November 09, 2005

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• APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 activates caspase 9 and thus initiates a cascade of proteolytic events leading to apoptotic destruction of the cell. Cellular phenotypes were measured using a yeast heterologous expression assay in which human Apaf-1 and other proteins necessary to constitute a functional apoptotic pathway were overexpressed. Apaf-1 variants encoded by APAF1 alleles that segregate with major depression in families linked to chromosome 12 shared a common gain-of-function phenotype in both assay systems. In contrast, other Apaf-1 variants showed neutral or loss-of-function phenotypes. The depression-associated alleles thus have a common phenotype that is distinct from that of non-associated variants. This result suggests an etiologic role for enhanced apoptosis in major depression. Damn right!
• Yeah...thought I'd link to the quickie abstract as only version one could see for free-like. But now that nice Mr.rocket88 has brought it right here to Monkey Town in all its multisyllabic deliciousness.
• Oh, those wacky protein apoptosis protease activating factors!
• I know! I was like, whatevaaar!
• Is this something akin to this situation? Or more of a 'factory defect' that causes premature breakdown?
• That is the coolest thing ever! OK, not so much for the grasshopper, but wow! I get the idea that it's a factory defect kind of thing...this protein contributes a little extra to something that happens to everyone; when we are stressed cells die in (I believe) the hippocampus. But if you have this protein, cells continue to be ordered to die without the stresser while someone's brain without it would cease cell death at that point and start to recover.
• Wheee! I'm controlled by a rogue protein! I'm starting a Doomsday cult on Saturday. You're all invited; I'm thinking a potluck, then a little presentation in the den followed by every last one of you granting me power of attorney, then charades.
• Is it something akin to this situation?
• "Pip pip peep peep pip pip peeep!" Well, in that case, the solution is obvious, MJ: switch to Mac. Ah, I'm not very good at charades. And do I have to bring new tennis shoes?
• Cool! Do we get to go in a spaceship? Is there a comet in the deal? Also:

  The Apaf-1 gene was discovered using large families from Utah that contain multiple cases of major depressive disorder.

