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What percentage of protein isoforms have different functions?
I am looking for studies on how many protein isoforms have different functions, preferably in human. We know that a great many, if not most, of human genes are alternatively spliced and that many produce different protein isoforms. Has anyone looked at how many of these isoforms have different cellular functions? If someone could point me to a published paper, that would be great.
If no such study has been made, can anyone recommend a database from which this information could be extracted? GeneOntology is gene based so the information cannot be found there. Genes will be annotated to specific terms, not their protein isoforms. Also, I would need to be able to do this in a high throughput manner, I am not interested in specific proteins but in what percentage of all isoforms have different functions.
Ideally, I would like to be able to extract, for every human gene, the list of the different protein isoforms it encodes and whether their functions differ, or at least what those functions are.

I don't think isoform specific information is in a database yet. Testing isoform specific functions is tricky since not all isoforms are expressed in all cell types. Recently have researchers been looking at splicing genome wide and figuring out which splice forms are in certain cells (differential exon usage in RNA-seq to infer different isoforms). As you have encountered, functional info is typically summarized by gene. Swiss-Prot mentioned by @MattDMo is one of the few db where info is hand-curated. If isoform specific function was annotated, it would probably appear there first

It seems that most functional annotation these days is inferred from sequence similarity to previously annotated genes/proteins: this is certainly true of high-throughput functional annotation. It's hard to know how many layers of inference there are between your query sequence and an actual experiment verifying the (possibly tissue- or condition-specific) function of a gene/protein. But alas, I digress...
One confounding factor for is that alternatively spliced isoforms share a lot sequence in common, which means that they might share best hits when searching against a database of annotated transcripts and end up getting assigned the same GO terms.
But as others have mentioned, I think the biggest limiting factor you will encounter is the low-throughput step: in many cases the experimental work required to characterize the functions of alternative isoforms simply has not yet been done.

Yes, that is the problem in a nutshell. Most (all AFAIK) high throughput experiments tag genes, not proteins and assign function to the gene as opposed to a specific isoform.

I would take a look at UniProt to begin with. It's my go-to whenever I need to look for isoforms or functional data, so it should help you as well. You could start by comparing the information in Swiss-Prot to TrEMBL, which are manually and automatically annotated, respectively. One issue that I've come across in my research on isoforms is that there often isn't a great deal known about them, as studies may have focused on just one or a few out of many possible. One way to get around this could be to use structure/function predictions based on sequence, then try to predict variations by looking at what's added or missing in the various isoforms.
I hope this helps...

Thanks, but I'm interested in whole proteome data. Uniprot has no parseable information on isoforms apart from how many a given protein has and their sequence. Sometimes the function field has some information, sometimes it doesn't.

I'd tend to agree there's very little data on this, esp given how many isoforms there are.  I believe that even some cases of pseudogenes may have function as a protein.  I'd bet that most of them have some unique functional aspects.
I think we'd all agree we can't prove that they do in all cases, but let me sketch out how these different functions might arise or are known.
Protein Isoforms usually come from two causes.  The first being that there are two very similar copies of the same gene, from a gene duplication event.  The second coming from alternative splicing.
Alternative splice isoforms are often missing or adding a few amino acids - the sequence is different.  This can be from truncation of a large portion of the protein such as the leptin receptor. Leptin receptor has two full length variants that have different expression patterns at different temperatures and import leptin into the cell at different efficiencies.  Leptin also has several short isoforms, where only a short portion that faces the cell interior is produced.  These variants compete with the full receptor to modulate the cells sensitivity to leptin.
As you can imagine, mapping all this out in just one case took years of work. Complete characterization of all human isoforms would take a long time.
Isoforms from gene duplication have many of the same properties as splice variant isoforms; they can have completely different regulatory machinery - popping up in different biological states than the main gene and they can vary in sequence a little bit or a lot.  It has been implied that these gene duplicates persist in the genome because they quickly find a new niche role.  This paper shows that 30% of 195 new genes that have shown up since two strains of fly have diverged are necessary for viability.
Evolution doesn't let genes sit around because they are completely identical; they can be removed as easily as they show up, only differential function will keep an isoform in the mRNA repertoire for a prolonged time.

Thanks shigeta but I would not call proteins coded for by different genes isoforms (and neither does the wikipedia page you linked to, it talks about alleles of the same gene). They are paralogs or orthologs depending on their evolutionary history. I would only use isoforms to describe products of the same gene. I am also assuming that most isoforms have different functions, hence my question. I am looking for data to back that assumption up.


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Are there eukaryotes without introns?
This question on the function of introns in eukaryotic genes made me think: I know that more basal organisms have smaller introns and fewer alternatively spliced exons compared to mammals. But are there eukaryotes whose genomes have no introns at all?

Well yeast has very very few if that counts. See here. I recently checked the number if annotated isoforms for 5592 yeast genes and NONE of them had more than one!

I don't believe so.  I have never come across a eukaryote that does not have introns although there are some genes that do not contain introns.  Some eukaryotes like ciliates actually contain other non-intronic intergenetic regions that seem to be nonfunctional.  These are called Internally Existed Sequences and are removed from the germ-line active micronucleus before going to form the transcriptionally active micronucleus.  Interestingly, introns are also present in these organisms and are present in both the micro and macronucleus.  These introns are spliced out in textbook fashion.  I believe one of the organisms where introns was discovered was in Tetrahymena thermophila with the intron in the rDNA sequence.

Could you expand with some examples?

@nico: examples of what, eukaryotes with introns or eukaryotic ciliates with non-intronic intergenetic regions?

thanks for the edit, I was speaking about the ciliates, as I did not know about that.

@nico, Tetrahymena thermophila's macronucleus contains about 15,000 copies of the gene that encodes for the ribosome.  I believe it was in this gene sequence that introns were first discovered.  The Nobel Price for the intron discovery was shared with another person as they both discovered it in different organisms about the same time.

source: Stack Exchange

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/

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Definition of Dye- Reduction Test?
Can some one give a simple explanation or definition on what a dye-reduction test is.

Dye reduction tests (and there seem to be loads of different ones) are simply assays in which a dye becomes decolourised to give you a visual indication of whether a certain process is occuring. Here you can find an example of a dye reduction test with Methylene Blue and Reazurin which indirectly measures the bacterial densities in milk and cream. See this google book for more info.

all_licenses: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/


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How prevalent is Taq polymerase in adding 3' A overhangs to the PCR product?
I am conducting a mutagenesis on a gene in vivo of which I need to ligate into an expression vector.  The primers I have designed overlap restriction sites of which I plan to use to ligate into the expression vector.  The parts between the primers I will try to create mutants with error prone PCR.
My concern is the 3' A overhangs that are created from Taq polymerase.  How prevalent is this?  If it is highly common, what is the best way to account for these additions when trying to ligate my PCR product into the vector?

I am not sure of a case where Taq doesn't add 3' A overhangs.
You could use TA cloning to clone your PCR product.  The basic principle is to use a vector with 3' T overhangs.  If you have a vector without these overhangs, you can use a terminal transferase + dTTPs to create them (or even Taq, but this is not as great because it adds a purification step to isolate the vectors with overhangs; terminal transferase is much more efficient).  You can then ligate your PCR product that has a 3' overhang.
Protocols for adding the 3' T overhangs to your vector are given in Zhou and Gomez-Sanchez 2000.

T4 polymerase does not add overhangs (it adds them but then deletes them), but I think this polymerase has too high fidelity for mutagenesis.

From what I understand, the A' overhang does eventually  fall off. However, TA cloning is a much easier route if you have a TA vector.

@Kevin: I have revised my answer to include a description of TA cloning, which does not involve T4 polymerase at all. (I assume you confused the letter A for the number 4.)

In any case if restriction sites flank the PCR product, then you can go ahead and perform a restriction digestion and ligation. If you are too concerned by the A overhang then you can use Pfu polymerase for PCR or alternatively treat the PCR product with Klenow.

Use pGemT to clone your PCR product into. It is exactly designed to take products with 3' overhangs and features blue/white selection so is pretty easy to do! Then you would cut out of pGem with the restriction sites you added during your PCR and ligate it into your expression vector.


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Why does contracting the iris allow less intense light to go in?
The iris contracts automatically in the presence of bright light. This makes a flashlight appear bright in darkness, but outside in daylight you can't even see it's light.
The iris is changing your sensitivity to the intenseness of light. But physically all is happening is the iris is getting smaller or larger. I can see how this allows less light to go in if it gets smaller, because it's less surface area. However, I would imagine this would change the field of view though if I didn't know any better. Why does it change the intenseness of light instead?

Imagine the iris like a shutter in front of a focussing lens (which, in fact, it is; see the diagram).

This means that any light going through the iris will be focussed on a very small point on the retina, and your eye is wonderfully developed in a way that this exact spot is the fovea, the only spot in the retina that allows you to see colour and high-resolution.
The iris does not modify the focussing function, it merely changes the amount of light going through into the lens to then be focussed onto the fovea. Imagine that every single object in your field of view reflects/radiates light in every possible direction - narrowing the shutter won't exclude parts of the field of vision, it will only exclude some of the rays coming in at very flat angles and thereby reduce intensity.
Only if your lens is deformed, focussing (adaptation) will malfunction (directing the gathered light to the wrong spot; or focussing the incoming light in front of or behind the retina) and blur your vision.


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Parthenogenesis in Bees
Parthenogenesis is defined as:
"A type of asexual reproduction in which egg develops without fertilization to form a new individual."
If parthenogenesis takes place in bees, a drone or male bee is produced.
My question is that parthenogenesis is the development of EGG into new individual so, how can egg be developed into male because egg won't have that "Y" chromosome required for male offspring?

