ennui

Do you think IQ tests are a useful way to measure intelligence; or do you think they're useful at all?

Haha, I was being sarcastic.

I think you should go for it. Do you have a BS/BSc in a life science at the moment? Assuming you do, doing a PhD will be a great opportunity and a great challenge. I can't imagine that you'll be doing many classes - PhDs here usually involve being in a lab all day, doing a research project. If the PhD is funded (which most are) you can even think of it as a job. My PhD is going to pay the same as if I had just started in a pharmaceutical company. If you don't have a bachelor's degree, you'll need to consider the financial side a lot more. They can cost a lot of money! A few years ago I read an advice column; a 50 year old woman wanted to go to college. She asked "am I too old to do this? It's a 4-year course. By the time I graduate I'll be 54!" - and the reply she got was "Well, how old will you be in 4 years if you don't do the course?" Life is all about new challenges, we have to keep ourselves busy!

How detailed does it have to be? It could be a good idea to first consider how a high or low pH would affect the E.coli. What would a high or low pH do to any cell? Think about the molecules in the cell and how these might change if put in an acidic or alkaline environment. Cells are mainly lipids, proteins and DNA. How might these be affected by, say, acid? Then you will need to think about the changes the cell will have to make to compensate for the non-neutral pH. There are some fantastic journals out there on this stuff. Here's one I found in about 10 seconds: http://www.ncbi.nlm.nih.gov/pubmed/15494746 Just do a PubMed search and you'll have more information than you can shake a stick at. Stick to reviews as they're easier..

That's a really strange and vague title. I have no idea what he could mean. I don't think you'd be to blame if you just did what you thought was best - if you get a bad grade, complain about the ambiguity.

It's a pretty straightforward process. Let's pretend a disease is caused by protein X, a cellular receptor which has a gain of function - you need to suppress its activity. 1. Find the protein or gene responsible. Map to the right chromosome. Clone it so you can experiment on it. 2. Use NMR or X-ray crystallography to determine its structure. Needs to be purified first. 3. Ask a chemistry lab to design an inhibitor. 4. Build a library of inhibitors and use molecular dynamics (MD) simulations, etc. to see which one matches best. 5. Synthesize this inhibitor and test it in vitro. If it works, step 6. 6. Mutate protein X in a mouse model, essentially giving the mice the disease. Test the inhibitor on them. This is in vivo testing. 7. Assess the toxicity of the drug inhibitor - do they have side-effects? 8. Do more testing, refine the drug using biophysics. 9. If it works and there are no serious problems, move on to a human model. 10. Apply for FDA approval, and do all the Phase I, II and III trials. This is a gross simplification and there are many variations in this process. But this is a hypothetical scenario of how a drug might be designed and tested. You can see how it pulls together the skills of molecular biologists, biochemists, structural biologists, biophysicists, geneticists, immunologists, pharmacologists, organic chemists, etc.

The cell cycle is controlled by lots of factors, like cyclins and cyclin-dependent kinases (CDKs). These are proteins which use phosphorylation to control things like protein synthesis, and also to allow the cell to progress through the stages of mitosis. And these proteins are usually always basally transcribed, and rise temporally when the cell needs to divide. In regards to DNA being able to fix things: if a cell is not responding to death-signalling to induce apoptosis (e.g. Fas receptor signalling) then it most likely has a mutation in one of the pathways. The DNA might not be able to fix this, because the tumour suppressor genes themselves could have a mutation. DNA is damaged thousands of times each day, and while we have a lot of mechanisms for DNA repair (e.g. non-homologous end joining/NHEJ or single-strand excision/BER) the system is not perfect. As we age, mistakes inevitably happen in DNA replication. So while we might have two copies of a certain tumour-suppressor gene; as mutations might be introduced in time, the copy-number of the protein product is no longer sufficient to perform its function, and a cancerous phenotype arises. Yes, cells need proteins to survive. But mutations in proteins are largely responsible for a lot of different cancers. The most notorious is arguably mutations in Ras - a protein involved in receptor tyrosine kinase receptor signalling. Any one of three point mutations (refer to my previous paragraph of mutations happening in the genome) will render it constitutively active, resulting in the transcription of proteins which lead to cell division, growth and angiogenesis. DNA is damaged by a huge number of causes. If you're familiar with DNA structure, you'll know that it's a sugar-phosphate backbone with bases attached to them, projecting into the equatorial of the helix. Chemical bonds can be broken or made if energy is provided, this will overcome the energy barrier necessary for another reaction. Now imagine you have a very high-power X-ray hitting a molecule of DNA.. what do you think will happen? The likelihood is that it will shear the DNA and result in a double-strand break. Other kinds of can cause the bases to be modified, so that the RNA polymerase and DNA polymerase make mistakes. It changes the DNA so that its shape changes, or so that the wrong base is replicated. Your last question repeats your first one, which I outlined above. DNA can repair itself through evolved pathways such as NHEJ and BER. Proteins recognise the break, and use their helicase/polymerase tools in order to fix it. If you're lucky, they can form a Holloday junction and use the homologous strand to fix the damaged one. But obviously this won't work in double-strand breaks. Yes, everyone is different and has different DNA. That's natural variation. But people all have the same DNA repair mechanisms. The reason why some people can smoke for 70 years and not get lung cancer is because they have "good genes" (forgive the crude term) or just luck. If you blindfold people and make them cross a road 10 times, by statistical possibility some people will cross safely for 10 times. Smoking doesn't guarantee cancer, it just significantly raises the risk.

