evolution - From which ancestor species did humans inherit orgasm?

Let's assume that pleasure from sexual intercourse might be indicative of some sort of orgasm. Then this would suggest that any evidence of autoerotic behaviour would point to the existence of orgasm, or certanly physical pleasure.

I found this quotation on the Wikipedia page for Animal sexual behavior, amongst a lot of information about mammals :

Many birds masturbate by mounting and copulating with tufts of grass, leaves or mounds of earth...

apparently from Bruce Bagemihl: Biological Exuberance: Animal Homosexuality and Natural Diversity. St. Martin's Press, 1999. ISBN 0-312-19239-8

If this is taken to imply that the last common ancestor of birds and mammals experienced this pleasure then we have got fairly deep into evolutionary history, although not as far as fish.

genetics - Mapping a mutation to known SNP, 3' UTR, miR

I've parsed out a very large TCGA cancer ssm (single mutation file) file to give me the essential information.

The ssm is in the following format:

['Gene name', 'Ensembl Gene ID', 'Chromosome', 'Chromosome start', 'Cancer Type']
['NTRK1', 'ENSG00000198400', '1','156849827', 'Prostate Adenocarcinoma (TCGA, US)']

From there I would like to grab each mutation and :

1. Map the chromosomal position to a known SNP (rs something output).


2. See if this snp is found in a 3'UTR


3. See if this snp is found in a miRNA


4. Missense or sense mutation


5. Any relevant genbank etc.. ids

I'd like to do this Python (I think BioPython is suited for this) for downstream applications.

biochemistry - During starvation, does the human body do anything to prioritize which organs receive nutrients?

The glycogen in the liver begins providing blood glucose. Muscle glycogen is used as fuel by the muscles, fat cells (adipose tissue) release fatty acids to manufacture ketone bodies in the liver and to be used by the brain as fuel, and body proteins are converted to glucose.

In short, the body's metabolism shifts to catabolic reactions.

If this continues for too long, you begin to see effects of starvation:

• Inadequate tear production


• Enlarged/tender liver


• Muscle atrophy


• Rashes, sores, or peeling skin

In short, deficiencies of energy, protein, iron, and zinc can really mess you up in the long term.

cell biology - Improving transformation efficiencies- induce supercoiling?

From my limited knowledge of science, I know transformation can be one of the hardest step in cloning, and that a large amount of research/trial and error has been done to improve on this step. I've heard electroporation is the most efficient technique, though I have no reference, and of course the cell, media and duration all have vital parts to play in the process.

However, I've never heard of supercoiling as an important factor. Size of the plasmid plays a large part in transformation, so intuitively it makes me think supercoiling the plasmid prior to transformation would improve the efficiency. I thought transformation was simply DNA diffusing through holes, but are parts of the plasmid required to bind/interact with the host?

Why aren't we suggested we supercoil prior to transformation? I have several thoughts but I'm just guessing:

• Is it because gyrase can disrupt the integrity of DNA?


• Or is it that it's just an expensive enzyme and the gain isn't worth it?


• Or perhaps supercoiling reduces efficiency of subsequent plasmid preps/transcription (though wouldn't the host's natural enzymes supercoil anyway?)

lab techniques - How long can I store autoclaved disposables and reagents?

Not really an answer I know, but too long for the comments...

This is still too broad a question. a well sealed, sterile plastic usually has a use by date, but can probably be used more than a year after you receive it. But these cases are not usually the issue.

Its sterile medium and chemicals, each of which needs to have their own due date. LB can be used months after autoclaving, but antibiotics break down chemically in weeks (ampicillin 1000x stocks lose their potency in a month). Even in the refrigerator Agar plates show colonies after a couple of months and dry out quickly.

So more details would be necessary and the case by case policy is the rule.

added in response to comments

Its really a matter of how well they are sealed. An autoclaved bottle will stay sterile forever, until something gets into the bottle - it depends on how well you have sealed things up and the storage conditions. For stuff sterilized in lab I would tend to use it within a couple of months. For eppendorfs we'd tend to sterilize a few hundred in a beaker and not worry about them...

Our experiments were working with purified protein were only medium sensitive to bio-contamination; they would be done in a few hours and then sterile filtered again. If you were purifying RNA for instance you would be much more paranoid I'm sure.

If you start to see contamination I would lower the use date and or improve your protocol.

Plastics that come sterilized and sealed by the manufacturer in 3-5 mil plastic bags have really long use by dates and I've used them for up to a year after we received them.

brain - How do we memorize something?

The current working theory (note this is still an open question, but there are many leads being followed):

Sensory systems receive a combination of signals from an event, which are initially bound to the hippocampus (this is called episodic memory). Then, typically during sleep, the memories are consolidated.

A simplified view is that consolidation basically consists of communication between the neocortex and the hippocampus, and the memories are thought to be "saved" in the neocortex. Thus, amnesia patients with hippocampal damage still have all their long-term memories, they just can't create new memories (because their old memories were already consolidated to neocortex).

Your neocortex has many subregions with many functions. One is the temporal lobe, where semantic memory seems to be stored. So your episodic memory may record several interactions apples and, over time, your semantic memory will be updated (as memory consolidation occurs) to "consolidate" your concept of "apple".

The temporal lobe is highly connected with the occipital lobe (where visual information is processed) and the two likely work together to identify objects using the consolidated information.

On the molecular level, how the memories are actually stored. The most well known concept is connectionism: different connection strengths between neurons carry different information. But there's also genetic expression going on, and there was recently some research on prion-like proteins contributing to memory as well as astrocytes.

Realize, of course, that a lot of this is cutting edge research... and therefore could be wrong or contain numerous oversights and simplifications.

perception - How can you test what color different people perceive?

It's impossible to be sure how another individuals brain represents the world. For all we know, they way they sense depth and up and down might be completely different. The representation of colour could be completely different. Both individuals could explain it as images, but if it were possible to move another individuals representation into another individuals brain - it's likely the other individual would experience an abstract sensation that would be difficult to compare to anything else that individual has experienced.

It could well be like having a compass attached to your body, sending nerve signals to your brain. You would not understand how to interpret it unless your brain has plenty of time to associate the stream of signals of direction with other signals such as your balance, vision and audio.

The brain is a very complex organ, and it probably starts out like a tiny, one celled blank sheet of paper. That blank sheet of paper is receiving continous streams of electronic signals from the various sensory organs of the body. Over time, synapses between your neurons will bond with other synapses, due to both of them receiving signals simultaneously. For example, if you are listening to music, you will hear various frequencies. Usually there will be a drum beat, which you will also sense as vibrations in the floor and your stomach. The neurons handling those two different signals will then bond together, so that at a later time - when you sense bass signals in the floor, but not in your stomach and by your ears - your brain will still recognize that drum beat in the floor as music. Some people might even feel like they hear the music.

The nerves are then going from the sensor to the brain in various ways and paths, and those connections are different for everybody.

Your brain will visualize stuff your way, and other people will visualize stuff their way and I believe those representations of objects and things are completely different for everybody. The representations will be compatible among different people, in such a way that physical laws are obeyed - but that is because the brain alters representations according to previous experiences.

So, knowing that it is impossible to be sure, I really do believe that everybody represents sensations completely different. They will be handled in similar regions of the brain due to physical similarities of the body, but within those regions in the brain there will be huge differences in representations.

I believe that if a human, unknowingly had a compass operated into his body at birth and connected to an arbitrary nerve, then that human would experience a heightened sense of direction that it could not explain as an adult. If another human had an identical compass attached to a completely different part of his body and connected to perhaps the nerve going from one of the ears, then that human would experience the same sense of direction.

Disclaimer; I am a computer programmer with a keen interest in virtualized intelligence - I have no education in the area of biology. :-)

botany - How to distinguish those flowers in outskirts: hawkweeds (Hieracium), hawksbeard (Crepis) and hawkbits (Leontodon)?

It's quite hard to answer this question and the best would be to follow a flora, which I'll not just copy informations from to past here.
So following are general observations subject to numerous exceptions.

Hieracium generally have lanceolate to oval leaves, not or little toothed, most hairy.

Crepis and Leontodon have generally Taraxacum-like leaves, that means, dentate to lobed.

Some Crepis have leafy stems (but some don't), while Leontodon always have their leaves concentrated to the base, forming a rosette.

[edit on 2014, october 2]

Be aware that there is another genus of the Asteraceae family which may be mistaken with the Crepis/Leontodon/Hieracium group, although it's easier to distinguish. It's the Hypochaeris genus.

