The organism may end up genetically very different, but most likely morphologically very similar in your scenario. While the mutations are random, the selection pressure from the environment is the same here and will most likely result in very similar structures - compare the bodyshape of dolphins and tuna - completely different evolutionary path, highly similar morphology due to the same environmental selection pressure.
NP-complete? So if I give your a protein sequence and a predication of its structure
you can tell if it is a correct predication with certainty? That is a big achievement.
That would be the relevant decision problem, yes. Unfortunately, there is no know efficient algorithm for that class of problems... So, for now we have to rely mostly on exponential-time algorithms.
Thanks, I'll have a look at it. I agree with you that Endnote isn't optimal. If refbase works for me, I might give it a go - however, not while I keep working on a 70% completed PhD thesis...
Sorry to say that, but you are overly optimistic here, as k98Sven stated above. I work in structural biochemistry, so let me clear up a few points here:
First of all, you can't at the moment crack the protein folding problem by throwing more computational power at it. We still lack lots on insight into many of the fundamental forces governing protein folding. Electrostatics at that level are a nasty thing, for example. The scale of the system would require a quantum mechanical treatment, but then again the total systems are too large, not to speak of problems with the basis sets and parametrization for a QM treatment. Oh, and the protein folding and design problem has been shown to be NP-complete.
Secondly, not all proteins even have defined structures. The class of so-called natively disordered proteins is large and might even comprise about 30% of the whole proteom. Those proteins only adopt structure in interaction with other proteins or other factors.
Third, in many cases the structure doesn't help you very much. True, a cancer causing mutation might have a clear structural effect. In other cases, it could perhaps just subtly alter electrostatics on a protein surface, causing a slight difference in its interaction with another protein, which finally gets amplified way downstream a regulatory cascade where it causes the final problem. Knowledge of protein structures is useful to clarify that, but you need to know the whole interaction network to fully understand it.
Fourth, the cell is crowded. Knowing the structure of an isolated protein in solution does not tell you all about its function in the cell, where it is in contact with lots of other proteins.
Fifth, not only structure determines the function of a protein, but also its dynamics. Proteins move, and these movements are intricately linked to their function.
Sixth, and final, if you want to use the structure of a protein as a basis for rational drug design, you have also to solve the design problem. How do you exactly build a compound with the desired properties? There is no completely rational approach implemented at the moment, much is just done by large-scale trial and error approaches.
Cells are way out of the nano-scale. Enzymes, on the other hand, are the only true available nanomachinery at the moment. However, they have some problems. First of all, I don't see protein based nanomachinery ever working outside of a reasonably well buffered aqueous medium, which severly limits its use for several fields of engineering. Secondly - to really get to the SF-level of nanotechnology, you would sooner or later need selfreplicating nanomachines. It might be possible to engineer enzymes to do that, but in biology, the self-replicating unit is the cell, not the enzyme, so again, we are way out of the nano-scale here.
A somewhat murky definition - "normal nature behaviour". Humans are not the only species to significantly alter their environment. Many prairies would be woodland, was it not for the huge impact of herds of herbivorous animals, for example. Where is the boundary? When does it become "unnatural" - by being a consequence of intelligence?
I don't really want to flame here - I completely agree that human impact on many ecosystems is out of bounds, but pinning this down to terms like "natural" is not really helpful. Oh, and we do not have the slightest chance of destroying "mother earth", even if we unleashed all our nuclear potential at once. Nature will cope, evolution will go on. Destroying the basis of our civilization, or even ourselves as species, however, is very well in the realm of the possible.
As I said, you concerns are not completely unfounded - just try to put them into less mystic and more well-defined concepts next time.
It is not like DDT is the only available pesticide - perhaps we chose on that doesn't tend to accumulate in the food chain this time? An interesting approach would be the use of Bacillus thuringiensis var. israelensis, a bacterium that is highly toxic for mosquito larvae. It is harmless to basically everything else, except for some kinds of insects, and has been used succesfully against other insect infestations. It can be aerosolized and sprayed just like a chemical pesticide.
Then there is Methoprene - a compound that is similar to an insect growth hormone. It targets specifically insect larvae and prevents them from reaching their next stage of development. Again, it can be used like any conventional insecticide, does not accumulate and is easily biodegradable and non-toxic to anything but insects. Has been successful in trials against mosquitoes as well.