Because the "Y chromosome" has nothing to do with sex determination in bees.  Instead, the number of X chromosomes determines the sex.  With only one X chromosome, the egg will develop into a male.  This is called a haplodiploid system of sex determination (the male bees are haploid, having only half the number of chromosomes).
EDIT: I should add that there are many systems of sex determination, not just XY or the haplodiploid system.  See the Z-W system (males are ZZ and females are ZW), the X0 system (the males are diploid for all but the sex chromosome), and temperature-dependent system of sex determination.

@MuhammadRafique: I have edited my answer to be slightly more accurate and provide additional information.

The Cape honey bee in South Africa can create female offspring without the queen being mated. Female stick insects can also produce female offspring without males, all daughters will however be clones of the mother. I guess this is a last resort to ensure survival in difficult times until a male is found to mate with.

can you add some references to this?


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Why does plucking nose hair cause tears in the eyes?
It's not a particularly sad or painful thing to pluck a few nose hairs, but it's common for the tear ducts to wet up when doing this.
I would like to know the physiological reason for the correlation, how/why are the tear ducts and nose hairs related in the human body?

unreferenced, but here you go: http://answers.yahoo.com/question/index?qid=20061231043153AAaJdCT

Is this for real?

Although I'm not sure, here's a working theory. The tear collection ducts feed into the nose. That's why when you cry you have a runny nose. When you pluck nose hairs you irritate the nasal mucosa, so that causes a reflex which attempts to flush out whatever might be causing a problem.

It might be an overstimulation of the sneeze reflex neural circuit, which causes tearing instead of sneezing. I do get a feeling similar to the "I'm about to sneeze" along with lacrimation.

Also, tears are an intrinsic pain response and considering the dermal-derivative nature of hair, there are loose nerve endings ensnaring the follicular area, so the sensory neurons detect pain and tears are a physical manifestation of the pain, cuing the body to avoid that stimulus again.

+1. Innervation of the nose is extremely sensitive.  It's primarily a combination of this and what Armatus said above, plus the fact that AndroidPenguin mentioned of the connection between the nose and tear ducts.


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Strange behavior of a DNA gel
I ran a PCR product of ~300 bp on a 2% TAE-agarose gel for 30 minutes. I used Sybr-safe as a DNA stain. Voltage was 80V.
When I imaged the gel, the DNA on the bottom half of the gel, including the ladder had disappeared (it showed no bands). The DNA in the top half looked-clear and well-separated, but the bands on the bottom were somehow missing.
What could be the reason? I've never encountered this before.
I know it's not due to gel overheating - I ran the gel in the cold room and when it was done it was cold to the touch.

Just stain your gel again for 10 min protected from light with slight agiation. DNA bands will appear again. Try!

If you use pre-staining, the stain migrates as well in the electric field and this can lead to some parts of the gel being unstained. This would look pretty much like you describe, the ladder being invisible as well points strongly to that part of the gel just being no stained properly.
It sounds a bit unlikely with your running parameters, I've only seen that with a very long running gel, but I also haven't used pre-staining for quite a while now. Ethidium bromide is positively charged and migrates in the opposite direction as the DNA, I have no experience with Sybr-Safe though and don't know if it behaves the same as EtBr in this regard.

I looked it up and the website does say sybr safe runs away from migrating DNA. I might have been off with the timing and this fits, thanks.

@Drosophila I'd just try to stain the gel again, if this was the reason the DNA should be visible then.

Yeah, I threw out the old gel but I ran a new one at a higher voltage and shorter time. It worked. I'll check your theory when I get some free time

Jut for reference, with 20min@100V running time I usually get the bottom ~1.5cm of the gel Sybr-Safe free.


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What is range of the number of individual organelles in cells
What is the range of the number of individual organelles in a cell?
I am not a biologist but I understand that there's one nucleus and sometimes lots of mitochondria, so I am after the total number.
I understand that different types of cell will have a different number of Organelles in them, (e.g. there might be some very simple cells with 10 but there might be some with many more than that) but I am after the range with some examples. (I need references)
This is for a computational model.
Thanks very much

This varies enormously between species, between eukaryotes and prokaryotes, plants and animals and within the cells of the same species. Also, what organelles are you interested in? Mitochondria? Chloroplasts? Lysosomes? Golgi? Vacuoles? Proteasomes? The list goes on... Have a look at http://en.wikipedia.org/wiki/Organelle

Yes @terdon definitely has a point. In fact, organelle concentration is very different even in different parts of a single cell. E.g. the axon terminals of neurons contain a lof ot mitochondria to provide ATP for continuous firing, while the cell soma (the main body, which can be more than 1m away) contains much fewer of them. Another case, most cells only have one nucleus. Certain cell types like skeletal and cardiac muscle or the placental trophoblasts however fuse and form multinucleated cells.

@terdon I am aware that there are many different types of organelle. I am interested in the range of the total number of organelle (from the simplest cell to the most complex)

BioNumbers is a database that contains exactly this sort of stuff.
For example, I took this from this site:
Number of mitochondria per cell:
Yeast Cryptococcus neoformans cell: ~34
Human HELA cell: ~6000
Mouse L cell: ~1000

that is a cool site!


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How did this spider evolve to mimic exactly a human face and arms?
So I came across something terribly amazing today, that is, a video showing this species of peacock-spider, that literally, transforms into a human face waving his arms about.
What could have possibly given rise to this?
I can understand the arms waving around, but why the uncanny human-face template, complete with eyes, nose, mouth, etc.
I do not believe this to be a case of anthropomorphism on my part, (seeing what I am familiar with), because I cannot imagine any other natural case where such symmetry in a pattern would closely resemble a human face.
Would appreciate any explanation. Thanks!

I agree with @Alan Boyd, the deaths head hawk moth is another good example.

I can't see any human face on that spider.

I think this really is just a case of what you refer to in your question as anthropomorphism. We are very, very good at seeing faces. Here are some more examples.
Addendum
This site has pictures of quite a few peacock spiders, and as far as I can tell these are all the same species (The only peacock spider mentioned on Wikipedia is Maratus volans).
The remarkable thing about these images is that individual spiders seem to have very different patterns on thorax and abdomen, and many of these are much less like human faces. This seems to me to weaken the case for some sort of mimicry.
Interesting fact: seeing faces and other forms where they do not exist is a psychological phenomenon called pareidolia.

Im not so sure... I mean, yes, anthropomorphism is a relevant scenario, but some of those faces (like the samurai crab) did evolve due to Japanese fishermen throwing back what they thought looked like crabs with samurai faces, and the solution converged. I am wondering if this face on this spider evolved out of similar feedback with humans and/or other mammals?

@Mohammad, I really doubt that the kind of selection that fishermen can provide would be stable enough or even exist over enough time to drive the evolution of such a trait. Even if it were, I find it far more likely that fishermen would chose the crabs that most looked like human faces rather than discard them.

@terdon What about the example with the moths in London who changed their wing color to a darker shade when the industrial revolution covered the city in ashes? I think human activity can provide stable selection in many cases.

@Drosophila Of course it can. But not when that activity affects only the small percentage of crabs that happen to have been fished by superstitious fishermen. The ashes you mention affected the entire population. Anyway, you have to admit that none of the examples mentioned in this thread are that human-like. They might look like faces to us, but a colon and a parenthesis looks like a face to us :). This is most certainly anthropomocentrism.

@terdon Absolutely, we do see faces everywhere. But we use a colon and parenthesis because they look like a face. My whole argument is that indeed there's antroporphism, but animals take advantage of that all the time. As for that spider, it is not trying to imitate a human face in particular. Rather, having a back that looks like a scary face may help with larger animals.

And to note: this is all rather hypothetical, of course. It's hard to get a direct answer to any evolutionary/ecological question, hence there's so much debate.

Argh, phone typing anthropomocentrism = anthropomorphism

Micheal Shermer shows a few interesting examples of pareidolia in this video: http://youtu.be/8T_jwq9ph8k?t=6m25s

The samurai crab story is probably a myth, spread by Carl Sagan; discussed here and here, among other places.

Peacock spiders certainly aren't mimicking human faces, and I strongly doubt they're mimicking anything at all. As others have noted, it's the combination of a fluke, and some anthropomorphising on your part (easy to do!).
The stunning colours and 'dancing' are actually part of a courtship display, and are most likely under strong sexual selection, rather than selection for any anti-predator function. The male-limited colours are only on display during courtship, and are otherwise flattened along the abdomen. It's also worth remembering that these spiders are tiny (< 5 mm), so the only other animals that are likely to be able to resolve those patterns in any detail are similarly sized organisms with decent eyesight (i.e. female peacock spiders).
Madeline Girard is in the latter-stages of her PhD on these guys, I'd recommend shooting her an e-mail if you're really interested.

In part, the way the spider resembles a human face is due to bilateral symmetry in the body shape and coloring of the spider. Bilateral symmetry evolved early in the animal kingdom to facilitate streamlining of the body (which makes it move faster in any fluid, including air and water), formation of a central nervous system and a head. Human faces (and bodies) are also bilaterally symmetric, hence the resemblance.
Another reason, as you note, is antropomorphism - the ability of humans to see a human face in many natural shapes and colorings. Other animals, including predators probably also have this ability to see faces in nature. This allowed the spider to evolve to imitate a scary face. This is called mimicry and it helps the spider ward off predators.

Thanks drosophilia. Do you think that in this particular case, this 'face' is used to ward off bigger, (ostensibly animals) who would recognize this as a 'face' of some sort? Or do you think it is just a relic of bilateral symmetry?

Not sure. Could be both, I think, since bigger predators may inadvertently crush the spider or use it at play. The scary face could stop them from doing that.

The subtitle of the video you linked to says it is a courtship ritual.

