Domain: jbc.org
Stories and comments across the archive that link to jbc.org.
Comments · 34
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Re:Meanwhile in ARM's Cambridge HQ
Why not try an all meat diet? Smarter people than you do: http://www.jbc.org/content/87/...
That's an old study, and the evidence from the China study directly contradicts it....
The conclusions drawn from the China Study data were in fact contradicted by the data. E.G. The highest univariate association was between wheat and cancer. But the author ignored that. The author chained together confounded univariate associations in a statistically incorrect way. Try looking here for an analysis by someone who actually understands statistics.
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Re:Meanwhile in ARM's Cambridge HQ
Why not try an all meat diet? Smarter people than you do: http://www.jbc.org/content/87/...
That's an old study, and the evidence from the China study directly contradicts it....
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Re:Logjam
>Why not try an all meat diet? Smarter people than you do: http://www.jbc.org/content/87/...
Because you'll become very unhealthy from nutritional deficiencies. There's a reason that people eat vegetables.
A lot of stupid people think they're smart. -
Re:Another layer
Why not try an all meat diet? Smarter people than you do: http://www.jbc.org/content/87/...
Interestingly that article you link to was published in February 1930, right near the start of the "Great Depression" and states that "These studies were supported in part by a research grant from the Institute of American Meat Packers". They were probably scared stiff that nobody would be left with enough pennies in their pocket to buy meat.
You want smart people? "It is my view that the vegetarian manner of living by its purely physical effect on the human temperament would most beneficially influence the lot of mankind. - Albert Einstein in a letter to "Vegetarian Watch-Tower", 27 December 1930 -
Re:epigenetics
Why not try an all meat diet? Smarter people than you do: http://www.jbc.org/content/87/...
200mg of liver every day for dinner is not my idea of enjoyable eating. Anyway, have you tried it? Has it worked out for you?
That's not my idea of a fun diet. Liver is ok. It's excellent when if it's from a well fed goose. Escargot are awesome. It worked out well. Steaks, eggs, roasts, chicken livers cooked in milk, much bacon. It's not expensive since you don't eat as much. It's energy and nutrient dense. I lost a lot of weight, all blood markers improved dramatically. It's hard to keep it up because it's simply hard to do when you aren't cooking all your own meals. My workplace canteen has no non-carb food offerings. Rice, potatoes and wheat is cheap. So I go back on it hard core when I need to recover the ability to fit into the skinnier jeans. But I'm too lazy to cook and pack a lunch every day, year after year. You need to keep in mind that it's a high fat diet, not a high protein diet. No one can eat a predominantly protein diet. It's not possible. Mostly fat, some meat, no carbs.
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Re:epigenetics
Why not try an all meat diet? Smarter people than you do: http://www.jbc.org/content/87/...
200mg of liver every day for dinner is not my idea of enjoyable eating. Anyway, have you tried it? Has it worked out for you?
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Re:Electron transport in biological systems
Are there any existing models of electron transport in biological systems?
Good question! The answer is yes, although they are not even mentioned in this unreviewed manuscript (which seems like hokum to me). Electron transfer in proteins is particularly well understood in the context of Marcus theory. The wiki article isn't great, but it has some good information and further references. A key insight is the "inverted driving force effect," an experimentally validated prediction of Marcus theory that electron transfer rates actually start to decrease if the transfer reaction is too exergonic (energetically favored).
Without going into a ton of detail, quantum effects are actually quite important for electron transfer, and some enzymes even encourage tunneling, mostly of electrons, as part of catalysis. Considering that the de Broglie wavelength of a 10 kJ electron is about 18 angstroms (biologically relevant scales), it's not really that surprising. Frequently, there are favored tunneling pathways through enzymes which electrons tend to follow.
Enzymes also sometimes utilize nuclear tunneling (i.e. tunneling proton/hydrogen/hydride), which is really, really cool. I am a fan of this paper which shows how tunneling is is encouraged through dynamic gating motions in a enzyme on the chlorophyll production pathway.
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Re:Assuming a grand meaning seems to be overreachi
As a current biochemist, I do wonder why the paper doesn't even mention Marcus theory or other previous work in enzymatic charge transfers. There really are some sweet quantum effects in biology, like enzyme-catalyzed proton tunneling, but I think the unreviewed manuscript under discussion here is hokum.
