Anything that is used as often as a comparator doesn't really matter, because you will quickly learn to recognize and recall it. Call "greater than" "susan" and after a few days you will know what "A susan B" means without even thinking.
However, if anyone found a better way to memorize things that you use once in a while (say, once a week or once a month); things like obscure class names in Java or particularities of certain R statistical packages (which parameter changes the direction of labels, was it "las" or "lus"? Does 1 mean "bottom" or "left" in the "pos" parameter? What was the name of that package that did this little thingy and had this nice function to produce such great plots...) then I would find the discussion not a complete waste of time.
If only there was something to help us with that... like, if there were environments or editors that would enable us to quickly search available libraries, autocomplete, look up manuals...
Except -- not even statistically. In real statistics, effect size matters; even a significant effect is unimportant if the effect size is small (see effect size in Wikipedia).
Psychological meta-analyses show that even though statistically significant gender effects may exist, their effect size is very small -- these differences are not important (see for example this paper by Janet S. Hyde, but also numerous other publications). There are few exceptions: males seem to have better dimensional orientation and women have a better ability to read other people's emotional state, but even in these cases the effect size is modest. The real difference is... the frequency of masturbation (Cohen's d ~ 1, but even that is not the largest effect that one observes on the daily basis in science).
Excuse me, but having a penis or a vagina does not have anything to do with considering anyone calling me a "fuckwad" to be offensive, rude and unprofessional. I am male, but I will not interact with anyone on that level. Maybe that is acceptable in where you grew up or with some people that you are interacting with; however, you need to be aware that for most other people, regardless of their chromosomal setup, this type of interaction is not only offensive, but also a sign of your lack of general competence and intelligence. A "stay away" flag, if you will.
And yes, if you need this type of interaction to do anything productive, if you are unable to either express the same without being offensive or parse a comment that does not include the word "fuckwad", then it is you who has a problem and it is a much more serious problem than scaring away smart and professional individuals, whatever their genitals may be.
I got my first computer in 1986; I was 13, and it was a ZX Spectrum with a build-in BASIC interpreter. When you switched on, you could start away programming. In fact, the computer came with a little book with programming examples and little games. I spend countless hours typing in listings that I found in newspapers. To even load a simple game you had to enter a command.
Since then, I learned C, tcsh, C++, bash, Perl, much later also Python and R. It was a step by step process, and I would never have started it (and became what I am now, that is, computational biologist) if not for this one computer with the BASIC interpreter.
I have kids now, and they have Android tablets. The sheer power, their parameters and their capabilities are overwhelming. I don't know how many instances of a ZX Spectrum emulator I could run on one of these, a thousand?
But even though they run on a system that is related to the system I am using every day, I would not know how to write a program for them to save my life. In theory, I know how I would approach it, I even set up once an Eclipse environment once, but I never got to even start a Hello world program. If I were 13, I would not even know that I can write a program myself.
It is amazing, but I think that actually, my kids will have a much harder time to learn programming than I had, and they will get much less fun in return...
John Maynard Smith introduced the game theory to evolutionary biology in the early 70's. It was a breakthrough at that time, however today it is scarcely news. Evolutionary biology, and in especially population genetics has been a highly mathematized discipline ever since before WWII, when it was developed by Fisher, Wright and Haldane. Later you had Hamilton and Maynard Smith. It is nice that computer scientists noticed that something exciting is going on here, but don't fall for press releases and insubstantiated claims.
Speaking as a scientist with 20+ years of experience in programming: we are unlikely to choose a programming language based on its elegance, ideas behind etc. Two primary factors are (i) who else is using a given language and (ii) what libraries for that language are out there. For example, exactly 0 of the languages mentioned in the original article are used by statisticians. Haskell might be cute to write a generic program with, but in R or SPSS I have all the cutting-edge statistical tools I need for my work.
Whenever I hear about a physicist who explains a problem from outside his area of expertise with a few simple equations, I think about this Saturday Morning Breakfast Cereal cartoon: http://www.smbc-comics.com/com...
Again, the press release is misleading. Worse, it fires back on the real and great accomplishment by suggesting it is something that it is not.
The scientists managed to squeeze key enzymes into different minuscule compartments of a cell-like structure. That in itself is fascinating and a great achievement; but that doesn't make an eukaryotic cell. It does not replicate; it does not synthesize the lipid-like structures; it lacks a cytoskeleton and a complex organization; the reactions going on are few and very simple. It is as much an eukaryotic cell as a neural net algorithm is a working brain.
However, it has working enzymes within little bubbles within other bubbles, which can be called "compartmentalization", a feature of eukaryotic cells that distinguish them from bacterial cells.
Nonetheless, this is a considerable achievment that has both a practical side and is a working model with potential to make in vitro experiments helping to understand the processes that go on in the real cells.
The problem is that anything above 400mg / day gets quickly removed from our organism. So no, we are not chimps (and btw, chimps also can't synthesise vitamin C naturally), and our organisms know pretty well how much vitamin C is needed.
Pauling specifically believed that overdose of vitamin C can prevent cancer. It was a very interesting hypothesis, and it was very important to test it. However, several large prospective studies undertaken in the 80's have, unfortunately for all of us, falsified that claim.
