Fritz vs. 'Them'

I would like to begin this post by apologizing to my mother for the headshot that appears in Bryan's last post. To any readers who don't know me personally: I promise I don't usually look like that.

My current thinking on the NCAA is fairly well-captured by a column that Bryan and I ran in the Middlebury Campus newspaper last week, and what I want to get into here is essentially an expounded version of that piece. For posterity: let it be known that Bryan and I penned the column before the NCAA changed its policy on feeding athletes. Call us game-changers.

The NCAA's (from henceforth, 'them') most basic orientation to its athletes is two-fold: to make sure that we are brand ambassadors for the national organization (see Bryan's post) and to ensure that we behave in a way that reflects positively on the brand. The latter point is, in my view, a vehicle to a deeper sort of criticism of how they conduct business.

Consider three anecdotes from my weekend in Lincoln:

1. In the athlete hospitality room, there was a staff member (Tyrone) on hand to ensure that we did not take an unreasonable number of snacks.
2. The championships featured an elaborate and fairly confusing credentialing system. There were certain areas designated for spectators, for athletes, coaches, media folks, etc. There were scores of staff stationed at choke-points to ensure that no one was in violation.
3.When we wanted to go to the field house to warm-up on Friday, they assigned us a volunteer to supervise as we waited for the bus. His name was Alex. I'm not sure what exactly he was looking out for, but I was probably the only athlete who spoke with him all weekend. This show was surely just as dehumanizing for the scores of "volunteers" as it was for us.

The point here is simply that they treat their athletes like children. This point isn't in itself that damning; many 18-22 year-olds probably deserve to be treated like children, and I happen to have the privilege to be part of an athletic program that trusts its athletes to drive college-owned vehicles, host recruits and do their own homework.

It is a bit suspicious, however, that this paternalistic attitude is paired with indulgence. When you're at the championships, they pay for everything: travel, hotel, meals, snacks, gear. I got the sense that all of this expense was supposed to make us feel important, like we were being celebrated for all of the hard work that it took just to qualify for the meet. For most of my teammates, this effect was realized; it just left me feeling like I was being manipulated.

Mark Emmert doesn't stand a chance.

Here is the part where I wave my English-major flag a bit. There is a word in literary criticism for this sort of indulgence that is used to cover up a less fun reality: carnivalesque. The idea comes from Mikhail Bakhtin, who thought of the carnival as a way for those in power to keep their subjects contentedly suppressed. The carnival presents a warped version of reality in which traditional standards and power structures are temporarily put aside and subordinates get to feel like they run the show, if only for a short while. Think Mardi Gras or, in a lesser sense, Halloween.

The NCAA championship doesn't feel like real life. It feels like a slightly altered form of real life in which people are constantly showering you in attention and free stuff, asking in return only that you abide by a few rules that easily go unquestioned in the face of so much free stuff. Bakhtin's point, and mine here, is that we should try to look past such a system to see what is really going on.

What is really going on at NCAA championship events is that athletes are being combed to be NCAA spokespersons who return to their real lives after a weekend of "carnival" to show off their flashy new gear and tell stories about how amazing it all was. As long as that system is working and we all continue to "participate" (their favorite word, but not in the way that Bakhtin uses it) in the big show, no one is likely to ask questions like "What does the NCAA do for me?" and "Why does all of this exist in the first place?" (or, if you are a Division-I men's basketball player, "Where is all this money going?") When people start to do that, they realize, it will mean an end to all the fun and games.

Image courtesy of Wikipedia

Tacit approval of what we don't approve of

Last month, I qualified for and Participated in the NCAA Division III Indoor Track & Field Championships.  While the weekend in Lincoln, NE, and the frantic fortnight leading up to the event could be the subject of decently-lengthed short story perhaps of interest to a non-trivial number of people, I'd rather use this space to talk about my first personal experience with the NCAA; specifically, the manner in which the NCAA uses its student-athletes as advertisements for itself.

Briefly, some background.  I qualified for the meet running the second leg of Middlebury's 4x400m relay.  Fritz Parker, blog co-contributor, ran the first leg.  Middlebury also qualified one guy in the mile, a women's DMR, a woman in the 400m (she ran the 800m leg on the DMR), and a woman in the high jump.  We arrived in Omaha, NE, on a Thursday night and left before dawn on the following Sunday.  The Championships were on the intervening Friday and Saturday.  In terms of performance, my relay came in 12th (out of 12, but saying we were 12th in the country sounds a lot better than last), but we also entered the meet seeded 12th (again, last).

