text:
On the effect of polluted air on health. Is it more gradual, or more immediate?
I've heard time and again that living in São Paulo (a large city in Brasil) takes 1.5 years from your life expectancy. The allegation is that this happens because of air pollution.
I am just wondering how air pollution harms humans. Is the effect cumulative? Or is it a more immediate effect that makes the elderly die sooner?

also: is there a better place for this question on the stack exchange network ?

I think it's fine for here, I removed the part about wanting to live there, as I think that doesn't have any bearing on the answer.

that's an interesting question, I've read once that the biggest concentration of centenarian was in Hong-kong, but they may have also more wealth and resources than people leaving in forests. But like you I wish I could live far away from that pollution cars/smokers/...

The main factors of urban air pollution are nitric oxides, carbon monoxide, and what is called in german "Feinstaub" (very small carbon-rich particles from diesel exhaust). However, do not forget heavy metals: street dust is especially metal-rich and is swept into the soil near the streets where children and farmed plants can take it up. Lead is a heavy metal that can be breathed in with the air. Last not least noise over a certain threshold is proven to be a cause of illness, even loss of life time (10 years near an airport, if I recall correctly, but airport noise is getting better while machines become more fuel-efficient).
To answer your question one would have to look at every single factor. Lead accumulates in bones and destroys your brain. I just see Brazil banned it too in the 80's so this one killer is no more.
http://en.wikipedia.org/wiki/Tetraethyllead
I have found a meta-study that reviews about 80 papers on the subject, especially the Sao Paulo studies, so this should fit exactly your questions:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093800/

Those 3 are the main problems, then ?
Which of those would fit the "cumulative effect" idea, and which would fit the "harms the elderly" ?

Please see the link I have added


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What controls the feeling of discomfort/comfort before and after sleep?
I'm interested in which biological systems or hormones are involved in the following phenomenon:
Before sleep it may be difficult to find a comfortable position, and muscular aches and pains are more evident.
After 8 hours of sleep, many more positions are comfortable, and muscle aches/tension are non-existent. Some time after awakening, the feeling disappears.
What causes the difference in feeling between prior to falling asleep and after? Are there some hormones involved? Is it caused by some form of thought/feeling inhibition (e.g., part of a brain "falls asleep")?
If I remember correctly, after long running muscles accumulate some compound that is a result of metabolizing energy without enough oxygen, which causes muscles to ache. Could a similar process be involved?

The compound you're thinking about is lactic acid. When oxygen is low, pyruvate is reduced to lactic acid to regenerate NAD+. It might have something to do with the aching related to sleep, but I'm not sure.

Any chance you're referring to Willis Ekbom Disease?

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What is the biological basis for a human's ability to think clearly and be aware while "fighting/competing"?
I'm interested in learning more about the biological systems or hormones or parts of the brain that affect short term (<15 minutes) ability to concentrate attention on the task and be aware of the situation.
I'm particularly interested in humans who are engaged in an activity that can be perceived as threatening: martial arts, competitive video games, sports and other activities which may be considered "fight or flight", but a scenario in which the person has chosen to stay and fight.
To clarify the question further: What is involved in the ability to make decisions based on the competitive situation itself, instead of responding with pre-learned techniques and tactics? In one case, a person may be aware of what his/her opponents are doing, while in other cases the same person may "rush in blindly" and attempt to execute techniques that were learned and worked before, but will not work in the current situation.
What influences this choice of responding versus acting on prior knowledge?

My answer to http://biology.stackexchange.com/questions/2931/does-stress-physically-age-our-body/2947 contains the processes that lead to high blood pressure. This pressure is a main factor why your brain has all substances it needs in fight & flight situations.

Actually, the opinion that I've encountered more often is that when faced with a real fight or flight situation, a person will respond with a pre-learned behaviour.

the last two paragraph read like a question that would find a better home at cogsci.SE.

This is true, it's well established that when people are under high stress, they are more likely to respond with learned behavior. The ability to act intelligently under pressure is probably mostly a result of gaining expertise in a particular domain so that you can recognize what's going on in a situation and figure out an appropriate response without having to engage in careful, explicit reasoning or do things you're not familiar with.