Klenner's observations from the 30's-50's have also not been confirmed by any kind of systematic study.
6000 mg vitamin C daily, not counting vitamin C in the food? That is a lot. Consult your physician and be very, very cautious about suggesting medical advice if you are not prepared to take moral and financial responsibility for it. Yes, vitamin C is important. Yes, increased intake of vitamin C has been show to have several health benefits, including reduced stroke and cardiovascular disease risks, especially in smokers. However, "increased intake" means "well below 1g/day".
6000 is 30-100 times the recommended daily dose. Although studies indicate that vitamin C intake at 2-4 g/day may not have large adverse effects (1), one has to be extremely cautious when recommending supplementing your diet by a 100x of a daily dose. The fact that you don't experience any adverse effects such as kidney stones (at least yet) does not mean that a person reading your comment will not suffer from that either.
Apart from the problems with the digestive tract, vitamin C can hamper endurance in physical exercises (2). Moreover, vitamin C not used by the organism (which requires as little as 100-200mg / day) is excreted (3). For that, it is metabolised to oxalic acid, which in turn can cause kidney stones (4 and the references therein). So yes, although problems with vit. C overdose do not seem to be common and are not comparable to overdoses of some other vitamins, at 6g/d saying that "C can't hurt" is very risky (especially as supplements can contain other vitamins as well, and the fat soluble vitamins A, D, E and K can cause severe adverse effects -- vitamine poisoning -- when overdosed).
The highest risk-free level of daily intake for vitamine C has been recently proposed to be 1000 mg (1g) (5, 6). People, before you install some shady software someone recommends at a biology-oriented website, ask your IT friend for advice. Before your follow medical advice from Slashdot, consult your physician.
"Rational by choice."
Prove it. Read the evidence based medical studies rather than trusting and spreading anecdotes.
Mtb is an intracellular pathogen. It invades our cells, the very same cells that are supposed to kill bacteria (the macrophages). This is why treatment of TB takes six months. Vitamin C, at a dosage lethal for Mtb as described in the article, cannot be used to kill the bacteria in our cells. The importance of the article is that it identifies a potentially intereseting difference between Mtb and other bacteria.
As for vitamin C, this is not some kind of a miraculous drug; it is just a co-enzyme required for a few particular reactions in our metabolic pathways. We, humans, are mutants, we lack the ability to synthetise vitamin C -- along with our cousins, the monkeys, although most animals do synthetise it on their own. Lack of vitamin C impedes the metabolism. However, only little of the co-enzyme is needed, and once vitamin C is no longer a limiting factor, it has barely an effect.
Think about that in terms of a network. If your wireless router is extremely slow, buying a new one will increase the speed of your connection. But what good is a super fast wifi router, if the outgoing connection runs at 10Mbit?
Vitamin C is also an antioxidant, and this is why some people (quite incorrectly) think that taking large doses of vitamin C are beneficial. However, there are two forms of this compound, L-ascorbate (vitamin C) and D-ascorbate; both are antioxidative, but only one is a co-enzyme. D-ascorbate, however, shows no beneficial effects.
Big pharma has not much interest in preventing the use of vitamin C in Mtb treatment. Mtb drugs are cheap, generic, and effective; the main reason why Mtb is a problem for much of the world is lack of fast and cheap diagnostic tools. You see, 2 billions (2e9, one third of worlds population) are infected with Mtb, and of these, only 10% will develop tuberculosis during their lifetime. However, we don't know which, why, and when. Also, when a person falls ill, it is not a quick process like a flu; rather than that, a person starts feeling unwell, caughing and becomes infectious over weeks before she finally decides to see a doctor. Here is a review article I wrote on TB and biomarkers: http://www.ncbi.nlm.nih.gov/pubmed/23181737 (full text behind a paywall, unfortunately).
Pauling believed that taking large doses of vitamines will prevent cancer and took large amounts of vitamin C throughout his life. In 1994, he died of prostate cancer.
Counting from the start of my PhD program, I have spent over 15 years doing science (biology) -- most of my grown-up life. I'm still doing science, it's my life. And what I have to say to you, young padawan, is not nice.
You are about to do the most thrilling (awesome, exciting, depressing, frustrating, crazy, fulfilling, everything at once) thing on Earth, you will be doing bloody science, and you think about getting...new hobbies? New interests? All that in a fashion of someone shopping for a new T-shirt? (ah, skydiving, seems nice, I'll take a pair).
How will you come up with ideas for your research if you have not enough curiosity and interest in the world around you, and you have to fish for interests / hobbies on Slashdot? This is how your question sounds for me: "I just got an apprenticeship at NASA, can someone give me an idea for a new hobby? 'cause I have none". If you need to ask a question like that, then better ask yourself whether PhD in science is really what you want.
Apart from that, if you already have anything that you like to do with your free time, plus you have some kind of relationship (or plan to have one), plus you will take your science seriously, you will have barely any time to pursue "new hobbies / interests". Go and read http://www.phdcomics.com/.