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Re:quantum tunneling?
Tunneling (mostly of electrons) is actually widespread in proteins, and its not hard to see why that is when you consider that the de Broglie wavelength of a 10 kJ electron is around 18 angstroms (these are relevant energy/distance scales in enzymes). Search "Marcus theory" for more information...
What's really cool is that some enzymes actually boost tunneling probabilities (e.g. through particular short-timescale motions) as an essential component of catalysis. In some cases, tunneling even occurs for larger particles like protons/hydrogens/hydrides. I really like this paper, for example, which shows how proton tunneling is essential in a light-activated enzyme involved in an early stage of chlorophyll synthesis in some plants.
Unfortunately, the unreviewed manuscript from TFA seems like nonsense to this biochemist. It doesn't seem to line up with, or even reference, any of the five decades of existing science in the area.
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Re:Complexity is not a property of the observer
biological systems, even at the single protein level, are doing things with electron conductance that can't be done in non-biological systems.
There really are some very cool quantum effects in biomolecules, for example enzymes which take catalyze electron tunneling and even proton tunneling. Electron transfer in proteins in particular is actually pretty well understood via Marcus theory. There is extensive theoretical and experimental work going back five decades in this area - all of which is totally ignored by the unreviewed manuscript under discussion.
biomolecules belong to an entirely new class of conductor that is not bound by the ordinary rules of electron transport
Unfortunately, your post and TFA alike do not appropriately distinguish between wildly different classes of "biomolecules."
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Re:Perspective from a chemist
There are some pretty cool examples of quantum effects in biomolecules (e.g. this paper about enzyme catalyzed proton tunneling, and Marcus theory for electron transfer), but this paper doesn't seem either to reference any of that past work at all, or make sense given that context.
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Re:Perspective from a chemist
I'm just a layman, but to my untrained eye this looks like word salad.
I'm a biochemist specializing in molecular biophysics, and I agree.
It's not always true, but as a general rule of thumb that some throwing "quantum" into a biology discussion is usually talking crap.
Definitely not always - there are actually enzymes which take advantage of electron tunneling, and even proton tunneling, for catalysis. Here's a particularly cool paper (no paywall) about a light-activated oxidoreductase which encourages a proton to tunnel.
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Link to #1
1) PDF version http://devbio.wustl.edu/InfoSo...
2) Commentary, 2004: http://www.jbc.org/content/280...
3) Wikipedia: http://en.wikipedia.org/wiki/L...
"The Lowry protein assay is a biochemical assay for determining the total level of protein in a solution. The total protein concentration is exhibited by a color change of the sample solution in proportion to protein concentration, which can then be measured using colorimetric techniques. It is named for the biochemist Oliver H. Lowry who developed the reagent in the 1940s. His 1951 paper describing the technique is the most-highly cited paper ever in the scientific literature, cited over 200,000 times."
The method combines the reactions of copper ions with the peptide bonds under alkaline conditions (the Biuret test) with the oxidation of aromatic protein residues. The Lowry method is best used with protein concentrations of 0.01–1.0 mg/mL and is based on the reaction of Cu+, produced by the oxidation of peptide bonds, with Folin–Ciocalteu reagent (a mixture of phosphotungstic acid and phosphomolybdic acid in the Folin–Ciocalteu reaction). The reaction mechanism is not well understood, but involves reduction of the Folin–Ciocalteu reagent and oxidation of aromatic residues (mainly tryptophan, also tyrosine). Experiments have shown that cysteine is also reactive to the reagent. Therefore, cysteine residues in protein probably also contribute to the absorbance seen in the Lowry Assay. [3] The concentration of the reduced Folin reagent is measured by absorbance at 750 nm.[4] As a result, the total concentration of protein in the sample can be deduced from the concentration of Trp and Tyr residues that reduce the Folin–Ciocalteu reagent.
