut out and the exons on either side of the intron are adjoined, like this:

exon1—intron—exon2 => exon1—exon2

Typically, this splicing occurs at the very edges of the intron (what I denoted with the “—” character). But in our case, a mutation within the intron is causing RNA splicing enzyme to recognize a new site: the splicer cuts within the intron (instead of at the very edge, as it should). So, we get something that looks like this:

exon1—intr—exon2

That’s a totally different mRNA molecule, and it's going to make our β-globin protein look (and behave) awfully strange.


 +1  (nbme20#6)

This is an interesting one. I like to remember it this way: in people with narcolepsy, all the “right kinds” of sleep are happening at all the “wrong times” of day. During the day, when a power nap would typically throw you immediately into REM, this kid is only entering Stage 1 or 2 (lightest sleep = slightest noises jar him back to reality). At night, when he should peacefully drift into Stage 1, 2, and so on, he instead completely zonks out. Classic narcolepsy.

From UpToDate: “Narcolepsy can be conceptualized as a disorder of sleep-wake control in which elements of sleep intrude into wakefulness and elements of wakefulness intrude into sleep.”


 +0  (nbme21#28)

Here’s one way to process-of-eliminate “decreased hydrogen-bond formation”: I’m not a big fan of this line of reasoning, but technically alanine as a side group has more hydrogens* for potential hydrogen bonding than glycine:

alanine: —CH3
glycine: —H

So, “technically,” alanine would permit more hydrogen-bond formation, which might allow you to eliminate that choice.

That said, it seems almost impossible to rule out (without very technical knowledge or some provided experimental data) that the slightly larger alanine does not impair hydrogen bonding between collagen molecules via steric (spatial) interference. In simpler terms, since alanine is larger, you would think that it must somehow interfere with the hydrogen-bonding that occurs with the wild-type glycine.

---
*Strictly speaking, it’s not the number of hydrogens but also the strength of the dipole that facilitates hydrogen bonding: a hydrogen bound to a strongly electronegative molecule like fluorine will “appear” more positive and, thus, hydrogen-bond more strongly with a nearby oxygen (compared with a hydrogen connected to carbon, for example).

Further reading:

  1. https://www.chem.purdue.edu/gchelp/liquids/hbond.html

 +2  (nbme21#21)

2,500 students ... but you find out during your initial screen that 500 already have the disease. So, strikeout those people. That leaves 2,000 students who don’t have the disease.

Over the course of 1 year, you discover 200 students developed the infection. Thus:

200 new cases / 2,000 people who didn’t have the disease when you started your study = 10 percent

Tricky, tricky NBME ...


 +0  (nbme21#21)

Also consider this great description from the NIH’s MeSH database:

INCIDENCE: The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.

https://meshb.nlm.nih.gov/record/ui?ui=D015994


 +2  (nbme21#49)

The synthesis of virtually all proteins (mRNA->peptide) occurs in the cytoplasm.[1] That’s where all ribosomes reside, after all. Ribosomes, which are mostly just rRNA (~2/3 rRNA + 1/3 protein*, by weight), are assembled in the nucleus but only do their stuff once they get to the cytoplasm.

For a protein to leave its original hometown of the cytosol and become a resident of the nucleus or, sayyyyyy, the endoplasmic reticulum, it needs to have a little string of amino acids which shout “I belong in the nucleus!” or “I belong in the endoplasmic reticulum!”

Proteins ultimately destined for the ER contain an unimaginatively named string of amino acids known as “signal sequence,” which, for the purposes of the Step 1, is always at the N-terminus. The signal sequence tells other cytosolic proteins, “Hey! Take me (and the rest of the peptide of which I am part) to the ER!”

In the absence of this signal, a protein will remain in its “default” home of the cytosol.

Here’s a nice schematic showing the flow of proteins from initial synthesis to final destinations:


Endnotes

  1. “The synthesis of virtually all proteins in the cell begins on ribosomes in the cytosol.” (Essential Cell Biology, Alberts et al., 2014, p. 492)

*If you really want your mind blown, consider that even the protein subunits that make up that 1/3 of a ribosome are themselves initially synthesized in the cytosol; later, they are transported back into the nucleus via the nuclear pore.


