Charaids

[gendanken]

Imagine a monster capable of killing almost everyone in Chicago.
In one year.
And this gigantic beast has in it the potential to delete a good 400 million people from a population estimate 50 years from now in one blow- so imagine a scientist that’s pleasantly writing out the numbers suddenly scratching out not 2, not 3, but 400 millions from the future population numbers he's estimated because this beast has cast its shadow on the paper.

This monster has to date claimed 20 million lives with close to 40 million more waiting in the wings- you expect a savage brute or at least a clever one in order to be this powerful but something like the AIDS virus is neither.
Its almost amazing in its stupidity- it kills by the simple act of being sloppy.

The trick to its power (its mutation rate and what it chooses for its target, immunity cells) is so simple it makes us- a species that put its own on the moon- look so helpless and dumb in the face of it.

Think about it- it has no DNA, no organelles, not even a legitimate cell wall to at least keep it alive on my desk or in a mosquito long enough to spread like malaria.
This thing and all its cousins are not even alive and yet can do so much harm via simple, random, mutation.

This tiny ‘ball’ of simple RNA will enter my immune cell by tricking it with protein, transcribe its RNA into DNA using my own genes and then, because its enzymes are so sloppy in transcribing, tons of mutated versions of the original are shot back out into the serum to hassle my immune system into a guessing frenzy of figuring out new antigens just to kill them all and keep up.

Its almost like playing charades with a decoy that speaks 100 different languages, and not only this but he’s a little retarded.
This means you’ll be spending all your energy not only trying to figure out what he’s gesturing (its code) but what language to use to communicate your guess (the antibody)
And every time you figure out at least a part of what he’s gesturing, he’s learned a new language or forgotten the language you’re speaking in.
In the meantime, the burglars waiting outside break in through your windows and steal all your money and jewels because you’re too busy obsessing over this endless game of charades.

Now, the flu or the small pox will spend all their time distracting smaller prey- the respiratory or digestive systems, which is equal to pestering the house plants until the human (immune system) comes along and sprays them off with pesticide but this little retrovirus goes directly after that human(immune system) and paralyses him with something as silly as a guessing game.
Using his own things(genes)

That’s what’s even more fascinating- that its so dependent on host DNA that technically I can’t even blame the virus.
Think about what this means- something like HIV doesn’t do anything to you; its not the same as a stonefish injecting its venom and then you dying from the neurotoxins.
You can with all the self-righteousness left in your dying body blame the stonefish for doing this to you. Damn the fish!

But with AIDS, you die from ‘cooties’, so to speak- benign things already there turned vicious because the body is distracted.....by a guessing game.

And if you consider here that as far as the genome goes, something like 95% percent of it is junk (meaning psudogenes or satellite ‘genes’ that don’t do anything other than replicate themselves or simply hack up cheap recipes for making enzymes that only serve its selfish purposes)- then the only conclusion is that the virus would starve without this junk.
And that the virus is not really the culprit.
And that vaccines and medicines are missing the point.

Then why not turn off these genes? They’re junk.

Embryos undergo something called methylation when in utero- as blastulas, every cell in that cluster has all its genes ‘turned on’, they can develop into anything, an ear, a nose, a heart cell.
With specialization in later stages, these genes are turned off by adding simple molecules directly to those genes (I’m sure its more complicated than this but I’m on a roll here)- methylation is where a methyl group ( carbon and hydrogen stuck together) is added to a base in the DNA, like cystocine.
This means that if you stick a methyl group onto this base wherever you find it on a chromosome, you jam it up, screw up the code it’s a part of, and keep it from reproducing itself.

Why not turn them off?

What’s the point of all that junk if all it does is jump around disturbing every other useful gene? That’s right, this junk DNA can replicate itself and jump from chromosome to chromosome disturbing other ‘good’ genes.
I’m not saying turn it all off, but if we’re capable of manipulating molecules to the point where we can capture individual atoms and draw with them in the micro world:

http://science.howstuffworks.com/fr.../stm/atomo.html

And if we’re capable of targeting specific genes and isolating them, maybe I’m missing something, but why not turn this junk off? Not all, but half?
This virus is innocent if you think about it.

Some 20 years now we’ve tried using drugs- one of which, AZT, is highly toxic and gave cancer; we’ve tried jamming its membrane, plugging up all its portals, we’re now trying to trick the poor thing with cocktails and all I see is us being distracted.
We’re aggravating an endless game with a retarded decoy.

I know it can’t be this easy (I'm no scientist so I'm sure I'm uber-generalizing) but HIV, when you think about it , is not necessarily a germ infecting a human’s system. Monkeys, cats and cattle are not affected by their versions of IV.

Its more like the human’s genes cannibalizing themselves.

 

[Roman]

Clever title for a thread.

I've read some recent stuff that some of these junk genes aren't really junk genes, but are expressed differently than what we're familiar with.
For instance, base repeats in dog nuclear DNA, previously thought useless, make dog snouts longer when present. Domesticus has been losing these genes for the past century, and with it their faces.

So targeting our genome and turning it off could be really dangerous. That, and it's been found that most gene therapy doesn't work, since you'd have to turn off every single gene in every single cell.

I also thought that AIDS actually killed your immune system by targeting, infecting and destroying white blood corpuscules.

I really liked this though. I think it's probably my favorite piece of yours I've read.
Not that that means anything to you.

 

[gendanken]

Roman:

Clever title for a thread.

Merci.
Came to me while nightmaring.

I've read some recent stuff that some of these junk genes aren't really junk genes, but are expressed differently than what we're familiar with.
For instance, base repeats in dog nuclear DNA, previously thought useless, make dog snouts longer when present. Domesticus has been losing these genes for the past century, and with it their faces.

Very interesting- I kind of thought of it this way but not in the way you put it.

For example, its been shown that you can 'trick' a female gamete into thinking that its pregnant. Or you can steal its nucleus and 'impregnate' it with a somatic cell's nucleus for cloning.
Technically, everything should be perfect- you have the paired up chromosomes you need to make babies.