The method was first proposed by Lowry in 1951. The Bicinchoninic acid assay and the Hartree–Lowry assay are subsequent modifications of the original Lowry procedure. -
Re:I just say
Replace the continuous Fourier Transform with an iterative Fourier transform
It doesn't matter. The discrete transform approximates the continuous transform; in the case we're discussing we can in fact calculate the continuous transform analytically. If one were to use the discrete transform with an explicit numerical example basically the same result would be obtained (down to numerical error modulo the window function, zero padding and discretization artifacts). That result being a distribution of non-zero amplitudes in frequency space rather than a delta function.
"No definite single frequency" is not equal to "no discoverable single frequency"
There is no single frequency, discoverable or otherwise. The physical reality is that a finite wave packet such as a shout or an electron must be characterized by a distribution of frequencies rather than a single frequency. It is impossible for a single frequency alone to produce a finite wave train. There are two ways to get a finite wave packet, either you have a window of some kind, which creates overtones in the frequency space, or you sum up lots of higher frequency waves, which amounts to the same thing.
The whole reason I brought this up is relevant to TFA: in my opinion the above approach gives the simplest, most accurate portrayal of why the uncertainty relation is a part of nature and not a technological limitation of some kind (we aren't "missing" any information which actually exists). To reiterate: 1) regardless of quantum mechanics, finite wave-trains create "uncertainty," that is a distribution of values which may itself be known exactly, and 2) quantum mechanical systems are finite wave phenomena. Therefore they exhibit what we call "uncertainty" - a distribution of values which can be sampled. Repeated sampling demonstrates that quantum mechanics predicts these distributions with extreme accuracy and precision.
Anyway, uncertainty is actually an important part of quantum mechanical technologies, more than a barrier. Especially in living systems, which use QM in various ways.
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Re:Actually
So you accept that they lied when they said it was beef, but they certainly wouldn't lie about this "beef" being unhealthy. My confidence wouldn't be so high.
What makes you think that meat is unhealthy?
Let's dig up some research on the matter: http://www.jbc.org/content/87/3/651.full.pdf
I didn't say that horse meat is unhealthy, I said that horse meat that was illegally sold as beef could very well be uninspected horse meat, which means it could be unhealthy, too.
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Re:Actually
So you accept that they lied when they said it was beef, but they certainly wouldn't lie about this "beef" being unhealthy. My confidence wouldn't be so high.
What makes you think that meat is unhealthy?
Let's dig up some research on the matter: http://www.jbc.org/content/87/3/651.full.pdf
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Re:Materials
For instance, how does one purify dNTPs at home?
You could do it the way Kornberg's group did when isolating DNA synthase to begin with. Their paper is even online, for free. It amounts to growing a lot of e coli (or grinding up a bunch of thymus), reducing the DNA to its component monomers by digestion with DNAse extracted from pancreas and snake venom phosphodiesterase (although one could use alkaline hydrolysis, too), and purifying them by ion-exchange chromatography through a Dowex resin. None of that is especially hard, nor requiring of high-tech apparatus. Well, maybe if you want to get and verify that it's 99+% pure...
It's way more time consuming than calling Promega, but hobbyist endeavors are all characterized by having more time than money.
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I suggest you read these.
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Re:cancer
HTLV-1 causes changes in gene expression resulting in adult t-cell leukemia. This year my advisor had a paper on this very research detailing some of the changes which are involved: http://www.jbc.org/cgi/content/abstract/277/51/49459 basically the idea is that the virus in its attempt to replicate its self using cellular machinery alters the expression of specific genes, Tax, CREB and histones. better explained from my advisor: "HTLV-I Tax functions to short circuit the normal regulation of cell cycle progression by abrogating the need for mitogen stimulation and blocking checkpoint controls, resulting in unregulated initiation of S phase." in other words, the virus kicks out some of the cell regulatory controls that at least in part prevent it from becoming a cancer cell.
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Re:Cancer applications?
I read through all the replies to your post, and I'm surprised nobody seems to be aware of anthocyanin research, especially cyanidin-3-rutinoside:
http://linkinghub.elsevier.com/retrieve/pii/S0304383505004647
http://www.jbc.org/cgi/content/abstract/M610616200v2
http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2001/49/i03/abs/jf001246q.html
Sorry about the first URL - it was the only way I could quickly figure out to get a link to the article. Just click on the Science Direct link on that page to view it (maybe the other link also works, but I didn't test it).