F. Parker             B. Holtzman             A. Nichols               P. Hetzler

As I mentioned, this weekend was my first direct experience with the NCAA.  Prior to my Participation, I had perceived the NCAA as two factions: the governing body of big-time college football (and basketball, but I don't follow CBB the same way I do CFB) and as the name of the national meet which I had spent four years trying to qualify for (much in the same way that, back in my day, Nike Indoor Nationals was the namesake of the national T&F meet run by the NSSF).  I never gave much thought to its governance over other sports and student-athletes.  The NCAA had never affected me before so I never considered it in that context.  The only NCAA regulation I ever cited was its ban on gambling as an excuse to get out of playing poker for money while home on school breaks.

That said, I have historically been a skeptic of the NCAA in regards to how it treated its high-profile athletes and teams.  I always thought the organization was out to get the odd athlete or program instead of protecting those athletes and programs (some examples, and it would be irresponsible not to mention that Oklahoma had to self report an NCAA violation because a few players ate too much pasta.  Thanks in large part to comments by Shabazz Napier, schools can now feed their athletes).  This historical skepticism was recently compounded by a renewed interest in the NCAA manifest largely by reading numerous news articles both criticizing and defending it.  With this in mind, I undoubtedly--perhaps subconsciously--approached my experience with disdain for the NCAA.

The NCAA Experience is one of continuous overstimulation.  Everywhere I looked, the NCAA was present.  From being constantly babysat to the countless number of blue logos emblazoned around the track, there was no escaping the watchful eye of the NCAA (nor the constant reminder that we were at UNL: popcorn isn't just popcorn, it's Husker popcorn; the time on the clock isn't simply just time, it's Husker Time, which, it's worth noting, was incorrect).  This made me uneasy.  Forgetting to wear my Participant badge made me feel like I was accumulating an NCAA infraction for each minute I was without it.

The NCAA has, in a sense, adopted the "everyone gets a trophy" attitude towards the championships.  By qualifying, I will eventually be sent an NCAA pull-over I can proudly wear around telling the world I Participated in an NCAA event, a drawstring bag, and a commemorative medallion.

(Side note--really wish I could do foot/endnotes on this blog: I am usually stoutly against the "everyone gets a trophy" attitude, but not in this case.  For example, I did not receive an All-American trophy by simply Participating, so there was some separation between the winners and the Participants.  Additionally, the commemorations are a nice reward for the accomplishment of qualifying.)

Right at the door to the track was an ad hoc gift shop selling shirts, sweatshirts, and hats with the NCAA logo and the event printed on them.  Items were flying off the shelves, appealing to the athlete's desire to be marked as a Participant when they return to their respective institutions (I'm guessing they don't have to wear a badge at school labeling them as a Participant).  I am guilty of purchasing apparel: I bought a quarter-zip sweatshirt and an Under Armour technical shirt.

Wearing my gear makes me uneasy on two fronts: first, I feel kind of obnoxious by showing such an outward display of my accomplishment.  Realistically, nobody cares that I Participated in the meet.  I also separate myself from my teammates; they don't need a reminder that we went to NCAAs--they all know we did.  Second, by wearing my gear, I passively tell the world I support the NCAA in whole when I staunchly do not.

We are Participants

The second point is what really gets me.  At most schools around the country, some segment of students (athletes?  student-athletes?  Participants?) are wearing NCAA sponsored apparel.  Here at Middlebury, I see students who have NCAA patches sewn on their backpacks, students carrying NCAA water bottles (officially sponsored by Powerade), etc.  Even when you're not at an NCAA event, the NCAA is present and ever-looming.  We Participants are propagators of its presence and the NCAA knows this.  It knows the Participants will display their free mementos and commemorations creating a walking advertisement out of every Participant.  When you add up EVERY athlete in EVERY sport in EVERY division, this number becomes quite large.  I'd wager 90% of them will show the world a piece of their memorabilia with some frequency.  This reminds everyone who sees such memorabilia a. that the NCAA exists and b. that Participating in an NCAA event is good.  To the second point, if one qualifies for NCAAs in something, one is obviously good at what they do.  The association of NCAA = good is immediate.  Unfortunately, there is not much depth to this association.  The achievement of making NCAAs is remarkable, but the associated approval of the NCAA--either by the wearer or viewer--is not questioned when it should be. 

This brings me to my concluding question: how can the accomplishment of competing in an NCAA event be separated from the NCAA (and thus tacit support of the NCAA)?  Students should not feel even the slightest amount of guilt about showing the world a memento of their accomplishment.  They should be proud of their accomplishment.  I am proud, damnit.  But I cannot, in good conscious, show my pride.  This, to me, is unfortunate and is a slight to every athlete in the country.