Hypochaeris have few but not so homogenous species as there are within the other genera.
Hypochaeris radicata (which may be the most common species in France and wester Europe) have all its leaves basal, forming a rosette and sticking to the ground (never erected). These leaves are always lobed (neither entire, nor toothed), with erected hard hairs covering there upper faces.
Hypochaeris maculata may be mistaken with some Hieracium : it have hairy smooth entire leaves wich are (all or mostly?) basal forming a rosette.

[Addition on August, the 5, 2014]

Also Leontodon and Hypochaeris have hollow stem just below the capitulum(1). When you press the stem just below the capitulum, you fell it flattens under your finger, and if you use the nail to make an incision in the stem, you will see it is hollow like a pipe.

NB : Taraxacum also have hollow stems but they are fully hollow (from the base up to the capitulum), while Leontodon just have the upper part of the stem which is hollow.

Leontodon are almost always monocephal, that means, the stems are not branched : they have only one capitulum per stem, while Crepis and Hieracium and Hypochaeris mostly (if not always) have branched stems carrying several capitula.

(1) the capitulum is the type of inflorescence in the Asteraceae family. It's also called "head" (and actually, "capitulum" is the latin word for head).

You may like to have a look at this page [in french] presenting some common yellow and ligulate weeds from the Asteraceae family to get some illustrations of what I explained here.

molecular biology - Problem on finding sequence of Taq polymerase

According to the paper here "Taq polymerase" is the DNA polymerase I from Thermus aquaticus. (Incidentally the paper has the complete sequence of the gene in question.)

You can find a protein sequence entry at NCBI here. This shows the sequence of amino acids in the protein, not the DNA sequence of the gene. Several lines from the top you will see:

DBSOURCE locus TTHDNAP accession D32013.1

with the last word highlighted as a link. Follow that link to the DNA sequence. That entry includes the line:

CDS 1..2499

which tells you that the initiator ATG of the gene is right at the start of the sequence shown, but that the 3026 bp sequence includes a lot of downstream DNA. If you click on CDS on that line it will highlight the coding sequence in the DNA.

A very cursory comparison of this sequence with the one in the paper that I linked to suggests that this is the same gene.

human biology - In theory, would it be possible to create an injection of Vitamins, Minerals, sugars etc so that eating was no longer necessary?

I am wondering, out of pure curiosity, whether with current medical & biological science, (or indeed with accepted probable future developments in those areas), in theory, would it be possible to create an injection of vitamins, minerals, sugars etc so that eating was no longer necessary, and in fact, an average life with average energy usage could be continued?

I am not a biological professional nor academic, however I thought this was closest to the mark. If there is somewhere more appropriate please direct me, and I shall delete the question and post it there.

Also, if no, would there be certain parts that you couldn't replicate in an injection or something of the like?

NB: This doesn't have to be an injection, any simple method of ingesting or attaining everything the body needs. This could be a pill, or anything. I simply used an injection as an example.

Thank-you very much.

Edit:
Having found this question,
Has there ever been an attempt to create nutritionally tailored food for adult human consumption?
I would like clarify. This has given me a lot of information, however, I am looking for any method APART from food. Thanks.

gene expression - How can a continuous RNA be transcribed in the lac operon?

RNA Pol doesn't worry about stop codons. Transcription termination can occur through the formation of a hairpin in the new RNA sequence, or through the action of Rho proteins. A lot of the time prokaryotes have polycistronic mRNAs, that is, mRNAs with multiple protein coding regions. The stop codons are detected during translation, so you will often have all three lac proteins being translated at once off of the same mRNA.

Here's a nice section on transcription termination, or look up Rho-independent or Rho-dependent transcription termination for more info.

ecology - What type of biome is this?

Well, first of all 812mm is a pretty precise value to be preceded by the word "about". "Mildly hot", on the other hand, is too vague a term for your question to be answerable. If you update your question with better parameters, you may get more helpful answers.

In any case, according to this page, a tropical savanna has mean monthly temperatures at or above 64°F (~18°C), which may or may not qualify as "mildly hot" by your standards, and annual precipitation averages between 30 and 50 inches which means between 762mm and 1270mm.

So, I what you are describing could be a tropical savanna, but as I said before, I can't tell unless you update your question with more information. Have a look at this site, it may be of help.

species identification - Strange looking mushroom found in a dead tree

I'm trying to identify this mushroom my sister found at her campus' lawn. It is brown, looks somewhat like a turtle or a brain and is growing inside of a dead tree trunk. Geographically the campus is in Haifa, Israel in case that helps. Any ideas?

Images:

human biology - What is the molecular basis of hangovers?

First, the hormonal and hemodynamic changes seen in hangover are distinct from those seen in alcohol withdrawal, so the advice to drink more is not good, even if some symptoms are in fact improved. See tables 2/3 in the cited review.

It appears the molecular mechanism of veisalgia (HA, a new word) is not well known.

1. acetaldehyde Part of it may be attributed to acetaldehyde but there is clearly more to it. The liver enzyme alcohol dehydrogenase 1 (ADH1) produces acetaldehyde from ethanol, and aldehyde dehydrogenase 2 (ALDH2) makes acetate from that, so the aldehyde does not exist for a long time, and is rather responsible for short-term illnesses.

2. ADH and diuresis

Hangover severity is proportional to antidiuretic hormone
concentration (46). Alcohol inhibits the effect of antidiuretic
hormone on the kidneys, thereby inducing diuresis that is out of
proportion to the volume of fluid ingested. As blood alcohol
concentration decreases and dehydration persists, the serum level of
antidiuretic hormone increases, maintaining water retention in
dehydrated patients with hangover. In our clinical experience,
hydration attenuates but does not completely relieve hangover
symptoms.

3. cytokines

The constellation of hangover symptoms (nausea, headache, diarrhea)
resembles that seen in conditions related to dysregulated cytokine
pathways (for example, in viral infections and after administration of
interferon-alpha). Alcohol alters cytokine production through a
thromboxane pathway. Levels of thromboxane B2 are elevated during
experimentally induced alcohol hangover (42), and the administration
of tolfenamic acid, a prostaglandin inhibitor, at the time of alcohol
consumption has a small prophylactic effect in reducing hangover
severity (9).

4. further substances

Congeners, the byproducts of individual alcohol preparations (which
are found primarily in brandy, wine, tequila, whiskey, and other dark
liquors), increase the frequency and severity of hangover (24, 39,
40). Clear liquors, such as rum, vodka, and gin, tend to cause
hangover less frequently.

So there are factors that aren't even identified exactly, and these could fit the mixing of drinks observation.

There are several reviews out there, just search for hangover at Google Scholar.

Wiese, Jeffrey G., Michael G. Shlipak, and Warren S. Browner. "The alcohol hangover." Ann Intern Med 132.11 (2000): 897-902. Online at http://dionysus.psych.wisc.edu/lit/topics/Hangover/WieseJ2000a.pdf

virus - What decides whether a lysogenic cycle or a lytic cycle will take place?

It depends on a few factors, such as how many phages infected the cell, whether or not the cell is in good growth conditions, and so on. If the cell is in stress or has low amounts of nutrients, the lysogenic pathway is typically activated.

The underlying mechanism has to do with a protein cascade involving either the cro or cI protein that is encoded by the virus. The cI protein is a repressor, and it will prevent the lytic genes from being transcribed. By default the virus will transcribe the lytic genes, so they must be repressed for lysogeny to occur. Similarly, cro is also a transcriptional repressor. The two proteins work in opposition to each other. cro binds to an operator, oR3, that is involved in repressing cI, which may prevent cI from being expressed and thus preventing it from repressing lytic genes (however the importance of this is debatable because if you replace oR3, the cell can apparently still lyse).

There are numerous other proteins, such as N and Q, that are involved. The N protein has to be transcribed by the polymerase ‘anti-terminating’, or reading through a termination signal. This will happen more frequently when the protein RNase III is present at high concentrations. The N protein is a lytic regulator. Thus, when there are high amounts of RNase III there will be more N expressed which leads to the lytic cycle. RNase III is not a viral protein. It is a host protein and the host expresses more of it when nutrients are abundant. This is how the virus is able to ‘sense’ if nutrients are high enough to enter the lytic cycle.

The whole system is way more complicated but this is it in a nutshell.

http://www.annualreviews.org/doi/full/10.1146/annurev.genet.39.073003.113656

genetics - Precursor miRNA and a mature miRNA

precursor miRNA is ~70mer RNA with a stem loop structure. It is cleaved by dicer to generate one or two mature miRNAs (from one or both the 'arms' of the stem ; called 3p and 5p which are ~22nt long). Refer to this review. (It is an old one and some facts might have changed, but the basics are there.)

Yes, there can be different precursors giving rise to same mature form. There are a few cases like that (check for entries like mir-x-y [where y can be 1,2,3,...], in miRbase).