Of course, this research is only in its infancy and could turn out to be a dead end, but I'm surprised nobody here seems to be aware of it. And I'm late to the discussion, so nobody will read this anyway....
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Re:Astoundingly disturbing and irresponsible
I'm afraid you don't, really.
a) Yes we do have a good picture of the jellyfish genome and what genes interact with the glow gene (warning PDF and sciency stuff.)
b) How are we supposed to have a "complete understanding" of the modified organism without making one? -
normal alien is a continuum
The summary:"Although 'alien' microbes might look like ordinary bacteria, their biochemistry could involve exotic amino acids or different elemental building blocks so researchers are devising tests to identify exotic microbes."
Here's the thing: there's unlikely to be a discrete line in the sand, beyond which life occurring on Earth can be called alien. In humans, we have DNA that transcribes into RNA and then translates into protein. Viruses just use RNA, dispensing with DNA, so they have a different elemental building block. Even in humans there are different building blocks: the RNA->protein translation for our main DNA has a different code than our mitochondrial DNA. Likewise, there are many bacteria that use amino acids not seen in the rest of the animal and plant kingdoms, and extreme thermophilic bacteria use ether-linked phospholipids (as do more common bacteria), that act like rivets holding the cell membrane together, rather than the bilipid membranes other bacteria, plants, and animals use. And once you start looking at metal-ion-based coenzymes, you can't stop finding weird and unusual things, especially if it involves moving ions or specific molecules around. Once you get past things that have either fur or flowers, there are more exotic chemistries than normal ones, it seems like. -
some perspective
from the abstract ( http://www.jbc.org/cgi/content/abstract/282/45/32844 )
On a mouse treadmill,
PEPCK-Cmus mice ran up to 6 km at a speed of 20 m/min, whereas controls stopped at 0.2 km.
6 Km vs 0.2 - thats a big difference !!
PEPCK-Cmus mice had an enhanced exercise capacity, with a VO2max of 156 ± 8.0 ml/kg/min, a maximal respiratory exchange ratio of 0.91 ± 0.03, and blood lactate of 3.7 ± 1.0 mM after running for 32 min at a 25 grade
control animals were 112 ± 21 ml/kg/min, 0.99 ± 0.08, and 8.1 ± 5.0 mM respectively.
The PEPCK-Cmus mice ate 60% more than controls but had half the body weight and 10% the body fat as determined by magnetic resonance imaging. -
more than just bias that I would be concerned abou
Well, not having read the study I can not comment on its significance; however, there is far more to blood transfusion dangers than NO depletion.
Lets get to some significant points: NO is produced locally at the tissues that need it.
RBC fragility is likely more significant than the effects of one vasodilator
Multiple unnecessary (or necessary) transfusions may lead to iron overload similar to that found in people with hemachromatosis
TRALI
I am not attacking their work, but there are so many other reasons to be vary of transfusions - the significance of this one seems like it would be minimal, but I do applaud their work in trying to minimize complications of transfusion.
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Re:Nature is nothing if not clever'so typical' of what? These are all statistical correlations, they haven't described any biochemical reaction path from VitD to cancer, so they are just making a partially educated guess. They are totally wrong about the VitD causation for auto-immune disease.
Vitamin D,25 is not the active form. Other metabolites, such as vitamin D,1,25 are the active forms. High vitamin D,1,25 can cause by itself a lot of the symptoms of auto-immune disease. Since D,1,25 is converted from D,25, the low D,25 is a result of rapid conversion to D,1,25. Adding more D,25 just adds fuel to the inflammatory fire.
Start here: http://vitamind.ucr.edu/biochem.html
It is not due to vitamin D deficiency but is caused by not having enough calcium in the diet.
Much of previous beliefs about Vitamin D are being changed, see this
from the USDA website [ href="http://www.ars.usda.gov/research/publication s/publications.htm?SEQ_NO_115=169216"
]
It is not due to vitamin D deficiency but is caused by not having enough calcium in the diet.
this paper describes the disregulation of the vitamin d metabolism in the disease process. Macrophages can drive the vitamin D,25 levels low by generating damaging high levels of vitamin D,1,25. So, the current knowledge that low vitamin D causes disease is backwards, low vitamin D can be a indication of a disease process that is driving the D,25 levels low, while driving D,1,25 high.