EPO: From Cytokine to Speed

Background

Last fall, I was enrolled in a metabolism course at Middlebury.  We were assigned a 40 minute presentation on a metabolic disease.  To the eleven other students in the class who were planning on going to medical school, this was an interesting topic and was designed with their interests in mind.  Metabolism is a fascinating field of study with many aspects, so I asked my professor if I could do my presentation on a different metabolic topic: PEDs.  After some preliminary research, I settled on presenting about EPO.  The following is what I came up with (there is some overlap with a previous post).

What is this "EPO" thing, anyway?

EPO--short for erythropoietin (derived from erythropoiesis, combining the Greek erythro meaning red and poiesis meaning generation; an erythrocyte is a red blood cell, or RBC--the cells responsible for transporting oxygen in the blood)--is a cytokine (protein signaling molecule) that induces red blood cell production by preventing red blood cell progenitors from committing apoptosis (cellular suicide or death) and allows them to proliferate and differentiate.  EPO occurs naturally in your body!  It is a 34 kilodalton glycoprotein that is about 165 amino acids long.  Roughly 40% of its weight comes from glycosylation, which is the addition of sugar groups to amino acid residues on the peptide chain (in the case of EPO, this is mostly N-linked glycosylations, mainly occuring on asparagine residues).  In addition to its primary role as an inducer of RBC production, EPO has a variety of secondary functions, including neural production during stroke (EPO can cross the blood-brain barrier) and implication in apoptotic pathways through the PI3-kinase pathway.  In the fetus, the EPO gene is expressed in the liver and after birth it is expressed in the kidney.  In addition to its well documented use as a PED, synthetic EPO is an incredibly successful drug in the clinic, used mainly to treat patients with anemia (RBC deficiency).  It has also been used in patients who have diabetes, Alzheimer's and cardiovascular disease.  There are some drawbacks, though, particularly in cancerous patients (many of whom are prescribed EPO): synthetic EPO has been shown to block tumor cell apoptosis, enhance tumor progression rates, increase the metastatic rate of cancer, and negating radiation treatment by assisting in tumor angiogenesis (for those of you keeping count, that's 4 out of the 6 Hall Marks of Cancer--original paper and follow-up; some of the more generally interesting and accessible journal articles you'll find).

How does EPO get produced in the body?

http://www.sciencedirect.com/science/article/pii/S0006295211004291

I'm going to start large and then get smaller.  EPO production is dependent on physiologic conditions: hypoxia in arterial blood running through the kidney or anemia.  Under these conditions, the EPO gene is expressed in the kidney and produces the EPO protein (this is known as the Central Dogma of Molecular Biology: DNA is transcribed into RNA, which, after processing, is translated into a protein).  EPO is then directed to cells expressing its receptor, EPOR.  Remember that EPO is a signaling molecule: that means it "swims" around the extracellular matrix and blood until it finds a receptor protein on the surface of a cell specifically tailored for it to bind to.  Compounds of EPO's size cannot move directly through the cell membrane to catalyze chemistry in the cell; instead, they bind to a receptor that can then catalyze many things inside the cell.  In this case, EPOR is a Type I transmembrane receptor protein (example).  Type I means that it is composed of alpha-helicesand transmembrane means that the protein sits directly in the plasma membrane and has parts of it exposed to the outside of the cell and into the inside of the cell.  EPOR is a member of the cytokine receptor superfamily, which is a group of cytokine receptors that have four conserved cysteine residues and a conserved Trp - Ser - X - Trp - Ser motif in the extracellular domain (conservation, in this sense, means those amino acid residues appear in roughly the same place in the amino acid sequence in many different proteins that have similar functions.  Conserved sequences are usually pretty important for function.  Wikipedia page).  EPOR is mainly expressed in red blood cell progenitors as they are nearing death either to rescue them from apoptosis or to induce their proliferation.  There has also been research showing EPOR being involved in RBC differentiation (specialization of a cell's function).

All right, we have EPO, and it's found a receptor.  What does it do now?

Previously, I briefly mentioned that EPO works via a JAK-STAT signaling mechanism.  I'm now going to go through that in more detail.  I truly believe that one does not need a background in biology or chemistry to understand what I'm about to explain.  All you need is a healthy dose of common sense, because when you think about what's going on, it does make sense.