Usually pre-miRNA is shortlived and is immediately converted to mature form. Therefore, in small RNAseq data, most miRNA reads (more than 90% [at least that's what I get]) come from mature form (pre reads would be longer [after adapter removal] and will contain sequences not retained in mature form). Most algorithms select for the mature reads.

It is difficult to determine which precursor gave rise to a certain mature miRNA, using an RNAseq data. The usual practice is to assign the average read count to each locus. E.g., for a mature form that has 3 precursors, each precursor is assigned 1/3 of the total mature reads. However, in most RNAseq experiments, the objective is to obtain the mature miRNA profile and which precursor gives rise to it becomes immaterial.

zoology - Why does ostrich meat look and taste more like beef than chicken?

There is a very plausible explanation here.

Basically, it explains that meat colour is due to the protein myoglobin (a haem-containing protein related to haemoglobin). There are two types of skeletal muscle: fast-twitch and slow-twitch (Wikipedia). Slow-twitch muscle is red muscle because it contains lots of myoglobin. Fast-twitch muscle is white muscle, containing less myoglobin. The Wikipedia link explains a little more about these muscle types and their functional differences. Evidently the lifestyle of the ostrich dictates that it have more fast-twitch muscle, and so it has red meat. It isn't unique in this: duck and goose are classified as red meat too.

Incidentally the role of myoglobin is to improve the rate of diffusion of oxygen from the haemoglobin in the capillaries through the cytoplasm of the myocytes to the mitochondria. It has also been suggested that it acts as an oxygen storage mechanism in diving mammals which have very high levels of myoglobin in their muscles, but this storage function is unlikely to be important in other mammals, despite what you may read in textbooks.

What are the methods for infering genetic interactions?

BioGRID is an interaction database, and they catalogue interactions by (among other things) the class of experiment that discovered them. See http://wiki.thebiogrid.org/doku.php/experimental_systems#genetic_interactions

Other than that, you should look at recent reviews and publications, but you will easily get lost unless you figure out some important particulars, like:

• What species? Yeast, worm, human, cell line?


• What sort of interaction? Synthetic lethality? Complicated, fancy epistasis?


• How much? Genome-wide? 2-3 genes?

zoology - Do fish break a water molecule to absorb oxygen?

The answer to this, I reckon, is that they don't.

They use molecular oxygen (O₂) dissolved in the water for respiration, where it acts as a terminal electron acceptor, just as we use molecular oxygen in the air for respiration. We can speak of the water as being oxygenated.

Water is split in photosynthesis, where reducing equivalents from water are used to reduce NADP⁺ (giving NADPH).

One of the great discoveries of biology, IMO, is that the oxygen formed in green-plant photosynthesis comes from water, not CO₂.

Tricarboxylic Acid Cycle (Krebs Cycle) Rant

Despite claims to the contrary, most infamously by Racker (1976, pp 28 - 29) and Wieser (1980), but also by Madeira (1988) and Mego (1986) for example, water is not split in the tricarboxylic acid cycle (Krebs Cycle). Banfalvi (1991) also sails pretty close to the wind on this one.

That is, reducing equivalents from water are not passed down the respiratory chain, or in any way used to make ATP, or are in any way a 'source' of free energy. Such claims, IMO, are nonsense.

The definitive answers to the Wieser (1980) paper are given by Atkinson (1981) and Herreros & Garcia-Sancho (1981). Both of these articles are models of clarity, and categorically refute the claims of Wieser (1980). Nevertheless, as shown by the references above, the controversy surfaces periodically.

The only sources of reducing equivalents in the TCA cycle are carbon compounds, and the only electrons passed down the respiratory chain are those 'held' in C-H and C-C bonds (Herreros & Garcia-Sancho, 1981). An ionization is neither an oxidation nor a reduction (see Atkinson, 1981) and neither is a hydration. Adding water to (say) a double bond does not make the compound any more oxidized or reduced. As far as oxygen and electrons are concerned, and to generalize from a biological point of view, what is has it holds - except in photosynthesis.

As you may have guessed, the splitting of the water in the TCA cycle is a pet rant of mine. Thanks for the opportunity of airing my views!

Edit 3

Found this one when searching Google (Brière et al, 2006). In an invited review for the American Journal of Physiology (Cell Physiology) at that!

Finally, TCA cycle should also be considered as a water-splitting process generating oxygen for acetyl-CoA oxidation [they quote Wieser]

So now the TCA cycle is producing oxygen from water. Wonders will never cease!

(end edit)

(end rant)

Edit 2

As rwst and Alan Boyd have drawn attention to, the concentration of dissolved oxygen in water is all important, and varies with (for example) temperature.

In air-saturated buffer at 25^oC the concentration of oxygen (O₂ molecules) is about 0.24 mM (0.24 μmoles/ml, or about 0.474 μg-atoms of oxygen per ml). [Chappell (1964)]. This figure decreases with increasing temperature.

Great question, BTW.

References

(Apologies for the incomplete Atkinson and Herreros & Garcia-Sancho references. I have a photocopy of these papers but have been unable to trace the full source. They are both in the 'Letters to the Editor' section of the February 1981 edition of Trends in Biochemical Sciences. They do not appear to be in Pubmed, or anywhere else on-line. Has anyone ever seen these references quoted, or can provide me with a full source?. I'll update if I find anything)

• Atkinson, D.E. (1981) TCA Cycle Confusion. Trends in Biochemical Sciences (February 1981 edition; full ref to follow)




• Banfalvi,G. (1991) Conversion of Oxidative Energy to Reductive Power in the Citrate Cycle. Biochemical Education, 19, 24 - 26 [see here] (pdf apparently free to all)




• Brière, J.J., Favier, J, Gimenez-Roqueplo, A.P. & Rustin, P (2006) Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation. Am J Physiol Cell Physiol, 291, C1114-20. [Pubmed] [pdf]




• Chappell (1964) The oxidation of citrate, isocitrate and cis-aconitate by isolated mitochondria. Biochem J., 90, 225-237.[pubmed] [pdf]




• Herreros, B. & Garcia-Sancho, J. (1981) TCA Cycle Confusion. Trends in Biochemical Sciences (February 1981 edition; full ref to follow)




• Madeira, V.M.C. (1988) Stoichiometry of Reducing Equivalents and Splitting
  of Water in the Citric Acid Cycle. Biochemical Education 16, 94 - 96 [pdf] (apparently free to all.)




• Mego, J.L. (1986) The Role of Water in Glycolysis Biochemical Education, 14, 130 - 131. (see here)




• Racker, E. (1976) A New Look at Mechanisms in Bioenergetics. Academic Press, New York.




• Wieser (1980) Textbook Errrors: The splitting of water by the tricarboxylic acid cycle. Textbook error or textbook omission? Trends in Biochemical Sciences, 5 (Issue 11), 284. [see here]. [pdf], apparently free to all.

What is a good Microbiology atlas for Bacteriology as online version?

Not sure what you are exactly looking for? If you change the question or comment I can update my answer...

NCBI's taxonomy site has a listing of bacteria. Encyclopedia of life is also great.

Then there's UCSC's microbial genome browser.

Biocyc is great reference for bacterial genes. to get into E coli, which is the model bacterium there's Port Eco featuring 130 E coli genomes.

Am Soc Micro has an excellent E coli/ Salmonella site based on their classic reference - you have to pay for access though.

evolution - Randomness in living systems

In an evolution mutations are often random and lead to differences in phenotype that can be adaptive under certain pressures. A lot of times mutation is a random process, but here are three cases I can think of off of the top of my head where I would say the organism is 'trying' to do it:

HIV is a retrovirus, which means in its viral form its genome is single stranded RNA, which is then converted into double stranded DNA within the host. That conversion is carried out by a virally encoded reverse transcriptase. This enzyme has a much higher error rate when making the RNA into DNA because it cannot proofread like our DNA polymerases. This means that HIV mutates incredibly fast. Many of these mutants are not very fit, but since there is so much selective pressure against staying the same due to attack from the immune system, some mutants will be much more fit if they can avoid that attack. Its a numbers game, and by making lots of random mutants HIV is very good at it.