Cancer is a tricky subject, and it's hard to appreciate the hows and whys without a background in the subject. First of all, cells need to replicate. Cells are being damaged all the time by internal causes (i.e. the oxygen species produced by the mitochondria) and also from external causes (U.V., mechanical damage, etc). Your whole digestive system works on the principle of shedding layers of cells (epithelium) whenever you swallow food. So replicating cells are not bad - this is, after all, how you developed as an embryo! Usually the body has various check-points in the cell cycle to make sure that the cells aren't misbehaving. So when they're replicating & dividing, they have a whole host of proteins to check that the cell isn't cancerous. You might have heard of the notorious p53 gene. It codes for a protein that is a major tumour suppressor. Say, for instance, that your cell's DNA has been damaged and it hasn't been repaired. Your cell wants to divide. This could lead to a very bad situation: the DNA damage could mean that the cell will go haywire and produce cancerous cells. It wouldn't replicate the genome properly, and the daughter cells would be aberrant. It's thanks to p53 and other tumour suppressor genes that the cell doesn't divide uncontrollably. p53 and other proteins arrest the cell cycle, stop it from dividing, and prevent carcinogenesis. There are a whole network of these proteins whose pathways resemble the London tube map - it's a complex network. It's when these tumour suppressors fail that cancer comes about. You're very right that some cells tell other cells what to do. Cell signalling is another facet of cancer. Cells need growth factors to tell them when to grow, makes sense right? Well, if you have a mutation in a growth factor receptor (i.e. HER2, found in breast cancer cases) that means it's on all the time, even when you don't need it to be, then you're going to get cells thinking they need to grow and divide when they don't need to be. You might get cancer if the body doesn't deal with it. You can probably see that this is a big, complicated subject. Lots of different things can lead to tumourigenesis. I don't think that food and drugs/pharmaceuticals are a big part of why we get cancer. The bigger culprits are things like smoking, sun exposure and many more besides. I can't think of any ordinary pain-killer which has been linked to cancer in epidemiological studies! Yes, certain everyday foods do contain carcinogens. It's surprising to think that even everyday foods like parsley, pepper, and other vegetables contain mutagenic compounds that can damage DNA. These have been identified through experiments like the AMES test. But this doesn't mean that ordinary foods really cause cancer: as I've shown above, the body has a good mechanism for repairing DNA damage. It's when you over-do it (by smoking, for instance) that the body simply can't cope with all the cellular damage and cancer might come about. A healthy diet is wonderful - but diets with high fat content have been linked to colon cancer, and excessive alcohol consumption has been linked to oral cancers. Excess is the thing to be avoided. If you want to learn more about how these foods are linked to cancer, try doing a search in Pubmed. At the moment a lot of research is going into developing drugs to target the pathways leading to cancer. As an example, drugs are being designed to inhibit the growth receptors that in some breast cancers lead to cells dividing uncontrollably. But research is limited because something that might work in the test-tube might not work in a human body. Human genetics is a wonderful and fascinating area, but even some basic things are still unknown, such as the organisation of chromatin at higher levels. New kinases are being discovered all the time. Imagine trying to repair a broken down car without having a full idea of what an engine looks like, or how it works. Cancer is a enormous field - 1000s of things can go wrong and lead to cancer. To fund one ordinary PhD project to study just one of these pathways (and a small part of it, at that) would cost around £90,000. You should now be able to easily imagine how the money can go quickly. So we have a good idea of why certain things cause cancer. Cancers might be on the rise because of lifestyle. Every summer I see people on the beach without appropriate sun-screen, and I still see teenagers smoking. So I wouldn't be so quick to blame things like drugs. A lot of great research is happening to develop pharmaceuticals to combat cancer, and if you don't think progress is happening quickly enough, donate to your local cancer charity to fund some research!