You can make precisely the same argument about the last common ancestor between humans and chimps, or the last common ancestor of humans and neandertals. In a general context, chimp brain is as complex as ours. Yet evolution happened in between, we can track it, and we can see that it did in fact modify the cognitive functions of that ancestor; chimps are not humans. And hell, even the developmental machinery that makes an egg develop into an adult vertebrate is complex and interdependent, and if what you are quoting were true, one would expect all vertebrate life remain at the stage of a fish.
The actual reason might be much more mundane: the initial small population of modern humans expanded so rapidly that any resultant genetic differences between populations are the result of neutral evolution (like genetic drift) rather than natural selection. This is also why genetic diversity is inversely correlated with geographic distance to Africa. Essentially, we are all still this same small initial population, but we expanded like a balloon, taking down - directly or indirectly - any other populations that might have existed at times (like the neandertals, denisovians and many, many other hominins).
Not even that. I would rather say: humans with these mutations had a higher chance to leave offspring. It's not like we are talking about a single mutation that is present in all humans native to Siberia, but rather that a frequency of certain genotype is higher in these areas.
It is off topic, but the ability to digest lactose as adults evolved somewhere between 5,000 and 10,000 years ago. The greatest ability to digest lactose as adults is clustered in the Arabian peninsula, southern Iran and Pakistan, far western Africa, and northern Europe (southern Scandinavia, Iceland, Ireland, Great Britain, Denmark, northern Germany, and northern France). I couldn't tell you though if the genetics are the same but it seems unlikely given the geographical clustering.
Yes, it is the same mutation you are talking about. The associated mutations (or "snips", SNP -- single nucleotide polymorphisms) are all the same, even in the West African tribes, and are thought to be of a common origin.
However, there actually is a known case convergent evolution of lactase persistence, fully described in this Nature Genetics paper: http://www.nature.com/ng/journal/v39/n1/full/ng1946.html . The authors analysed genotypes of East African pastoral tribes where lactase persistance is also widely spread, and found several alternative mutations in the same regulatory region. The most common of these mutations is thought to be ~ 7000 years old.
Of course not only in the mitochondria. Reactive oxygen species are also one of the first lines of defense against bacteria; macrophages generate reactive oxygen in the phagosomes - when macrophages ingest a live bacterium, it then becomes surrounded by a membrane, forming a phagosome. It is best explained with a picture: http://textbookofbacteriology.net/Phago.jpeg
Next, the phagosome changes into what is called phagolysosome, which is like a death cage for the bacterium. All sorts of nasty enzymes and molecules get injected in this space, including enzymes producing reactive oxygen species.
However, immune cells can also release oxygen directly into bloodstream. Given the cytotoxicity of ROS, this is like detonating nukes in your blood vessels, and can result in collateral damage. However, this stuff totally happens. Neutrophils can undergo a sort of harakiri, releasing DNA-bound bacteriocidal proteins in form of a sticky NET ("Neutrophil Extracellular Traps"). Proteins in NET generate extracellular ROS. It's a bit like gutting yourself and strangling the enemy with your own intestines.
So yeah, our own immune system produces ROS when it is fighting bacteria. The desired effect is local and limited to bacteria, but collateral damage is known to exist, and antioxidants can help to contain it.
That said, the hypothesis is not even that (a proper hypothesis), but more like a vague idea: how could you test it scientifically?
Post scriptum: erratum and an additional explanation
"cognitive and brain development" -> "cognitive functions and brain development"
"gene is not important" -> gene itself might be important, but its precise sequence might not matter because different variants are able to fulfill the same function. The problem is that a synonymous mutation usually is not visible to natural selection, but that doesn't mean that a non-synonymous mutation is always visible; many non-synonymous mutations are effectively neutral.
Also note that the whole story works only for protein coding genes, because we can easily tell "important" (non-synonymous) from "non-important" (synonymous) changes. However, first of all there are many important genes which do not encode proteins, for example the regulatory microRNAs or structural RNAs. It is not easy to tell which mutations are neutral, and which aren't. Second, there are regulatory regions that can matter a lot; again, it is hard to tell which mutation will have an effect. For example, the famous lactase persistence mutation is a mutation in a regulatory region, not in the gene itself; it messes up the switch of the gene that all other mammals use to turn off lastase production in adult animals. It does not alter the sequence of the protein coding region.
Such cases can still be worked on, for example by looking whether there are mutations in regions that are otherwise conserved in other species. Unfortunately, this is nowhere as sensitive or specific as considering the dN/dS ratio.
1. Just like the article says and unlike the Slashdot summary suggests, shiver-free thermogenesis is old and all mammals share it.
2. The researchers found traces of positive selection in a gene involved in shiver-free thermogenesis.
3. How do you look for traces of selection? A mutation in a DNA fragment coding for a protein can have two effects: either it changes the corresponding amino acid in the protein sequence (non-synonymous mutation), or it does not (synonymous mutation). This is because genetic code is redundant and different codons code for same amino acids, so a change from one codon to another does not have to change the protein. Synonymous mutations are assumed to be neutral for evolution (although they are not, not always).