thinking and decision making under stress or pressure is significantly reduced.  its sometimes called the 'fight or flight' condition.
This is a pretty well established phenomenon.  Here's a great radiolab segment on stress response.  Psychologist John Gottman notes how our ability to have a conversation where we can even listen to what someone else has to say is practically nil when we are emotionally saturated (frustrated or upset that is).  Even a mildly stressful conversation with your own spouse can shut down most rational processes.  Gottman can predict couples who overcome this problem which is highly corellated with divorce btw - but most of these couples remove stress in conversations rather than learn to work under pressure as it were.
Jonah Lehrer wrote about how tests to rank quarterbacks in their ability to respond on the gridiron are basically non correlated.  I know there have been criticisms of Lehrer, but this is a good piece and well grounded.  The point is that its hard to tell a-priori whether someone will perform under stress and given different sorts of stress.
In the japanese space program they would screen candidates by making them do highly repetitive tasks like folding 1000 origami cranes.  NASA was just doing interviews with panels of psychologists.  That wasn't infallible.
Such a test would be valuable for fighter pilots, astronauts, maybe presidents too! but it doesn't seem to really exist at this point.
In the end you can winnow out those who break into a sweat in the interview, but to know who is going to really take the beach, I think that the only real answer is to see if they make it through a 'live fire' (or whatever) experience.
Or as Clint Eastwood summed it up: "A man's got to know his limitations."
(apologies to the ladies there - you can know your limitations too).

Very good answer! I especially appreciate the reference about how rational processes can be suppressed. If one relies on rationality in dealing with such situations, one may be surprised.

thanks @AlexStone - also good reading the day before US elections... ;)

I recalled a while ago that I saw a presentation on the concept of "Flow".
Here's an overview by the author :Mihaly Csikszentmihalyi: Flow, the secret to happiness
The kind of difference in cognitive capacity while engaged in such events can be described as flow. I'm still not certain as to what is causing the difference in the cognitive ability at these times, even in the same person.

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What is the effect of a pure-oxygen environment on a plant?
Just read What's the effect of oxygen deficit on plants? ; and wondered whether the opposite would have any effect on a plant.
That is to say, if a potted plant were placed under a bell-jar and the air within replaced by pure oxygen would the plant starve? If the environment/soil were loosely radioactive, would it make a difference?

why would radioactivity make a difference?

@RichardSmith: Guesswork on the radioactivity bit; wondering whether the combination of the environment in which cells are liable to uncontrolled change may be driven by an environment which threatens the survival of the plant as a whole.

Ask yourself, where would the plant take the carbon for construction of all kind of molecules, most important the cell membrane and cell wall of newly divided cells. Plants do not eat! So they have to get their carbon from somewhere else.

Liable to starve then, I guess ...

If the plant is potted, thre could be co2 from the soil, as well as from plant respiration. But at such high o2, photosynthesis would be inefficient.

As hinted in other answers, the key problem with a pure oxygen environment would be the inability to photosynthesise caused by the absence of carbon dioxide.
The overall equation for photosynthesis (the process in which energy from the sun is harnessed to fix inorganic carbon dioxide into organic molecules that  are of use to the plant) is:
6CO2 + 6H2O → 6O2 + C6H12O6
The carbon dioxide required for photosynthesis is obtained from the atmosphere by diffusion through stomata on the leaves.  Therefore if the atmosphere contains no carbon dioxide (i.e. in the scenario you suggest) photosynthesis would not progress, meaning glucose used by the plant in respiration would not be replaced.
This would eventually lead to the cessation of cellular respiration due to a lack of reactant.  This would cause the plant to die.

It leaves the possibility that glucose for respiration only is taken from the cell wall/membrane, something that e.g. Mycobacteriae actually do.

The plant could still photorespire which means it is unlikely to die. It's impossible for it to grow, but it won't die(right away, or maybe at all).

Keep in mind, there is a chance that a growing plant in a sealed environment with pure oxygen WOULD SURVIVE because of the carbon dioxide discharge of aerobic bacteria in the soil. Consider that by the time a seed would sprout, the soil bacteria would have already had days to a week to metabolize CO2 as a waste product. This question depends on manifold variables (chiefest of which dealing with the environment and especially the size of the biome).


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Does a plant have to be alive for its roots to prevent erosion?
One argument often given in favour of saving current and planting additional plants/saplings is the roots hold soil together and prevent soil erosion.
Unlike plants that may be uprooted, a large tree may only be chopped down; its roots continue to remain buried. Do these, now dead, roots continue to prevent soil erosion, or does the plant have to be alive and kicking?
My guess is the latter, perhaps because absorption of water possibly 'compresses' the soil over the root.

You don't need to deprecate yourself like that, if a question is truly off the deep end, someone will comment. :)

The roots do actually continue to hold soil without being alie.  The stabilizing properties are structural in nature.  You begin to lose those though as the roots decompose, and the important roots against erosion, millions of fine root hairs, will go first. But leaving the roots in on a dead tree will help for a bit, but isn't a long term solution.