  Ummm....How could they tell? MJ, I've looked at the archives, and you haven't been having enough of these (which you richly deserve) ==> )))). Lots of people here care about you. You are a valued and treasured person. We miss you when you go quiet. Really. so, will your brains start drooling through your ears (or is that caused by too much 80s goth rock)?
• Well, of course they discovered rogue proteins that want you to kill yourself. Now they can make oodles of money selling some sort of drug based on some sort of syndrome based on the complications of this discovery. Of course, the side effects will include insomnia *and* hypersomnia, along with cold chills, hot flashes, and a tendency to suffer sexual dysfunction while driving heavy machinery ... But hey! The drug companies make more money. I just don't want anyone to start thinking they're doing all this work for the good of humanity. If you do, you deserve what you get.
• I deserve co-fluoxetine, quetiapine and novo-buproprion. The side effects include reduced anxiety, less disruptive rage and not killing myself. Boy, am I being duped by Big Pharma. It should be obvious to all that nobody working in any association with research and development of psychiatric drugs has any family member or close friend who has ever been diagnosed with depression. That is because they are ingeniously constructed robots that power themselves down at exactly 5 pm and return to their storage pods, drawing only enough power to laugh maniacally through the night.
• The first sign is spending too much time laughing at filter comments. Especially the ones that aren't funny. I propose they call this chromosome-12 gene depression predisposition the Eeyore Factor.
• Done and done. I'm calling the White House now.
• 1: I don't get this. I can't access it. 2: What?! Is this for real, girl? 3: I don't get some of these highly tecnichal and smugly referential terms. 4: I will pray for your good health, MJ.
• Oh, I'm healthy alright, as long as I have my flagons of magic elixer. If not *poof* I turn into hissing spitting bobcat girl. Like so; with and without.
• hon, you're dead Check with another forum type thingie if you don't like this.
• I'm starting a Doomsday cult on Saturday. You're all invited; I'm thinking a potluck, then a little presentation in the den followed by every last one of you granting me power of attorney, then charades. Memo to moneyjane: don't serve the Kool-Aid until after the power of attorney thing.
• And do I have to bring new tennis shoes? Do we get to go in a spaceship? Is there a comet in the deal? Yes Yes No ...don't serve the Kool-Aid until after the power of attorney thing. Oh, I know that now, believe you me. Boy was my face red! No...wait...that was after the carbon monoxide trial run.
• Hmmmm...first I got nanners, then my brains started drooling through my ears, and stirfry thinks I'm dead. I am ever slightly confused. It's probably the drugs. That you'll have to pry from my cold dead hands!
• You see, my answer to this is to try to kill my brain before it kills me.
• Seriously though...this may be very good news. As drivingmenuts noted, there are a lot of side effects with drugs used to treat depression. Most of those classes of drugs are of the "clean up in aisle five" variety; used to restore and/or more effectively use serotonin, etc. after levels have gone haywire. The idea here is that intercepting this protein's cell seppuku messages may prevent the levels from going wonky in the first place. Which may mean it works quite differently and may not have the same type of side effects.
• But your particular brain is so cute and furry and nice...like a kitten in your head. Don't do it Chy!
• It's more like a horny toad.
• Boy was my face red! No...wait...that was after the carbon monoxide trial run. All I know is that the basement is getting full, and I'm sick of digging. Time to get a bigger basement, or stop poisoning the guests. And I've got shovel-hands. Will you look at these callouses!
• Ah, hellow and greetings to all youse assembled monkeys heah. I have read wit great int-erest your collective comments and jokes and like that. But I regret - I am truly sorry to say that I have detected - the most minute amount, you unnerstan' - of sarcasm and also the poking fun of, as it regaads my frien' an' associ-ate, Big Pharma. Y'see, Big Pharma don' like no makin' fun of, akay? An' any o' youse who likes the livin witout tha gasses an' trowin' up an' whatnot had best show some respect for Mr. Pharma 'cause you don't wanna be on the waiting list for medimications, aiight? Okay. So next time maybe it's not your little tread here we rearrange? Capiche? *looks around* /drives_off
• Monkeys stare agog at pete's retreating tail lights Cut to; A banana falls to the ground in slo mo, intercut with black and white mushroom cloud stock footage. Cue music; O Fortuna Run credits
• well, they discovered the The APAF-1 gene (Apoptosis Protease Activating Factor 1), which produces the apaf-1 protein. this protein activates a series of events leading to the destruction of youe cells. certain forms of the gene seem to overreact, leading to increased apopstosis (aka cell death... but in this case, ordering the cells to self-destruct when they're not ready to die.) in the hippocampus. (all of us experience changes in this part of the brain when we're faced with stressful situations. while most people rebound, those with a genetic predisposition for depression end up 'brain-damaged' and crazy.) so, the hypothesis is that this apopstosis overdrive is involved in the cause of major depressive disorders... and so as moneyjane notes, this opens the door for new, and possibly more effective, treatment options & research.
• Generally speaking, the understanding of how the brain works is somewhere between wishful simplification and voodoo. We need oodles more discoveries like this. So today Monkeys, we're going to pair up in the laboratory, remove the tops of our hairy craniums and have a little diggin' and a little show and tell. First one to the hippocampus wins!
• Oh! *waves hand* Who wants to be my partner? I can get you a win with minimal collateral damage! Unless your hippocampus isn't where my neuroscience book says it is...
• Sadly, my cranium isn't as hairy as it used to be.
• Here ya go, I have hair to spare. Why is it Curly? It's from Down there
• Austrailia?
• Never heard of it.
• oh, so this was a joke the whole time. Gosh, I'm dense. I guess I could have spun my earlier statement of concern as some kind of injoke. But I won't.
• No, it's not a joke, and I appreciate your statement of concern very much; however mental illness is still stigmatized (even as within the mentally ill population taking psychiatric medication is often stigmatized) and it's not easy for many people to simply announce they're nuttier than a fruitcake. So we post scientific discoveries like APAF-1 and make goofy comments instead :)
• MonkeyFilter: Do we get to go in a spaceship? MonkeyFilter: Hmmmm...first I got nanners, then my brains started drooling through my ears. MonkeyFilter: ...somewhere between wishful simplification and voodoo. MonkeyFilter: It's not easy for many people to simply announce they're nuttier than a fruitcake. I am! I am! *Jumps up and down waving hands
• OK, understood (as much as possible).
• Monkeyfilter: I still don't get it.
• MonkeyFilter: Sadly, my cranium isn't as hairy as it used to be. MonkeyFilter: First one to the hippocampus wins! MonkeyFilter: Check with another forum type thingie if you don't like this. MonkeyFilter: Time to get a bigger basement, or stop poisoning the guests. MonkeyFilter is one way to deal with having a lousy day.