There are 44 species of peacock spider known to date and each species has a unique pattern on the thorax. Although this patterns can often resemble human faces, the likelihood of this being is the case is almost impossible because that would mean that humans would have to be present right at the beginning and throughout the evolution of these species.
They are endemic to Australia and as you may know Australia has vast areas of Australia that have only been inhabited humans for short periods. The process of evolution take much longer than a few generations. This similarity should be seen as more of a beautiful coincidence than any sort of mimicry
source - MSc dissertation written on the fascinating little creatures

Australia has vast areas that have never been inhabited by humans? Such as...? Indigenous Australians have roamed the country for a long, long time before white folks occupied the place. And a link to your source would be helpful.

@GeorgeLilley It would be great if you could add some of these ressources. Or a link to your thesis if this is possible.

My apologies, my source is my own MSc dissertation so the infrmation is from several reliable sources.                                                                        By uninhabited I meant areas that have not been inhabited by any permanent residence, rather than roaming semi/non-permanent residence. The process of evolution takes a very long time as i'm sure you know so for these spiders to mimic human faces it would have to of had that influence for more that a few generations period.

Unfortunately it has been many years since I did this piece of work so the sources I used are not to hand.

No need for apologies! The Australian Indigenous peoples were indeed nomadic. If you could adjust your answer I'm happy to remove that downvote. Having lived in Australia with a cultural anthropologist as lifelong partner I happen to be more critical than most :) But without references and leaning on memories only the answer is under-sourced.


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How do axon terminals report to the soma?
It is important to bear in mind that the distance between a neuron's axon terminal and its soma can be extensive, up to about 1m in the human body. The fastest transport along the axon is 400mm/day (For this purpose I suppose Source: Wikipedia).
Of course the axon terminals also need to be supplied with a steady stream of proteins to maintain normal turnover, for example the terminal may need enzymes which metabolise the neurotransmitter, membrane proteins for signalling, vesicle coating and membrane fusion proteins etc.
However, sudden changes are possible in the level available of a certain protein. An example could be sudden depletion of SNAREs (required for vesicle fusion in neurotransmitter exocytosis) caused by botulinum toxin.
My question is, does the terminal somehow report back to the soma in any way if a certain protein needs to be made available more or less? And if so, how? Especially considering that retrograde transport, according to Wikipedia, gets up to 200mm/day only. If that was the mechanism for feedback, it would create a large discrepancy between signals received at the soma and the terminal's actual state.

Have you looked into the role of Oligodendrocytes and other Glial cells? The myelin sheathe is part of another cell, which has intimate contact with the Axon. I wouldn't be surprised if Schwann Cells (etc.) actually provide many of the metabolites and proteins to the Axon and Axon Terminal.

As far as my teaching has gone, glia provide scaffolding and in some cases are involved in metabolising small molecules, but not in any way proteins. And if they do, that just makes the question even more interesting - how would the axon terminal feed back to another cell when it needs more or less of a protein?

We can consider the classical example of Long Term Potentiation.
CREB is a transcription factor which is activated during LTP by phosphorylation.
Your reasoning about the delay between signal and transcriptional response is correct and thats why neurons have local translation factories near the dendritic spines and gene regulation (fast responses) is mostly post-transcriptional. (there is no article which says exactly so but you can refer so some articles  which report that miRNA-repressed genes are reactivated upon certain signals. They hint that post translational regulation is very important in neurons)
http://www.cell.com/neuron/abstract/S0896-6273%2809%2900939-8
http://nar.oxfordjournals.org/content/40/11/5088


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Western blotting of lung samples
I have been working on lung samples to perform western blotting. I have two related questions about this:

I get very nonspecific results: at times nothing at all, at times it glows on membrane but doesn't take up on x-ray film. What are the common causes of these errors and how might I avoid them?
I am interested in assaying GPCR expression. When I am assaying for GPCRs, do I need to prepare the lung samples in a specific way (that is different from sample preparation for Western blots of other proteins)?

You may be interested in this: http://biology.stackexchange.com/questions/7205/how-to-do-western-analysis-to-lung-tissue

I wrote the answer to the above question, please let me know if you're still having issues. Just leave a comment with @MattDMo in it.


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Cyanobacterial photosynthetic oxygen yield
I am somehow not convinced that biotic factors are solely responsible for creating 21% of atmosphere (around 40 million moles of oxygen).
There may be additional issues here. Since cyanobacteria produced oxygen, it should have developed antioxidant machineries. By the time cyanobacteria flourished, some dependent heterotrophs must have evolved and they also would need antioxidants, as they are expected to thrive in close proximity to the autotrophs. There is a likelihood that aerobic respiration co-evolved with biotic oxygenesis. This would have further delayed the build up of oxygen in the atmosphere.
Does anyone have an idea of what is the photosynthetic oxygen production rate per gram biomass of cyanobacteria? Since photosynthesis must have happened mostly at the surface of the water (limnetic zone), the total biomass would be restricted. Then it might be possible to calculate the time required to achieve the oxygen levels of 21%.
This measure can indicate whether the current theory is plausible or not.

Some of these points are addressed briefly at http://hoopermuseum.earthsci.carleton.ca/stromatolites/OXYGEN.htm and again at http://www.scientificamerican.com/article.cfm?id=origin-of-oxygen-in-atmosphere

This is a study on the O2 production rate of one of the fastest growing species of cyanobacteria. The theory is not just someone's idea, it's a conclusion made from trends which were discovered during the course of conducting countless experiments.

thanks. I asked this question a while back. There is also a nice recent article in nature about the Great Oxygenation Event


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What controls the southern range of willows?
Many willows (Salix spp.) grow in northern states but do not grow in southern states, for example Salix viminalis.
What mechanisms control the southern range of temperate hardwoods such as willow? Is it disease? Temperature sensitivity of respiration? Water use efficiency?

The distribution of temperate hardwood forests, as well as deserts, tundras, savannahs, and other ecosystems, is determined primarily by average climate conditions, specifically average annual temperature and precipitation. You can see how biomes are related to climate in this figure, taken from Whittaker (1975):

Temperate forests tend to be between 2.5-17°C, and between 800-2500 mm precipation. These are not exact boundaries but reflect long-term climate conditions. As climate changes, so will the distribution of the biomes.
Temperature is important in many ways.  For example, most temperate trees go dormant during the winter. This requires metabolic preparation by the tree. If the weather turns cold too fast, then the trees may be be properly prepared. Alternatively, if the weather warms to quickly the trees may not be able to come out of dormancy properly. This technical report (Coder 2011) provides more detail.
The precise mechanism that restricts the distribution of any one species would require experimental determination. As it turns out, Populus trichocarpa (black cottonwood), plus other Populus and Salix (all in the family Salicaceae) are quickly becoming model organisms for study. This should shed more light on specific distribution limitations, such as changes in soil nutrients, light intensity, or other environmental parameters. There are now regular symposia held on these model organisms. You can read an introduction to one symposium here (Tognetti et al. 2011).
As a side note: One must be careful about the mapped distributions of popular trees like willows. Many species, including Salix viminalis, have been introduced far outside their native range, including through out the eastern United States, as shown by the map you linked to. The native distribution of the species is the Palearctic (Eurasia), shown here.
Literature Cited
Coder, K.D. 2011. Trees & cold temperatures. Environmental Tolerance Series WSFNR11-12, Warnell School of Forestry and Natural Resources, University of Georgia, USA.
Tognetti, R. et al. 2011. Fifth international poplar symposium: Poplars and willows: From research to multipurpose trees for a bio-based society.
Whittaker, R.H. 1975. Communities and Ecosystems. MacMillan Publishing, New York, USA.

little typo: 80-250 mm --> 800-2500 mm. +1 for this broad nice answer.

@Hav0k - Little typo, big difference. Thanks for catching it.


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How exactly does marijuana damage brain cells?
I've heard that THC can cause permanent damage to brain cells. I've also heard this reffered to anti drug propaganda. Another theory i've read is that temporary effects reduce intelligence but long term results are not affected. If Marijuana does cause permanent brain damage how does it do so? How exactly does it kill the cell?

@terdon provides some relevant info in a comment here: http://biology.stackexchange.com/questions/7693/whats-the-difference-between-life-expectancy-of-cigarette-smoker-and-general-po

@dd3 that post is more about smoking.. Marijuana can be consumed in many more ways..

Bear in mind that THC is only the strongest of all the physiologically active substances contained in marijuana (several hundred different ones according to our lecture). Hence, the effect of marijuana can be different from pure THC, especially if the mixture contains toxic leftovers from processing the drug.

There is no damage of brain cells, as in the context of lesions in neurodegenerative disorders. There are, however, two mechanisms attributed to the memory loss associated with cannabis/marijuana and these are purely physiological responses.

Astrocyte mediated: CB1R (cannabinoid receptor) in astrocyte gets activated and promotes glutamate release. This glutamate induces Long Term Depression in post synaptic neuron.
Synaptic currents can cause both LTP and LTD. The properties of the synaptic current wave dictates the outcome. Please refer to review articles on LTP and LTD for more information.
GABAergic interneuron mediated: CB1R activation in GABAergic interneurons (inhibitory neurons) causes activation of mTOR pathway and promotes protein synthesis. CB1R activates mTOR through PI3K/Akt.


text:
How do you store membrane proteins?
We're producing some membrane proteins and they aren't amenable to freeze thaws even when we add glycerol. The proteins are solubilized in detergent above the cmc so they should be in micelle form in solution. Currently, they are being held at 4C. I'm curious what is the best way to store them for long term use?

this sounds like a case by case issue,but i'd be interested to see what someone with experience would say.