I wouldn't be too worried - that was basically the situation in the UK during the BSE epidemic. But, then again, the oral, inter-species infectivity of BSE is low. For hundreds of thousands of infected cows that were ultimately consumed by humans, we have a total of slightly above 100 vCJD cases - and the numbers won't rise significantly, by all projections.
Well, prion diseases are rather unique as they have three possible etiologies - transmitted, genetic and spontaneuos. Transmission can happen by ingestion of contaminated food, by surgery, especially neurosurgery and perhaps - this is not conclusively shown yet - via the mucous membranes. Genetic is clear - some gene defects facilitate the misfolding of the native form of the prion. Lastly you got the spontaneuos forms, where, with low probability, the healthy form of the prion protein spontaneously misfolds into the diseased form.
Now, for Alzheimer's we know genetic causes and most likely spontaneous causes. There have been lots of transmission experiments, but non of them succeeded in transmitting the disease. As such experiments are rather harsh - implanting diseased tissue into healthy brains of test animals, it can quite safely be said that a direct transmission is simply impossible here.
Don't think so - I work in prion research. It is somewhat similar with regard to the basic mechanism, but there is no indication that Alzheimer's is transmissible.
Well, your focus is a bit too heavy on the developed countries here. I suggest you look at the world wide numbers, which are dominated by the HIV infections in Africa and Asia. In this larger context it is not by any means a specific problem of homosexual communities.
Re:The Growing Problem of Alzheimer's
on
Visual Test Diagnosis
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· Score: 2, Interesting
I don't see gene therapy as the most promising path towards a cure for Alzheimer's disease. First of all, as with most neurodegenerative diseases, the cause of disease is poorly understood and not necessarily purely genetic - in fact, in most cases, I suspect a strong environmental influence, as well as a certain number of "spontaneous" cases caused by stochastic conformational events. So, we are in fact dealing with a multitude of causes, making a causal therapy like gene therapy an unlikely candidate. I rather expect to see more symptomatic treatments, approaching the problem at the level of the protein misfolding that causes the accumulation of the A-beta plaques. There have been some immunological approaches, kind of a vaccination against Alzheimer's, but the results are not too promising at the moment. Anti-misfolding agents are under heavy investigation, not only against Alzheimer's, but also against CJD, Parkinson's and similar, but nothing significant has made it out of the lab yet. The basic mechanisms are still very poorly understood.
Good point on admitting the uncertainty of absolute transcendent values. I am not sure about this point either - but I am quite sure that such values, should they exist, are not to be found in the oral tradition, later written down, compiled and altered for various political reasons, of some ancient middle-eastern tribes...
Slashdot Mirror
Nuclear grenades? Try this.
Ebony? Nirnroot? Call me when they start giving out Skooma.
FHTAGN!
And what exactly is your agenda, spamming this completely off-topic drivel here?
That is an inescapable natural moral precept that nothing and no one can outrun.
Actually, this is a couple of words.
The organism may end up genetically very different, but most likely morphologically very similar in your scenario. While the mutations are random, the selection pressure from the environment is the same here and will most likely result in very similar structures - compare the bodyshape of dolphins and tuna - completely different evolutionary path, highly similar morphology due to the same environmental selection pressure.
That would be the relevant decision problem, yes. Unfortunately, there is no know efficient algorithm for that class of problems... So, for now we have to rely mostly on exponential-time algorithms.
Thanks, I'll have a look at it. I agree with you that Endnote isn't optimal. If refbase works for me, I might give it a go - however, not while I keep working on a 70% completed PhD thesis...
First of all, you can't at the moment crack the protein folding problem by throwing more computational power at it. We still lack lots on insight into many of the fundamental forces governing protein folding. Electrostatics at that level are a nasty thing, for example. The scale of the system would require a quantum mechanical treatment, but then again the total systems are too large, not to speak of problems with the basis sets and parametrization for a QM treatment.
Oh, and the protein folding and design problem has been shown to be NP-complete.
Secondly, not all proteins even have defined structures. The class of so-called natively disordered proteins is large and might even comprise about 30% of the whole proteom. Those proteins only adopt structure in interaction with other proteins or other factors.
Third, in many cases the structure doesn't help you very much. True, a cancer causing mutation might have a clear structural effect. In other cases, it could perhaps just subtly alter electrostatics on a protein surface, causing a slight difference in its interaction with another protein, which finally gets amplified way downstream a regulatory cascade where it causes the final problem. Knowledge of protein structures is useful to clarify that, but you need to know the whole interaction network to fully understand it.