But it has trouble attaching itself to the uterus- its almost as if there is something extra that's missing, found in the paternal DNA.
What it is?
I don't know, I bet its already known what it is but I'm too illiterate to understand it (with names like p2333FuqU-20 sprinkled in obscure lab speak, would you?)

But you'll find this “magic” in junk DNA.

So targeting our genome and turning it off could be really dangerous. That, and it's been found that most gene therapy doesn't work, since you'd have to turn off every single gene in every single cell.

I know- I did admit I was overgeneralizing:
"(I'm no scientist so I'm sure I'm uber-generalizing)"

What's more, the most important use we have for this 'junk' DNA is forensics.
All that fancy detective work in fancy labs mapping out a person's fingerprints? Impossible without this nuclear 'garbage'.

But are you sure turning off one or a few means turning off everything?

I could have sworn we could go in mice and monkeys to switch cancer growth genes on and off.

I also thought that AIDS actually killed your immune system by targeting, infecting and destroying white blood corpuscules.

Which is, essentially, your immune system.

I'm pointing out the absurdity of its method. Its like a sloppier, slower version of a cold virus (of which, to date, there are some 200 mutant versions).

Not that that means anything to you.

Nonsense!

My heart swells with worms when I hear you say this is your favorite.
(really, thanks)

 

[Roman]

Gendanken,

I know- I did admit I was overgeneralizing:

You just made it sound like it was only a game of charades with a retard. Not quite, because our retard is actually an insidious sneak theif who actively disables out security perimeter to let other crooks in.

What's more, the most important use we have for this 'junk' DNA is forensics.
All that fancy detective work in fancy labs mapping out a person's fingerprints? Impossible without this nuclear 'garbage'.

Yeah.
Actually, I look at the stuff almost everyday. I'm using microsatellites to see if ant colonies are distributed horizontally or vertically in the canopy. On fed money .

What do you think of this new super AIDS that's been coming out? It only has a 2 month incubation period, compared to 10 years.

 

[gendanken]

Rrrrroman:

What do you think of this new super AIDS that's been coming out? It only has a 2 month incubation period, compared to 10 years.

It completely confirms that we're stupidly teaching it how to kill faster.

That these people (mostly homethexual) develop full blown AIDS so soon after being 'infected'-
That none of them have ever been treated with drugs or vaccine-
and that the virus already knows how to combat a drug that's never been used by that host its in now.
ONLY MEANS
that its learned this new skill in some other host.

We're teaching it, in the same way we're teaching simple microbes we're already immune to how to change by abusing antibacterial products.
Something so silly- can you imagine? Dying from cold sores one day because all this frantic handwashing and room spraying with antibacterial "perfumes" in it have bred superstrains we taught how to mutate.

Take Russia for instance- the prisons are stuffed with prisoners hacking up TB, the state spends millions treating them all with no effect, they send them back out because the prisons are crowded and lo and behold the population begins to come down with new strains of TB. Why?

Those prisons are tuberculosis classrooms. Keep your fingers crossed and these new strains may cross the Pacific one day and come to California.

Better yet, Alaska.
Where you live.
*funeral grin*

In the 80's and 90's, new AIDS cases were easily diminished by the simple use of condoms. And now, looky looky, a superstrain.

You just made it sound like it was only a game of charades with a retard. Not quite, because our retard is actually an insidious sneak theif who actively disables out security perimeter to let other crooks in.

Actually-

"Now, the flu or the small pox will spend all their time distracting smaller prey- the respiratory or digestive systems, which is equal to pestering the house plants until the human (immune system) comes along and sprays them off with pesticide but this little retrovirus goes directly after that human(immune system) and paralyses him with something as silly as a guessing game.
Using his (the 'human's', metaphor for immune system) own things (genes)."

How's that?

Its a lucky retard, not a clever one.
It just so happens to fuck with big prey.

And, concerning gene therapy- maybe I'm missing something but all I see is the use of other viruses to inject modified DNA into abnormal genes or replacing good genes with bad ones.
In other words, the cutting out and putting in of 'better' genes.

So complicated.

Why not something so simple as jamming the useless code? Not all, but half? With methyllation, all you're doing is jamming up certain bases in choice locations on a chromosome with a couple of molecules- its something like wetting the wings on a fly.

This happens in embryos all the time, completely natural.
Those jammed cells will replicate, soon replacing current cells with their modified daughter cells.
To where every last cell in your body will contain these harmless, jammed up chromosomes.

I hear they can even insert a completely artificial chromosome into the body as backup DNA, to where every cell will eventually have 47 chromosomes opposed to 46.
That's a whole chromosome just sitting there not bothering anybody (theoretically).

I’m sure the body wouldn't react to something so innocent as carbon and hydrogen molecules jamming up chunks of garbage DNA.

( I know , I know- you’ll again remind me this junk DNA is not really “junk”. Yet we undergo mutations due to radiation, toxins, you name it and still not suffer a spike in abnormal births or abnormalities. Because the mutations are usually taking place in garbage DNA)

I think my thread is dying.

 

[zyncod]

You are technically right that not having the "junk DNA" would make the viral genome insertion more likely to be in the middle of an important gene (ie, an RNA polymerase gene) and thus kill the cell. However, "turning off" any part of the genome in vivo is an absolute impossibility. If you accept the premise that methylation is a hindrance to HIV insertion (and the data is far from clear on that), there is still the problem of selectively methylating certain parts of the genome in cells that are circulating through the blood/lymph. It will never ever be done. Ever.