http://www.jbc.org/content/282/28/20059.short

Signaling that occurs via cytokine receptors is promoted by enzymes in the cell known as protein tyrosine kinases (PTKs) and is thought to be terminated by enzymes known as protein tyrosine phosphatases (PTPs; I will revisit this idea in a bit).  Like I said before, EPO is directed to cells expressing EPOR.  EPOR sits in the membrane as a homodimer (a dimer is two proteins associated with one another; thus, a homodimer is two of the same protein associated with one another) in an inactive conformation.  EPO comes in and binds to the receptor dimer and causes it to change conformation, activating it.  This idea of active and inactive conformations dependent on ligand binding or ambient conditions is a huge theme in biology; it provides a simple mechanism to turn proteins/enzymes/receptors/etc. on and off.  Upon the conformation change, JAK2 (a random kinease--seriously, JAK stands for Just Another Kinase.  Kinases are enzymes which phosphorylate things), which is associate with EPOR, is activated via an autophosphorylation mechanism (phosphorylating itself).  Phosphorylation is the addition of a phosphate group (PO4(3-)) to a moiety.  Phosphorylation is the way by which just about everything in the cell is activated; when you hear about ATP (adenosine triphosphate) being the energy currency of the cell, it activates things by putting one of its phosphate groups on that thing and becomes ADP (adenosine diphosphate).  This autophosphorylation, in addition to activating that particular JAK, promotes further autophosphorylation of other JAKs and promotes further kinase activity.  This is a positive feedback loop, which means when this thing happens, it makes more of either itself or another thing happen.  Upon the autophosphorylation of JAK2, eight tyrosine residues on the cytoplasmic side of the cell (the inside) are phosphorylated (tyrosine phosphorylation happens a lot in protein signaling pathways).  The tyrosine phosphorylation leads to SH2-dependent recruitment of STAT5.  SH2 is a conserved protein domain (in larger proteins, different parts of the protein will fold up and form their own ball-like structures that act basically independently from the other domains/rest of the protein) that is roughly 100 amino acids long that selectively binds or docks to phosphorylated tyrosine residues on other proteins.  STAT5 (Signal Transducer and Activator of Transcription 5) is activated by this selective docking.  Once STAT5 has been activated, presumably via phosphorylation, it forms an antiparallel dimer with itself (proteins aren't symmetrical and have some form of directionality, so in this case, the two STATs are running in opposite directions of one another, kind of like a two-way street) and translocates to the nucleus.  The nucleus of the cell has its own membrane (well, it really has two, but that's besides the point), so the STAT dimer manages its way through those membranes into the body of the nucleus.  Once it's in the nucleus, it acts as a transcription factor for important erythro-regulation genes as well as possibly activating GATA-1, another transcription factor for erythro-regulating genes.  Transcription factors are proteins that promote the expression of a gene into a protein (running through the Central Dogma: DNA --> RNA --> protein).

References

1. Bodary, P. F.; Pate, R. R.; Wu, Q. F.; McMillan, G. S. Effects of acute exercise on plasma erythropoietin levels in trained runners. Med. Sci. Sports Exerc. 1999, 31, 543-546.

2. Chateauvieux, S.; Grigorakaki, C.; Morceau, F.; Dicato, M.; Diederich, M. Erythropoietin, erythropoiesis and beyond. Biochem. Pharmacol. 2011, 82, 1291-1303.

3. Klingmüller, U.; Lorenz, U.; Cantley, L. C.; Neel, B. G.; Lodish, H. F. Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell 1995, 80, 729-738.

4. Kretz, A.; Happold, C. J.; Marticke, J. K.; Isenmann, S. Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/AKT pathway activation. Molecular and Cellular Neuroscience 2005, 29, 569-579.

5. Maiese, K.; Chong, Z. Z.; Shang, Y. C. Raves and risks for erythropoietin. Cytokine Growth Factor Rev. 2008, 19, 145-155.

6. Roels, B.; Bentley, D. J.; Coste, O.; Mercier, J.; Millet, G. P. Effects of intermittent hypoxic training on cycling performance in well-trained athletes. Eur. J. Appl. Physiol. 2007, 101, 359-368.

7. Sasaki, A.; Yasukawa, H.; Shouda, T.; Kitamura, T.; Dikic, I.; Yoshimura, A. CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J. Biol. Chem. 2000, 275, 29338-29347.

8. Schindler, C.; Levy, D. E.; Decker, T. JAK-STAT signaling: from interferons to cytokines. J. Biol. Chem. 2007, 282, 20059-20063.

9. Smith, J. A. Exercise, training and red blood cell turnover. Sports medicine 1995, 19, 9-31.

10. Tong, W.; Zhang, J.; Lodish, H. F. Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways. Blood 2005, 105, 4604-4612.

11. Yao, Z.; Cui, Y.; Watford, W. T.; Bream, J. H.; Yamaoka, K.; Hissong, B. D.; Li, D.; Durum, S. K.; Jiang, Q.; Bhandoola, A.; Hennighausen, L.; O'Shea, J. J. Stat5a/b are essential for normal lymphoid development and differentiation. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 1000-1005.