Now, if you look at many possible variants of a gene and collect many different mutations, you can calculate whether the ratio of non-synonymous to synonymous mutations (called the dN/dS ratio) is (i) higher (ii) lower or (iii) quite like expected. Depending on the outcome of the test, you can say:
- if it is higher than expected, then there is a positive selection force at work (the gene is pushed towards change) - if it is lower than expected, then we have a case of purifying selection; the gene is being actively maintained as it is, and any non-synonymous mutations are being removed from the population - if it is neither lower nor higher, the gene is just not important
4. So, nice, you found that a gene related to non-shiver thermogenesis shows traces of positive selection. So what?
The answer is, not much. You do not always know which mutation was the one being selected. And even if you can pinpoint it, very often you will not be able to say what it actually does. So fine, you have a leucine replaced by arginine at position 186 in a protein chain; you might be able even to model the new sequence and see a delicate shift in the structure of the protein. How does it relate to the protein function? What has been modified or improved? No idea.
5. OK, why is that important? It is important because much of the genetic variability of the humans that we know is thought to have been fixated by genetic drift and other neutral evolutionary effects (like surfing the wave of colonization) - rather than selection. There are few examples of selection known. Light skin is one of them, and is thought to be an adaptation to the vitamin D deficiency caused by lack of sun at high latitudes. Mutation that keeps lactase being produced throughout life is another one. There were independent (convergent) events in both cases, by the way.
Look, humans are special. Special in the sense that humans are genetically extremely uniform, and the genetic differences between, say, native Australian, a blond-haired, blue-eyed Swede and a member of the Mbuti people from Africa are all together much smaller than between two chimpanzee individuals from groups living a few hundred kilometers apart. And moreover, these few mutations specific for some people but not for other seem to be more or less neutral in their character.
Finding differences that are *not* neutral, that are actually doing something is therefore an interesting thing. Notably, the few existing differences like that are linked to mundane things like metabolism or immune response (yes, some people are special because they don't fart after drinking milk, how is that for a superior race), and not, for example, to cognitive and brain development. The latter differences are found between humans and other primates.
The problem is that it does not describe very well how science has actually progressed, in the past or the present.
As mentioned, this is philosophy, not science, so it is hard to confront different and contradictory views.
For example, there will be some who will tell you that the popperian concept of falsification is one of the most influential ideas of the XX century, responsible for the dramatic progress in understanding of our world that happened in the XX century. Not least because of the statistical hypothesis-testing framework, and there is little doubt about the influence of XX century statistics on progress in science.
But yes, it does not fit the copernican revolution.
But then there's the (at least) equal and opposite error, which I call Haldane's Error - the belief that anything not currently explained by science must perforce be supernatural and can never be explained by science.
Oh, what a beautiful quote, I will steal it for my students. It is simply grand... given the career and persona of J.B.S. Haldane, son of J.S. Haldane, who was one of the most influential evolutionary biologists and geneticists of all time.
Firstly, please note that Thomas Kuhn's view of how science happens is one of many possibilities. On one side of the spectrum, you have Popper and his younger collegue, Imre Lakatos; on the other end, you have Feyerabend and his "everything goes". Unfortunately, all that is philosophy, so itself is not science and cannot be verified experimentally or backed up with meaningful statistics. Thus, depending on whom you talk to, you will find arguments for Popper or for Lakatos or for Feyerabend or for Kuhn, all coming from the same field of science.
Personally, I value the popperian hypothesis-falsification paradigm a lot, especially since it fits so nicely with classical statistical hypothesis testing, and I insist on teaching it to students (I am a biologist), but I am well aware of its limitations.
Unfortunately, when reading texts of the great philosphers of science, one has the impression that all they really wanted to explain was "the big stuff", the grand theories, the grand revolutions or paradigm shifts. It is easy to argue for paradigm shifts if you focus on Copernicus and Einstein. It is much harder to immerse yourself in the day-to-day reality of scientific work, the millions of manuscripts generated, the propagation of ideas, their deeply intertwined relationships, as no idea, however genial, ever materializes itself from nothing.
I would not agree with that. Yes, very often, cat is not necessary, strictly speaking; for example, the list of arguments could be directly passed to grep in this case. However, personally I consider it to be bad style. A verbose cat (i) doesn't cost anything in terms of memory or CPU (if it does, then 1981 called, they want their computer back), (ii) facilitates or invites additional filters, for example adding sort -u (or sort | uniq, as I would rather have it), (iii) makes the whole pipeline more readable.
I find it especially funny when people who do not hesitate to launch a terrible misuse of resources (also know as a "Web browser") hesitate to put an additional cat command to a long pipeline.
Slashdot Mirror
Anything that is used as often as a comparator doesn't really matter, because you will quickly learn to recognize and recall it. Call "greater than" "susan" and after a few days you will know what "A susan B" means without even thinking.
However, if anyone found a better way to memorize things that you use once in a while (say, once a week or once a month); things like obscure class names in Java or particularities of certain R statistical packages (which parameter changes the direction of labels, was it "las" or "lus"? Does 1 mean "bottom" or "left" in the "pos" parameter? What was the name of that package that did this little thingy and had this nice function to produce such great plots...) then I would find the discussion not a complete waste of time.