Can't you just store the cells you use to produce the protein and thaw them when you need them to produce more? Like that you wouldn't need to store the protein itself for a longer time.

You could always just add sodium azide and keep them at +4, so they don't have to go through a freeze/thaw at all.

@Suvidu, I would counter that if the purification protocol is a pain, it's a valuable investment to be able to scaleup effectively.

I've heard some MPs like lac permease can be scaled up, others are more delicate.  do you have an assay, or even crude crystallization conditions? that would really help of course.

I work with membrane proteins and in my experience some proteins can be frozen and thawed without any problems, other proteins just don't like that. It's linked to the stability of the protein. If you really need to freeze the protein you may think about playing around with different detergents to see if you can improve the stability of the protein.
General rules:
- freezing membrane proteins at -80°C without glycerol
- avoiding protein freeze-thaw cycles, making aliquots before freezing
- keeping them at 4°C only for short term use
- after concentration always spinning the protein (10 min at 100k for example) to precipitate aggregated material. Aggregation causes aggregation, so you want to get rid of it.

Hello metionina. This is an informative answer. Can you, if possible, add reference to the protocol that you follow.

I couldn't find any published protocol, probably because every membrane protein behaves very differently. This is what I learnt working with membrane proteins and what people mostly do where I work. Then, again, every membrane protein is different and I suppose you could find what I said true, partially true or false for your protein. These are for me general things I would do when working with a new protein.

If i were to have a blind attempt at your question, it is never a good idea to freeze thaw any protein, not even cell lysates. Thats the whole point of glycerol use, which we use in our lab at 50% (v/v) to store bead bound proteins. Thats also why antibodies and restriction enzymes are stored in glycerol since freeze thawing antibodies dissolved in water often leads to their degradation, although you only tend to store stuff in glycerol, like restriction enzymes, if the concentration of the protein is very very high. One golden trick I use is aliquoting my samples and snap freeze them in liquid nitrogen and store in -80 freezer. I'm curious as to what happens with your protein, does it degrade after a freeze thaw cycle? (I'm aware that transmembrane proteins are notorious when it comes to storage/maintenance due to their awkward hydrophobic transmembrane region so its best to speak to an x-ray crystallography expert, if there is some one like that roaming around your research lab :), since they have face problems like this quite frequently and have excellent suggestions). Are your proteins GST tagged and bound to glutathione agarose beads? or you use HIS tags and nickel beads and elute the purified protein through imidazole? i suspect it is GST in which case its probably not a good idea to snap freeze although I have (somehow) had frozen glycerol beads at -20 and they were fine after use. I have had a friend talking about protein purification and the fact that protein isolation has to be done fresh so you might have to go down that root if your current method is not ideal. Also one last question, are you purifying you protein bacterially or they get secreted into the media? I suspect if its a membrane protein you are using the cell based system since if it was E. coli you were using (as suggested above) you could have just had your protein expressed through IPTG and just washed you cell pellet in STE buffer and spun it down hard and stored the pellet at -20, in which case would save you some time in the purification process. The use of Na azide is a good idea too but I only use it for primary antibody storage which is already dissolved in the block buffer such as 5%-BSA-TBST for WB and store the whole thing at 4 oC and Na azide is there to prevent BSA and the Ab going off.
The main problem many many people have, including my self is that the majority of times, over expressed protein is insoluble or just doesn't get expressed in certain systems so you are very lucky to have a working system.
This is all I know about protein storage. I hope this helps.


text:
When is wing growth in the bat complete and how soon can bats fly after wing growth is complete?
I was reading this paper by Cretekos et al (2008), in which they state that wing development in the bat is not complete until after birth - the wing continues to elongate postnatally.  This would suggest that bats are unable to fly immediately after birth, and a brief web search confirms this.
However, I would like to know:

When is wing growth (by which I simply mean outward growth or extension) complete?
When are bats able to fly?  (Are there other developmental processes that take place after wing extension that delay this process?)

The ability of the forelimbs in bats (as well as in other tetrapods) to grow depends on the proliferation activity and ossification of cartilage in growing zones of the bones. Adult bats do not grow (as is the rule for mammals) and wing parameters (wing span and area) show growth curves with more or less pronounced plateau, which asymptotically leans to "adult" values. (This reflects progressive ossification of the cartilage.) As one could intuitively expect, variability in wing relative parameters decreases with age, meaning that juveniles before their first flights show more diversity in wing shapes than flying juveniles and those, in turn, approach gradually the narrow variability of these parameters of the adults.
Juvenile bats start performing their first short flights even before weaning. The main requirement for the flight ability per se is a certain threshold value of wing loading. Sustained flights start roughly half-way to maturity and correlate with the emergence of the above mentioned plateau on the growth curves. The flight abilities improve together with aerodynamic characteristics of the wing: duration of flight increases, beat frequency decreases, but beat power increases etc.

Some references:

Jones (1967)
Buchler (1980)
Hughes et al (1995)
Isaac, Marimuthu (1997)


text:
How do the variable portions of antibody genes look in cells which don't produce antibodies?
There are several families of antibodies found in mammals.  They may have two or more antibody domains which contain heavy and light chains.  The variable regions of the light and heavy chains genes in the chromosome are spliced in antibody producing cells so that each cell produces a different antibody, with a unique sequence of amino acids in the variable regions.
Here's a cartoon:

The variable regions are disproportionately large here, but it gives some idea...
What I'm having trouble finding is how the DNA regions of these genes look in cells which don't produce antibodies.  Are they the same as that in the germline?  Do they undergo recombination but are not expressed?
Any help would be appreciated.

I can't find a definitive reference, but I'm pretty sure that Ig gene rearrangement is a phenomenon that is restricted to lymphoid cells. See WP http://en.wikipedia.org/wiki/Recombination_activating_gene for an assertion that expression of the specific recombinases is limited to lymphocytes.

If "cells that don't produce antibodies" means generally all other kinds of cells (e. g. skin cells or so), then the answer is: yes, the DNA regions are the same as the germline. The VDJ recombination bharat_iyengar mentioned is a controlled procedure that has to be initiated and doesn't occur randomly.
If you refer to lymphoid cells that do not yet express antibodies, the answer is: that depends. It depends on the state the cell is in, because it is done in distinct steps (pre-B cells are different from pro-B cells).

Perhaps you want to ask how VDJ recombination is regulated in non lymphoid cells..
Well even in immature lymphoid cells VDJ recombination is regulated. And also Ig genes are suppressed in T-cell and TCR genes are suppressed in B-cells..
Also, the recombination of Ig is suppressed in T-cell and vice-versa.
RAG-1,2(Recombination activating gene) downregulation partly does the job, but not fully.
Earlier reports say that transcription in the locus is essential and epigenetic regulation of transcription in turn regulates recombination.
But what it exactly means is that accessibility to the RSS (Recombination signal sequences) is limited in a repressed chromatin and recent reports say that nucleosomes are appropriately positioned over the RSS to control recombination.
Have a look at these:
http://www.cell.com/abstract/S0092-8674%2802%2900675-X
http://www.sciencedirect.com/science/article/pii/S0952791506000057
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC204470/

Thanks for pointing out how many varieties of cells have VDJ recombination.  It sounds like getting a germline Ig sequence would be the typical result.

There are the IgG sequences in the germline along with several pseudogenes. They are kept repressed..
Have a look at this. Perhaps this is what you are looking for: http://www.ncbi.nlm.nih.gov/igblast/showGermline.cgi

Also, check this out.

This is why I normally try to avoid immunology - the cell differentiation and function leads to as many new questions as answers... thanks!

immunology always full of anomalies :P


text:
Perception of distant lights without glasses
I am fairly short-sighted and wear glasses pretty much all the time. Naively, I would expect that when I take my glasses off, the image I see should look very much the same as as a photograph that's out of focus, or an image to which someone has applied a Gaussian blur filter. In bright conditions this is mostly true, but at night if I look at distant point sources of light, the blurry halos around them appear to have quite a complex structure, and a fairly well-defined edge. Why is this?
To make it clearer what I mean, and at the same time to make a hypothesis about the answer, here is a public domain image of some lights, taken with a camera out of focus:

(image source.) Notice that the image cast by each light is not simply a uniform circle. They are each slightly hexagonal; they are slightly brighter around the edge than in the middle; and there are distinct nonuniformities in the brightness in the interior of each shape.
What I see is actually fairly similar to this but much more extreme. The shape formed by a light is much further from a circle, being very irregular in shape and distinctly elongated in one direction. (This latter is perhaps not surprising given that I have a strong astigmatism.) The bright edge to the shape, and the non-uniformities in its brightness, are much more pronounced than in the camera image.
Now, in the photograph I know that the hexagonal shape is due to the hexagonal aperture in the camera. This can be ruled out in my eyes because my pupils are definitely circular. (Unless some light also passes through parts of the iris?) I would guess that the bright edges are caused by diffraction, and that the nonuniformities are caused by defects in the lens and/or dirt on its surface. I suppose that diffraction and lens aberrations must be the causes of what I see when looking at distant lights without my glasses.
So in the end, my question is mostly just, am I right about this? Are the shapes I see the result of defects in my eye's optics, and which specific anatomical features of the eye are likely to be their main causes?

This isn't an answer, just speculation. In dim light, your rods are primarily responsible for perception (cones don't work very well). Cones are also more concentrated in the center of the retina, which would mean that rods are more concentrated at the edges. Something to do with focusing in nearsighted people might explain this.

dd3's suggestion makes sense to me but I wonder if you could add a short paragraph to explain the 'structure' a little more?

@daniel I'm not sure if I can easily describe it in words. If I get a chance some time I will make a sketch.

@Nathaniel Could just be refraction playing tricks on your eyes.