And what you call 'retardation' is actually a very clever evolutionary strategy. Viruses produce many, many offspring per host cell they infect. Therefore, the kind of fidelity that you see in our genome replication is a definite hindrance in viruses. We produce, if we are female, at most 40 offspring during our reproductive lifespan. So having a high mutation rate would kill a lot of our offspring. Which is not really acceptable with only 40 offspring. However, with each virus capable of producing thousands upon thousands of offspring, it would be stupid to have each offspring virus exactly the same. The host immune system could outmaneuver it. But a high mutation rate takes care of this problem. It's the same reason that we reproduce sexually. Variation is a good thing in evolution. The hyper-variability of viruses is what allows their evolution to proceed so quickly. They are alone in all forms of life in the phenomenon of "nested genes." Essentially, a metaphor for nested genes would be an entire book (genome) that is a palindrome. You can read it backwards as well as forwards and sometimes sideways as well. The fact that this occurs in viruses indicates that this level of evolutionary adaptation is required to survive the competition (solely their siblings). So 'retard' is essentially a slur at a lifeform that will be present until all other life on this planet is gone - but it's stupid, so it doesn't count.

 

[Hercules Rockefeller]

Imagine a monster capable of killing almost everyone in Chicago......

gendanken,
Interesting post , but I believe that there are a number of dubious assertions and false analogies.

The trick to its power (its mutation rate and what it chooses for its target, immunity cells) is so simple it makes us- a species that put its own on the moon- look so helpless and dumb in the face of it.

This is not specific to HIV. There are a number of viruses that have low-fidelity polymerases eg. influenza virus. This is why there are so many strains of flu virus and why a new vaccine cocktail has to be formulated every year to deal with them.

The whole first half of your post implies your awe with how the HIV works, and I agree that retroviruses are pretty amazing. But from other perspectives, HIV is a 100-pound weakling of a virus. In many ways, influenza is a far deadly virus than HIV, depending on your criteria.

For instance:

Deaths due to AIDS in the US -- In 2003, the estimated number of deaths of persons with AIDS was 18,017.
(<small>http://www.cdc.gov/hiv/stats.htm</small>)

Deaths due to the flu every year in the US -- About 36,000 Americans die on average per year from the complications of flu.
(<small>http://www.cdc.gov/flu/about/qa/disease.htm</small>)

Furthermore, HIV can take years to kill its victims, whereas some other viruses (such as smallpox and Ebola) kill their victims within a week.

******************

But that's all rather semantic stuff. Where the whole post turns suspect is from here onwards…..

And if you consider here that as far as the genome goes, something like 95% percent of it is junk (meaning psudogenes or satellite 'genes' that don't do anything other than replicate themselves or simply hack up cheap recipes for making enzymes that only serve its selfish purposes)

No, that’s not correct. Pseudogenes do not represent any significant percentage of the human genome. Of the pseudogenes that do exist, only a small percentage actually hijack cellular resources – “conventional pseudogenes” are expressed to varying degrees depending on the extent of their degradation, whereas “processed pseudogenes” are generally totally inactive as they lack the 5’ UTR regulatory regions of the parental gene. (I won’t go into the difference between conventional pseudogenes and processed pseudogenes here – you can look into it yourself if you are interested.)

- then the only conclusion is that the virus would starve without this junk.

No, I don’t see that as a logical conclusion at all. Sure, natural polymorphic diversity in non-coding genomic regions between different people is bound to influence susceptibility to at least some diseases, but that doesn’t mean you can go ahead and say the HIV <B>relies</B> on such regions. HIV causes AIDS by killing T-cells. If you can say that this relies on any particular host genes, then those genes would be the genes for the cell surface receptors that the virus uses to enter the T-cells and the genes for nucleic acid and protein synthesis in general. It’s got nothing to do with ancient inactive pseudogenes.

What's the point of all that junk if all it does is jump around disturbing every other useful gene? That's right, this junk DNA can replicate itself and jump from chromosome to chromosome disturbing other 'good' genes.

No! Now you’re confusing pseudogenes/“junk DNA” with transposons – two totally separate entities. Pseudogenes don’t move around the genome, it’s transposons and retroviruses that do that. There have been literally millions of different transposons that have hoped around the genome over the course of human evolution, but very few active transposable elements remain today. Once again, this has nothing to do with HIV and AIDS.

<blockquote><I>"The nucleotide sequence of the human genome provides a rich "fossil record" of the activity of transposons over evolutionary time spans. For example, the DNA-only transposons appear to have been very active well before the divergence of humans and old world monkeys (2535 million years ago); but, because they gradually accumulated inactivating mutations, they have been inactive in the human lineage since that time. Likewise, although our genome is littered with relics of retroviral-like transposons, none appear to be active today. Only a single family of retroviral-like retrotransposons is believed to have transposed in the human genome since the divergence of human and chimpanzee approximately 7 million years ago. The nonretroviral retrotransposons are also very ancient, but in contrast to other types, some are still moving in our genome. As mentioned previously, they are responsible for a fraction of new human mutationsperhaps 2 mutations in every thousand."

<B>Source</B>:Molecular Biology of the Cell (4th Ed) by Alberts et al.</I></blockquote>

And if we're capable of targeting specific genes and isolating them, maybe I'm missing something, but why not turn this junk off?

Well, taking on-board your new-found knowledge of pseudogenes and transposons, perhaps you can see that you haven’t identified anything of relevance to HIV/AIDS that we can “turn off”. Furthermore, this suggestion of “turning genes off” leads into a whole area of misunderstanding that frequently appears in internet science forums – the difference between how scientists can manipulate the genomes of model organisms in the lab as opposed to what we can do to adult humans.

There are a number of well-studied animal model organisms that are utilized in the lab: the fruitfly (<I>Drosophila melanogaster</I>), the nematode worm (<I>Caenorhabditis elegans</I>), the frog (<I>Xenopus laevis</I>), the chick (<I>Gallus gallus</I>), the zebrafish (<I>Danio rerio</I>), the mouse (<I>Mus musculus</I>) and more. A major reason that these organisms are used for basic research is that they can be easily genetically modified such that the animals carry extra genes (“transgenes”). Although the precise techniques vary from organism to organism, the basic approach is the same: introduce your extra gene(s) into a single-celled embryo (ie. a fertilized ovum, aka a zygote). Often this is achieved by direct microinjection of the DNA into the cell. The transgene(s) integrate into the genome of the single cell and, thus, are copied and passed on to every subsequent cell as the embryo develops. As a result of this, we have great control of both the temporal and spatial expression of the transgene. In other words, because the transgene is present in every cell of the animal, we have the ability to express it in every cell, or to design the transgene such that it is active only in certain types of cells (although present in all cells). Furthermore, we have the ability to control when it is expressed, such as during embryonic development or once the animal has reached adulthood.