Fourth, the cell is crowded. Knowing the structure of an isolated protein in solution does not tell you all about its function in the cell, where it is in contact with lots of other proteins.
Fifth, not only structure determines the function of a protein, but also its dynamics. Proteins move, and these movements are intricately linked to their function.
Sixth, and final, if you want to use the structure of a protein as a basis for rational drug design, you have also to solve the design problem. How do you exactly build a compound with the desired properties? There is no completely rational approach implemented at the moment, much is just done by large-scale trial and error approaches.
Cells are way out of the nano-scale. Enzymes, on the other hand, are the only true available nanomachinery at the moment. However, they have some problems. First of all, I don't see protein based nanomachinery ever working outside of a reasonably well buffered aqueous medium, which severly limits its use for several fields of engineering. Secondly - to really get to the SF-level of nanotechnology, you would sooner or later need selfreplicating nanomachines. It might be possible to engineer enzymes to do that, but in biology, the self-replicating unit is the cell, not the enzyme, so again, we are way out of the nano-scale here.
Shortcoming: No decent reference/literature managment system available.
Workaround: Use MS Office+Reference Manager/Endnote, unfortunately.
I don't really want to flame here - I completely agree that human impact on many ecosystems is out of bounds, but pinning this down to terms like "natural" is not really helpful. Oh, and we do not have the slightest chance of destroying "mother earth", even if we unleashed all our nuclear potential at once. Nature will cope, evolution will go on. Destroying the basis of our civilization, or even ourselves as species, however, is very well in the realm of the possible.
As I said, you concerns are not completely unfounded - just try to put them into less mystic and more well-defined concepts next time.
Most insulin today is produced by genetically engineered bacteria carrying the gene for human insulin.
Define "natural", please.
Then there is Methoprene - a compound that is similar to an insect growth hormone. It targets specifically insect larvae and prevents them from reaching their next stage of development. Again, it can be used like any conventional insecticide, does not accumulate and is easily biodegradable and non-toxic to anything but insects. Has been successful in trials against mosquitoes as well.
So, why DDT?
It does the same in Opera 8.5.
I wouldn't be too worried - that was basically the situation in the UK during the BSE epidemic. But, then again, the oral, inter-species infectivity of BSE is low. For hundreds of thousands of infected cows that were ultimately consumed by humans, we have a total of slightly above 100 vCJD cases - and the numbers won't rise significantly, by all projections.
Now, for Alzheimer's we know genetic causes and most likely spontaneous causes. There have been lots of transmission experiments, but non of them succeeded in transmitting the disease. As such experiments are rather harsh - implanting diseased tissue into healthy brains of test animals, it can quite safely be said that a direct transmission is simply impossible here.
Indeed. Early-onset Alzheimer's is caused by mutations in the Presinilin gene family. For an overview, look here.
Don't think so - I work in prion research. It is somewhat similar with regard to the basic mechanism, but there is no indication that Alzheimer's is transmissible.
Well, your focus is a bit too heavy on the developed countries here. I suggest you look at the world wide numbers, which are dominated by the HIV infections in Africa and Asia. In this larger context it is not by any means a specific problem of homosexual communities.
I don't see gene therapy as the most promising path towards a cure for Alzheimer's disease. First of all, as with most neurodegenerative diseases, the cause of disease is poorly understood and not necessarily purely genetic - in fact, in most cases, I suspect a strong environmental influence, as well as a certain number of "spontaneous" cases caused by stochastic conformational events.
So, we are in fact dealing with a multitude of causes, making a causal therapy like gene therapy an unlikely candidate. I rather expect to see more symptomatic treatments, approaching the problem at the level of the protein misfolding that causes the accumulation of the A-beta plaques.
There have been some immunological approaches, kind of a vaccination against Alzheimer's, but the results are not too promising at the moment. Anti-misfolding agents are under heavy investigation, not only against Alzheimer's, but also against CJD, Parkinson's and similar, but nothing significant has made it out of the lab yet. The basic mechanisms are still very poorly understood.
That is why you get up once per hour to go outside and get a smoke.
Good point on admitting the uncertainty of absolute transcendent values. I am not sure about this point either - but I am quite sure that such values, should they exist, are not to be found in the oral tradition, later written down, compiled and altered for various political reasons, of some ancient middle-eastern tribes...
Exactly my dieting concept - lost me about 40 pounds last year by the same method. A nice overview on the topic can be found here.