@Nathaniel or could be floaters. http://en.wikipedia.org/wiki/Floater

@TheLastWord it's definitely something to do with refraction, and not floaters - the effect is the same for every distant light source, whereas floaters would be intermittent. The question is why my eye's optics (plus processing by my visual system) produce a different effect from that of an unfocused camera lens. I'll try to get around to sketching it one of these days.

@WYSIWYG merry Christmas.

@Nathaniel merry christmas to you too. Don't mind that I voted to close. It is difficult to really know what you perceive and therefore answering this question is difficult.

@WYSIWYG I think approximately 50% of the population will not have any difficulty knowing what I perceive. However, I will edit the post to make it clearer.

@Nathaniel As you said you can make a sort of diagram to explain the perception. BTW what did your ophthalmologist say regarding this?

@WYSIWYG see the edit. In making it clearer I may have answered most of it myself, but I hope you can understand what I mean now. I've never spoken about it to an opthalmologist, because it's a subtlety of perception that only occurs at night, so I've never thought to mention it. (I suspect that it's what everyone shortsighted sees.)

@WYSIWYG I think you're being a bit hasty here.  There is an extensive body of literature on the physics (and psychophysics) of vision that can be brought to bear here.

@jonsca After the edit it is fine.. Before that it was a little difficult to understand what perception OP was referring to. I retracted the close vote

This phenomenon is known as bokeh.

You are right in the hexagonal shape being produced by the iris (of the camera), and from this, it is clear why this happens: The iris blocks out some of the light travelling into it, and a shape approximating that of the camera's iris aperture is projected onto the CCD.
The same thing happens for the eye. The iris will block out a portion of the light, causing the bokeh to approximate the shape of the iris aperture (aka the pupil), which is roughly circular for humans. Animals with non-circular pupils will perceive differently shaped bokeh. If the lens suffers from astigmatism, it will also result in non-spherical bokeh being projected onto the retina.
This stackexchange link goes into greater detail on Gaussian blur vs bokeh.

It seems like you're saying that the shape of the human pupil is hexagonal? If so, I would like to see a reference for this.

@fileunderwater No, I am not. The hexagonal shape of the bokeh in the OP was caused by the hexagonal shape of the camera iris. I will reword the answer to prevent this misunderstanding.


text:
Differences Between Protein Motifs and Protein Domains?
I am in a 300-level molecular biology class and am unclear about this concept and how to delineate motifs versus domains of proteins.  Any suggestions would be much obliged.

These are completely different concepts, which sometimes may be connected.
A motif in biology is a mathematical model, typically of a sequence, that predicts which sequences belong to some defined group. For example, a DNA sequence motif can characterize the binding site of a transcription factor, i.e. which sequences tend to be bound by this factor. For proteins, sequence motifs can characterize which proteins (protein sequences) belong to a given protein family. A simple motif could be, for example, some pattern which is strictly shared by all members of the group, e.g. WTRXEKXXY (where X stands for any amino acid). There are also more complex motif models.
Protein domains, on the other hand, are a structural entity, usually meaning a part of the protein structure which folds and functions independently. So, proteins are often constructed from different combinations of these domains.
So how are motifs and domains related? Well, when you think about protein families, it makes sense not only to look at the whole sequence but also to focus on individual domains. Since they are a elementary functional-structural units, it makes sense to find sequence motifs for individual domains. So, you often find that a protein contains multiple domains, each domain characterized by having a sequence that matches the motif of its family.

adding to the answer of @Bitwise:
Motif is just a statistically well represented pattern in a data. It can be a sequence or even a structure. Motifs CAN be sometimes associated with particular functions

@WYSIWYG thanks for the clarification, I was going to mention structural motifs but forgot to write it.

This was very helpful, thanks for the reply. :)

The principal difference is that domains are independently stable, while motifs are not.
Here is a bit on motifs: http://www.sinauer.com/pdf/nsp-protein-1-16.pdf
A motif can be part of a domain.  From there:

The second, equally common, use of the term motif refers to a set of
  contiguous secondary structure elements that either have a particular
  functional significance or define a portion of an independently folded
  domain.

Expanding on the comment made by @WYSIWYG, a motif is just a pattern. For proteins this pattern can either refer to a string of amino acids — a sequence motif — or the conformation and interaction of residues in space — a three-dimensional structural motif.
It is important to qualify the term ‘motif’ to indicate precisely what is meant.
Sequence motifs
A good illustration is the ATP-binding motif:

GXXGXFKS(or T)

This illustrates that not all positions need be specified (X) and that in some positions alternatives may occur (S or T).
Structural motifs
One type of structural motif involves small hydrogen-bonded structures such as beta-bulges, Schellman loops and beta-turns. A beta-turn is illustrated:

It can be simply defined as “A motif of four consecutive residues and one H-bond in which a H-bond occurs between main-chain CO of residue-1 and main-chain NH of residue-4”. Alternatively, subcategories can be defined in terms of the dihedral angles at residues 2 and 3.

After the peptide chain of a protein has been organised into successive stretches of secondary elements, combinations of such elements are first arranged into distinctive groups called super secondary motifs. Several neighbouring secondary elements and supersecondary motifs are folded and twisted further into compact globular cluster called a domain.

Do you have a reference to this?


text:
What's the Evolutionary Purpose of Religion?
I would imagine the answer to this question would be that religion tends to cause greater compliance of individuals within society, so it is pro-society. Plus these religions tend to incorporate some knowledge obtained by trial and error, an example of this is the fact that in Judaism the consumption of swine is forbidden which would be an evolutionary advantage seeing how swine is notorious for its parasitic constituents. Additionally religion offers an explanation for some of the phenomena that were once and still are poorly understood. Such things include near-death experiences. It also adds to motivation and tends to confer some other advantages such as a decreased rate of suicide due to the condemnation of suicide by the majority of religions.

This sounds to me as social advantages, not evolutionary ones. Not everything needs to have an evolutionary advantage.

In my opinion, social evolution is a continuation of biological evolution. In that sense, the question might be considered legitimate here.

In terms of genetic evolution, religion itself cannot really be considered to have an evolutionary advantage or disadvantage, as it is not anchored in any genes. This means that it is not an evolutionary trait and hence the principles of evolution do not apply to it. However, religion is a product of underlying capabilities of the brain (for example imaginative capacity?), and these are genetic and evolutionarily advantageous. Aside from this, asking for the 'evolutionary purpose' of anything is the wrong way to approach the topic, as things do not evolve to have a purpose but they simply evolve and stick around unless they produce a net disadvantage compared to a competing version of the same trait.
You could look at religion from a memetic point of view however, i.e. as an idea which competes with other ideas. The idea of religion has many aspects to it that would help it to 'survive', i.e. not be forgotten. These include the drive to tell other people about it, ease of understanding, the claim of exclusivity, addressing many social cravings, and filling in gaps of knowledge for which explanations are desired.


text:
Is it possible to make bacteria vulnerable to antibiotics it's resistant to?
Since bacteria becomes resistant to antibiotics after an unfinished course, is it possible to do anything to be able to get treatment with the same antibiotic again, and reverse the resistance in the bacteria?
Or, the bacteria with the resistance will stay resistant forever (until death)?
Edit:
There are some websites that are claiming that some natural remedies might be effective, like taking "Honey", which doesn't seem to be medical facts.

@Sancho I have edited my question, and added that some sites claims that it is possible.

To confirm, is the claim: "It is possible to make bacteria vulnerable to antibiotics that they are currently resistant to"

@Sancho , Yes, that is it exactly, the title of the question has been edited (by wertliq) to say that.

I think you may be starting from a misconception. Each individual bacteria has a fixed level of resistance that generally doesn't change throughout its life. Antibiotics easily kill those that are less resistant, leaving behind the more resistant bacteria to spread. There is no resistance that was "gained" by any individual bacteria, so nothing to reverse. A better summary of your linked question would be "bacterial populations become resistant" rather than "bacteria become resistant". This might not change what your question is, but wanted to point this out.

What would make this much clearer is a link to a notable source that makes the claim you're questioning... then we'll be able to pin down exactly what is meant and get a good answer for you.

This question doesn't have any claim associated with it, but rather wants to know if a certain biological process is possible, I think that because of it this question should be on Biology.SE and not here..

Perhaps it is useful to first consider how resistance is gained:
If you treat a population of bacteria with an antibiotic, some may die and some may live.
If none die, they are obviously resistant.
If all of them die, then all of them were sensitive, meaning that the size of the population and the variation were not large enough in order for some of the bacteria to be resistant. One approach would be to try to get larger genetic variation by inducing mutations with some mutagen. In addition, you can take a larger population. This would in effect let you sample a larger part of the genetic space to see if you can find a resistant strain. Of course it is possible that this will not work.
If some die and some are resistant, the situation is slightly more complicated. One possibility is that those which lived are genetically resistant (their DNA is different). To see if this is the case, you take those which lived and treat them again with the antibiotic. If they all live, they are resistant. Another possibility is that they are scholastically resistant. This phenomenon is known as bacterial persistence. What happens is that there is a genetic switch that randomly bestows resistance in some fraction of the population, let's say 10 percent. If you now take this population and reapply the antibiotic, only 10% of the population will survive. This interesting mechanism allows the bacteria adapt more quickly, since they do not have to make modifications to their DNA.
I am guessing that if the bacteria are genetically resistant, they will stay resistant. If the bacteria are scholastically resistant, it might be possible to affect the genetic switch which causes the persistence. This, in addition to reducing the size of the population, might cause a situation where none of the bacteria in the population are resistant long enough to survive.

You've explained how bacterial resistance develops, but you haven't explained how it might go away (except an allusion in your description of bacterial persistence).

@dd3 Sorry about that, I misread the question. I will edit it slightly and will keep it just since it might be useful for someone.