But there is only one organism in which we can precisely <I><B>remove</B></I> genes: the mouse. This is because of the existence of mouse embryonic stem (ES) cells that can be cultured and manipulated <I>in vitro</i>. The precisely modified ES cells can then be used to generate whole new animals.

All this is in contrast to what we can do with humans. Whilst human ES-like cells do exist, performing the same embryonic manipulations in humans (ie. removing genes) is currently ethically and practically not possible. Of course, modifying genes in humans has its most immediate relevance to inherited genetic diseases. Such diseases cause illness because all the cells of the person are carrying a mutation in a particular gene. A particular part of their physiology goes wrong because that particular gene is necessary for the normal functioning of that part of the body. So the question becomes: how can we permanently fix the genetic defect? Obviously, children and adults are a long way from being single-celled embryos, so we cannot inject a normal copy of the mutated gene in the same way we do with model organisms in the lab. We cannot just “alter their DNA” at will in the same way.

“Gene therapy” is the great hope for genetic diseases. This is the idea that we introduce a functional copy of the mutated gene specifically into the cells of the body that need it. But so far, gene therapy has been a great disappointment and has not come close to living up to the hype that surrounds it. This is primarily due to the inability to find a convenient and reliable way to introduce the new functional copies of the necessary gene into the cells of the body that need it. Modified viruses remain the most likely mechanism as they are naturally able to introduce their own genetic material into human cells. The idea is to modify a virus such that it is not longer causes an infection but retains its ability to introduce DNA into cells, then “infect” the necessary tissue in the patient with this virus carrying the new functional gene. Simple as this idea may be, it remains a very difficult thing to achieve. This technique has been used successfully to introduce DNA into the cells that line of lungs in order to cure cystic fibrosis, however CF remains just about the only disease that has ever been cured by gene therapy. One of the other great gene therapy success stories was the apparent curing of boys with sever immune deficiencies (the so-called “bubble boys”) by introducing new genes into their bone marrow by repopulating the marrow with modified stem cells.

I remember a quotation from a researcher who wrote a review on gene therapy. He modified a well-known property market phrase to summarize the problem. He said…

“The three biggest problems with gene therapy are delivery, delivery and delivery.”

That sums it up very succinctly.<P>

 

[QuarkHead]

And if you consider here that as far as the genome goes, something like 95% percent of it is junk (meaning psudogenes or satellite ‘genes’ that don’t do anything other than replicate themselves or simply hack up cheap recipes for making enzymes that only serve its selfish purposes)- then the only conclusion is that the virus would starve without this junk.....

Then why not turn off these genes? They’re junk.

Last things first. You call it "junk" DNA (I don't). Whatever. There are no genes in junk DNA to turn off.
You also assert that pseudogenes and satellite "genes" -you mean satellite DNA - don't do anything. Ha! Consider this...

Chromosomes are made of DNA (and other things besides - leave that for now). They also do something rather important. First - they are stable structures, which means they have to have a telomere. That is a satellite of a certain sort. Second they have to pair, seperate etc during mitosis and meiosis. For that they need a centromere. More satellite DNA.

Then they have to align as best they can and reciprocally exchange. Now, the greater the extension of homology between chromosomes, the more accurate that alignment will be, and therefor less recombinational errors will occur through mismatch recomination. Non-coding DNA helps in that. It is a fact that, the sequence divergence seen in the non-coding DNA in populations exceeds that seen in coding DNA, it is nowhere near what you might expect if the non-coding were doing absolutely squiddly-dit.

With specialization in later stages, these genes are turned off by adding simple molecules directly to those genes (I’m sure its more complicated than this but I’m on a roll here)- methylation is where a methyl group ( carbon and hydrogen stuck together) is added to a base in the DNA, like cystocine.

Dead right it's more complicated. Ask Herc.
So what - methylation is a carbon and a hydrogen stuck together? Like CH? Er....I don't think so.

This means that if you stick a methyl group onto this base wherever you find it on a chromosome, you jam it up, screw up the code it’s a part of, and keep it from reproducing itself.

Oh...spare us, please.

Why not turn them off?

Turn what off? Non-functional DNA? Huh?

That’s right, this junk DNA can replicate itself and jump from chromosome to chromosome disturbing other ‘good’ genes.

But that's NOT right. Non-coding DNA doesn't "jump around"

Monkeys, cats and cattle are not affected by their versions of IV.
.

Wrong - at least 2/3 wrong. HIV is a form of human T-cell leakemia virus, that's why it was originally called HTLVIII. Cats have FeLV, and monkeys definitely have simian HIV. These are not exactly the same, nor do they exhibit the same pathologies, but they are of the same family of viruses

 

[gendanken]

Hercules:

gendanken,
Interesting post , but I believe that there are a number of dubious assertions and false analogies.

Ha.
Oh trust me- I'm groping an elephant in the dark here.
Which is why (grin) I'm ecstatic you've finally showed up.
Welcome.

This is an idea I'd been carrying around for some years now from connecting what I know about viral functions with what I’ve read on genetics, embryology and specialization.
I damn well know its way too generalized- there are millions of things still unknown in every field from chemistry to astronomy- so this is more of a laymen’s What if? (gedanken) to be laughed at by the scientific community.
Trust me, its already been laughed at/slighted by an ancient friend.

I’ve more than acknowledged that this is waaaaaay too generalized, to the point of being, well, ‘stupid’.
(*cough* Galielo, Bruno, and Huygens were laughed at as well. Darwin was almost decapitated by conservatives *cough*)

All I needed was something like you to come along, those 'in the know' to shed light in dark corners.

But there is only one organism in which we can precisely remove genes: the mouse. This is because of the existence of mouse embryonic stem (ES) cells that can be cultured and manipulated in vitro. The precisely modified ES cells can then be used to generate whole new animals.