Here's a study that gets at this question, examining how root decay of felled trees impacts slope stability. http://www.springerlink.com/content/q328v49v72w14762/


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How is hibernation/aestivation different from anesthesia?
How do hibernation/aestivation happen?
I read on wikipedia that a squirrel injected with the body fluids of a hibernating fellow is more prone to hibernation. If hibernation/aestivation are driven by biochemicals and not merely the weather, can the process be induced in higher beings such as humans to replace surgical (etc) anesthesia? How is the one different from the other?
p.s. Or perhaps to induce hibernation for the trip across the Solar System (+:

What makes you think that changes related to the seasons are not "biochemically induced"?

Because there appears to be a temperature component involved leading to either deep or shallow 'slumber'.

surely, but all of these things are mediated by hormones (or in general blood-borne molecules) at the end of the day...

I'm assuming you're referring to general anesthesia, which still encompasses many types of mechanisms. Here's an interesting article about whether humans can hibernate. It's not a true scientific paper, but it brings up some interesting points.

@nico: don't have an argument to present against that ... perhaps this is a ppoor example, but if a person has a sneezing fit whenever it's going to rain - that wouldn't necessarily mean the fit was caused by hormones

@Everyone: I said hormone, but I could have said chemical. What I mean is that if you have an external influence (wheather, temperature, humidity, whatever) on your body, it will convert it to some chemical signal at some point.

But that applies to voluntary actions too - even moving a muscle is ultimately a biochemical process ( I could be wrong though ...)

Neurons are ultimately electrochemical, but nearly all biological decision-making over minutes, hours, or longer is hormones/chemical signals in the blood or brain. Tiredness, puberty, hunger, allergies, sweating, thirst, how bees know when their queen is dead, etc are all chemical or hormonal.

I'm going to answer the question of whether aestivation/hibernation can be activated in humans or other apes, because it's more interesting.
Mammals, as a clade, have three major subgroups. Bats, shrew-likes, rodents, and then everything else including primates. One family of the shrew-likes hibernates, some rodents(but not all) and some bats can hibernate or enter a period of extended torpor. The only kind of primate that can hibernate is the dwarf lemur, which does so in a strange way(fully asleep for 6-8 months, little regulation of body temperature). Other hibernating animals regulate their temperature but keep it low, and wake to roll over or whatever every couple of days. Plus lemurs are on the edge of the mammal cladogram, so they're just pretty weird.
Phylogenetically, it's not likely(imho, but I'm not a mammalian phylogenetics expert) a primate ancestor of humans has ever had the ability to hibernate. It seems more likely that primates lost the ability if it was a capability of mammalian ancestors and dwarf lemurs re-evolved it. It's possible atavistic remnants of such a system might still exist, but extensive hormonal and possibly surgical treatments would be required to induce it. Not to mention you can wake animals from hibernation by poking them, so it probably would be a substandard anaesthesia method.


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Do egg laying animals experience a pregnancy?
Does a female animal that lays eggs experience a pregnancy-like period of time, where she will feel and behave differently as if she were fertilized and her body is prepared to lay a fertile egg, not a sterile egg (like the chicken eggs we eat)?
For example,

does the egg takes more time to be formed?
is it different in size?
maybe the animal will feel hormonal changes that cause it to increase body heat to help her sit on the egg, etc.?

Can you elaborate on what you mean by "fill deferentially", as it's not very clear what you are trying to say there.

And can you also clarify what "pregnancy-like period" refers to? A "period" can refer to two things :P And the short answer is yes, but I don't fully understand the question.

@jonsca, jello, "deferentially" was a typo, the hour was late and I was tired. "Pregnancy like period" - a period of time, when the animal will fill/act differently than every-day, or have changes to her body that are do not happen unless she is going to lay a fertile egg.

@IlyaMelamed See if that's closer to what you were aiming for.

@jonsca, yes it's.

I think this varies quite a bit.  many egg laying species are periodic and have a mating season (e.g. sparrows, salmon).  Others create eggs continuously (e.g. chickens, ants).

@shigeta, in guess that this means that a full answer will need to touch on both types. For example what happens to a sparrow or a salmon that doesn't mate on its season, and as asked before is there a difference between laying a fertile and an infertile egg from the POV of the chicken/ant.

In oviparous animals the egg retention phase in the uterus is brief. After fertilization eggshell mineralization is triggered but it seems the initial triggers of the pathway is not understood. The uterine fluid is rich in calcium and bicarbonates and calcium carbonate, in the form of calcite, precipitates around the egg. Shell mineralization is quite a rapid process and there are some specific proteins involved in this pathway. Have a look at these:
http://www.ncbi.nlm.nih.gov/pubmed/22201802
http://hera.ugr.es/doi/15773115
In ovo-viviparous animals the egg is retained in the uterus for a longer time and embryo is quite developed when the egg is laid (happens in boas). You can call it a sort of "pregnancy".
However progesterone pathway exists in birds and is involved in oocyte maturation
Oxytocin pathways also exist in birds, acting through oxytocin homolog Mesotocin, and perhaps they cause development of maternal care as they do in mammals.
This article talks about effects of oxytocin on birds but not exactly about its role in maternal care.
However i believe that the shell size and mineralization time shouldn't differ much between unfertilized and fertilized eggs in oviparous animals.