A related, but different case is found in the diversity generating retroelements of certain bacteriophages. These are double stranded DNA viruses that infect bacteria. The bacteria these viruses infect could mutate to escape the viruses by losing a certain receptor that the virus binds to. It was observed however that the the virus would mutate incredibly quickly to bind to a different receptor, a lot faster than would be expected for a DNA virus. Also, it was found that these viruses contained reverse transcriptases, which is bizarre, since there is no reverse transcription step in a dsDNA viral life-cycle (so we thought). To make a long story short, this virus will transcribe the DNA that codes for its binding proteins into RNA, then use its reverse transcriptase to turn that RNA BACK into DNA, but uses a sophisticated targeting strategy so that it only mutates the region that is used for binding to the bacteria. It will only mutate adenine residues, leaving the C's, T's and G's alone. This is a much more clever system than HIV, because this virus uses site-specific mutations on its binding feet, and doesn't mutate its core proteins, the mutation of which would probably just lead to viruses that couldnt replicate. Here a reference for the interested: http://www.nature.com/nature/journal/v431/n7007/abs/nature02833.html

Just so you dont think this is reserved to viruses, we do this as well with our immune system. In order to recognize antigens in attacking pathogens, our immune cells have two methods for making diverse, random, receptors. First is V(D)J recombination, where the multiple diverse copies of the V, D and J regions of antibodies and receptors are combined at random to make one set. Wiki says theres 3x10^11 possible combinations here. After that, theres also somatic hypermutation during the proliferation of B cells. In this process, the random mutation rate is hugely increased in the region of the B cell receptor gene, specifically for making slightly different versions of the already 'OK' receptor to make it a great receptor.

General theme: raising your mutation rate, either across the board(HIV) or specifically (DGRE and SHM) is a good way to intentionally add randomness for a beneficial purpose (to the extent that you can attribute 'intent' to a viral particle).

What would happen if you slowly crushed a live brain?

It depends on what part of the brain you are "crushing."

When we do brain surgery we often do exactly what you describe. That is, we open the skull and often remove part of the brain. However, in our case usually the part we are removing is diseased or malfunctioning to begin with.

There are areas of the brain that are known as eloquent and those that are considered "not eloquent." This is an overly simplistic but educationally instructive way to classify things. Eloquent brain regions are those regions that when disturbed will cause an obvious and devastating neurological injury. Examples are primary motor/sensory cortex, broca's area, wernicke's area etc. Noneloquent areas are those that can be damaged or resected and the sequelae are less obvious. For example, you can remove quite a bit of frontal lobe before you notice a problem. However, an appropriate and sensitive behavioral test/instrument may still pick up the deficit.

Damage to the brainstem and thalamus is more devastating and even small injury to this area can cause major deficits and changes in the level of consciousness. Injury to different levels of the brainstem produces different level of consciousness. Again, it really depends on the precise location and extent of injury and there is no single answer to your question.

As the brain itself has no pain receptors the patient would not really feel much pain even if you caused major deficits. However, again it depends on the location. You could theoretically irritate thalamic sensory regions and cause chronic pain syndromes but your lesion would have to be pretty precise.

human biology - Ill effects of urea and NH₃ on metabolism

The denaturing effect of Urea is mostly at very high concentrations. (~Molar levels)!

Physiologically, urea, a product of the breakdown of retired amino acids, will build up rather quickly if it weren't secreted in the urine. Looking into this, it doesn't seem as there is a clear understanding of why this causes a disease, though the buildup of a waste product definitely is a unifying concept.

Uremia - kidney failure - causes a build up of urea in the blood as the kidney eliminates urea from the blood into the bladder. The specific effects of Urea on cell metabolism are probably numerous as the symptoms: anorexia and lethargy, and late symptoms can include decreased mental acuity and coma. Other symptoms include fatigue, nausea, vomiting, cold, bone pain, itch, shortness of breath, and seizures.

Being a metabolic waste product, it certainly would interfere with and inhibit any enzyme that produced urea - the Urea cycle in particular. Its clear that uremia is ultimately associated with cell death, oxidative stress, some cell signalling and proliferation.

I'm just googling around here, but I don't think there is any one single answer as to what goes wrong when the cells are exposed to too much urea.

evolution - Why don't flies avoid the motorway?

I also got an answer via email that I think is worth sharing.

Mrs Price:

I'm not answering officially as I’m probably wrong but…

The main point mentioned is that because flies have such a short
lifespan, so they should evolve faster than elephants or other slow
growing species. While this is true, and there are many examples of r
(ruderal) species evolving rapidly* evolution is not a predictable or
sensible process, and there are many other factors that contribute to
evolution other than a short generation time.

One main question to consider is… how many flies are there? And how
much of that population is affected by the road fatalities? Whilst
there are over 23,000 insect species in the UK, your question
specifically concerned flies so… An average fly lives for around 35
days and can lay roughly 750 eggs in her lifetime, so fly numbers are
bloody huge! Although a small proportion of flies may be killed by a
car, the proportion will be so small as to make no impact to the
overall population; therefore the driver for evolution is not strong
enough to have an impact on the species as a whole.

Another reason why motorway deaths may not have a significant impact
on the fly population is due to when the flies breed. Even if
motorways killed 90% of all flies, the fact that many insects breed
hours after hatching from their egg means that the population is still
able to reproduce. Killing something after it has bred is again not a
driver for evolution, it would have to be a very strong force that
kills a high number of individuals before they have chance to breed.

In summary, motorway deaths affect such a small amount of individuals
that it does not have a significant impact upon their populations, I
imagine that many many more of them get killed in spider webs each
day, however the idiots are still flying into those too!

Hope this helps :)

• *The peppered moth changed colour from mottled to black due to the
  population from the industrial revolution and then to white once the
  air pollution had cleared as the ones that stood out had such a high
  predation rate




• *in the last 50 years some fish species have evolved a much smaller
  body size due to the advantage of escaping through a net and being
  able to carry on breeding

evolution - Why does sexual selection evolve beautiful features?

I think I can expand on the answer by @boo2060.

The evolution of female mate choice depends on females achieving higher fitness by choosing certain males over others. At the broadest scale, there are two mechanisms by which this can occur, direct benefits, and indirect benefits.

Direct benefits
These are material things that (surprise) directly benefit the female. This might be the provision of food by the preferred male, access to a good territory or shelter that is under the control of the preferred male, protection by the preferred male, that sort of thing. Females will accordingly favour male traits that advertise potential direct benefits. These might include male size/condition/colouration, or even built structures like those of the bowerbirds. Basically, these traits show that the male knows how to look after himself, and by extension, he knows how to look after her (as males in good condition generally inhabit the best habitats and will offer the best protection and parenting).

Indirect benefits
These don't do much for the female, but they increase the genetic quality (and thus potential fitness) of her offspring. This is a much more complicated area of mate choice, and can be split into a bunch of (non-exclusive) hypotheses (below). And of course, attractive males may well offer both direct and indirect benefits.

Sensory bias: Males may, by chance, possess a trait that holds intrinsic appeal for a female. The best explanation might be that it mimics the colour or shape of a food source (e.g. fruit) that the animal eats, and thus the animal has pre-evolved preference for that colour or shape (e.g. red patches). From that point, males with more of that trait, whatever it is, will tend to be more attractive, for no rational reason. This hypothesis is sound, but is currently lacking good empirical evidence.

Fisherian sexy sons: This can in fact lead on from an initial sensory bias. Females may choose males that they find 'sexy', because their offspring will also be sexy, and thus be successfull in reproduction. This can lead to 'runaway' selection for sexier and sexier sons, at considerable survival cost for males. In this case, natural selection and sexual selection work in opposing directions.

Indicator mechanisms: This is the handicap principle or 'good genes' principle. If a structure is costly to produce or maintain, or increases the risk of predation, and yet the male possessing it is still alive, he must have good genes to have withstood such a handicap. It may also advertise that the male is not infested with parasites. The extravagant plumes of birds may be largely explained by this one, but also sexy sons and sensory bias.

Genetic compatibility: Individuals seek partners that are genetically compatible. A certain proportion of the fitness of the offspring depends on the specific combination of genes (i.e. it's not additive), and individuals that can signal or detect signals in such a way that they can choose compatible partners will have an evolutionary advantage. The best example is scent (e.g. preference for dissimilar MHC immune genes - see the human t-shirt experiment).

These mechanisms are well known in theory, but not always well-supported by evidence (yet). This is probably the best reference.

neuroscience - Least painful way to die

The American Veterinary Medical Association (AVMA) has thought about humane methods of euthanasia quite a bit and has an extensive (102 p. PDF) set of guidelines for the euthanasia of animals. The guidelines are not the same for all animals. Some examples:

Companion animals (e.g., dogs and cats): injected barbiturates are recommended

Laboratory animals (e.g., mice and rats): injected barbiturates are acceptable as are inhaled agents (isoflurane, carbon dioxide).

As for humans, you might look into the physician assisted suicide literature. I think that these generally use a sequence of drugs. As far as natural deaths, kidney failure is supposed to not be very painful.

cell biology - Does endo- and (or) exocytosis require energy? Do they belong to active / passive transport?

Just to extend the answer from @Amory slightly, I think that the terms active and passive transport are best kept for describing transmembrane movement of molecules.