Just an addition to the above answer........ In cases where resistance is because of overexpression of a certain gene such as an efflux pump, because of promoter mutations, the WT will outcompete the mutant because of the latter's additional cost of gene synthesis. In cases where a receptor mutation causes insensitivity to a drug then perhaps the mutant may underperform in processes where the receptor is vital. And WT can outcompete the mutant. If there is no trade-off for a mutation then it wont go away

Bitwise has explained how antibiotic resistance develops in bacteria.  To address how it might go away: as long as the antibiotic is around, there is selective pressure on the bacteria to preserve the parts of their genome that confer antibiotic resistance.  If, for example, some bacteria developed mutations that made them no longer antibiotic-resistant, these bacteria would die, and thus, only the antibiotic-resistant bacteria would reproduce.
For antibiotic-susceptible bacteria to develop and persist, you'd need to take away this selective pressure (no more of the antibiotic around to kill the antibiotic-susceptible bacteria) so that there would be no particular advantage to carrying non-mutated copies of the antibiotic-resistance gene(s). Of course, the natural rate of mutation is not that high, so I think it would take time for antibiotic-susceptible bacteria to reappear (unless there was a mutagen around).
EDIT: antibiotic-susceptible bacteria would become more prevalent if there was a way to select for them, over antibiotic-resistant bacteria. For example, if there were conditions under which maintaining antibiotic-resistance genes becomes unfavorable, antibiotic-susceptible bacteria would reproduce more often/faster (see the term fitness), and thus become more prevalent. However, this does not change the mutation rate - only selects for things that have already evolved.

The other answers describe the situation well for an individual, however there have been cases in the past where antibiotic resistance has emerged and been outgunned by medical advances to overcome this specific resistance.  A good example of this co-amoxyclav.
The original Amoxicillin, a  β-lactam antibiotic, was previously effective against a good range of bacteria.  However antibiotic resistance then developed when some bacteria began producing  β-lactamase, an enzyme which degraded the  β-lactam ring rendering the drug (and all within its class) useless against them.
This resistance was then countered when a way to inhibit the β-lactamase the bacteria were producing was discovered.  Clavulanic acid does this, leading to the mixture of its potassium salt with Amoxicillin.  The mixture (coamoxyclav) allows the amoxicillin to still be effective against the previously resistant bacteria, as the resistance they have been developed is being inhibited in parallel.
For this reason in a hospital setting it is more common to prescribe Co-amoxyclav rather than a beta-lactam antibiotic in isolation.


text:
Confusion related to a term probe-by-background interaction
I was reading a paper related to bioinformatics where it uses the drug response on the cancer cells and the gene expression of the individual cells are studied to find any useful insights. Specially, using the gene expression of the cells a predictor of the drug response is created.
They have stated that just using the correlation between the gene expression and the drug response might not be a good predictor. But the genes interact through signaling pathways to drive a particular drug response.
What these guys have done is like used PCA on the gene expressions of the cancer cells to use the components which preserve the greatest variance.
Actually, I didn't get what they mean by probe-by-background interaction and how it is calculated.
Can anyone please explain. I googled for a while but didn't get it.
Here are some quotes from the paper where the term is used

Towards this end, we have compared how well drug response can be
  predicted by simple statistical models, which either directly relate
  probe and background networks to drug response or consider
  probe-by-background network interactions.
To generalize this approach, the term ‘probe’ could be
  replaced by individual transcript expression levels measured through
  other gene expression methods. Similarly, ‘background networks’ and
  principal components are used interchangeably. Generally, ‘background
  networks’ could be represented by any data reduction method that
  summarizes the expression of a gene network. We demonstrate that
  probe-by-background network interactions significantly enhance drug
  response predictions, over and above the predictive power garnered
  through utilizing individual probes and background networks alone.

cross-posted with BioStar: http://www.biostars.org/p/68510/

Posting the paper here is likely to get everyone into trouble, as the content is owned by Nature Publishing Group.  I added a link to your post - at least a few of us do have institutional access. Also, I do not expect anyone to try to read the article from screenshots.

Rather than including screenshots, can you provide a few examples of where the authors use the term that you are unsure about? Just a sentence or two, quoted, would be fine and within fair use, I think.

I rolled back your edit. We do not want screenshots, as that is very likely a copyright violation. My suggestions was to quote several instances where the term is used.

The "probe by background" interaction is the response of different probes as a function of background gene expression. For example, depending on which of the 6 backgrounds a probe is in, the drug response may go up or down. Probes as a function of background is probably easier to imagine than background as a function of probe (which is equally valid). For 39,115 probes and 6 background networks, there are 234,690 interactions.
In a technical sense, "probe by background" is the interaction term in the linear model that the authors fit for each drug. The details of the analysis are in the supplemental methods. The model they fit is
Drug_Response ~ Probe + Probe * Background + Background

which translates to "Drug response is modeled by Probe, the interaction of Probe and Background, and Background". The middle term (with the *) is the interaction term. Here is a page that helps to explain how to understand significant interaction terms in linear models.

I didn't understand how it is calculated. I mean probes are the original probes. Background are formed by applying PCA and taking the best 6. I didn't understand how this interaction term is calculated. How do I know which background a probe is in

I didn't understand how it is calculated. I mean probes are the original probes. Background are formed by applying PCA and taking the best 6. I didn't understand how this interaction term is calculated. How do I know which background a probe is in. Also I didn't get why it is called background. I mean they have just applied PCA to capture the decorrelated basis which capture the most variance. Why is it called background?

I am wondering if they  used the ttest values for the interaction term?

I just found out that it is just the product of the probe values and the background values. However, they have mentioned probe-by-background term(paired t-test P-value=7,510^-5, paired Mann-Whitney test P-value=5.210^-5). What is meant by this?


text:
Is it possible to pet/groom birds?
I wonder if it's possible to pet a domestic crow, or an owl. Do birds respond to grooming as cats or dogs, for example? If so, then how does one pet a bird?

Birds do groom, but not like mammals do. People tend to call their grooming behavior preening. Preening removes dirt and parasites, arranges the feathers nicely, and distributes oils over the feather (very important for waterfowl.)
To answer your question better, we need to look at the specific species. Lots of birds preen each other socially, so if you wanted to pet a bird (in a way it likes) it's good to know how the species behaves.
You mention crows and owls. Crows are social so they may preen each other; they're also sophisticated (cultural) so it's hard to generalize. A 'bird nerd' on YouTube shows convincing footage of such behavior. I think family groups of crows preen each other, but I don't have a source.
Owls tend to be solitary and would not understand preening behavior from a human. A social species of owl might preen; I don't know. Of course, if you just go ahead and pet your owl like a dog, it may appear to like it. It's hard to say if it does like it...it's easy to anthropomorphize a bird with binocular vision!

I know first hand that Diamond, a tame Pionus chalcopterus, will sometimes respond to having his head and neck scratched in an interesting manner: he may make "panting" or "huffing" noises unique to this activity, lean his forehead or beak against my hand, and half-close his eyes.
I'll add to Ryan's answer by pointing out another use of preening: peeling the cover from newly-grown pin feathers.
How to (safely) pet
It's important to read body language correctly. Just as in Manderan it's funny to call your mother-in-law a mountain horse, you must learn the distinction between "scratch my neck" and "stay back or I'll bite".  The ruff is raised normally as a signal of aggression.
Bring your hand up to his level wrist up and fingers trailing down in a relaxed posture. Make sure he sees it, without startling him.  Human hands are not "natural" to non-domesticated species, so give him a few seconds to process.  Higher thinking is slow and an optional "mode" so to speak.  If he wants to be petted, he'll engage or remain neutral and undisturbed.
Diamond has learned through consistancy that a natural but superficial agressive signal is understood as "give me space", so a horizontal body position with beak in-line like an arrow (the "T-Rex position") and a slight (symbolic) darting motion means you should withdraw. But he may change his mind in a few minutes now that the subject has been raised.

The general points are:

understand his body language
be consistent in your own actions and associated meanings. They're learning a pidgeon with you (pun intended), not like dogs that intuitively know humans,
give hime time to "think".
develop a routine


text:
Chiral (a)symmetry of curly hair (and fur)
Some people have curly hair, as well as fur of some animals can be curly.
However, shapes which are curly are not mirror symmetric, much alike screws or chiral molecules.
The question is whether curly hair in a given species (say, humans, but I don't stick to this example) are in the same proportion left-handed and right-handed?
One can easily imagine that chirality of molecules (e.g. keratin) gives rise to macroscopic chirality of curly hair. However, it is far from obvious whether this effect is strong enough.
EDIT:
I am interested mostly in data. It might be easy (yet misleading) to convince oneself that there should (or there shouldn't) be relation of microscopic to macroscopic mirror symmetry (or lack of it).
(E.g. in some other cases there is such effect - e.g. with left/right orientation of body organs like heart, or asymmetry of left and right brain.)

curliness of hair is not because of an enantiomeric form of keratin. It is dependent on the way keratin is packed in the intermediate fibers.

@WYSIWYG a link might help the OP...

Please refer this research done by L'oréal on keratin organization and hair texture and shape.
I believe one can also find an answer in classical textbooks like MBOTC-Bruce Alberts. This is a commonly asked question in cell bio/protein structure exams.

Plus.. all amino acids exist as L-enantiomers in proteins. Few exceptions in  cell wall peptides of gram +ve bacteria

@WYSIWYG Here keratin was only a guess. Chirality of  intermediate fibers equally interesting to me. However the main question is: is proportion of left- and right-handed curly hair 1:1 in humans?