One interesting point for Slashdot readers, is that a lot
of the lastest Vitamin D research is being driven by computer
modeling of the Vitamin D molecule and the various nuclear receptors it affects. see http://winmlm.neostrada.pl/vitamindbook/vitamindne wresearch.pdf
I would like to be clear that I'm not disagreeing with the result that higher VitaminD is correlated with Cancer. I'm just pointing out that it is likely not as simple as somebody eating too many eggs,
and just needing to cut back.
However, I do disagree with the side comment made that high Vitamin D might cause autoimmune disease. The research (and my personal experience) is that Vitamin D disregulation is caused by the autoimmune disease and clears up when the disease clears up. -
The Old Way of Scientific Publishing Needs to Go!
All the reasons made for the continuation of the status quo are just excuses that benefit only the owners of the journals. One justification for the high cost of the journals is printing. But who really needs to go to the library to read the Journal of Biological Chemistry or the Proceedings of the National Academy of Sciences in their dead tree format anyway? If a library really needs a paper copy, perhaps they can just send out the PDFs to a third-party printer to print and bind it. I don't think we need Elsevier to do the printing and distribution. The internet already performs the distribution process very efficiently. So the traditional for-profit scientific journal publishers need to go the way of blacksmiths and scabbard makers. As for the world's premier science journal, Nature, perhaps Google or the Gates Foundation or Warren Buffet can just ask them what is their projected profit from the sales of subscriptions and archived articles for the next 10 years, pay them twice that amount, secure the copyright to past articles and future publication the journal and hire the entire editorial board. I don't think it would cost a lot. Now that would be a service to mankind.
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Re:Random error produces error control mechanism?
Case in point: the HIV virus. It's an RNA virus. Most enzymes cells use for replicating DNA (called DNA polymerases) have a proofreading skill: if they detect that what they're reading is incorrect they'll rip it out and try again. Most RNA polymerases lack proofreading skill (because it's expensive: it takes a lot of energy, and RNA is, in the grand scheme of things, considered throwaway material, a transition from the data storage system to the actual machinery.) So, the viruses that rely on RNA as their data storage have a much higher rate of mutation. The result is that they have a vastly higher rate of nonviable viral particles, and a small number of extremely viable particles, which have found, by chance, better ways of evading host immune response. It's a main reason that HIV is so difficult to treat or cure.
Here is some information about reverse transcriptase error rates. In contrast, here is some for one of the DNApolymerases. As I recall, in eukaryotes there are three DNA polymerases, and only DNApolyIII has bidirectional proofreading ability (I may be wrong) so only it can scan finished DNA, but all three can scan DNA while it's being built. In contrast, I don't believe there are any enzymes that can scan finished RNA (since it's not, to my knowledge, found double-stranded in anything we've found, and you'd have no way of determining that there was an error) so the best you can hope for is really good DNA->RNA fidelity, and as I said earlier, there's not much evolutionary pressure FOR that in the rest of nature, while there's some evolutionary pressure AGAINST it (because it's expensive) so if it were to exist, it would only exist in things that would benefit from it, those being small RNA viruses that are much less likely to have either the history, the machinery, or the overhead to afford proofreading replication enzymes. Besides which, if their gain (number of viruses produced for each cell infected) is high enough, they A: don't care about individual viral particle loss from bad fidelity, and B: actually benefit from high mutation rate because of its help in evading host response.
whew. that was wordy. sorry. -
Re:There will never be an AIDs cure.
It's not as if HIV integrates itself into the victims cromosomes,
Yes, it is. HIV has an enzyme called integrase that cuts a host chromosome and inserts the HIV genome. Here is a paper that talks about retroviral integration. Figure 1 shows a diagram of HIV being spliced in, and Figure 3 is a pretty picture of integrase itself. ...Like all other cells, T cells die off and get replaced, so if the patient goes on a treatment that kills off all free HIV (that is, HIV in the act of reproduction), they will eventually be free of it.