The first post is practically a buffet of pseudoscience. I wonder why people believe crazy things?

It's always nice to see people going into med school to learn about the body, and to actually help people.

Social sciences appear to be where the breakthroughs are happening.

I'm sceptical of any drug being called a 'miracle', it instantly dashes all of my hopes of it being useful. Everyone knows the best miracle drug is ethanol.

That's a good example. I should have said 'physics problem' rather than 'physical problem'. Just edited.

All of the amino acids will contribute to catalysis (the main function of an enzyme) either directly or indirectly. This is because the polypeptide chain undergoes a conformational change, and needs to have very specific biophysical constraints. In a lot of enzymes, even one mutation can lead to a loss or gain of function resulting in disease. This isn't to say that all amino acids are directly in the active site. But it means that the whole shape of an enzymatic protein is important for function. The active site contains the catalytic portion of the enzyme. As someone previously said, you can divide amino acids into groups. This might mean that if you have a mutation resulting in phenylalanine to tyrosine, you might be lucky and the enzyme could still work. This is because they are both aromatic and quite similar. Also, you might get away with a glycine being mutated to an alanine. Again, they're very similar. But the amino acids outside of the active site are still crucial. If you imagine an enzyme being divided (for simplicity's sake) into two halves: a catalytic core, and the other half. The "other half" might not look very interesting, but if there's a substitution of a isoleucine to a proline, it will likely destroy any Beta-sheet structure, resulting in an altered overall shape. The catalytic core (active site) will be truncated (through loss of molecular architecture) and likely rendered nonfunctional. As an example, there was a very interesting paper in Science from 1994, which investigated how acetylcholine is broken down by acetylcholinase in the brain. As it turns out, a couple of histidine residues and a few acidic residues in the catalytic site were responsible. But it didn't explain how the acetylcholine actually got in the active site - it was buried in the middle of the enzyme, with no apparent 'gap' for the AcChl to penetrate. They eventually found a "back door" completely separate from the inner active site. It was on the "back" of the enzyme, and consisted of a cluster of charged groups which basically attracted the acetylcholine into the centre of the molecule. It was remarkable and novel, and even more progress has been made on this enzyme. So what am I trying to say with this disjointed, nonsensical rant!? Well, I'd encourage you to consider the enzyme as a whole and not just the active site. Consider how all the amino acids will contribute not just to the chemistry of the active site, but also to the architecture of the protein itself. Residues outside of the active site will have surprising roles aiding the function of the enzyme, such as a 20-25 stretch motif of glycines and alanines being used to bind DNA in a nuclease. So in a way you have nearly all the amino acids contributing to the function of the enzyme: catalysis. After understanding the overall portrait of the protein's chemistry, it's then a good idea to consider the active site. As a good example of a well-studied active site, you would to well to look up the protein subtilisin. It's been commercially exploited and so lots of money has been invested into analysing its chemistry. In a nut-shell, you have a catalytic triad in the active site. It's a peptidase. I would draw a diagram, but I don't know how. Sooo.. To quote Wikipedia(!), "The charge-relay network functions as follows: The carboxylate side chain of Asp-32 hydrogen bonds to a nitrogen-bonded proton on His-64's imidazole ring. This is possible because Asp is negatively charged at physiological pH. The other nitrogen on His-64 hydrogen bonds to the O-H proton of Ser-221. This last interaction results in charge-separation of O-H, with the oxygen atom being more nucleophilic. This allows the oxygen atom of Ser-221 to attack incoming substrates (ie. peptide bonds), assisted by a neighboring carboxyamide side chain of Asn-155." I'm sure that it'll be easy to find academic journals more credible than Wikipedia. But that's still a good summary. For further details, there are some great Nature and Science papers on this catalytic chemistry. It's taught as a classic example in a great deal of university biochemistry courses. Hope this helps!

Thanks for the reply. But could you explain this in more detail? Is this to say that in eukaryotes, you generally have one ORF that can be spliced differently (e.g. antibody recombination); but in prokaryotes you have several ORFs that are tandemly linked by an intron spacer?