This is a great question. I am betting there is no data or precious little. You suggested a mechanism and I think that has led to confusion in the answers. Maybe just edit it down to the essential question? What is the ratio of L-/ R- chirality of curly hair? +1.

@daniel You are right that suggesting an answer was distracting. In any case, it seems there is no data. Maybe I should run a survey among friends or so. :)

Microscopic chirality is not at all necessary to explain curly hair (or other objects).  All that is required is flexibility. Once hair gets long enough, it collides with itself, and is pushed off to one side or another, forming a chiral curl.
For some anecdotal evidence against microscopic chirality, find someone with large diameter hanging curls in their hair. Those seem to often curl straight back on to themselves. A more compelling anecdote is that curled objects, including hair and telephone cords (if anyone still remembers those) can be pulled through themselves and chirally inverted. Sometimes there will be some resistance, but that could be the keratin or plastic or whatever having set in its shape over time, rather than being preferentially formed that way.
These are obviously both anecdotal though, and the idea that there is some slight chiral preference isn't ruled out. I'm not even opposed to the fundamental idea of transitive chirality through several orders of superhelicity (look at DNA), but it just hasn't been my empirical experience. As Ryan points out, if it were a strong effect, all hair would curl the same way, and straight hair wouldn't exist at all.
Just to provide a bit of data, this paper demonstrates that hair curvature is based on the distribution of 4 different cell types in a follicle. The keratin (and many other proteins associated with) intermediate fibrils were associated with curvature, but only to the extend that their compositions were different in the 4 cell types. But the curvature was based on the distribution of the cells themselves.  Chirality wasn't specifically studied in the paper, but I think (given that they were staring at individual fibers with an electron microscope) that they would have noticed it had it existed.
Cortical cell types and intermediate filament arrangements correlate with fiber curvature in Japanese human hair
http://www.sciencedirect.com/science/article/pii/S1047847708002980

Naturally straight and curved human scalp hairs were examined using fluorescence and electron microscopy techniques to determine morphological and ultrastructural features contributing to single fiber curvature. The study excluded cuticle and medulla, which lack known bilateral structural asymmetry and therefore potential to form curved fibers. The cortex contained four classifiable cell types, two of which were always present in much greater abundance than the remaining two types. In straight hair, these cell types were arranged annularly and evenly within the cortex, implying that the averaging of differing structural features would maintain a straight fiber conformation. In curved fibers, the cell types were bilaterally distributed approximately perpendicular to fiber curvature direction with one dominant cell type predominantly located closest to the convex fiber side and the other, closest to the concave side. Electron tomography confirmed that the dominant cell type closest to the convex fiber side contained discrete macrofibrils composed of helically arranged intermediate filaments, while the dominant cell type closest to the concave side contained larger fused macrofibrils composed of intermediate filament arrangements varying from helical to hexagonal arrays approximately parallel to the longitudinal fiber axis. These findings concur with the current hypothesis of hair curvature formation and behavior.

I know that microscopic chirality is not needed to explain curly hair. The question is whether it plays any role, e.g. in shifting the ratio of clockwise and counter-clockwise curly hair from 1:1. (Thanks for the link, anyway; too bad for me that it is under a paywall).

Keratin's handedness does not directly give rise to the curls of hair. One has to cross many many length scales to move from the keratin scale to the whole hair fiber. There's an animation here that shows those many length scales. But here are some other arguments if you're inclined...
If the superhelicity of keratin effected the curling of hair, all hair would twist in the same direction, because the keratin superhelix always twists in the same (left-handed) direction (for the naturally occurring proteins.) But that isn't the case. At least not for my hair!
Or you can ask, if the keratin superhelix gives rise to curly hair, then how is this effect mitigated in straight hair? The structure of keratin isn't directly giving rise to the long-range patterns of hair. The keratin filaments are being arranged in particular ways, and the long-range behavior is independent of the short-range superhelicity.

Orders of magnitude difference of scale is not itself and argument against (see edit of my question).


text:
Can I heat Trizol?
I wonder if I can heat Trizol reagent for 30 min 65C. The goal is to disrupt protein-RNA complex while inhibiting nucleases. (I can't use RNasin cause it's inactivated in 65C, and can't use RVC cause reaction contains EDTA).
I realize that heating Trizol is not safe and its vapors are hazardous, but i can perform it in the hood.

As far as I know, Trizol disrupts protein-RNA complexes on its own - check the protocol. Also, phenol, a major component, is flammable. I don't know what the flash point of Trizol is, but I would be extremely careful. This protocol claims you can heat it. Does your experiment not work at RT?

Heating wont be a nice idea. But if your cells are too resistant to lysis then you can keep the tubes in a warm water bath. However, bring it back to RT before adding chloroform.
BTW what sample is this?

If you are worried about safety, contact your university's Environmental Health and Safety office (or the equivalent). They can (should, and will) advise you on safety issues.

What kind of cells or complexes do you have? I have worked a lot with Phenol based reagents but never found problems to work with it at room temperature. Besides that Phenol is volatile, especially at higher temperatures. You will have to do that in a good fume hood, otherwise this is a serious health issue. And definitely cool down before adding Chloroform.

Working with hot phenolic solutions is rarely been done due to the dangers of this. Phenol needs to be handled in the fume hood anyway, at higher temperatures it gets even more volatile. So if you plan to do this, do it with extra care to avoid injury.
There is one paper that describes this method for bacteria, but this should work for other samples as well: "Evaluation of isolation methods and RNA integrity for bacterial RNA quantitation". However, there is another method, which was developed for extracting RNA from plant material infected by bacteria which is also worth a try (although it might need some adaptation), which works without hot phenol: "An optimized method for the extraction of bacterial mRNA from plant roots infected with Escherichia coli O157:H7".

So what happens if you don't keep your phenol:chloroform in the fume hood? Because I haven't. Am I going to die? I also occasionally touch a gel that contains ethidium. Should I be writing my will?

You should be very careful with Phenol as this causes nasty and long lasting chemical burns. It basically desintegrates the cells, thats why we use it for setting the nucleic acids free. Inhaling is a bad idea. EtBr on the other hand should be handled with care, but most guides about the dangers are overrated. It is mutagen (can cause mutations) and teratogen (can cause damages to the developing embryo) but I haven't seen any proof yet, that it is cancerogen (except when causing mutations). This is different for benzene for example, which is directly cancerogen.

Also: EtBr has a very good water solubility (which means it doesn't cross the skin barrier very easy, especially not as a charged molecule) and it is light sensitive. So use it with care, but don'T overreact.


text:
Confusion related to the use of PCA to determine the background network
I was reading this paper related to use of gene expressions for predicting the drug response. I have this confusion, the paper has used PCA on the covariance matrix formed by the genes to get what is called the background network as they say.
I don't know the essence of background in this case. I know PCA gives us components which preserves the greatest variance and used for dimension reduction. What they mean by background network. Is it pathways ?

For reference, previous question regarding this paper: http://biology.stackexchange.com/questions/7800/confusion-related-to-a-term-probe-by-background-interaction

Could you include a bit more information on the paper so we can understand more easily?

Perhaps, the background is the set of genes which are not represented by the first few principal components

I am by far not an expert, but I read the paper and maybe I can help clarifing things a bit.
Let's start with the simplest answer to your question:
In the last paragraph of the Introduction paper the authors say

"Throughout this manuscript [...]'background networks' and principle components are used interchangeably." ([1] Torkamani and Schork, Genetic background and drug response, The Pharmacogenomics Journal (2012) 12, 446-452; doi:10.1038/tpj.2011.35)

So they did not "use" PCA to get the background networks, they just call the PCs background models to indicate how they interpret it: As stated earlier in the introduction

"...interacting networks cannot be expected to correlate strongly with drug response, as their influence may only be observed when the major determinant of drug response and the interacting network complement one another or are both at a synergistic state. A major problem with identifying these interaction partners [...] is the extremely large number of possible partners [...] and [...] that individual genes are unlikely to accurately represent the overall state of a biological network." [1]

As far as I understand the article, they suggest PCA as a kind of compromise: Ignoring interactions would miss associations of all networks lacking a single gene representing the network's state accurate enough. Including all interactions is infeasable due to the huge number of gene-pairs. By PCA, the number of interactions can be decreased by orders of magnitude while keeping a maximum on information (as in variation): Instead of using the interaction (as in product) of all probes with all probes, they only consider those of all probes with the first six PCs.
I think, in this context 'background' is not used in the meaning of 'background noise' but of 'cultural background' - instead of assesing individual interactions, genes are assigned a 'background'. Since this corresponds to a) the biological network(s) they belong to and b) the principle components(s) they contribute to, those two ideas are used synonymously by calling PCs 'background networks'.


text:
Can animals use the nitrogen in chitin to build proteins?
Fungi and insects contain chitin, which is about 6% nitrogen.
Can an animal - like me - make use of this as a nitrogen source to build proteins?
Are there any animals that can do this?
Are there other uses an animal can put Nitrogen from this specific source to?

The first answer is that humans cannot.
Chitin is a major component of the exoskeleton of insects and other arthropods, the cell wall of fungi and bacteria, the perisarco of hydroids and is also present in the epidermal cuticle or other surface structures of many other invertebrates. After cellulose, chitin is the most abundant naturally occurring biopolymer.
Chitin is a polysaccharide consisting of multiple units of N-acetylglucosamine (N-acetyl-D-glucos-2-amine) linked together with a bond-type β-1, 4, of the same glucose units forming the cellulose. Therefore, the the chitin can be regarded as a cellulose in which the hydroxyl group on each monomer has been replaced a group of acetilammina.
Pepsin in the stomach cleaves peptide bonds that bind together the amino acids of proteins, thus forming small peptides and amino fragments.
From the organoleptic point of view, chitin is considered a fiber, like cellulose and chitosans, suggesting it is indigestible.
Some herbivores, such as goats and some ruminants can digest cellulose, breaking them down long chains of polysaccharides. Similarly, echinoderms can eat shellfish, sea urchins and mussels and digest chitin, breaking mechanically only ones with hard shells.