Very intresting.
I didn't know that.

Mike West, a geneticist turned author, wrote a book on cloning where the implications are that you can indeed take isolated genes (removing them) and inject them into other cells.

Maybe I read it wrong, but here in chapter five "Race Against the Clock" he writes on telomerase, an enzyme suspected in the apparent immortality of the germ line:

"We (g: his company 'Geron') obtained a patent protection for the entire gene, which we later named "hTERT"- for human telomerase reverse transcriptase. We now owned exclusive rights to the gene, and we could perform the crucial test of the whole telomere hypothesis.
Of the twin components of the telomerase, we already knew the RNA component was ubiquitous in both mortal (g: somatic) and immortal (g: haploid) cells.
Therefore, we reasoned, we had no need to add it to mortal cells.
But the catalytic component, the gene called hTERT, was epxressed only in immortal cells and was undetectable in mortal.
Therefore, what would happen if we added it to mortal telemorase-negetive cells?"

He then goes on to describe the introducing of this isolated gene into somatic cells and then assaying them to see if any bands showed in the gel- which depending on the sequencing would show that the gene had been incorporated.
It had!

Which kind of freezes you on that page for a second if you think about what he is actually saying and if he indeed is not a quack- he’s talking about literally turning back the clock on aging.
A kind of philsopher’s stone ground down to molecules.

That you could literally take some "magic” genes found only in haploid cells, genes responsible for an enzyme that can replicate each strand of chromosome without shortening it with each replication the way somas do, and inserting them into old, sickly cells to fix up its shortened DNA.
That the central reason to why we age is because of DNA shortening at each replication.

That I can take cells from aging skin, inject them with this gene or take those chromosomes and enucleate them into a female gamete cell, and breathe life back into the shortened DNA by some genetic sleight of hand found only in gametes.
Insanities!

If I read it wrong, please tell me.

(getting distracted, will stay on topic)

This is not specific to HIV. There are a number of viruses that have low-fidelity polymerases eg. influenza virus. This is why there are so many strains of flu virus and why a new vaccine cocktail has to be formulated every year to deal with them.

The whole first half of your post implies your awe with how the HIV works, and I agree that retroviruses are pretty amazing. But from other perspectives, HIV is a 100-pound weakling of a virus. In many ways, influenza is a far deadly virus than HIV, depending on your criteria.

Not necessarily 'awe'.
Actually, you can’t blame me. I'm a child of the 80's and much like the children of the 50's who cringed at COMMUNISM or NUCLEAR BOMB, we from the 80's were incubated with nightmares at the very mention of AIDS or DRUGS or GANGS.

I agree as well, I've just looked at it on the grander scale. It pales to malaria.

Furthermore, HIV can take years to kill its victims, whereas some other viruses (such as smallpox and Ebola) kill their victims within a week.

Hence, the 'retard'.
The lent in lentivrirus is there for a reason.

No, that’s not correct. Pseudogenes do not represent any significant percentage of the human genome. Of the pseudogenes that do exist, only a small percentage actually hijack cellular resources – “conventional pseudogenes” are expressed to varying degrees depending on the extent of their degradation, whereas “processed pseudogenes” are generally totally inactive as they lack the 5’ UTR regulatory regions of the parental gene. (I won’t go into the difference between conventional pseudogenes and processed pseudogenes here – you can look into it yourself if you are interested.)

How about this:

If we look on the entire genome as that which codes for proteins. Which is scant.
And then look on the rest which does not.
Which is humongous.

Anyway, THIS:

No, I don’t see that as a logical conclusion at all. Sure, natural polymorphic diversity in non-coding genomic regions between different people is bound to influence susceptibility to at least some diseases, but that doesn’t mean you can go ahead and say the HIV relies on such regions. HIV causes AIDS by killing T-cells. If you can say that this relies on any particular host genes, then those genes would be the genes for the cell surface receptors that the virus uses to enter the T-cells and the genes for nucleic acid and protein synthesis in general. It’s got nothing to do with ancient inactive pseudogenes.

Is precisely what I needed.

That the virus uses your own DNA is pretty much obvious. It comes in RNA and comes out DNA- all on its own it self-transcribes into DNA but without host DNA its pretty much fucked.

Where I began groping was in the guessing and not knowing if the same thing that happens in sickle cell anemia, say, was happening here. You're right, I can't say it relies on such regions but by god one of the most essential to this virus are genes coding for reverse transcriptase and these would not be ‘junk’ if we cut the definition down to that which codes for protein and that which does not-

"The commonest protein recipe in the entire human genome is the gene for a protein called revere transcriptase. Reverse transcriptase is a gene that servea no purpose at all as far as the human body is concerned. If every copy of it were carefully or magically removed from the genome of a person at the moment of conception, the person's health, longevity and happiness would be more likely improved than damaged. And reverse transcriptase is an extteremstely useful-nay essential- part of the genome of the AIDS virus: a crucial contributor in its ability to kill and infect its victims"

Now, its easy to call something like this junk (I'm guilty of this)- its not junk- and I keep in mind that the person who wrote this is only a ‘science editor’ (Matt Ridley, “Genome”).

A major portion of the non-coding regions on our chromosomes are almost equal to non-coding regions found in mice.If it were simply junk and useless, there’d be no reason for it to still be there replicating themselves exactly after millions and millions of years spent evolving.

There seems to be something essential in it to mantaining complicated life forms- crickets, ibex, chimps, moles, humans.
Prokaryotes, apparently, DON'T have this 'bagagge'

Someone' recently put it beautifully:

"Anyway. What's interesting is that prokaryotes don't have this junk.
He called the junk 'ancient' and this is how it's often portrayed. As
a remnant of an ancient past. But, if this were the case then why
don't single cell organisms also have junk?
The answer? Because the junk is a form of coding that adds complexity
to cells. As complexity increases, the maintainence overhead increases
as well. (This is interesting in that I first heard this mentioned
about the brain.) There is a chart that shows that there is a point in
time where the overhead overwhelms the coding method of the
information. This point is reached in the upper end of single cells.
Beyond this level of complexity the 'junk' begins to appear."