So your answer is that the animal doesn't feel any serious change between laying a fertilized and an unfertilized egg?

i dont know in what sense you are talking about.. parthenogenesis or what they do with chicken in poultry.. i think the behavioral response will be the same but observations in poultry chicken can be misleading..
there is a practice called forced-molting which poultry industry adopts in order to increase the egg yield.. during molting the reproductive tract of the hen again becomes capable of egg-laying.. So definitely there is some endocrine response after egg laying and perhaps the hen doesn't "know" if its a viable egg or not


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Do drugs always degrade after they have passed their expiration date?
I have been wondering for some time whether several drugs really have an expiration date.
Let's narrow the scope and think about only "common" drugs, e.g NSAIDs, antibiotics etc.
For example, would antibiotics in the pills get deactivated or decomposed?

Question sounds appropriate. I suggest reading http://www.quora.com/Drugs-and-Pharmaceuticals/What-does-it-mean-for-a-medicine-to-have-an-expiration-date

Could you clarify whether you're interested in antibiotics, activated carbon or about expiration dates in general?

@bobthejoe: thanks that link really helped, but I guess it would be good to have something similar written here as an answer just to gather more knowledge on this site.

It really does depend on the drug in question

@RoryM: ok then, you're suggesting that the question is too wide and can't be answered exhaustively. Then I'll reduce the scope.

@zeller I consolidated all of the updates down and reworked the title with what I think is your intent, if this is not the case, feel free to roll it back.

Drugs do not have to degrade after their expiration date and passing the expiration date has more than one possible meaning.
First of all chemical compounds vary in their susceptibility to breakdown over time.  If they are kept away from oxygen, high temperatures (or kept in very low temperatures), and they are of a robust chemical nature, they might be stored for much longer than their expiration date and remain just as strong.
Over time, pharma compounds will chemically break down and lose their potency.  In many cases, you will find that they simply don't do anything when you take them.  This link cites a study that many drugs can retain their potency 15 years after they are made.
There are important exceptions.  Two examples are tetracycline and acetaminophen (tylenol) whose breakdown products can increase the tendency for these drugs to induce liver damage.


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Why don't all ants have wings?
Since the new queens-to-be have wings, it means that ants either evolved from insects that can fly, or insects that can fly evolved from ants, or that we have a case of parallel evolution (which is unlikely).
Now, what evolutionary benefit is there to not have wings?

I think, "common" ants just don't need wings for their daily life... Here you can find the reason why males and females have.

I know why the wings exist to begin with, thus the exact wording of my question.

Sorry then, I misinterpreted you. Though in this case I guess your question is rather philosophical... Maybe it's because of the principle of laziness: don't do what you don't have to do.

Certainly ants evolved from insects that could fly.  All the earliest wasps (ants are specialized wasps) could fly.
Building and maintaining wings is expensive in terms of energy.  That's an obvious evolutionary advantage to not having wings.  So if there's insufficient benefit from having wings then there's selective pressure against having wings.

You could say that ants evolved the ability of having wings only when needed

Building on Noah Snyder's answer…
Having wings could also be expensive in other ways. For example, energy aside, maybe the growth of wings relies on some special nutrients, which were scarce in the environment of the first ancestors of modern ants. So the ant colonies that grew smaller wings (or no wing at all) thrived.
Having wings could also cost them their lives. Maybe the workers in ancestor colonies used to be small and had a tendency to get stuck in spider webs (not having enough in-flight momentum or brute strength to break off the web), and somehow the queens and drones are less affected (because they don't tend to go to the same places as the workers to begin with, maybe; but that's unlikely: I see plenty of queens stuck in spider webs in Hong Kong in the mating season).
In fact, I believe the nutrient-driven path is quite likely. When you think about it, there is a huge behavioural component to this trait. If I remember correctly, all female ants are equal at birth. Whether a certain female becomes a worker, a soldier, or a queen depends on what it is fed as it develops. So the scenario could be that some ancestor colonies arrived in a place that didn't have an abundance in nutrients for wings. Some of those colonies tended to reserve the said nutrients to the reproductive casts (queens and drones), and this strategy proved successful, so the trait got amplified over time. So it becomes a matter of less wings, not smaller wings.