However, hydrogen bonds between adjacent polymer guarantee the substance a remarkable hardness. This feature, combined with its flexibility and the fact that it is degradable by endogenous enzymes, chitin is an excellent material for the production of wires for surgical sutures, bandages and also synthetic leather. Chitin also has the unusual property of accelerating the healing of wounds in humans, closely related to chitosan (a more water-soluble derivative of chitin) and to the immune system of plants and animals.
EDIT
Yes, @mart. Echinoderms use chitin for producing proteins, similar to how herbivores use plant cell walls, which consist mainly of polysaccharides (non-nitrogen compounds), to produce the proteins (nitrogen-containing compounds), that serve us also (since we are not able to digest the grass).

More sparing use of formatting might make your answer easier to read

Counted my bad English, I will very gratefull if you do it :)

Those animals that can digest chitin, do they use the contained N for protein building or other purposes?

This answer should not have been accepted in my opinion. It contains a ragbag of mainly irrelevant information and then it gets its key fact wrong. Humans have the potential to digest chitin as they have the genes for chitinase. The doubtful assertion that the the product of chitin digestion (Nacetyl glucosamine) is used for protein synthesis (i.e. converted to amino acids) rather than used for the synthesis of polysaccharides is not backed by any references or links so we cannot judge whether it is correct.

This article suggests a certain amount of chitin digestion is possible.
http://www.bio.unipd.it/agroecology/download/pdf/papers/2009/Chitin-Chitinases-Paoletti-From-Binomium-Chitnchitinase-Recent-Issues-Fp-Version.pdf
I can't quantitatively say how much of any of the myriad potential chitin sources (fungal, crustacean or other arthropods) would be digested within a 'normal' time frame in the human digestive system. That work should probably be undertaken, though.

You might summarize the key points of the article, including the fact that humans do have chitinase genes. I would cut your last line, which is a matter of opinion on research priorities. It's not the sort of work that I would fund.


text:
What's the mechanism of action of Levomepromazine's analgesic effects?
I have absolutely no idea as to how Levomepromazine elicits its analgesic effects so please do direct me to journal articles and other credible sources with you, the answerer, making a summary of Levomepromazine's mechanism of action in your answer.

According to Drugbank and the articles cited below, Levomepromazine is an antagonist of several different receptors: These include dopaminergic 2, dopaminergic 4, alpha-1 adrenoceptor, 5HT-2, histamine type 1 and muscarinic-cholinergic receptors.
References:

Evidence for the use of Levomepromazine for symptom control in the
palliative care setting: a systematic review
Muscarinic cholinergic and histamine H1 receptor binding of
phenothiazine drug metabolites
Levomepromazine receptor binding profile in human brain—implications
for treatment—resistant schizophrenia
Phenothiazine drug metabolites: Dopamine D2 receptor, α1-and
α2-adrenoceptor binding


text:
What is a good review book/source for microbiological diagnosis?
I am trying to find the diagnosis figure for different bacteria where phases are illustrated.
I am using at the moment: 1) First Aid for the USMLE Step 1 2013 and 2) Medical Microbiology by Murray et al, 7e.
What is a good review source for basic microbiological diagnosis?

I would suggest:
Koneman's Color Atlas and Textbook of Diagnostic Microbiology
by Elmer W. Konema


text:
Macroevolution vs. microevolution
Where is the line usually drawn between macroevolution and microevolution?
I thought that, although similar processes govern both, the line was at the species level, with macroevolution being changes at the above-species level and microevolution being changes within a species (something like changes in allele frequencies).  (So it's a question of timescales?)
However, I heard someone talk about microevolution among different species of Drosophila, specifically referring to copy number variation.  Was the choice of "microevolution" to describe this process (more likely) due to the similarity between Drosophila species or the type of change in the gene? Or at this level, is the distinction rather arbitrary?

Let's start with a word of caution: on the internet, the terms macroevolution and microevolution (especially together) are usually used primarily in creationist rhetoric. As such, it is usually best to avoid them, especially when talking to a lay audience. The main mistake creationists perpetuate when thinking about micro-vs-macro evolution, is that the two are somehow different and distinct physical processes. This is simply not the case, they are both just evolution. The scientific distinction between the terms, comes not from the physical world around us, but from how we choose to talk about it. When a biologist says "microevolution" or "macroevolution" they are actually signaling what kind of questions they are interested in asking, or what sort of tools they plan on using.
Verbal and empirical theories
In verbal and empirical theories, the micro-macro distinction is usually one of timescales. A person in the macroevolutionary paradigm, usually asks questions above the level of individual species, as Evolution 101 writes (emphasis mine):

instead of focusing on an individual beetle species, a macroevolutionary lens might require that we zoom out on the tree of life, to assess the diversity of the entire beetle clade and its position on the tree.

Empirically, macroevolutionary answers to these sort of questions are usually ones that don't have access to detailed evolutionary histories or direct experiment. Instead, the method tends to be ones that use geology, fossils, and back-inferences from broad differences/similarities of existing species. As such, most macroevolutionary theories tend to be descriptive, instead of predictive. Most of paleontology can be classified under the macroevolutionary paradigm.
If someone explicitly says that they are looking at microevolution then this usually refers to a contrasting methodology that tends to be heavy on direct experimental manipulation. Most importantly, microevolutionists tend to have access to rich and detailed evolutionary histories. As such, it is not surprising that you saw a study that identified itself as microevolutionary while looking at different species of Drosophila. The fruit fly is one of the widest used model organisms, and as such the study you are referring to probably experimentally manipulated populations of fruit flies and collected a rich dataset of genetic changes in the generations of fruit flies that they studied.
Of course, most studies are at intermittent levels, and no this isn't called meso-evolution (except by silly people). If you are not clearly using the macroevolutionary nor the microevolutionary paradigm but still looking at evolution, you would just simply say 'evolutionary' without any prefix.
Formal and mathematical models
For formal and mathematical theories, the micro/macro distinction is also one of methods used by the theorist not of the underlying domain they are studying. Mathematical modeling of evolution falls into two broad categories: frequency-dependent and frequency-independent models. Frequency-dependent models almost never make the micro-macro distinction. Although you could argue that dynamic models in evolutionary game theory are micro, and static equilibrium concepts like ESS are macro, but I doubt theorists would endorse this view. As such, I will focus on the frequency-independent models.
For frequency-independent models, they key concept is the fitness landscape -- a way to map each genotype to a fitness. If the model tracks a population (a distribution over vertices in the fitness graph) on a static fitness landscape, then it would typically be just called an evolutionary model (the word microevolutionary is seldom used explicitly in this field). However, if the authors assume that mutations are extremely rare and thus any mutant goes to fixation before a new one arises then they can use Gillespie (1983, 1984) to replace the population by a single "typical individual" occupying one vertex of the fitness graph. At this point, the model becomes macroevolutionary and the underlying rule for calculating fixation probabilities would be the microevolutionary component. This approach is often also coupled with an alternation of change in fitness landscape followed by mutations and a selective sweep. Fundamentally, though, macroevolutionary models are just convenient (or tractable) approximations to a real underlying evolutionary dynamics. This should never be forgotten.
Strange example bridging the gaps
Finally, it is important to stress that the macro- and micro-evolutionary paradigms are not necessarily exclusive and do not have to correspond to a difference in timescales! This is best done with an example of a respected theoretical study that mixes everything together. Kauffman & Weinberger (1989) used their newly developed NK model or rugged fitness landscapes to study maturation of the immune response (Tonegawa, 1983). The developed a macroevolutionary mathematical model because they used Gillespie's trick to replace a population by a typical individual by abstracting away from the underlying microevolutionary calculation of fixation probabilities. However, their model was studying evolutionary dynamics within the human immune system (so timescales of days to weeks) and was tuned by parameters gathered by empirical microevolutionary studies that tracked individual nucleotide changes (Crews et al., 1981; Tonegawa, 1983; Clark et al., 1985). Lastly, the study results can be used to inform a question typical of verbal macroevolutionary theory: Are there any examples of sudden leaps in evolution?.
As such, the above study used a formal macroevolutionary model, informed by empirical microevolutionary work, to help us understand a question typical of verbal macroevolution while looking at a physical process that operated on the incredibly short timescale of days to weeks. No wonder people are so confused by the micro-macro "divide"!

References
Clark, S.H., Huppi, K., Ruezinsky, D., Staudt, L., Gerhard, W., & Weigert, M. (1985). Inter- and intraclonal diversity in the antibody response to influenza hemagglutin. J. Exp. Med. 161, 687.
Crews, S., Griffin, J., Huang, H., Calame, K., & Hood, L. (1981). A single V gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell 25, 59.
Gillespie, J.H. (1983). A simple stochastic gene substitution model. Theor. Pop. Biol. 23, 202.
Gillespie, J.H. (1984). Molecular evolution over the mutational landscape. Evolution 38, 1116.
Kauffman, S. and Weinberger, E. (1989) The NK Model of rugged fitness landscapes and its application to the maturation of the immune response. Journal of Theoretical Biology, 141(2): 211-245
Tonegawa, S. (1983). Somatic generation of antibody diversity. Nature 302, 575.

Thank you for the well-referenced and very detailed answer.  I did try to look this up myself but kept getting creationist websites, so I was hoping you might answer :)

@dd3 no problem! It was a fun question and got me to think more carefully about the micro/macro distinction and actually write something down. I might end up making a blog post out of this later, so thanks for that! :D