Tuesday, July 24, 2007

Intellectual S&M

Today I was reflecting on the fact that in just a little less than two weeks, I am scheduled for my oral candidacy exam/proposal defense. I was reflecting on this as I was washing my SDS-PAGE. I washed it so well that I washed it right down the sink. Somewhere, out there, is my gel with sample.

I realized upon this reflection that I am an idiot. Seriously—and I don’t just mean about washing my gel down the drain. I am going to mention the clinical relevance of my work and yet I realize that I know little to nothing about ischemia, sepsis, reperfusion, asthma, and erectile dysfunction. Heck, I have spent the entire day attempting to pronounce ischemia and find myself getting tongue-tied. Why can’t medical terminology be phonetic? I have come to the conclusion that in less than two weeks I need to attain a medical degree. I have sort of neglected the big picture in the secluded world of basic science/research.

To compound matters, I babble when under periods of stress. To make matters worse, I tend to blurt out the first thing that enters my mind when I am nervous around my advisor. My proposed theory of “electron transfer to oxyhemoglobin via NOS” was a doozey during one lab meeting presentation. Not my proudest moment.

Fellow graduate students, being supportive of my upcoming defense have been kind enough to recount their experiences of their oral candidacy exam. Being grilled for 5 hours of questioning, feeling like an idiot, and reduced to a puddle of tears? Heck, I am already there! No need to go through the formality of this defense then. I have reached full blown panic mode/attack. No exaggeration here. Someone, somewhere, please shoot me with a tranquilizer gun filled with some CNS depressant.

Yet, there must be a silver lining in every cloud I always say. For starters, my department has not asked me for my presentation title, so perhaps they have forgotten to make this known and officially invite the “public”. Yes, I can do without making a public spectacle of myself. Also, I am told that presentations are my forte. Even during the course of non-sequitors, I will hold my own. Given enough time and verbosity, I can make anything believeable. Or maybe I am just good at wearing down my audience?

I have also come to the conclusion that sadists conceived graduate school. Those attending graduate school are masochists. Therefore, a perverted intellectual relationship of S&M exists within the confines of learning.

I would much rather face a hungry bear while slathered in honey than face my oral candidacy examination. Seriously. Give me a bucket of honey and point me in the direction of the nearest bear infested woods and I will go to town.

At least against the bears, I stand a chance…



Anonymous Anonymous said...

You need to run your gels at night when there are no distractions in the lab.... At night, be wary of the lab gremlin :}

Thursday, July 26, 2007 7:13:00 PM  
Anonymous Anonymous said...

No erectile dysfunction for me
despite being in a beer coma :}

Here is what I know about the role of NOS in ischemia / reperfusion and sepsis. Hope it helps...

NOS Pathophysiology in Ischemia/Reperfusion Injury: During neuronal ischemia, glutamate uptake and transport reversal ceases increasing synapse glutamate levels. Ischemia/reperfusion injury in the nervous system is associated with calcium influx mediated by glutamate stimulation of NMDA receptors. Calcium / calmodulin binding activates nNOS for NO synthesis. The overproduction of NO by initial nNOS and subsequent iNOS activation leads to neuronal cell death by depleting cellular energy and toxic peroxynitrite formation. NO reacts with cis-aconitase inhibiting glycolysis. Mitochondrial iron-sulfur cluster enzymes are inhibited by NO impairing oxidative phosphorylation. If calcium influx is sustained, intracellular stores of L-arginine will become sub-saturating decoupling NADPH oxidation from product formation. The arginine-subsaturated NOS generates the reactive oxygen species superoxide and hydrogen peroxide by the decay of ferrous-dioxy and peroxo-heme NO biosynthesis intermediates respectively. Dismutation reversal forms superoxide. The cellular toxin peroxynitrite is generated by the reaction of NO with superoxide. Peroxynitrite alters cellular chemistry and structure by nitrosylating tyrosine, breaking DNA strands, and modifying the bases and deoxyribosose of DNA. Inflammation associated poly(ADP-ribose) polymerase-1 (PARP-1) mediated activation of the NF-KB pathway in microglial cells induces their sustained expression of iNOS causing secondary late phase damage to the post ischemic neurons.

NOS Pathophysiology in Septic Shock: Sustained upregulation of vascular smooth muscle cell and endothelial cell iNOS expression induced in septic shock by cellular components of gram negative bacteria leads to insufficient arterial pressure for adequate tissue perfusion and oxygenation by preventing smooth muscle contraction. Stimulation of sGC (soluble guanylate cyclase) cyclic guanosine monophosphate (cGMP) production in vascular smooth muscle cells by vascular endothelium derived NO generated basally and in response to receptor agonists and the shear force exerted against blood vessel walls by circulating blood counteracts sympathetic nervous and renin angiotensin system mediated vasoconstriction. cGMP dependent protein kinase in smooth muscle cells activates myosin phosphatase. Myosin phosphatase dephosphorylates the regulatory light chain of myosin. The phosphorylated state of the myosin regulatory light chain is requisite for myosin head ATPase activity. Hydrolysis of ATP by the myosin head is the basis for the conformational change which triggers its cycling crossbridge formation with actin filament subunits making possible muscle contraction. Microcirculatory vasoconstriction caused by selective eNOS inhibition in animal models of septic shock is deleterious indicative of a beneficial role of eNOS in septic shock

Thursday, July 26, 2007 10:50:00 PM  
Anonymous the sacrificial gel said...

gurgle!! gurgle!!! gurgle!!!

Thursday, July 26, 2007 10:54:00 PM  
Anonymous the sacrificial gel said...

I lost my molecular weight marker in a walleye attack :{

Friday, July 27, 2007 3:43:00 AM  
Anonymous the sacrificial gel said...

My resolving gel has been gashed by the propellers of a Great Lakes ore carrier :(

Friday, July 27, 2007 4:22:00 AM  
Blogger Katie said...

What lab gremlins? Although I periodically do hear about the lab gremlins. Thanks for the NO/NOS info.

The Scacrifical Gel,
Yes, but we all know that now you are in a better place...

Friday, July 27, 2007 12:12:00 PM  

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