 +1  (nbme21#23)

Vasoconstriction (narrowing of a tube) will cause the flow rate to increase through that tube, which decreases radial/outward pressure. The faster a fluid moves through a tube, the less “outward” force it exerts. (This is known as the Venturi effect.)


 +14  (nbme19#4)

Inability to maintain an erection = erectile dysfunction. So now the question is "Why?"

Fatigue, difficulty sleeping, difficulty concentrating is starting to sound like depression. "Difficulty concentrating" might be interpreted as impaired executive function or the beginnings of vascular-related dementia (dementia related to small but numerous cerebral infarcts), but on Step 1 dementia will be blatant (i.e., "lost his way home," "wandering," etc.).

Depression is actually common after a debilitating event like stroke, as you might expect. With depression comes a loss of sexual interest and desire—that is decreased libido.

One can make the argument that a "vascular patient" might have some issues with his "pipes" (arteriosclerosis, parasympathetic/sympathetic dysfunction) and, for this reason, nocturnal erection should be decreased; but note that nothing is mentioned about long-standing vascular disease (no hx of hypertension).

As a result, the best answer choice here is C. (Libido decreased but nocturnal erections normal.) The big question I have is, how the heck does this guy know he's hard when he's asleep!!? :p


 +0  (nbme20#29)

[deleted]


 +0  (nbme21#39)

Stem actually states, “On questioning, the patient does not know the date [time], the name of the hospital [place], or the name of her nurse who had just introduced himself [person].” So, pt is disoriented to time and place (Choice A); that is definitely concerning -- as would be depressed mood (Choice E) and the other choices -- but “inability to understand severity and prognosis” is the most concerning since that is the very definition of capacity. Inability to understand = lack of capacity.


 +0  (nbme24#25)

EBV is not a “respiratory virus” -- it’s a B cell virus. It infects B cells; not laryngeal cells.

Even though you might associate it with the “upper respiratory tract” (=kissing disease), it doesn’t cause respiratory inflammation since that’s not its trope. B cells are its trope! That’s why EBV is implicated in Burkitt Lymphoma, hairy leukoplakia and other blood cancers. (EBV is also known as “lymphocryptovirus” -- it was originally discovered “hiding” in lymphocytes of monkeys.) So, EBV = think B cells. From the MeSH library:

The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.

https://meshb-prev.nlm.nih.gov/record/ui?name=HERPESVIRUS%204,%20HUMAN


 +0  (nbme24#48)

The duodenal lumen (and pancreatic proteases like CHYMOTRYPSIN) is the site where pancreatic enzymes (“endopeptidases”) cleave large polypeptides into smaller bits (=dipeptides,tripeptides). It is at the BRUSH BORDER where the smallest kinds of peptides (dipeptides,tripeptides) are broken down into their amino acids, which finally can be co-transported with Na+ into the intestinal cell.

I think about it this way:

  • stomach acid denatures and “opens up” proteins (without specific cleavage);
  • pancreatic enzymes then cleave denatured polypeptides into smaller bits;
  • brush border enzymes finally break down tiniest peptides into absorbable amino acids.

 +1  (nbme21#21)

Don’t forget that incidence is the number of new cases which emerge in an unaffected population. Incidence is trying to get at the question -> “In a given year, how many new people develop this disease?”

In other words, you cannot count people who already have the disease. You have to exclude those people from your calculation. You want to know, among all the people out there who DO NOT have the disease, how many times this year was someone (newly) diagnosed?

Said differently still, you don’t want to “double-count” people who developed the disease before your study. As an epidemiologist, that would screw up your sense of how infective or transmissible a disease is. You want to know, “from time1 to time2 how many new cases emerged?”


 +0  (nbme24#2)

After the cuff is tied, the cells and tissue distal to the cuff will continue consuming ATP (ATP->ADP), but no fresh blood will be delivered to “clear” what will be an accumulating amount of ADP and other metabolites. ADP (=Adenosine) is itself a proxy of consumption and drives vasodilation of arteries! (Evolution is smart!) Increasing ADP/Adenosine in a “local environment” is a signal to the body that a lot of consumption is occurring there; thus, arteries and arterioles naturally dilate to increase blood flow rates and “sweep away” metabolic byproducts.