Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors
Haitao Youa,1, Shigeki Tsutsuib,1, Shahid Hameeda, Thomas J. Kannanayakalb, Lina Chena, Peng Xiac, Jordan D. T. Engbersa, Stuart A. Liptonc, Peter K. Stysb,2, and Gerald W. Zamponia,2
Edited* by Stanley B. Prusiner, University of California, San Francisco, CA, and approved December 21, 2011 (received for review July 5, 2011)
N-methyl-D-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrPC), a key copper-binding protein in the CNS. Acute ablation of PrPC by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrPC interacts with the NMDAR complex in a copper-dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Aβ1–42 (10 nM–5 μM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Aβ1–42, copper chelators, or PrPC inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady-state NMDAR currents and neurotoxicity. We propose a physiological role for PrPC, one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Aβ1–42 might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrPC-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor.
If you area true long you don't acre and should avg down at some point or add...for traders the direction is down...I expect to see the 5's ...ignore GS and you usually end up paying for your arrogance.
Suns of beeches! But you know what this means, don't you? The bigz are gonna sell the news. Boo Yah!
I'm neither - I Buy and Sell it everyday - Since $7.00 - Did'nt mean to get you so upset .
Allo, i took you off ignore just to enlighten you a little. Short term does look like a head and shoulders forming, MM's shaking the tree, however have you ever looked at a weekly chart? It shows an inverse H+S forming with a possible move up to the $4 area. Remember from failed moves come fast moves. See you at $4 and we take it from there.
Sentiment: Strong Buy
One of the opportunities before BLOX is the coming and massive move facing public and private networks to ipV6. This will be mostly in America as China and Africa have a big head start, and somewhat EU. Will this sustain the multiple here I don't know, but many of their customers will be calling their acct. reps once their forced to make this move. If one of you guys who knows more than me and can can somewhat quantify this for BLOX I'd love to hear it. I sold all 500 shares yesterday morning as I'm playing with scared money. With my luck they blew out the quarter and looks to open today north of 40. Best to all of you still in.
While a short squeeze is possible any time given the lack of liquidity in this stock, I would be dissappointed to find that the stock is moving up for that reason. I tend to believe that the stock is actually moving up due to the Real Deal Poker acquisition which I think was terrific. There could be some short sellers exiting based on the continually improving outlook for MGT, but I don't think there is much to indicate a squeeze.
Also, Nasdaq has not released the 8/31 short numbers for MGT yet. They did tick up slightly from 7/31 to 8/15 moving from 356K shares short to 371K shares short. As of 8/15, with the low trading volume the days to cover were estimated at 6.8 days.
Eventually all the lies will backfire and this market will come crashing down. The next crash will wipe us out for good. Everything is based on lies, propaganda, debt and money printing.
Why these guys on CNBC talking about 200,000 or so is beyond me. This is a services economy, did they ignore retail sales, mickey D's monthly sales and more??? Some forecasters!!
Sounds like a plan, but don't forget Obama previously told the Israelis to kiss his tush. They may want to feed him humble pie first.
is it any wonder why joe public is shunning the market? CNBC ratings at 20 yr low!
admit it every one of us is scared to declare victory because in 2 minutes the whole scenario will reverse you on your head.
I've been doing an interesting trade recently 20 put options then 20 call options on the close play the swings. it's been working perfectly