So these non-coding regions would be more like overhead.
But I was also considering the weird cases of HIV or Gulf War Syndrome where serum tested negative for any type 'infection.' Test and tests were done until they finally got down to the genes and found them almost as if at war with themselves; radiation, pesticide, drugs- in short, all kinds of environmental agents can disturb these regulatory genes as if throwing a switch.

To where this overhead becomes antagonistic, and I’m picturing Jews waiting for the shower to come only to receive Zyclon B.

To cut all this ‘junk’ out would be the same as destroying every shower head on the planet.
The assumption is all shower heads rain down poison which is ridiculous.

Its this assumption I've always known to be flawed.

Yet people who today are immune to HIV are descendant from those long ago who were immune to the Plague.

No! Now you’re confusing pseudogenes/“junk DNA” with transposons – two totally separate entities. Pseudogenes don’t move around the genome, it’s transposons and retroviruses that do that. There have been literally millions of different transposons that have hoped around the genome over the course of human evolution, but very few active transposable elements remain today. Once again, this has nothing to do with HIV and AIDS.

Thank you.

Well, taking on-board your new-found knowledge of pseudogenes and transposons, perhaps you can see that you haven’t identified anything of relevance to HIV/AIDS that we can “turn off”. Furthermore, this suggestion of “turning genes off” leads into a whole area of misunderstanding that frequently appears in internet science forums – the difference between how scientists can manipulate the genomes of model organisms in the lab as opposed to what we can do to adult humans.

You have no clue what I would do to go to medical school and slave through whatever program they put you through just to be able to work in a lab.

Either that or get a degree in Astronomy, but it all takes money and other things.
You're one lucky motherfucker to have what you have.

“The three biggest problems with gene therapy are delivery, delivery and delivery.”

That sums it up very succinctly.

Indeed.

Zycod:

You are technically right that not having the "junk DNA" would make the viral genome insertion more likely to be in the middle of an important gene (ie, an RNA polymerase gene) and thus kill the cell. However, "turning off" any part of the genome in vivo is an absolute impossibility. If you accept the premise that methylation is a hindrance to HIV insertion (and the data is far from clear on that), there is still the problem of selectively methylating certain parts of the genome in cells that are circulating through the blood/lymph. It will never ever be done. Ever.

I thought as much.

But is there nothing, not even a teeny itty bitty truth or possibility, in my post to Roman? :

"Why not something so simple as jamming the useless code? Not all, but half? With methyllation, all you're doing is jamming up certain bases in choice locations on a chromosome with a couple of molecules- its something like wetting the wings on a fly.

This happens in embryos all the time, completely natural.
Those jammed cells will replicate, soon replacing current cells with their modified daughter cells.
To where every last cell in your body will contain these harmless, jammed up chromosomes."- Gend

If mutations are inherited with every generation, why not something like this? It too would be a mutation, albeit imposed, but still falling under that rubric.

And what you call 'retardation' is actually a very clever evolutionary strategy. Viruses produce many, many offspring per host cell they infect

I second that motion.

We love boasting human perseverance, human this, human that, human boobiesboogablah but evolutionary speaking the alapha and omega are neither the cockroach nor God nor the human.

Its these clever little microvevicles so intrepid we find them living in scalding thermal vents and pools of sulfuric acid.
Muhhahahhahahhahahhahaha.....

Quarkhead:

Oh...spare us, please.

No, spare me asshole.

If you'd spend half the time you put in being antagonistic into your fancy contempt (hey! lookame! I'm correcting Gendanken! suck my balls!)- you'd acutally slow the fuck down enough to read I'm not a scientist and admit to being too general.
Way to general.

So what - methylation is a carbon and a hydrogen stuck together? Like CH? Er....I don't think so.

That’s CH3-.
Methyllation is something common in embryos.

http://www.ncl.ac.uk/ihg/research/developmental/stem/project/977
http://www.cc.ndsu.nodak.edu/instruct/mcclean/plsc431/geneexpress/eukaryex5.htm

And carbon and hydrogen ‘stuck together’ is an organic methyl group. Methylation is the tagging groups much more complicated than this onto nuclear bases-at any rate


My god, my hands have never hurt this bad. How you people do this all day every day, I don't know.

 

[gendanken]

Wrong - at least 2/3 wrong. HIV is a form of human T-cell leakemia virus, that's why it was originally called HTLVIII. Cats have FeLV, and monkeys definitely have simian HIV. These are not exactly the same, nor do they exhibit the same pathologies, but they are of the same family of viruses

Your little lesson is uncalled for, Showedoffodis.

I was pointing out that cats and simians and cows can live with a variant of immunodefficiency disease and not be as affected as we are.
Sootey mangebeys for example, where its thought HIV juumped from, live with SIV without getting sick.

Its why xenotransplantation is risky.

 

[Dr Lou Natic]

Even I have to admit the title is good.
AIDs jokes are my weakness.

 

[QuarkHead]

Quarkhead:

No, spare me asshole.
(hey! lookame! I'm correcting Gendanken! suck my balls!)-

How eloquent! Pure poetry!

 

[gendanken]

QuarkHead:

How eloquent! Pure poetry!

*cocks ear*

What's that?
Got nothing to say?
Chance at playing pedant sabotaged some?

Something you'll never see in your pointless cynism- you don't fucking matter to people like Asimov or Feynmann.
There's always a Pleasure to Finding Things Out

Rightly, or wrongly.

 

[QuarkHead]

you don't fucking matter to people like Asimov or Feynmann.

Hm..is that because they're both dead, I wonder?

 

[gendanken]

And, no show.
Total time allotted for: 10 days.
Days gone over: 2


The only thing I've learned here is to write junk as 'junk'.
And Hercules has yet to explain what he means by the only genes that can be removed or manipulated are that in mice- which is odd, considering that geneticists have fondled oops experimented, removed, replaced, and modified genes in organisms from tadpoles to human beings.
But he’s a no show.