If only there was something to help us with that... like, if there were environments or editors that would enable us to quickly search available libraries, autocomplete, look up manuals...
Oh wait.
...I can only refer you to this Saturday Morning Breakfast Cereal cartoon:
http://www.smbc-comics.com/?id...
This.
Except -- not even statistically. In real statistics, effect size matters; even a significant effect is unimportant if the effect size is small (see effect size in Wikipedia).
Psychological meta-analyses show that even though statistically significant gender effects may exist, their effect size is very small -- these differences are not important (see for example this paper by Janet S. Hyde, but also numerous other publications). There are few exceptions: males seem to have better dimensional orientation and women have a better ability to read other people's emotional state, but even in these cases the effect size is modest. The real difference is... the frequency of masturbation (Cohen's d ~ 1, but even that is not the largest effect that one observes on the daily basis in science).
Excuse me, but having a penis or a vagina does not have anything to do with considering anyone calling me a "fuckwad" to be offensive, rude and unprofessional. I am male, but I will not interact with anyone on that level. Maybe that is acceptable in where you grew up or with some people that you are interacting with; however, you need to be aware that for most other people, regardless of their chromosomal setup, this type of interaction is not only offensive, but also a sign of your lack of general competence and intelligence. A "stay away" flag, if you will.
And yes, if you need this type of interaction to do anything productive, if you are unable to either express the same without being offensive or parse a comment that does not include the word "fuckwad", then it is you who has a problem and it is a much more serious problem than scaring away smart and professional individuals, whatever their genitals may be.
I got my first computer in 1986; I was 13, and it was a ZX Spectrum with a build-in BASIC interpreter. When you switched on, you could start away programming. In fact, the computer came with a little book with programming examples and little games. I spend countless hours typing in listings that I found in newspapers. To even load a simple game you had to enter a command.
Since then, I learned C, tcsh, C++, bash, Perl, much later also Python and R. It was a step by step process, and I would never have started it (and became what I am now, that is, computational biologist) if not for this one computer with the BASIC interpreter.
I have kids now, and they have Android tablets. The sheer power, their parameters and their capabilities are overwhelming. I don't know how many instances of a ZX Spectrum emulator I could run on one of these, a thousand?
But even though they run on a system that is related to the system I am using every day, I would not know how to write a program for them to save my life. In theory, I know how I would approach it, I even set up once an Eclipse environment once, but I never got to even start a Hello world program. If I were 13, I would not even know that I can write a program myself.
It is amazing, but I think that actually, my kids will have a much harder time to learn programming than I had, and they will get much less fun in return...
John Maynard Smith introduced the game theory to evolutionary biology in the early 70's. It was a breakthrough at that time, however today it is scarcely news. Evolutionary biology, and in especially population genetics has been a highly mathematized discipline ever since before WWII, when it was developed by Fisher, Wright and Haldane. Later you had Hamilton and Maynard Smith. It is nice that computer scientists noticed that something exciting is going on here, but don't fall for press releases and insubstantiated claims.
Speaking as a scientist with 20+ years of experience in programming: we are unlikely to choose a programming language based on its elegance, ideas behind etc. Two primary factors are (i) who else is using a given language and (ii) what libraries for that language are out there. For example, exactly 0 of the languages mentioned in the original article are used by statisticians. Haskell might be cute to write a generic program with, but in R or SPSS I have all the cutting-edge statistical tools I need for my work.
Whenever I hear about a physicist who explains a problem from outside his area of expertise with a few simple equations, I think about this Saturday Morning Breakfast Cereal cartoon: http://www.smbc-comics.com/com...
Again, the press release is misleading. Worse, it fires back on the real and great accomplishment by suggesting it is something that it is not.
The scientists managed to squeeze key enzymes into different minuscule compartments of a cell-like structure. That in itself is fascinating and a great achievement; but that doesn't make an eukaryotic cell. It does not replicate; it does not synthesize the lipid-like structures; it lacks a cytoskeleton and a complex organization; the reactions going on are few and very simple. It is as much an eukaryotic cell as a neural net algorithm is a working brain.
However, it has working enzymes within little bubbles within other bubbles, which can be called "compartmentalization", a feature of eukaryotic cells that distinguish them from bacterial cells.
Nonetheless, this is a considerable achievment that has both a practical side and is a working model with potential to make in vitro experiments helping to understand the processes that go on in the real cells.
...suffer from amnesia. Passwords generally don't, so I would not worry about that particular problem.
And now excuse me, I need to water my keyboard.
"fully enclosed mini desktop computer that could be taken anywhere without the need for cabling or setup"
So, basically, a laptop?
Seriously -- how is that news? People have been doing it for years now. Here is a random google link from 2012: http://blog.parts-people.com/2012/12/20/mobile-raspberry-pi-computer-build-your-own-portable-rpi-to-go/
The problem is that anything above 400mg / day gets quickly removed from our organism. So no, we are not chimps (and btw, chimps also can't synthesise vitamin C naturally), and our organisms know pretty well how much vitamin C is needed.