To add to that, one other factor which may have prompted the evolution of winglessness is competition and niche differentiation. The ancestors of ants were winged predatory wasps, and the first ants were also predatory, but wingless. There could have been an advantage in specializing on ground-dwelling prey, which could have been more efficient to hunt/handle for wingless individuals.

When is it good to have wings?
When you need to move a great distance in as short a time as possible with minimal risk.
Clearly wings would have enormous benefit at a time when you need to get far away from the nest really quickly, perhaps at a time when you believe the weather would be particularly favourable. This benefit increases exponentially when procreation is involved.
When is it bad to have wings?
Almost any other time.

When it is raining.

Rain and wings just do not go well together. If you get hit by a raindrop while wearing wings you are basically stuck where the drop lands until it evaporates completely.

When it is windy.

I rest my case.

When you are under attack.

Agility, while wearing wings, just cannot be considered one of your evolutionary advantages.

When you are trying to gather/carry food back to the nest.

Surely an ant trying to carry a piece of a leaf, however small, would consider wings a severe burden.

When times are hard foodwise

The protein investment in wings would surely be better spent on survival when food is scarce.

Encounters with birds suck

Wings make you incredibly easy to grab hold of in mid-air, unless of course you can shed your wings when stressed, and many ants can (while obviously butterflies and moths cannot).
Wings or No Wings?
Surely my arguments suggest that having no wings would be a serious advantage in almost any situation except on the rare occasion when you need to move a long way really fast. Clearly the ant has an amazing skill to only have wings when they are needed and not at any other time.
Added after a number of comments
You have to remember that much of an ant's work is maintaining the colony as a collective. Preserving its cohesion, feeding the young, caring for eggs. The whole point of having a colony is to have far fewer individuals spread out, in danger, gathering food. This is to reduce the risk of complete colony death, which is essentially the death of the queen and therefore the gene pool of the colony.
You have to look at each ant colony as a single individual when you look at them on an evolutionary scale. In this way the life or death of one, or even 1,000 ants is not important, it is the survival of the colony. From this perspective, wings are dangerous for all my reasons above. The only time they are of value is during diaspora and that is the only time ants have them, which I think is incredibly clever.
Evolving a detachable appendage to an ant is like humans evolving detachable breasts at menopause. An astonishing achievement even humans have failed to achieve.

It could easily be good to have wings when under attack - if you can fly away from a conflict that's a whole extra dimension of escape routes compared to those available to a flightless animal.

Many smaller winged insects use the wind to aid dispersal, see this paper for example. Wings are extremely useful in many situations, hence their evolution despite the major energy investment.

Also flying could easily improve foraging or hunting success at a greater rate than the increased protein cost of growing and maintain wings. Unless you can provide some referenced support for your reasoning I think I disagree with almost all your points, so -1

@RichardSmith - I thought we were talking about ants. Flying away is a huge negative in a "Colony" species.

@StephUnna - Wind dispersal would only be of value during a diaspora. At any other time, wind would just scatter the colony.

@RichardSmith (Also ...) - If they could evolve to fly in formation, thus preserving the colony then I would agree. Keeping together is much easier when everyone walks and you can smell/taste where your colleagues have been.

@OldCurmudgeon it wasn't clear until you added that last section that you were only talking about ants; it sounded like you were making general statements about when it's good to have wings and then specialising the case for ants.

@OldCurmudgeon and all your points about colony living being better without wings are disproven by wasps and bees, which have the same colonial constraints but retain wings throughout their adult life stage.

@RichardSmith - Wasps and bees are what ants would become if they had wings. Wings would enable them to feed off the far more cost-effective nectar and pollen rather than the leaf cellulose they actually feed on. Essentially, if ants had wings we'd call them bees.

That's my point exactly - your arguments for wings being bad for ants either apply equally to wasps/bees and are therefore invalid, or would only apply once ants had lost their wings, and therefore don't explain why they don't all have them.

@RichardSmith - interesting discussion - my arguments do not apply to bees because bees, although still a colony species like ants, feed primarily on nectar and pollen, a much richer foodstuff that can support powerful and robust flying mechanisms and sufficient brain power to find your way home and communicate 'good' locations. Ants feed primarily on the cellulose of leaves or what fungus breaks it down into. This is an energy-poor foodstuff that cannot support the energy required to fly[citation needed].

@OldCurmudgeon so you're assuming the move to leaf cellulose as a food source must have predated the loss of wings - if not, there was another driver for loss of wings. You're right about one thing: [citation needed] :)

Note that ants communicate the location of important places (like food source) via pheromone trails. It's not possible to follow pheromone trails while flying, so they couldn't use flying for foraging.