And the second thing learned is that you, QuarkHead, are a cancerous retard- the point was that people like you are nothing to a bon vivant if not a harmless wart cynically drying up into a harmless tumor.

The Bon Vivants don't die- their zeal, curiosity, and love of life lives to eons past the tomb, you fucking corpse.

So to sum up:
Instead of saying junk, we can divide any genome into coding and non-coding sequences.
1. The sections of chromatin involved in protein production are essential to that organism.
2. The sections of chromatin not involved in protein production are not as essential as those sections that are involved in protein production.
3. Some sections actually code for protein, but as its useless protein (as reverse transcriptase) for the organism its therefore not as essential as number 1.


This does not mean that non-coding sections are junk as even to this day there are theories and theories about passive DNA being something like overhead monitoring a protein making factory.
And gene therapy in many cases seems to backfire where genes are removed, altered, and re-injected into the body

Yet all in all, we *are* unsure of what a large proportion of these satellites actually do.
We *are* unsure of why these patients do well for a while and then die.
We *are* unsure why some clones thrive while some don’t.

The common theme is that while we are sure of the outcome, there is a big uncertainty in that certainty.
And that uncertainty, to me, is that barren region of parasitic DNA.
Its there where you find Gendanken groping in the dark, not knowing if she’s right or whistling in the wind, but by god we read this again:

"The commonest protein recipe in the entire human genome is the gene for a protein called revere transcriptase. Reverse transcriptase is a gene that serves no purpose at all as far as the human body is concerned. If every copy of it were carefully or magically removed from the genome of a person at the moment of conception, the person's health, longevity and happiness would be more likely improved than damaged. And reverse transcriptase is an extremely useful-nay essential- part of the genome of the AIDS virus: a crucial contributor in its ability to kill and infect its victims"

Its by fiddling with the genome that we’d cure something like AIDS, not a vaccine, a vaccine seems absolutely useless.
Technically, anything that breaks down the immune system is AIDS- bubble boy could technically be said to have been born with AIDS or heroin and cocaine could technically be called AIDS as both break down the immune system.

Its those ‘junk’ parts of the genome that are tantalizing in this sense.

Take the bufo frog- I’ve learned that only a scant 20% of its genome codes for protein, while 80% is a lagging bulk of passive DNA. Scientists can go in and remove/tweak the passive parts, inseminate an adult bufo with the final product,and the offspring are born as if nothing is missing.

Think about it.

Therefore, this thread as all others has died and here a lone voice comes to the funeral.
Until next time, precious readers.
Muhahhhahahha..

Exeunt..

 

[Hercules Rockefeller]

….But he’s a no show.

I’m a bit busy, ya know? :bugeye:

And Hercules has yet to explain what he means by the only genes that can be removed or manipulated are that in mice

No, I never said that at all. What I said was…

But there is only one organism in which we can precisely <I><B>remove</B></I> genes: the mouse.

Notice that I specifically mentioned <I><B>“removal”</B></I>; I did not mention any other sort of manipulation.

….which is odd, considering that geneticists have fondled oops experimented, removed, replaced, and modified genes in organisms from tadpoles to human beings.

No, that statement is not correct. Reiterating what I said in a previous post, it is almost trivial to <B><I><U>insert extra genes</U></I></B> (endogenous or exogenous) with their own promoters (endogenous or exogenous) into the genomes of any of the commonly used model organisms: the fruitfly (<I>Drosophila melanogaster</I>), the nematode worm (<I>Caenorhabditis elegans</I>), the frog (<I>Xenopus laevis</I>), the chick (<I>Gallus gallus</I>), the zebrafish (<I>Danio rerio</I>), the mouse (<I>Mus musculus</I>) and more. Although the precise techniques vary from organism to organism, the basic approach is the same: introduce your extra gene(s) into a single-celled embryo (ie. a zygote). Often this is achieved by direct microinjection of the DNA into the zygote. I do this routinely in zebrafish embryos. Alternatively, modified retroviruses or transposons can be used in some systems.

BUT……we have no control on the integration site of these transgenes, nor do we have fine control on the transgene copy number.

In <I>Drosophila</I> and <I>C.elegans</I> there are highly characterized transposon systems that can be used for insertional mutagenesis. When these transposons are stimulated to excise from their integration point, they take a chunk of surrounding DNA with them creating a mutant allele. Thus, in these model systems we can <B><I><U>remove portions of genes</U></I></B>, but this removal cannot be precisely controlled. Often the resulting deletion will create a hypomorphic allele rather than a null allele.

So, whilst it is easy to <B><I><U>insert</U></I></B> genes in all these organisms, there is no way to <B><I><U>precisely remove</U></I></B> genes so as to create a null allele. The mouse is the only organism in which we can <B><I><U>precisely remove</U></I></B> a specific gene (“knockout mice”) and <B><I><U>precisely replace</U></I></B> a gene with a different gene (“knockin mice”).

Again reiterating what I said in my previous post, the reason for this is that we have a variety of mouse ES cell lines that can be manipulated <I>in vitro</I>. There is no other organism from which ES cells have been isolated (except for humans – see below). Very broadly speaking, to remove a specific gene a DNA targeting construct containing arms of homology complementary to the flanking sequence of the gene is made with a reporter gene (commonly <I>lacZ</I>) inside the arms. This construct is transfected into the ES cells. The cells are then screened for instances where homologous recombination has occurred between the arms of homology of the targeting construct and the corresponding segment of genomic DNA. Homologous recombination at each end will swap out the genomic DNA for the reporter gene in the construct. It's a rare event, but there are millions of cells in a dish so you can generally find at least of couple of targted clones. Does that make sense?

By using homologous recombination in ES cells, precise targeting of an allele, down to the single nucleotide level, can be achieved. Once ES cells carrying the desired recombination event have been isolated, the ES cells can then be injected into a blastocyst to create mosaic mice carrying the targeted allele. Mosaic mice are then bred to identify and produce germline carriers.