Pauling specifically believed that overdose of vitamin C can prevent cancer. It was a very interesting hypothesis, and it was very important to test it. However, several large prospective studies undertaken in the 80's have, unfortunately for all of us, falsified that claim.
Klenner's observations from the 30's-50's have also not been confirmed by any kind of systematic study.
6000 mg vitamin C daily, not counting vitamin C in the food? That is a lot. Consult your physician and be very, very cautious about suggesting medical advice if you are not prepared to take moral and financial responsibility for it. Yes, vitamin C is important. Yes, increased intake of vitamin C has been show to have several health benefits, including reduced stroke and cardiovascular disease risks, especially in smokers. However, "increased intake" means "well below 1g/day".
6000 is 30-100 times the recommended daily dose. Although studies indicate that vitamin C intake at 2-4 g/day may not have large adverse effects (1), one has to be extremely cautious when recommending supplementing your diet by a 100x of a daily dose. The fact that you don't experience any adverse effects such as kidney stones (at least yet) does not mean that a person reading your comment will not suffer from that either.
Apart from the problems with the digestive tract, vitamin C can hamper endurance in physical exercises (2). Moreover, vitamin C not used by the organism (which requires as little as 100-200mg / day) is excreted (3). For that, it is metabolised to oxalic acid, which in turn can cause kidney stones (4 and the references therein). So yes, although problems with vit. C overdose do not seem to be common and are not comparable to overdoses of some other vitamins, at 6g/d saying that "C can't hurt" is very risky (especially as supplements can contain other vitamins as well, and the fat soluble vitamins A, D, E and K can cause severe adverse effects -- vitamine poisoning -- when overdosed).
The highest risk-free level of daily intake for vitamine C has been recently proposed to be 1000 mg (1g) (5, 6). People, before you install some shady software someone recommends at a biology-oriented website, ask your IT friend for advice. Before your follow medical advice from Slashdot, consult your physician.
"Rational by choice."
Prove it. Read the evidence based medical studies rather than trusting and spreading anecdotes.
(1) http://onlinelibrary.wiley.com/doi/10.1111/j.1753-4887.1999.tb06926.x/abstract
(2) http://ajcn.nutrition.org/content/87/1/142.short
(3) http://ajcn.nutrition.org/content/69/6/1086.short
(4) http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2362.1998.00349.x/full
(5) http://jama.jamanetwork.com/article.aspx?articleid=189543
(6) http://www.pnas.org/content/93/8/3704.short
Mtb is an intracellular pathogen. It invades our cells, the very same cells that are supposed to kill bacteria (the macrophages). This is why treatment of TB takes six months. Vitamin C, at a dosage lethal for Mtb as described in the article, cannot be used to kill the bacteria in our cells. The importance of the article is that it identifies a potentially intereseting difference between Mtb and other bacteria.
As for vitamin C, this is not some kind of a miraculous drug; it is just a co-enzyme required for a few particular reactions in our metabolic pathways. We, humans, are mutants, we lack the ability to synthetise vitamin C -- along with our cousins, the monkeys, although most animals do synthetise it on their own. Lack of vitamin C impedes the metabolism. However, only little of the co-enzyme is needed, and once vitamin C is no longer a limiting factor, it has barely an effect.
Think about that in terms of a network. If your wireless router is extremely slow, buying a new one will increase the speed of your connection. But what good is a super fast wifi router, if the outgoing connection runs at 10Mbit?
Vitamin C is also an antioxidant, and this is why some people (quite incorrectly) think that taking large doses of vitamin C are beneficial. However, there are two forms of this compound, L-ascorbate (vitamin C) and D-ascorbate; both are antioxidative, but only one is a co-enzyme. D-ascorbate, however, shows no beneficial effects.
Big pharma has not much interest in preventing the use of vitamin C in Mtb treatment. Mtb drugs are cheap, generic, and effective; the main reason why Mtb is a problem for much of the world is lack of fast and cheap diagnostic tools. You see, 2 billions (2e9, one third of worlds population) are infected with Mtb, and of these, only 10% will develop tuberculosis during their lifetime. However, we don't know which, why, and when. Also, when a person falls ill, it is not a quick process like a flu; rather than that, a person starts feeling unwell, caughing and becomes infectious over weeks before she finally decides to see a doctor. Here is a review article I wrote on TB and biomarkers: http://www.ncbi.nlm.nih.gov/pubmed/23181737 (full text behind a paywall, unfortunately).
Pauling believed that taking large doses of vitamines will prevent cancer and took large amounts of vitamin C throughout his life. In 1994, he died of prostate cancer.
Counting from the start of my PhD program, I have spent over 15 years doing science (biology) -- most of my grown-up life. I'm still doing science, it's my life. And what I have to say to you, young padawan, is not nice.
You are about to do the most thrilling (awesome, exciting, depressing, frustrating, crazy, fulfilling, everything at once) thing on Earth, you will be doing bloody science, and you think about getting ...new hobbies? New interests? All that in a fashion of someone shopping for a new T-shirt? (ah, skydiving, seems nice, I'll take a pair).
