Better method: Open bottle with some red wine in it. The flies get in but never get out. This was the standard trick to catch escapees in our fly genetics lab... Of course we had to prepare fresh, nearly empty red wine bottles every now and then...
Concerning null results, however, you really do need to make an effort to publish them. Otherwise other scientists may waste time and money duplicating efforts that don't go where it seems they might.
Exactly my position - and I spend a lot of energy on that. But mostly, I am going nowhere with it. You can manage to pull it off if you heavily discuss your null result in some positive terms (e.g. "prion protein helix 1 does not change conformation under any of the applied environmental conditions. We hypothesize therefore that it has some protective "gatekeeper" function preventing the conformational change of the whole prion protein").
Having seen the development of biochemistry in the last decade, I really feel it to be in quite a sad state. While you can publish pure, fundamental research, you have nearly no chance of getting funding for it, if your proposal doesn't scream "MEDICAL RELEVANCE!!!! POTENTIAL PATENTS!!! SAVING THE WORLD FROM CANCER; AIDS, BSE!!!!!" all over it.
And where the hell do you get your null results published? In my field, biophysics, this is extraordinary difficult - though it could save lots of work for many other scientists. At least here in Germany, biochemistry is not just basic research anymore. You have to prove RELEVANCE in your grant proposals - and this means mostly medical, and thereby ECONOMICAL, relevance. This doesn't leave much room for null results.
It's about forcibly killing Panislamic radicalism over the next several decades, perhaps in a generation, without letting it run its natural course over the next 2 to 3 centuries.
Nice troll there, young fellow. Perhaps you should sometimes let reality slightly modify your worldview, won't you? Iraq was the only solidly secular state in the region. That for sure has changed now. Nice work there.
Re:mechanism for variable expression in vertabrate
on
Prions, Darwin's Friend
·
· Score: 4, Informative
I wouldn't compare this effect to plasmid based inheritance. As far as I understand the article, the yeast prion PSI is a suppressor of nonsense mutation. This means that PSI works at the level of translation, the production of proteins from genetic information. Translation is normally a well regulated process which terminates at so called stop codons. PSI now enables the yeast translation machinery to read over this stop codons, thereby producing longer proteins with somewhat altered functions, or even new proteins which where silenced by stop codons. At this point this mechanism does not created inheritable phenotypes. Nevertheless, the group of True et al. found inheritably changed phenotypes in some PSI+ stems. This might be - and I'm speculating here - due to the production of altered replication proteins by this mechanism, which then introduce more mutations into the yeast genome.
In this light, the mechanism of yeast prion action is more akin to some error prone repair and replication mechanisms in bacteria, which are triggered by stress and result in an increase in spontaneous mutations. This is different from plasmid transfer, which is a directed transfer of well-defined genetic information
In case of mammalian prions, I see no indication of a similar mechanism. Human prion protein huPrP is a cell surface protein which does not interfere with the translation apparatus or with genetic processes in the nucleus. It rather appears to be involved in regulatory processes which transduce signals from outside into the cell. Yeast and mammalian prions share no common characteristics except for the ability to exist in to different conformations and to autocatalytically propagate one of these conformations. In general, prions are no functionally homogenous group. Another example would be the prions of slime molds, which play a role in the exchange of genetic information by cell fusion. Here the prion-conversion mechanism creates some kind of incompatibility groups, shutting down the fusion zone if two cells belonging to different compatibility groups try to fuse.
The prion phenomenon is a basic biophysical characteristic, it has not to be bound to a certain function. The fact that yeasts and fungi have found a way to use this physical property of certain proteins does not implicate that other prions have to have useful functions also. It is absolutely possible that mammalian prions are a purely pathological phenomenon.
You want to simulate the motions of the protein over time. This is a sequential problem which can't be parallelized very well. Calculations for every time step are possible in parallel, but these are to small units to make a distributed calculation useful. In addition, most current molecular dynamics systems don't scale to well on parallel systems. AMBER for example doesn't gain significant performance if run on more than 64 nodes.
They are not novel. Up to now, mice could only be infected using brain homogenate from already infected animals. For the first time the group of Prusiner succeeded in creating infectious material de novo from purified prion protein generated by transgenic bacteria.
Surface area is definitely a good point. In the case of prion protein, aggregation in vitro can be significantly enhanced by regular ultrasound treatment which breaks up existing aggregates, thereby increasing the number of reactive sites.
1.) The cellular prion protein PrP(C) is no
complex, just a single chain of 231 amino acid residues. The misfolded form PrP(Sc) aggregates into large complexes. Up to now it is unknown if there is only one single pathological conformation. Details of the aggregate structure are also unknown, except for low-resolution electron crystallography data (at about 7 angstrom resolution), which suggests a triangular beta-helical structure of the misfolded form.
2. Modelling the structural conversion of PrP(C)->PrP(Sc) in a molecular dynamics simulation is not feasible at the moment. The spontaneous refolding of prions is apparently a very slow process, suggesting a large energy barrier for the conversion reaction. This leads to prohibitively long simulation times needed. I've done some unfolding simulations of prion structures, which, up to now, gave no hint on a possible path for refolding.
The War on Prions FUD has already begun. The USA considers prions a possible bioweapon. At least one prion scientist i know had problems getting a visum for the USA... Going paranoid for a moment, prions could make an interesting bioweapon. You wouldn't need to target people, but rather cattle. The economic impact of a full-scale BSE epidemic in a beef-producing country would be quite impressive.
I think this is the only article in the history of Slashdot that could make GNAA comments, trolling and general bad behaviour -- ON TOPIC! I would humbly ask the moderators not to mod said classes of comments up, though...