These techniques are all specific to mice. Of course, there are human ES cell lines that have been identified and <B>in theory</B> the same techniques could be used to create gene targeted humans. But, there are a number of differences between murine and human ES cell lines and we do not know for sure that the cells we are calling “human ES cells” are, in fact, true embryonic stem cells. They behave like stem cells <I>in vitro</I> and when we introduce them into mice. But the definitive experiment to prove that a cell is an ES cell is to inject them into a blastocyst and demonstrate that they give rise to cell types of all three germ layers. As I discussed above, this is done routinely in mice with murine ES cells but has not been performed in humans with human ES cells as it is practically difficult as well as ethically and legally forbidden.

One more thing of interest: the advent of cloning whole animals by nuclear transfer has opened up the possibility of gene targeting without ES cells. In fact, the Roslin Institute has done just that. They produced gene targeted sheep. This can be done because after transplantation of the donor nucleus into the enucleated egg, the new embryo is cultured <I>in vitro</I> until it can be implanted into the surrogate mother. This presents a brief opportunity for homologous recombination. Whilst possible, this is far too technically difficult to do routinely…yet. Of course, gene targeted farm animals was the whole impetus behind Roslin’s animal cloning in the first place. A herd of cloned goats/sheep/cows that produce a pharmacologically valuable human protein in their milk is potentially worth millions, maybe billions.<P>

 

[gendanken]

It's a rare event, but there are millions of cells in a dish so you can generally find at least of couple of targted clones. Does that make sense?

Much.

Well, let me see.
What you're calling homologous recombination on stem cells is something so precise it can get down to the nucleotide level of a germline.
And its only successful on murine (nice word, murine) lines so far- yes?

But when applied to human stem cells, its pretty much a guessing game.
As with drosophila, worm, chick and frog lines.
Right?

The goal is to excice a portion (allele) out that leaves its recess on the chromosome null, without disturbing the rest of the sequence which would defeat the purposes if otherwise by introducing a mutation you have no control over.

Only with mice can you achieve this.
So when one hears 'cloning' or the hype about transfecting modified blood cells back into the marrow of a boy with SCID, don’t get too exited.
What you've just told me, is the reason why these patients don't do well.

Do you realize how simple they make it look sometimes?
You read a book here and there where some scientist is raising your hopes up about immortality (poetic eyewash for "regenerative medicine"), you hear him talk about sitting in a lab and cloning sheep and monkeys with stem cells and it all sounds like fast food.

No one ever mentions that the only animal that responds this way, so neatly, is the mouse.
The way they have it makes sheep, cattle, pig, fly, worm, toad all look like mice.


Why oh why could I not have been born rich to go to medical school? Or enough to go get a degree in Astronomy?

FUCK THE WORLD.

At any rate, my idea (which is likely is nothing if not funny to you) doesn’t call for removal of anything, but that's beside the point.


You, sir/madamme, are an asset to this thread.

 

[QuarkHead]

And the second thing learned is that you, QuarkHead, are a cancerous retard- the point was that people like you are nothing to a bon vivant if not a harmless wart cynically drying up into a harmless tumor.

Yep - that's me!

The Bon Vivants don't die- their zeal, curiosity, and love of life lives to eons past the tomb, you fucking corpse.

Correction. les bon vivants live fast, die young.

1. The sections of chromatin involved in protein production are essential to that organism.

True - but DNA, not chromatin. That's a different chap entirely.

2. The sections of chromatin not involved in protein production are not as essential as those sections that are involved in protein production.

I tried to explain to you before why that may not be so. But - OK- maybe not as important in protein coding (production is a different part of the apparatus)

3. Some sections actually code for protein, but as its useless protein (as reverse transcriptase)

As a molecular geneticist, I really cannot understand that statement. Clarify.

Its there where you find Gendanken groping in the dark, not knowing if she’s right or whistling in the wind, but by god we read this again

Er...whistling in the dark? If you want knowledge we can help. If you want abuse, I think we may be able to oblige.

 

[gendanken]

Correction. les bon vivants live fast, die young.

No, los Gran Estupidos Rebeldes do.
And, you missed the point.

True - but DNA, not chromatin. That's a different chap entirely.

Allright.

But there’s no reason to bicker over quarks and leptons when discussing the mechanics of a hurricane.
At least for now.

As a molecular geneticist, I really cannot understand that statement. Clarify.

No, as a cynical prick you won’t understand that statement. Not as a molecular geneticist

I’ve posted it countless times, thrice:

“The commonest protein recipe in the entire human genome is the gene for a protein called revere transcriptase. Reverse transcriptase is a gene that serves no purpose at all as far as the human body is concerned. If every copy of it were carefully or magically removed from the genome of a person at the moment of conception, the person's health, longevity and happiness would be more likely improved than damaged. And reverse transcriptase is an extremely useful-nay essential- part of the genome of the AIDS virus: a crucial contributor in its ability to kill and infect its victims”

Hercules has cleared up alot of things, Mr. Q.
You're like..in the way?

If you want knowledge we can help

Amusing.

Dude said ‘we’- you, sir, are the useless mummy fit for 'teaching' in a classroom.

Go away.

 

[zyncod]

Gendanken -

The goal is to excice a portion (allele) out that leaves its recess on the chromosome null, without disturbing the rest of the sequence which would defeat the purposes if otherwise by introducing a mutation you have no control over.
Only with mice can you achieve this.
So when one hears 'cloning' or the hype about transfecting modified blood cells back into the marrow of a boy with SCID, don’t get too exited.
What you've just told me, is the reason why these patients don't do well.

"Knocking out" a gene is different from inserting a gene. Treating somebody with SCID involves inserting a gene. For example, in some of the mice I work with, the recombinase (Rag) gene for reassorting antibody genes has been "knocked out." This creates a disease in mice analogous to SCID. To treat this, you would insert a viable Rag gene and the mice would no longer have SCID. We can insert genes in pretty much every organism in the world. Knocking them out is a different story. So mice knockouts have absolutely nothing to do with gene therapy in humans.