How will you come up with ideas for your research if you have not enough curiosity and interest in the world around you, and you have to fish for interests / hobbies on Slashdot? This is how your question sounds for me: "I just got an apprenticeship at NASA, can someone give me an idea for a new hobby? 'cause I have none". If you need to ask a question like that, then better ask yourself whether PhD in science is really what you want.
Apart from that, if you already have anything that you like to do with your free time, plus you have some kind of relationship (or plan to have one), plus you will take your science seriously, you will have barely any time to pursue "new hobbies / interests". Go and read http://www.phdcomics.com/.
And get out of my lawn.
This reasoning is a fallacy.
You can make precisely the same argument about the last common ancestor between humans and chimps, or the last common ancestor of humans and neandertals. In a general context, chimp brain is as complex as ours. Yet evolution happened in between, we can track it, and we can see that it did in fact modify the cognitive functions of that ancestor; chimps are not humans. And hell, even the developmental machinery that makes an egg develop into an adult vertebrate is complex and interdependent, and if what you are quoting were true, one would expect all vertebrate life remain at the stage of a fish.
The actual reason might be much more mundane: the initial small population of modern humans expanded so rapidly that any resultant genetic differences between populations are the result of neutral evolution (like genetic drift) rather than natural selection. This is also why genetic diversity is inversely correlated with geographic distance to Africa. Essentially, we are all still this same small initial population, but we expanded like a balloon, taking down - directly or indirectly - any other populations that might have existed at times (like the neandertals, denisovians and many, many other hominins).
Not even that. I would rather say: humans with these mutations had a higher chance to leave offspring. It's not like we are talking about a single mutation that is present in all humans native to Siberia, but rather that a frequency of certain genotype is higher in these areas.
It is off topic, but the ability to digest lactose as adults evolved somewhere between 5,000 and 10,000 years ago. The greatest ability to digest lactose as adults is clustered in the Arabian peninsula, southern Iran and Pakistan, far western Africa, and northern Europe (southern Scandinavia, Iceland, Ireland, Great Britain, Denmark, northern Germany, and northern France). I couldn't tell you though if the genetics are the same but it seems unlikely given the geographical clustering.
Yes, it is the same mutation you are talking about. The associated mutations (or "snips", SNP -- single nucleotide polymorphisms) are all the same, even in the West African tribes, and are thought to be of a common origin.
However, there actually is a known case convergent evolution of lactase persistence, fully described in this Nature Genetics paper: http://www.nature.com/ng/journal/v39/n1/full/ng1946.html . The authors analysed genotypes of East African pastoral tribes where lactase persistance is also widely spread, and found several alternative mutations in the same regulatory region. The most common of these mutations is thought to be ~ 7000 years old.
Of course not only in the mitochondria. Reactive oxygen species are also one of the first lines of defense against bacteria; macrophages generate reactive oxygen in the phagosomes - when macrophages ingest a live bacterium, it then becomes surrounded by a membrane, forming a phagosome. It is best explained with a picture: http://textbookofbacteriology.net/Phago.jpeg
Next, the phagosome changes into what is called phagolysosome, which is like a death cage for the bacterium. All sorts of nasty enzymes and molecules get injected in this space, including enzymes producing reactive oxygen species.
However, immune cells can also release oxygen directly into bloodstream. Given the cytotoxicity of ROS, this is like detonating nukes in your blood vessels, and can result in collateral damage. However, this stuff totally happens. Neutrophils can undergo a sort of harakiri, releasing DNA-bound bacteriocidal proteins in form of a sticky NET ("Neutrophil Extracellular Traps"). Proteins in NET generate extracellular ROS. It's a bit like gutting yourself and strangling the enemy with your own intestines.
So yeah, our own immune system produces ROS when it is fighting bacteria. The desired effect is local and limited to bacteria, but collateral damage is known to exist, and antioxidants can help to contain it.
That said, the hypothesis is not even that (a proper hypothesis), but more like a vague idea: how could you test it scientifically?
Post scriptum: erratum and an additional explanation
"cognitive and brain development" -> "cognitive functions and brain development"
"gene is not important" -> gene itself might be important, but its precise sequence might not matter because different variants are able to fulfill the same function. The problem is that a synonymous mutation usually is not visible to natural selection, but that doesn't mean that a non-synonymous mutation is always visible; many non-synonymous mutations are effectively neutral.
Also note that the whole story works only for protein coding genes, because we can easily tell "important" (non-synonymous) from "non-important" (synonymous) changes. However, first of all there are many important genes which do not encode proteins, for example the regulatory microRNAs or structural RNAs. It is not easy to tell which mutations are neutral, and which aren't. Second, there are regulatory regions that can matter a lot; again, it is hard to tell which mutation will have an effect. For example, the famous lactase persistence mutation is a mutation in a regulatory region, not in the gene itself; it messes up the switch of the gene that all other mammals use to turn off lastase production in adult animals. It does not alter the sequence of the protein coding region.
Such cases can still be worked on, for example by looking whether there are mutations in regions that are otherwise conserved in other species. Unfortunately, this is nowhere as sensitive or specific as considering the dN/dS ratio.
1. Just like the article says and unlike the Slashdot summary suggests, shiver-free thermogenesis is old and all mammals share it.