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How would I explain different properties of the same protein in different species?
I recently finished an experiment where I analyzed the rate of ATP hydrolysis of Heat shock protein 104 in three species of fungi. They have shown to all have different rates of ATPase activity. How would I explain these findings based on structure/ATP affinity?  The experiment was done in vitro.
The species under consideration:
Candida albicans,
Saccharomyces cerevisiae,
Schizosaccharomyces pombe

The experiment was done in vitro?

Yep, it was done in vitro.

(i) I used an NADH-PK Linked Assay where I looked at the absorbance decrease when NADH is oxidized to NAD+. They were all pure proteins. (see: NADH-coupled microplate photometric assay for kinetic studies of ATP-hydrolyzing enzymes with low and high specific activities) (ii) All the Km values were different, ranging from 2mM-4mM and I used ATP concentrations ranging from 0mM to 10mM.

Have you checked sequence similarity/identity, especially of the nucleotide contacting regions (otherwise known as the P-loops I think)?

Do you know any databases where I could find the amino acid sequences of these protein orthologs?

The NCBI protein database or UniProtKB would be the first places I would search. Other databases exist, but these are my personal favourites

What TomD says about contributing proteins, here's an excerpt from the InterPro entry: A small adaptor-like protein, ClpS, modulates the activity of ClpA and is an important regulatory factor for this protein [4]. It protects ClpA from autodegradation and appears to redirect its activity away from soluble proteins and toward aggregated proteins.

As nobody has answered this good question, I'll have a go.
Firstly, let me state that I have little-or-no knowledge of heat-shock
proteins. What follows are some general observations and thoughts.

It would not be unusual for the same enzyme from different
species to have different kinetic properties. For example, yeast and
horse liver alcohol dehydrogenase (EC 1.1.1.1) vary quite dramatically in this regard
(see below).
It is  to be expected that the same
protein from different species will have different amino acid sequences.
Even the sequence of cytochrome C (~104 amino acids), one of the most
conserved proteins, differs between species. There are 44 amino-acid differences
between human and yeast cyctochrome C, for example (although there is no
difference in amino acid sequence between the human and chimpanzee
proteins) [see Creighton, 1993, p116, quoted below].
This fact alone could explain the kinetic variation, but it might be
very difficult (and require a lot of work) to pinpoint what differences
in amino acid sequence (if any) account for the observed differences in
kinetic constants.
In the case of hsp104, a quick alignment (out of curiosity)
of the amino acid sequence of the  Saccharomyces
cerevisiae and Candida albicans enzymes showed quite a number of amino acid differences between these obviously homologous proteins.
I used the
TCoffee
sequence alignment algorithm (a new version of ClustalW) at the
xPASy server. (I received an alignment score of 98).
For the record, the accession numbers used are the following:
hsp140 from  Saccharomyces cerevisiae, 908 amino
acids, Accession Number AAA50477
hsp140 from Candida albicans, 899 amino acids, Accession
Number AAK60625
Of course, the observed kinetic differences may not be due to
amino acid sequence differences at all, or may not be
only due to such differences.  Post-translational
modification (such as phosphorylation) and differences in quaternary
structure are other possibilities.
I notice from this
reference (Parsell
et al., 1994)  that hsp104 from
Saccharomyces cerevisiae forms oligomers in the
presence of ATP, and this might be very important in any explanation of
kinetic differences. (My whole knowledge of hsp140 does not extend
beyond this excellent paper).
Yeast and horse liver alcohol dehydrogenase (ADH) are
homologues and catalyze an identical reaction.  Both also contain zinc.
However, the yeast enzyme is a
tetramer, whereas horse liver ADH is dimeric.
Another difference worth
pointing out is that in vivo yeast ADH functions as
an aldehyde reductase (making ethanol), whereas liver ADH functions as
an ethanol dehydrogenase (in alcohol elimination). [I am aware there are
other isozymes of yeast ADH, which may have different functions].
As an ethanol dehydrogenase, the yeast enzyme has a
kcat value of 455
s-1 (pH 7.05, 25oC;
Dickinson & Monger, 1973) whereas the horse liver enzyme has a
kcat value (for ethanol
dehydrogenation) of only 1.67 s-1 (pH 6.0,
25oC; Dalziel, 1962, 1963).
In the reverse direction, the
kcat for acetaldehyde reduction is
3850
s-1 for the yeast enzyme (pH 7.05,
25oC, Dickinson & Monger, 1973), whereas it
is only 125 s-1 for the liver oxidoreductase (pH
6.0, 25oC; Dalziel, 1962, 1963).
How can we explain these kinetic differences from an analysis of
structure? In my view this is a very tough question.  It may be due to some or all or none of the differences I have highlighted.
Perhaps the question needs to be rephrased as follows: Is there any fundamental
difference, at any level, in the catalytic mechanism, or in the form of the enzyme in
solution, or in the amino acid sequence, or in the tertiary or quaternary structure, that can reasonably account for the observed kinetic variation?
Are the differences worth explaining?  Perhaps one needs to go no further than to record the individual variation under rigorously-defined reproducible conditions?