In the case of exocytosis the only transmembrane event is when a secreted protein is first inserted (usually cotranslationally) across the endoplasmic reticulum membrane. I'm not aware of any evidence that this uses more energy than that already expended during polpeptide elongation by the ribosome. At that point the secreted protein is topologically extracytoplasmic, and everything else is achieved by rounds of vesicle formation and fusion of vesicles with target membranes.

The same is true in reverse for endocytosis. Any molecule that is internalised in an endocytic vesicle is still extracytoplasmic unless some process specifically moves it across the membrane of the vesicle, or a downstream organelle such as the endosome. At that point whether the transport process was active or passive would depend upon the properties of the carrier system.

molecular biology - What is the purpose of Y-shaped adapters in Illumina sequencing?

Normally, when you need two unique adapters, say A & B, on either end of unknown insert sequences, cohesive-end ligation is difficult because the insert sequences are "unknown". So you have to do blunt-end adapter ligation, in a reaction containing Unknown Inserts + adapter A + adapter B. This can result in 3 possible versions of insert-ligated product: A-insert-A, B-insert-B and A-insert-B, among which only A-insert-B is the only desired product.

1) Ligation of A-tailed inserts with Y-adapters gives you 100% A-insert-B.

2) Lets now assign a directionality to the insert - say from base 1 to base 400. Following Y-adapter ligation, you will have 2 kinds of insert-ligated products per insert: A-Insert (1-->400)-B and A-Insert(400-->1)-B, both of which are very useful. Each will create a separate clonal cluster and you will get sequence information starting at both base 1 and base 400 of the insert, since in single-read sequencing, the instrument always sequences from Adapter A. However, to know that both these sequences belong to the same insert, one will need to do paired-end sequencing.

human biology - How do people who have lost both of their legs produce red blood cells?

Red blood cells are produced in the red marrow which...

"is found mainly in the flat bones, such as the pelvis, sternum,
cranium, ribs, vertebrae and scapulae, and in the cancellous
("spongy") material at the epiphyseal ends of long bones such as the
femur and humerus." - Wikipedia

So you are partly right; the femur is associated with red blood cell production, or Erythropoiesis to give it it's technical name, but there are other bones within the human body that also do this job. The process of erythropoiesis is stimulated when the kidneys detect low levels of oxygen in the blood stream and stimulate production of the hormone erythropoietin. Further, the role of the tibia and femur in erythropoiesis also decreases with age whereas...

"the vertebrae, sternum, pelvis and ribs, and cranial bones continue
to produce red blood cells throughout life." - again from the wiki page

So I'd suggest it is unlikely that loss of the legs would have a major impact on the production of red blood cells in adults. I imagine that with the loss of legs comes some reduction in functionality of erythropoiesis but also a lower requirement of red blood cell production (less blood capacity = less blood cells needed = less blood cells need to be produced). I can't find any studies which explore the ability or needs of amputees and non-amputees with regards to red blood cell production.

biochemistry - How are the correct tRNAs transported to the ribosome?

The only way I can imagine this happening is that all types of tRNA+amino acid reach the ribosome, bombarding the ribosome, and the ribosome will 'accept' only the one that matches what it is waiting for.

Yup, basically. This is an extremely cool figure showing the process. There are various elongation factors that aid the process, such as EF-Tu, which essentially waits until there is a good codon-anticodon match before hydrolyzing GTP and allowing the tRNA/amino acid to enter the ribosome.

This process can be particularly salient when you look at a concept such as codon-usage bias. Certain tRNAs are more common in the cell, so if a given mRNA uses codons to match those tRNA instead of matching other degenerate but less common anti-codons, translation will occur faster. This is more obvious in organisms such as E. coli where growth is paramount.

human biology - Can a person die instantaneously from internal damage to the brain?

Please consider this only as a starting point (although a lengthy one), and a race against an acute onset of tl:dr ...

A person cannot die instantaneously from internal brain damage (under everyday circumstances). The reason is the non-centralized architecture of the brain and that consciousness is a global phenomenon which underlie the activity of many brain structures.

These brain structures are themselves comprised of a cellular hierarchy, with each cell being self-sufficient for at least a time regime in the order of minutes. As such the brain underlies to some extend the study of networks and robustness thereof. The brain also maintains a scale-free organization . Actual Scale free networks in nature are known to be robust.

Instantaneous in this context means a consciously discernible difference in time, which is on the order of tens of milliseconds (See: Inspection time, mental chronometry).

Also I narrow the medical cause of death down to a intracerebral haemorrhage, systemic shock or hypoxia. I definitely leave out all (rare) CNS-immunological phenomena (e.g. explosive brain death, Immune reconstitution inflammatory syndrome related,... )

But, effects that can mimmick instantaneous brain death are very plausible.

Notably, this question can be answered despite there being no rigorous consensus model of consciousness.

---

Consider the following just as pointers, but not as qualified, thoroughly sourced information, - contrary to a paper or review ( I will gladly include your resources, or turn this post into a community wiki if demand to do so exists):

Consciousness:

The brain weighs only 2% of the human body mass, yet consumes 20% of the total energy at rest. Crucially the brain can deplete oxygen at a great rate, which is proportional to the brain activity in various regions, giving rise to indirect measurements of brain topology and images like these:

"Visualization of a DTI measurement of a human brain"-2006, 
author: Thomas Schultz, DOR: 25/09/2012

Humans have different states of consciousness which show different overall patterns of brain activity. As such the result a scientist would witness through an high-resolution fMRI/PET scanner in a stroking-individual would differ during sleep, sleep/wake transition or various levels of awareness during the days. Stroking and the effects on the brain is studied quite extensively with rats(See: rat, fMRI, stroke).

Moreover the brain activity, fine-anatomy and orchestration of brain utilization differs from individual to individual. In short the brain is what neurologists call "plastic" Neuroplasticity is the change of entire brain structures, and the brain itself from experience and physical stress/trauma (on the brain).

We are biologial enetities which have evolved to be in-sync with the planetary rotation and solar energy influx. As such brain activity changes during the day, in accordance with our circadian rythm or biorhythm, and if it weren't for artificial lightning brain activity would change over the seasons as well.

Connecting all the dots: Describing brain death in a seconds-regime comes down to which areas in an individual brain consume the most oxygen and "shut down" first, and which processes steer brain activity till organic shutdown.

Since Stackexchange has a strong programmatic background, to put it in a somewhat programmatic analogy:

The output of a memory dump and its analytic result depend on the hardware, the software and the state of the application. Unfortunately the software is spread across processors, has multiple threads and applies a genetic algorithm with dynamic recompilation.

Death Definitions:

The notion of instant death is a cultural meme (which one can witness in child's play) and is further propagated in the media. Additionally "death" is a highly political matter...
"Death" has numerous legal definitions (throughout various cultures) medical definitions and biological definitions depending on the context. Legal definitions depends on the culturally dependent legal corpus, medical definitions on the state of (pragmatic) technologies. The medical definition of human death is influenced by the legal definition. The legal definition in turn is influenced by politics.
The biological definition of death depends on the context and a threshold thereof, which in turn describes the level and and of hierarchical systems or one large system comprised out of systems such as organs. An organ is the collection of units in one structural one to serve a common purpose.

Finally to answer more accurately, a person cannot (under everyday circumstances) shutdown brain activity within the time-interval of one reaction time-unit or 'cycle', but may transition between discernible states of global brain-activity. Such states may only be measurable with functional Imaging techniques and classifiable using computer algorithms.

molecular biology - Preparation of normal DNA polymerase

This is a very ambitious project for a DIY-er. To explain why, I'm going to use the example of DNA polymerase I from E. coli.

DNA polymerase I is the most abundant DNA polymerase in the E. coli cell, but nevertheless is still only present at around 300 copies per cell

Ishihama Y et al. (2008) Protein abundance profiling of the Escherichia coli cytosol. BMC Genomics. 9:102.

This was the first DNA polymerase that was ever purified, in the laboratory of Arthur Kornberg

(Enzymatic Synthesis of Deoxyribonucleic Acid : I. PREPARATION OF SUBSTRATES AND PARTIAL PURIFICATION OF AN ENZYME FROM ESCHERICHIA COLI Lehman, MJ et al. (1958) J. Biol. Chem. 33:163-170.).

In this paper a method of purification is described that starts with 60 litres of culture. There is also this statement:

"One kilo of E. coli yields less than 10 mg of the purified enzyme."

I'm guessing that you have no experience of protein purification, so I'll just tell you that this is very discouraging: these days, with overexpression, people expect to get mg quantities of their protein from just a few grams of bacterial cells.

This is a clear illustration of why it is pretty much unthinkable for you to set out to purify an enzyme like this using small-scale methods, and explains why techniques of overexpression and the use of affinity tags have revolutionised protein purification.