2. The researchers found traces of positive selection in a gene involved in shiver-free thermogenesis.
3. How do you look for traces of selection? A mutation in a DNA fragment coding for a protein can have two effects: either it changes the corresponding amino acid in the protein sequence (non-synonymous mutation), or it does not (synonymous mutation). This is because genetic code is redundant and different codons code for same amino acids, so a change from one codon to another does not have to change the protein. Synonymous mutations are assumed to be neutral for evolution (although they are not, not always).
Now, if you look at many possible variants of a gene and collect many different mutations, you can calculate whether the ratio of non-synonymous to synonymous mutations (called the dN/dS ratio) is (i) higher (ii) lower or (iii) quite like expected. Depending on the outcome of the test, you can say:
- if it is higher than expected, then there is a positive selection force at work (the gene is pushed towards change)
- if it is lower than expected, then we have a case of purifying selection; the gene is being actively maintained as it is, and any non-synonymous mutations are being removed from the population
- if it is neither lower nor higher, the gene is just not important
4. So, nice, you found that a gene related to non-shiver thermogenesis shows traces of positive selection. So what?
The answer is, not much. You do not always know which mutation was the one being selected. And even if you can pinpoint it, very often you will not be able to say what it actually does. So fine, you have a leucine replaced by arginine at position 186 in a protein chain; you might be able even to model the new sequence and see a delicate shift in the structure of the protein. How does it relate to the protein function? What has been modified or improved? No idea.
5. OK, why is that important? It is important because much of the genetic variability of the humans that we know is thought to have been fixated by genetic drift and other neutral evolutionary effects (like surfing the wave of colonization) - rather than selection. There are few examples of selection known. Light skin is one of them, and is thought to be an adaptation to the vitamin D deficiency caused by lack of sun at high latitudes. Mutation that keeps lactase being produced throughout life is another one. There were independent (convergent) events in both cases, by the way.
Look, humans are special. Special in the sense that humans are genetically extremely uniform, and the genetic differences between, say, native Australian, a blond-haired, blue-eyed Swede and a member of the Mbuti people from Africa are all together much smaller than between two chimpanzee individuals from groups living a few hundred kilometers apart. And moreover, these few mutations specific for some people but not for other seem to be more or less neutral in their character.
Finding differences that are *not* neutral, that are actually doing something is therefore an interesting thing. Notably, the few existing differences like that are linked to mundane things like metabolism or immune response (yes, some people are special because they don't fart after drinking milk, how is that for a superior race), and not, for example, to cognitive and brain development. The latter differences are found between humans and other primates.
The problem is that it does not describe very well how science has actually progressed, in the past or the present.
As mentioned, this is philosophy, not science, so it is hard to confront different and contradictory views.
For example, there will be some who will tell you that the popperian concept of falsification is one of the most influential ideas of the XX century, responsible for the dramatic progress in understanding of our world that happened in the XX century. Not least because of the statistical hypothesis-testing framework, and there is little doubt about the influence of XX century statistics on progress in science.
But yes, it does not fit the copernican revolution.
But then there's the (at least) equal and opposite error, which I call Haldane's Error - the belief that anything not currently explained by science must perforce be supernatural and can never be explained by science.
Oh, what a beautiful quote, I will steal it for my students. It is simply grand... given the career and persona of J.B.S. Haldane, son of J.S. Haldane, who was one of the most influential evolutionary biologists and geneticists of all time.
Firstly, please note that Thomas Kuhn's view of how science happens is one of many possibilities. On one side of the spectrum, you have Popper and his younger collegue, Imre Lakatos; on the other end, you have Feyerabend and his "everything goes". Unfortunately, all that is philosophy, so itself is not science and cannot be verified experimentally or backed up with meaningful statistics. Thus, depending on whom you talk to, you will find arguments for Popper or for Lakatos or for Feyerabend or for Kuhn, all coming from the same field of science.
Personally, I value the popperian hypothesis-falsification paradigm a lot, especially since it fits so nicely with classical statistical hypothesis testing, and I insist on teaching it to students (I am a biologist), but I am well aware of its limitations.
Unfortunately, when reading texts of the great philosphers of science, one has the impression that all they really wanted to explain was "the big stuff", the grand theories, the grand revolutions or paradigm shifts. It is easy to argue for paradigm shifts if you focus on Copernicus and Einstein. It is much harder to immerse yourself in the day-to-day reality of scientific work, the millions of manuscripts generated, the propagation of ideas, their deeply intertwined relationships, as no idea, however genial, ever materializes itself from nothing.
You earned yourself a Useless Use of Cat Award!
I would not agree with that. Yes, very often, cat is not necessary, strictly speaking; for example, the list of arguments could be directly passed to grep in this case. However, personally I consider it to be bad style. A verbose cat (i) doesn't cost anything in terms of memory or CPU (if it does, then 1981 called, they want their computer back), (ii) facilitates or invites additional filters, for example adding sort -u (or sort | uniq, as I would rather have it), (iii) makes the whole pipeline more readable. I find it especially funny when people who do not hesitate to launch a terrible misuse of resources (also know as a "Web browser") hesitate to put an additional cat command to a long pipeline.