Before such questions may be answered, it is important to establish the nature of the observed kinetic differences.  What follows are merely some guidelines, most of which you are probably aware of.

Is the velocity versus enzyme plot linear in all cases at both high and low substrate concentrations? That is, in kinetic jargon, is the   ν vs [Eo] linear?  As the enzyme is known to form oligomers in the presence of nucleotides (see above), this might be an important control.  Does doubling the enzyme concentration exactly double the rate, and does halving the enzyme concentration exactly half the rate (at both high and low substrate concentrations)?
An example of an enzyme where the ν vs [Eo] is often not linear is phosphofructokinase.
I notice you are using a coupled assay with two coupling enzymes.  What effect does doubling the amount of one and/or both of these enzymes have on the observed rate?  It should have none, otherwise the assay is not valid.
The substate is ATP.  Almost certainly, the 'true' substrate for the enzyme is MgATP2- (correct me if I am wrong about heat-shock proteins). How much Mg++ do you have there?
In determining kinetic parameters for ATP-utilizing enzymes one needs to be aware of ionic equilibria during experimental design. Failure to do so may give rise to spurious kinetic effects.
A solution containing ATP and Mg++ will contain many ions, probably only one of which is the substrate for the enzyme, and whose proportion will vary with concentration.  It is essential that this is taken into account. The problem and posssible solutions are explained very well by Cornish-Bowden (2003, pp 86 - 89) and by Storer & Cornish-Bowden (1976).
One experimental design is to keep the concentration of MgCl2 in constant excess over total ATP concentration (CB recommends 5mM).  This is an important one.
Are Michaelis-Menten kinetics obeyed in
all cases? Is there any evidence for substrate inhibition, or substrate
activation?
Are the double-reciprocal plots (Hanes plot,
Lineweaver-Burk plot, Eadie-Hofstee plot) linear in all cases?.  Non-linearity may be an indicator of kinetic complexity, or of poor experimental design.
If you plot the kinetic data for all three enzymes on a single double-reciprocal plot what sort of a pattern do you get?  Competitive? (no
differences in kcat, but
differences in Michaelis constants).
In comparing enzyme kinetic parameters the Michaelis constant has the big advantage that it is independent of enzyme concentration.  Thus any differences are likely to be 'real' and not due to errors in, say, protein concentration.
But what about Vmax? If, say, you determine that the maximum velocites differ by a factor of 1.4, can you be certain that you are not inadvertently adding slighly more enzyme in the higher case, and that the catalytic constants are in fact identical?
As I said above, these are just personal thoughts.  Most you probably already aware of.

References

Creighton, T.E. (1993) Proteins. Strutures and Molecular Properties. 2nd Edn. W.H. Freeman & Company.
Cornish-Bowden (2004) Fundamentals of Enzyme Kinetics 3rd Edn. Portland Press, London.
Dalziel, K. (1962) Kinetic Studies of Liver Alcohol Dehydrogenase. Biochemical Journal, 84, 244-254.[pdf]
Dalziel, K (1963) Kinetic Studies of Liver Alcohol Dehydrogenase and pH
with Coenzyme Preparations of High Purity.  J. Biol. Chem., 238,2850-2858. [pdf]
Dickinson, F.M. & Monger, G.P. (1973)  A study of the kinetics and mechanism of yeast alcohol dehydrogenase with a variety of substrates. Biochemical Journal,  131, 261-270.  [pdf]
Parsell, D.A., Kowal, A.S & Lindquist, S. (1994) Saccharomyces cerevisiae Hsp104 Protein. Purification and Characterization of ATP-Induced Structural Changes. J. Biol. Chem.,  269, 4480-4467. [pdf]
Storer, A.C. & Cornish-Bowden, A. (1976) Concentration of MgATP2- and Other Ions in Solution. Calculation Of the True Concentrations of Species Present in
Mixtures of Associating Ions. Biochemical Journal 159, 1-5 [pdf]

Some very good ideas, thank you! Another interesting thing I forgot to mention, is that I found evidence of substrate inhibiton of C. albicans at about 1mM ATP concentration. Perhaps this would add some valuable knowledge to the evolutionary relationship between these orthologs?