There are a lot of articles highlighting the importance of physics in biology. Advances in physics often leads to an advance in biology. Protein structure is one of the fields that has benefitted enormously from physical techniques such as X-ray diffraction, atomic-force microscopy and more besides. And more recently, there have been advances in gene expression understanding due to semiconductor physics. But is the reverse also true? Has biology ever helped the progress of physics? Have biologists ever turned their attention to a physics problem and solved it?

I've read from various sources that generally speaking, eukaryotes have monocistronic DNA. It codes for one protein. Bacteria/prokaryotes on the other hand, have polycistronic DNA. They can produce an mRNA strand which codes for multiple proteins. Yet I've read a few articles in New Scientist saying that the average amount of protein products from a single eukaryotic gene is somewhere between 5 and 6. I know that splicing exists in eukaryotic genomes; but wouldn't this mean that the DNA is polycistronic? Can anyone help me understand this?

One of the big problems here is that Tangointhenight is not considering the quality of his references. Cherry-picking a selection of URLs from the Internet does not count as evidence, nor does it shake the foundations of physics. I could have a browse around the Internet and find hundredsof URLs saying that unicorns exist; there are faces on Mars; Satan runs the world governments; Jehovah was a UFO, etc. but it wouldn't make them true. I'll use one of the worst links provided as my case-in-point. Answers in Genesis is not a science website. It's a website for religious rhetoric. This isn't to say that something isn't true just because it comes from an ill-researched site: it means that the overall quality of their scientific writing is poor, and the likelihood of them producing an erudite scientific article is low. As an example, look at the writer's references. They're mostly in the early 1980s: physics is a fast paced field, and unless the paper was groundbreaking or seminal, it's not a good idea to go for journals or books these old. The only good use for them is to track progress of ideas and concepts, or for antiquarian use. Moreover, he cites H. Arp. This is a man who supports a great deal of fringe ideas and refuses a stack of contemporary evidence contrary to his theories. When you scout the Internet looking for these controversial physics websites, it might be a good idea in future to be a little more critical of the sources.

That website (You Stupid Relativists) looks like an acid trip. I have the sneaking suspicion that the author is here trying to promote it.

Everything we know about biology is wrong. I'm planning to write a PDF on it, and proclaim myself the Biology Messiah. The problem is that every biologist in the world thinks differently to me, therefore, they are wrong. I can prove my theory that all Biology is actually caused by tiny sub-atomic rabbits by saying how biology is "too interested in measuring." Who needs more evidence than that? Take that, science.

I read the essay he posted a link to. I'm not a physicist, but even I can see it's very flawed. The author (Stephen) glosses over scientific topics without any scientific rigor. As an example: "Physics sees this attraction as being the result of dislike charges. This begs the question of how dislike charges cause attraction. On this question physics remains silent. It has a mathematical expression of attraction as an effect and doesn’t desire anything more." First, there's a contradiction. One can't say that physics "remains silent", and then proceed to say that it offers a mathematical expression. A mathematical expression is not "remaining silent." Second, electrostatic charges are explained very well by physics. It's hard to even know what "something more" the author is referring to. If you've explained something with experiment, developed a great theory, and you even have a mathematical basis... I can't see what more you'd want. The author then goes on to explain his interpretation of a crude experiment while only giving bizarre pseudoscience as justification. He uses the sentence "I decided that the attraction was the result of the pith ball absorbing emission from the glass rod, and that this emission forms an unbroken material connection between the two objects." I might decide that the Moon is made of cheese; but without the scientific data to back it up my claim is useless. Where are the repeat experiments? The statistics? The falsification? How is Stephen's interpretation proven? Words such as "emission" are used without any explanation. Emission of what? How were these emissions identified and proven - since they deviate from standard scientific thinking? It's all just waffle, if anyone takes the time to read it. It's as if someone has done a beginner's course in "Philosophy of Science" and posted their first essay online. It's shabby work.

I'm more of a piece of paper kind of guy.

That's pretty helpful, thanks. I googled a couple of diagrams, too. I have a terrible time with orientations and the double-strandedness of genetics. Holliday junctions are a nightmare for me to wrap my head around, too.

Is there one? I didn't notice. Yes please, that would be good.

As I've delved further into science, I've realised how much research depends on animal testing. Lots of experiments in genetics and medicine are based on knock-out mice, rabbit-developed antibodies, and many more besides. Personally I'm a vegetarian. However, I ultimately believe that human life (and happiness) is more important than other animals. I'd probably do animal testing if it was necessary for medical research. What are your thoughts on this in vivo stuff? Do you think animal testing is good, bad, or something else? Are animal models required for biological and medical advancements?