And it gets worse: even if you did manage to purify some DNA polymerase I from a bacterial source you would find that it is actually not very good at making DNA. This is because as well as extending primers in a 5'>3' direction, it is is very good at degrading DNA in the same direction. In other words as the enzyme moves along a template molecule, copying it, it will degrade any existing DNA that it meets "ahead" of its direction of travel. This is why the most commonly-used form of this enzyme in research is the "Klenow fragment", a fragment of the polymerase that lacks the 5'>3' exonuclease activity. This fragment was originally made by treating DNA polymerase I with the protease subtilisin, but it is now expressed from an engineered polA gene. Klenow fragment polymerase was used in the original PCR experiments (it had to be added afresh at every cycle).

I don't know how much money you have to spend on your projects, but in fact these enzymes can now be bought relatively cheaply. I don't think that you can expect to make them for yourself, without this becoming the actual project.

Finally, if you can get hold of a strain of E. coli with an expression plasmid for Taq polymerase then you really could make your own very easily - I've done this myself (but I no longer have the strain) and the heat stability of the enzyme makes the purification trivial. It would be much easier to use your own Taq with a heated water bath than to try to make DNA polymerase I. But obviously it depends upon what you are trying to do: Taq polymerase may be unsuitable for other reasons.

biochemistry - PEG-silane treatment: why incubate for 18 hours at 60 degrees Celsius?

The binding of proteins (and cells) to glass (or silicon) surfaces can be prevented by coating the glass with polyethylene glycol (PEG) groups. PEG-silane is a reagent used to create this coating.

PEG-silane (the image shows a methoxy- version) (image taken from here; no connection) will coat glass surfaces because the silane portion (right hand end of the structure shown) will react with -OH groups on the glass surface.

I can't help with the part of the question about time and temperature of incubation, but it seems longer and hotter than protocols I have seen. Perhaps the indium tin oxide (ITO) coating on the slides has something to do with it?

nutrition - Is the amount of phosphoric acid added to colas enough to disrupt the function of the kidney over the long term?

The phosphoric acid in cola will contribute to dietary intake of phosphate. I may be missing something, but, since the transporter functions to reabsorb phosphate that has been filtered out at the glomerulus, excess phosphate will spill over into the urine.

According to Wikipedia the RDA for phosphorus is 700 mg and the tolerable upper intake level is 4000 mg. Coca cola contains 17 mg phosphorus (as phosphate) 100 ml^-1 (which is 340 mg in 2 L)

According to this source,

in the United States, an average person drinks 412 8-ounce drinks — or 3296 ounces — of Coke per year.

This works out at 9 oz per day = 266 ml = 45 mg phosphorus

For comparison (from here):

• white flour contains 595 mg 100 g^-1


• one boiled egg contains 220 mg


• canned salmon contains 240 mg 100 g^-1

endocrinology - Why is epinephrine not part of the somatic nervous system?

You are confusing different functional systems. Epinephrine released by the adrenal medulla circulates in the blood and indeed dilates the blood vessels in skeletal muscle. This ensures that enough oxygen and nutrients are available for the muscles to perform in a fight/flight response.

The somatic nervous system utilises acetylcholine not as a hormone but as a neurotransmitter. It is not released into the blood but only into the tiny (about 10nm wide) gap (synapse) between the nerve cell's axon terminal and the next nerve cell or muscle cell respectively.

This release by the somatic nerve cells causes an electrical potential in the muscle which makes it contract.

In summary:

The somatic nervous system controls the muscles because it stimulates the contraction which makes e.g. your arm move. Epinephrine released into the blood by the adrenal medulla serves to ensure the muscles have the blood supply they need in a stress response (e.g. a dangerous situation).

Along with muscular blood vessel dilation, epinephrine in the blood for example also stimulates the heart to beat faster and stronger, and dampens down mechanisms involved in digestion - essentially it does everything necessary to allow a quick escape or a strong fight.

reproduction - Cytoplasmic determinants - protostomes and deuterostomes

The two distinct types you have mentioned in your question (determinate/indeterminate cleavage) are actually called autonomous specification and conditional specification, respectively.

In the case of the former one, if we were to remove a blastomere, it would still produce the previously determined type of cells, while in the case of conditional specification the cells, which are going to be produced, depend entirely on the neighbouring ones. The latter's ability to alter their fate is called regulation.

As for answering your questions, cytoplasmic determinants are spread unevenly in deuterostomes as well, as otherwise no axis could be developed.

You might be interested about this answer as well.

I've used the following book as source: Gilbert, S. (2000). Developmental Biology [ online version ]

genetics - What is the frequency of double-hets between parent and child?

Say both parent and child are genotyped for all SNPs. In this setup we are only looking at variant positions between one parent and child - so neither parent nor child are homozygous reference (no AA/AA) in the millions of positions we are studying.

Assume all variants are biallelic and there is no de novo mutation (no AA/BB or BB/AA)

P    C
AA   AB
AB   AA
AB   AB
AB   BB
BB   AB
BB   BB

What is the fraction of AB/AB among these possibilites?

We are looking at all positions in the genome so the minor allele frequency (MAF) of B allele varies. You can choose whatever B frequency you like.

Atomic force microscopy: depth penetration?

Taken right from the Wiki page you linked to:

AFM only images the surface of a specimen, to a maximum depth of 10-20 µm and a maximum scan area of 150 µm x 150 µm. Compared with scanning electron microscopy, SEM has a much larger depth of penetration and scanning area (~1 order of magnitude greater). AFM is also a much slower scanning method.

senescence - Telomere elongation methods?

What sort of telomere elongation methods are there currently?

Would this stop aging? (edit: No, probably)

I couldn't turn up anything good on google. I was thinking that maybe you could sequence the telomeres, trim them all at a certain point, and then engineer a polymerase molecule to extend from that same point. Is this how it's done?

What is the difference between vegetable and fruit?

A true fruit is a ripened ovary that usually starts ripening when it is fertilized. And vegetable is any vegetative part of the plant which is edible and contains stored food probably in the form of starch.
These definitions are not exact as there are a lot of fruits which are fruits but do not strictly follow the given definition. See Syconus, Composite fruits, Sorosis.etc

Classification is based on several different criteria, for example the mode of reproduction, arrangement and design of flowering parts and flowers and also on the basis of habitat and habit.

biochemistry - Is breathing in deodorant fumes dangerous for my brain?

You can definitely absorb alcohols by breathing them in. But doing do is far less efficient than drinking alcohol, so you don't have anything to worry about on that front.

To address your concern we have to answer two questions: how much alcohol is transfered per unit time and is there a local dosing effect due to proximity to the blood brain barrier.

It is probably pretty obvious that while alcohol evaporates rapidly compared to water, it still takes quite awhile. Imagine trying to inhale a glass of whiskey. You would get a serious headache but 30 minutes in you would still have an almost full glass of whiskey and no alcohol buzz. For an amusing anecdote relating how hard it is to get drunk off of inhaling even from a machine designed for it, see here

As to the second point - Fortunately, the blood brain barrier is a two way street for alcohol, which means that you can't get drunk in your brain if you don't have high levels of alcohol in your bloodstream. The two would dialyze into a reasonably balanced equilibrium.

bioinformatics - 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.

human biology - Is the eyes' movement discrete?

When tired and it was dark, I noticed that if I focused on a dim light source and moved my eyes fairly rapidly sideways, the resulting images that lingered for a short while were not smoothly blurred together, but were discrete.

I assume this is not due to the brain's inability to process the data fast enough or the retinas not repairing fast enough when light breaks part of them down, so I am lead to the conclusion that eyes (if not generally, sometimes) move in very small sudden jolts rather than smoothly.

Is this correct? What is the reason for this (is it due to the eye muscles being unable to sustain motion for a long time, or something to do with the mechanics of the eye)? Was this result anomalous?

human biology - Is diabetes mellitus a sex-linked disease?

Is either of them a sex linked disease? Can either one be inherited? My book says, "this disease is transmitted as a recessive genetic characteristic." What does this mean?

Neither are sex-linked. Type 1 can be directly inherited (in a non-Mendelian fashion), but Type 2 genetic factors mostly increase risks. "Recessive genetic traits" are traits that only express themselves when ONLY the recessive alleles are present in the organism (a dominant allele, if present, will 'overpower' recessive one).

Longer info:

Diabetes mellitus Type 1 (Juvenile Diabetes) is inherited, but it is autosomal with complex dominant/recessive rules:

Type 1 diabetes is a polygenic disease, meaning many different genes contribute to its onset. Depending on locus or combination of loci, it can be dominant, recessive, or somewhere in between.