Quite right. Which leads to the question why this guy had to collect 10000 screen names + user data? It would have sufficed to show that it can be done and to report it to the company, and, if the company shrugs it off, to the user base. Finding and reporting weaknesses is one thing, exploiting them yourself for greater effect is at least questionable.
Slashdot Mirror
Therefore we took precautions... Anyway they were all harmless, I tell you, harmless, MUWAHHHHHAAHAHHA
Well, I guess if cockroaches are outlawed, only outlaws... Err... forget it....
Better method: Open bottle with some red wine in it. The flies get in but never get out. This was the standard trick to catch escapees in our fly genetics lab... Of course we had to prepare fresh, nearly empty red wine bottles every now and then...
You surely meant
In Space... No One Can Hear You Scram
Exactly my position - and I spend a lot of energy on that. But mostly, I am going nowhere with it. You can manage to pull it off if you heavily discuss your null result in some positive terms (e.g. "prion protein helix 1 does not change conformation under any of the applied environmental conditions. We hypothesize therefore that it has some protective "gatekeeper" function preventing the conformational change of the whole prion protein").
Having seen the development of biochemistry in the last decade, I really feel it to be in quite a sad state. While you can publish pure, fundamental research, you have nearly no chance of getting funding for it, if your proposal doesn't scream "MEDICAL RELEVANCE!!!! POTENTIAL PATENTS!!! SAVING THE WORLD FROM CANCER; AIDS, BSE!!!!!" all over it.
And where the hell do you get your null results published? In my field, biophysics, this is extraordinary difficult - though it could save lots of work for many other scientists. At least here in Germany, biochemistry is not just basic research anymore. You have to prove RELEVANCE in your grant proposals - and this means mostly medical, and thereby ECONOMICAL, relevance. This doesn't leave much room for null results.
But, but... I **NEVER** inhaled!!
Wrong conclusion - this only proves that UNIX was designed by chimps...
Just be sure to have a lot of space in your trunk for all the punched tapes containing the data for your navigation system....
Nice troll there, young fellow. Perhaps you should sometimes let reality slightly modify your worldview, won't you? Iraq was the only solidly secular state in the region. That for sure has changed now. Nice work there.
In this light, the mechanism of yeast prion action is more akin to some error prone repair and replication mechanisms in bacteria, which are triggered by stress and result in an increase in spontaneous mutations. This is different from plasmid transfer, which is a directed transfer of well-defined genetic information
In case of mammalian prions, I see no indication of a similar mechanism. Human prion protein huPrP is a cell surface protein which does not interfere with the translation apparatus or with genetic processes in the nucleus. It rather appears to be involved in regulatory processes which transduce signals from outside into the cell.
Yeast and mammalian prions share no common characteristics except for the ability to exist in to different conformations and to autocatalytically propagate one of these conformations. In general, prions are no functionally homogenous group. Another example would be the prions of slime molds, which play a role in the exchange of genetic information by cell fusion. Here the prion-conversion mechanism creates some kind of incompatibility groups, shutting down the fusion zone if two cells belonging to different compatibility groups try to fuse.
The prion phenomenon is a basic biophysical characteristic, it has not to be bound to a certain function. The fact that yeasts and fungi have found a way to use this physical property of certain proteins does not implicate that other prions have to have useful functions also. It is absolutely possible that mammalian prions are a purely pathological phenomenon.
If you already screw the tiles, what do you need the cyber-chicks for?
Now that would be pure communism, wouldn't it? And we cannnot allow that, yes?
You want to simulate the motions of the protein over time. This is a sequential problem which can't be parallelized very well. Calculations for every time step are possible in parallel, but these are to small units to make a distributed calculation useful. In addition, most current molecular dynamics systems don't scale to well on parallel systems. AMBER for example doesn't gain significant performance if run on more than 64 nodes.
They are not novel. Up to now, mice could only be infected using brain homogenate from already infected animals. For the first time the group of Prusiner succeeded in creating infectious material de novo from purified prion protein generated by transgenic bacteria.
Surface area is definitely a good point. In the case of prion protein, aggregation in vitro can be significantly enhanced by regular ultrasound treatment which breaks up existing aggregates, thereby increasing the number of reactive sites.
2. Modelling the structural conversion of PrP(C)->PrP(Sc) in a molecular dynamics simulation is not feasible at the moment. The spontaneous refolding of prions is apparently a very slow process, suggesting a large energy barrier for the conversion reaction. This leads to prohibitively long simulation times needed. I've done some unfolding simulations of prion structures, which, up to now, gave no hint on a possible path for refolding.
The War on Prions FUD has already begun. The USA considers prions a possible bioweapon. At least one prion scientist i know had problems getting a visum for the USA...
Going paranoid for a moment, prions could make an interesting bioweapon. You wouldn't need to target people, but rather cattle. The economic impact of a full-scale BSE epidemic in a beef-producing country would be quite impressive.
>So what are you doing on Slashdot?
He probably printed it to paper and hands his hand-scribbled responses to his typing monkey. At least that's my guess.
You know, there are cheaper paper weights available...
There should be a way to mark a whole article "-1 Troll"...
Well, in contrast to people still making lame clippy jokes, clippy can be turned off...
I think this is the only article in the history of Slashdot that could make GNAA comments, trolling and general bad behaviour -- ON TOPIC!
I would humbly ask the moderators not to mod said classes of comments up, though...
Quite right. Which leads to the question why this guy had to collect 10000 screen names + user data? It would have sufficed to show that it can be done and to report it to the company, and, if the company shrugs it off, to the user base. Finding and reporting weaknesses is one thing, exploiting them yourself for greater effect is at least questionable.
So is copyright...