Unfortunately, the half-life of the relevant immune cells is measured in years. For a cure you need to wait until the expected number of infected cells is significantly smaller than one, which would take many decades.Worse, based on the existence of brain damage in HIV victims, there is a good chance that HIV occassionally integrates itself into astrocytes, which live a very long time. Astrocytes are pretty important, too, so you probably would not want an add-on therapy that simply kills all infected cells.
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Funny.
I was just on Some Random Website the other day reading about how before hops found its way into beers (sometime around the fourteenth century, I think), its principle use in Europe was as a medicinal herb. Usually brewed as a tea, as I recall.
Another Fun Beer Fact: before the British "discovered" how to put hops in their beer, the primary flavoring agent they used was creeping charlie. Ever since I found that out, I've always kinda wondered what that would taste like
...Another plant that seems to have tremendous health benefits (fightin' cancer, and alzheimer's, and as a general anti-inflammatory, etc.) is turmeric -- which is one of the primary ingredients of curry.
Hmmmm
... beer and curry ... the British must live fer freakin' ever. -
Re:A brief history of Medicine
Thank you for your condescending attitude. Perhaps it may be of use to you too look at your linked references. Also, you may want to google "triclosan", a common ingredient in antibacterial soaps.
The first hit I received from "mechanism of triclosan" was this:
Mechanism of Triclosan Inhibition of Bacterial Fatty Acid Synthesis (I apologize if you can't see this, I'm at a university and never know if people can see the links to journals I post)
So as you can see, triclosan affects the cell chemically.
Now, when these soaps say they kill 99.9% of all germs, guess which 0.1% they're not killing. I'll also give you another guess as to which ones keep reproducing.
Triclosan isn't the only antibacterial, for example, bleach (sodium hypochlorite) is also commonly used. Here is a reference to bacterial resistance to bleach. (Actually I was quite surprised myself to see this)
Kearns AM, Freeman R, Lightfoot NF (1995). "Nosocomal enterococci: resistance to heat and sodium hypochlorite." J Hosp Infect 30(3): 193-199.
I would love to continue this diatribe, but I have a chemistry Ph.D. to complete. -
Re:Why not do as Most online mags do ?.
They have a relatively large circulation and a quite general coverrage. Specialized journals such as the Journal of Biological Chemistry http://www.jbc.org/ and Journal of Virology http://jvi.asm.org/ (two that I'm very familiar with) also add targeted advertising (just like google but without the guess work). I haven't read any journals targeted towards this audience, but my guess is there's advertising in those as well. These scientists must use some resources, whether it's software, raw materials for experimentation or equipment and likewise there are companies that must provide these materials. Perhaps it's not enough income to get a project like this off the ground, but it might be just enough to maintain it. In any event, I wouldn't discount the possibility of providing targeted advertising as a means of income to supplement costs of providing this service.
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Re:-1, Uninformed
Phew, thank goodness someone else said it first. Here's links to a couple of articles about the active chromophore in the fish, vs. the active prion that causes BSE/vCJD. Good images in the flourescent protein article.
Repeat after me, everyone: Eating GM food will not cause my genes to be modified. -
Re:-1, Uninformed
Phew, thank goodness someone else said it first. Here's links to a couple of articles about the active chromophore in the fish, vs. the active prion that causes BSE/vCJD. Good images in the flourescent protein article.
Repeat after me, everyone: Eating GM food will not cause my genes to be modified. -
Re:Does anyone here understand the purpose of thisWhat you say is true for some large journal publishers, but certainly not for all. Remember that while many major journals are for-profit and have the interests you describe, many other journals (possibly more) are actually published by non-profit academic societies who have more interest in disseminating their information than in profit (although many of them still have serious issues with the control of their content, of course).
In fact, as it happens, LOCKSS is being worked on in association with HighWire Press at Stanford (disclosure: also my employer
:), which publishes the online versions of nearly 200 major scientific journals and has a _very_ good relationship with a large number of publishers. They also list the Journal of Biological Chemistry and Science Online as "partners".I wouldn't be so quick to dismiss the interest that the non-profit academic societies have in preserving this information.