That results in some interesting, albeit complex, expressions:

The risk of a child developing type 1 diabetes is about 10% if the father has it, about 10% if a sibling has it, about 4% if the mother has type 1 diabetes and was aged 25 or younger when the child was born, and about 1% if the mother was over 25 years old when the child was born.

Diabetes mellitus Type 2 does have genetic components, but the vast majority merely increase the risk of developing Type 2 Diabetes. Environmental factors play a large role in Type 2.

Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60-80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.

taxonomy - An unexpected mushroom in my garden

My grandma is a great fan of mushrooms and knows quite a lot about them. About 10 years ago, she started throwing out mushroom remnants in one special place, in order to grow her own mushrooms. In fact, for last three years we found some parasol mushrooms (Macrolepiota procera).

Today she found something, that nobody at home can classify. From what I searched, it might be Cortinarius privignoides, but it is marked as almost extinct here in Poland, so I doubt this classification. Maybe you have seen this or know what it really is:

The hat is light brown with faint violet shades, the leg on the outside is partly violet too, but the inside is all white.

Some more photos:

All three

The gills are lighter brown, also with a violet tone

The cut through the leg

The cut through the hat

At my parents' house I found one more mushroom atlas, and a new candidate: Cortinarius traganus, but one thing is not right - the ones that I have don't have a smell and gassy webcap should smell and taste bad.

neuroscience - Which Receptors are Involved in the antidepressant effects of SSRIs?

You're right, those are all important! There are several good reviews on the mechanism of action antidepressants. I like Molecular Pharmacology, by Nestler, or even Principles of Neural Science, by Kandel. I think a textbook is going to be your best bet, in terms of getting up to speed here, as this is largely an already-researched issue, but here are some good review articles as well:

1. Bonhomme et al., 1988


2. Charney et al., 1981


3. Norbert & Esposito, 1998


4. Spencer, 2012

If you have a more specific question, let me know!

genetics - Phenotypic Variation of cattle - looking for academic sources

Can someone please point me in the direction of a good academic article on the following:

What are possible sources of phenotypic variation of different 400 day weights of cattle?

Furthermore how much variation is likely to be due to each contributing source?

I have tried the following searches in google scholar:

• Phenotypic, genetic, environmental cattle weight


• Phenotypic variation cattle weight


• Phenotypic variation


• Phenotypic variation, genetic


• genetic variation, dam, sire

human anatomy - What negative effects can pinhole glasses have on the body?

Probably not many side effects except in specific instances, but no benefits either. My guess is that there are potential side effects because these glasses reduce the amount of light that the eye receives and restrict the visual field. Therefore, the restricted visual field would be bad for activities such as driving, in which you need your peripheral vision. And the reduced light makes objects appear dimmer, so it is harder to see with them at night. I also imagine (just a guess) that they would be bad for very young infants, who are almost always born without perfect vision and require some visual stimulation to correct.

There are probably many reasons why optometrists use a pinhole occluder for diagnostic purposes, but never prescribe it as treatment...

evolution - Why are urban birds still scared of humans?

Perhaps counter-intuitively, fear of humans is often a learned behaviour. There are accounts, such as one made by Charles Darwin following his visit to the Galapagos islands;

In Charles Island, which had then been colonized about six years, I saw a boy sitting by a well with a switch in his hand, with which he killed the doves and finches as they came to drink. He had already procured a little heap of them for his dinner, and he said that he had constantly been in the habit of waiting by this well for the same purpose. It would appear that the birds of this archipelago, not having as yet learnt that man is a more dangerous animal than the tortoise or the Amblyrhynchus, disregard him, in the same manner as in England shy birds, such as magpies, disregard the cows and horses grazing in our fields.

From "The Voyage of the Beagle" - http://www.ling.upenn.edu/courses/hum100/Beagle17.html

Birds born and bred in proximity to humans will have learned that we are actually to be avoided.

Ducks and swans, for instance, (and this is quite anecdotal) live in very close proximity to a lot of humans in cities, and feel confident walking picking up food. However if you try to get close to one they are very quick to get out of the way. The only exceptions to this are learned behaviours, such as when someone stands and feeds them.

In the wild animals may be cautious of humans if we are much bigger than them, but if they have no experience at all of human contact they may just ignore them. This quite often happens with film crews in Antarctica, as in the below image from the BBC's Frozen Planet series.

nutrition - Has there ever been an attempt to create nutritionally tailored food for adult human consumption?

Shortest answer: there's nothing special in human biology, you could totally make it

Short answer: Bachelor chow!

I would totally buy this stuff if they made it. The closest I have now to bland, flavorless, zero thought/effort food is Wheaties.

longer answer:
Seriously though, dogfood for humans wouldn't be that hard to make. If you just took everything from the RDI guidelines (the Recommended Daily Intake from which they calculate the percentages you find on food labels) and mashed it all together into a thick brown paste you would get all of the macro and micro nutrients that you theoretically require. Precise proportions are irrelevant because:

a) everyone is a little different, and

b) to some extent, our bodies are able to fine tune our digestive tracts to fit our specific diets (presumably this tuning would occur even faster if you ate the exact same thing for every meal). You're a mammalian omnivore. Enjoy it!

You probably shouldn't try to live on something like this for the rest of your life, since there's plenty of research suggesting that there are other micronutrients, such as phytocompounds (i.e. plant stuffs), that are poorly understood but may be beneficial to humans. One thing to note here is that any health claims about any antioxidant that is not on the list of essential vitamins (vitamin C is an antioxidant on the list) are almost certainly bunk and/or hokum.

The upshot is that you would only need, at most, utterly minuscule quantities of these miscellaneous micronutrients. You would be fine(ish) for at least a few months. For related reasons, your statement:

The composition is also known for human babies. This is manufactured as "baby formula". Everything baby's organism needs to be healthy (and to grow).

is largely correct but somewhat flawed. While it is true that many babies are raised solely on formula and subsequently turn out just fine, there are some things that you can only get from mother's milk. For example, the mother passes on components of her own immune system to her baby through her milk, which then help to strengthen the baby's own immune system. These are the kind of subtle but useful compounds which are encountered in a "natural" diet but which could never realistically be included in people chow.

evolution - Is there variation of AT/CG ratio along species?

That ratio is essentially, as WYSIWYG pointed out, called GC-content. In actuality, GC-content is reported as $(G+C)/(A+C+G+T)$, converted to percent; i.e., what percent of the genome is G or C.

There is vast variation in GC-content, both amongst species and within a given species' own genome. For example, in humans the first intron and exon are generally more GC-rich than following introns/exons.¹ Genes themselves are often found in higher GC areas,^2,11 in particular CpG islands are found near a large number of (mammalian) promoters.³

Across species, there can be a big difference. Yeast and Arabidopsis are both around 35%^4,5 whereas Plasmodium falciparum is around 24%;⁶Carsonella are even lower, at around 16.5%.¹⁴ On the other hand, the plankton Emiliania huxleyi is around 65%⁷. We can use these differences to study genomic history. Bacteria often have genes from all over the place thanks to horizontal gene transfer, and GC-content can be used to differentiate between their own genes and those from horizontal gene transfer;⁸ a good example is the CRISPR-Cas system,⁹ even in a virus!¹⁰

Here's a list of a few things genomic GC-content is correlated with:¹⁵

• genome size


• whether the bacterium is free-living or not


• the environment


• aerobiosis


• nitrogen utilization

In the lab, high GC-content often means a harder region to work with, as the presence of three instead of two bonds (between A and T) requires more energy to break;¹² anything involving primers can be made more annoying, including (especially, to some) sequencing. There is a theory that high GC-content would be an adaptation to high temperatures, to avoid DNA damage, but that is controversial.^13,16,17,18

speculative - Why Didn't Evolution Cause the Human Body to become Streamlined?

If streamlining makes movement/locomotion quicker and easier, why didn't the apes evolve into life-forms that had streamlined bodies (much like fish)?

As with everything in Evolutionary Biology, you must ask yourself: Gain vs. Cost?

In your specific case, the Gain is very little. Air isn't nearly as dense as water, so a streamlined form won't show a major benefit unless the organism is traveling very, very quickly. This is why you see it in birds; raptors can travel over 100mph while diving, and at those speeds small changes in drag can mean the difference between dinner and starving. Smaller birds often make very quick turnabouts and changes in direction mid-flight where, again, small changes in efficiency can mean the difference between life and death. The cost was is worth it.

For apes and monkeys, moving very quickly isn't a case of living or dying. That's what we evolved opposable thumbs and prehensile feet(/tails) for. You don't need to run fast when you can climb a tree and simply get away from any predators on the ground. After we came down from the trees permanently, our larger brains allowed us to use tools to fend off predators - which, again, is much simpler than evolving an aerodynamic form that won't make a difference until you're running at the speed of a car.

So, in lieu of becoming a land-shark, we have hands that can use keyboards and minds that can invent the keyboard. Unfortunately, while the gains are many, the costs do include both a very long period of time where humans are helpless without parents, and an absolutely terrible form of locomotion with our upright stance on forward-pointing knees. Though you won't catch Cheetahs digging sewers anytime soon.

neuroscience - How does a pinched nerve cause pain (at the molecular level)?

As AndroidPenguin described the nociceptive pathways are activated by inflammation or noxious chemicals.

Sometimes pain can arise independent of active nociceptive pathways. Most evident in cases of Neuralgia and perhaps in case of Pseudoneuromas.

In certain cases the injured nerve causes disinhibition of the pain pathways arising from the dorsal horn of spinal cord. This disinhibition is because of loss of the nerve function.
Sometimes increased nociceptor drive can activate dorsal horn of spinal cord which will now respond to normal mechanosensation also [1].

Phenotypic switching is also possible [2].

PS: Both these articles are inaccessible to me at this moment. Refer them for more details.

vaccination - What is the efficacy of Pertussis booster vaccine among different age groups?

The Murray Microbiology book says that it is prefentially 10 years, similarly Estonian and Finnish health associations.

However, my professor says that it can be 5-7 years.

I started to think if the age is affecting here to the result.

When should you take booster vaccination of Pertussis if you are
a) 25 years old,
b) 50 years old,
c) 70 years old, and
d) 90 years old?

My professor says that there is no significant studies about the efficacy of Pertussis booster vaccination among different age groups.
Is this true?

evolution - What preceded ATP synthase?

ATP Synthase is ubiquitous throughout life on earth and so most probably evolved within the last universal common ancestor (LUCA) before that lineage diversified into the various kingdoms of life.

It is suggested that the functional domains comprising the ATP Synthase complex were cobbled together from pre-existing sub-units, each with with a related activity (e.g. the union of a proton motor with a DNA Helicase with ATPase activity), which seems reasonable, although a bit vague in the details.

The fact that a primitive ATP Synthase arose in the first place suggests that ATP already had a central role in cellular metabolism and so begs the question, what preceded ATP Synthase in the role of generating ATP in the LUCA cell?

Thanks in advance.

definitions - What is the difference between abiogenesis and spontaneous generation?

As we all should know, abiogenesis and spontaneous generation are far from identical. For one, spontaneous generation was disproven with Pasteur, and abiogenesis seems to be a solid scientific theory. However, one can loosely summarize both as "the emergence of life from non-living materials" which, at the very least, is confusing for the layman.

My question is: What truly differentiates abiogenesis from spontaneous generation? For example, if abiogenesis were to happen again, how would we differentiate the two terms?

Is time the most contributing factor (abiogenesis happened over hundreds of millions of years)? Or the fact that abiogenesis generates "primitive organisms", while spontaneous generation assumes the generation of evolved, complex organisms?

climate change - What are some possible causes that might explain why the global temperature has remained relatively constant in the last decade?

First - I do not know if this is the best site to pose this question. That said, this appears to be the most appropriate place post this question.

Consider this chart:

The chart was retrieved from here here.

I am curious as to whether anyone has any thoughts regarding this trend - note, however, that this is one chart among several that I came across on reputable site. All seem to depict this observed "capping" effect between roughly 2000 and 2010+. Unfortunately, I don't have much to offer right now since I am still looking into it.

Any input is appreciated.

biochemistry - What are the units of enzyme activity?

This refers to the turnover number (a.k.a k_cat or k₂) of an enzyme and is usually calculated using Michaelis-Menten kinetics. Jump to the summary at the end if you want a simple answer. If you want a more thorough answer, consider the following chemical equation:

[E] + [S] ⇌ [ES] → [E] + [P]

This says that a certain concentration of enzyme mixed with a certain concentration of substrate will first combine and form a complex depending on the enzyme's affinity for the substrate. Then the enzyme complex will generate a product depending on the enzyme's ability to convert the transition state into product. The k₁ constant is the arrow moving from [E] + [S] → [ES] and the k_-1 is the arrow moving from [ES] → [E] + [S] (they oppose each other). The k₂ constant is the arrow moving from [ES] → [E] + [P].

V_o = [ES]k₂

• V_o - this is the rate that product is being formed, which can be measured.


• [ES] - this is the concentration of enzyme-substrate complexes.


• k₂ - this is a constant value comparing the two.

This can also be expressed in terms of maximum rate:

V_max = [E]_Tk₂

• V_max - V_max is catalytic rate when [E]_T = [ES] (when all of the enzyme present is bound to substrate/saturated).


• [E]_T - [E]_T is the total enzyme concentration. [E]_T = [E] + [ES].


• k₂ - the k_cat is the catalytic constant. It is a constant indicating how quickly an enzyme can convert substrates into products. It is easily observed by this equation.

Summary

So k₂ is basically an indicator of how efficiently or quickly an enzyme operates. Not all enzymes follow standard Michaelis-Menten kinetics. For example, the allosteric properties of some enzymes cause a non-linear saturation curve. Because of this, the turnover number is commonly referred to. The turnover number's units of s^-1 indicate one product molecule per second, so a turnover rate of 3000 means you can create 3000 products in 1 second at V_max.

species identification - What is this marmot-like animal (Tigray, Ethiopia)?

I was searching what are the animals I frequently saw in the north of Ethiopia. I took some bad quality pictures.

For me it looked like a large squirrel, local people called it a rat, and on the internet I find rock hyraxes are quite frequent in the region, but they appear not to have a long tail like the animals I saw, and they don't have the white lateral line

cardiology - Calling for Free Online Data for Paediatric ECG?

I need free online data about heart murmurs to study these:

heart murmur frequency , S2 heart sound frequency and its split,
murmur timing, and duration, murmur intensity, S3 sound presence and
intensity, S1 presence and intensity, presence of ejection sounds and
arrhythmias

I will cite your source then if I can use your data freely.

I would really have the same data as used in this paper:

Heart energy signature spectrogram for cardiovascular diagnosis
Vladimir Kudriavtsev, Vladimir Polyshchuk and Douglas L Roy

No pediatric ECG data here

• beecardio (aggregation of many ECG databases)

Does anyone have simple data for my task?

I remember that some CD of some book has some standardised nicely organised sounds that you can use freely.

behaviour - Why is yawning contagious?

Yawning is contagious in humans, which means that, in general, it is more likely that a person yawning after perceived (by sight, hearing, or both directions) yawning issued by another person. The frequency of infection varies throughout the day, with a peak in early morning and late evening.

A recent study conducted by Ivan Norscia and Elisabetta Palagi (University of Pisa) has provided the first evidence that the behavioral contagion of yawning is associated with the empathic bond between people. The study showed that the infection follows the same gradient of empathy: is greatest in close relatives (parents / children / grandchildren, brothers, stable couples), decreases in friends, then acquaintances in (people connected only by a third, external, ie work or a friend in common) and reaches a minimum in the unknown.

Various studies of clinical, psychological and neurobiological suggest and support the link between the yawn contagion and empathy. For example, the infection begins to occur at 4-5 years of age, when children develop the ability to identify, in a proper way, the emotions of others. In addition, the infection is reduced or absent in people who have problems related to empathy, how people with autism, and is positively related to subjective scores of empathy based on tests of psychological type. Finally, the areas of the brain related to the emotional sphere overlap, in part, with those involved in the response to yawn, with a possible involvement of mirror neurons.

Yawning has been observed among various primates. In these cases the yawn is a threat gesture, a way of maintaining order in the primates' social structure. Specific studies were conducted on chimpanzees and stumptail macaques. A group of these animals was shown a video of other conspecifics yawning; both species yawned as well. This helps to partly confirm a yawn's "contagiousness".

In animals, yawning can serve as a warning signal. For example, Charles Darwin, in his book The Expression of the Emotions in Man and Animals, mentioned that baboons yawn to threaten their enemies, possibly by displaying large canine teeth.

see yawn

autism

Gordon Gallup, who hypothesizes that yawning may be a means of keeping the brain cool, also hypothesizes that "contagious" yawning may be a survival instinct inherited from our evolutionary past. "During human evolutionary history, when we were subject to predation and attacks by other groups, if everybody yawns in response to seeing someone yawn the whole group becomes much more vigilant and much better at being able to detect danger.

Personally, I can make an observation. Cats yawn as specific means to calm people, and especially to reassure the other cats and the pups. In order, they stretch, yawn, lie down, half close theyr eyes as if they start to sleep. When the whole group repeats the gestures, the majority of them (now calm) actually falls asleep.

EDIT @kmm