+1, I've read a few of your answers now, and I've gotta say that I'm pretty impressed. Always logical, straight-forward, complete, and referenced. Great to have you in the community :)

Me too. Personally (no maths...) impressed by "magnesium", by the way. Maybe interestingly, I would have very strictly stung to the formulation of the question: it's about one and the same protein, and including all it's properties, and that might include one and the same way to react to different concentrations of magnesium. Now I see what makes a very bad mathematician out of me - to put one and the same into a different context surely does not change that one and the same thing as such. Thank you!


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Is there any biological reason that professional swimming is dominated by white people?
I suppose that the question should be turned around to "Why is it extremely rare to see black people competing in professional swimming?" because it is the absence of this phenotype while watching the Olympics that caused me to ask this question.
So,

why are there very few black people competing at world class level swimming?

While I'm here I may as well ask the question:

Why are black people faster sprinters than white people when it comes to world class level?

And of course I want biological reasons.

Why would you downvote this?

It will get downvoted because it's perceived as racist to highlight or suggest biological differences between races (I'm not saying I agree with the downvotes). The answer to your question is no, there's no biological basis, the explanation is most likely cultural.

+1 agree with @Richard Smith, strongly disagree with the downvoters. There is nothing racist in this question, although it has to do more with anthropology than with biology. It would be like downvoting a question asking why Asian people get drunk easily because it is racist. In any case, when you downvote a question you should leave an explanation so that the question can be improved. 6 downvotes and no explanation so far.

Hmm, I was sure that we had the question on Skeptics but I can’t find it now. Since the black/white divide isn’t a meaningful biological distinction (i.e. it is not correlated with genetic background – which, incidentally, is also why I cringe whenever I hear “race” applied to this, because it’s just wrong) the real reason is almost certainly cultural, not biological.

+1 the question is not racist, but I suggest to edit the question and replace 'race' with 'phenotype'. I'm sure there is a good cultural explanation, but this does not rule out genetic basis: Asian people get drunk easily because of the DNA. Looking forward for a GWAS study of olympic players: it will be very interesting!

Well, a friend of mine, an annoying one mind you, keeps telling me that he saw a SCIENTIFIC program on tv which explained that there aren't many black swimmers because they don't float as well, I remember it had something to do with bone density or lung capacity, I forgot..

Yeah I've been told about the bone density one, sounds like a load of rubbish.

It's not biological, it's simply an education issue, and googling would give you:
Just under 70% of African-American children surveyed said they had no or low ability to swim. Low ability merely meant they were able to splash around in the shallow end. A further 12% said they could swim but had "taught themselves".
http://www.bbc.co.uk/news/world-us-canada-11172054
Unlike the UK, where learning to swim is enshrined in the national curriculum except in Scotland, the ultimate responsibility in the US often lies with parents.

if you look at kenyan runners they have a similar acculturation to running - nearly every child there tries. on the upper end of the sport, there are genetic advantages i'm sure, but the more kids who try the sport, the more exceptional athletes will be found.

@shigeta: +1 for acculturation

@rwst Good evidence is seen for this in the pool also - Chinese athletes are now starting to be more competitive in swimming than they used to be thanks to more training. Also it would be great to see some of the endurance athletes from developing countries, like the superb Kenyan distance runners, try cycling from a young age but the cost of the sport is generally prohibitive to those in developing countries, hence it is dominated by Europeans (and increasingly North Americans -excl. Lance now.) whereas running is free!

Really interesting Radiolab podcast episode about Kenyan runners here: http://www.radiolab.org/story/runners High probability of trying the sport + cultural pain tolerance + high altitude + genetics (e.g. thin ankles)

While its true that training is important, black people do have a higher body density compared to caucasians. It is of course possible to train any type of human to swim at world-class level, but people saying that "floating just a little less well doesn't change anything" have a very dim idea of swimming technique. It's just the same as saying "being 1.5m tall will absolutely not decrease your chance to enter the NBA".

I've recently seen this video: Juan Enriquez: Will our kids be a different species?, in which the speaker discusses differences between humans currently inhabiting the planet. At one point in the video,he does touch on the olympics and mention that a lot of the Olympic powerlifters have a certain gene expression.
Power lifting is quite different from swimming, but from the top of my head, I can recall that people from east Africa excel at running. So the difference may be genetic, at least on some level.
The idea of differences between races is very "not politically correct", and as the speaker suggests, we still live int he world that remembers the Holocaust.

The presence of absence of any genetic effect would be completely overwhelmed by the disproportionate makeup of the pool(haha) of young swimmers. It's not impossible, but it's definitely negligible in the present day.


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Can parents' learned traits be transmitted genetically?
I am wondering whether a behavioral trait (e.g. fear or stress experienced in the lifetime of the parent) can be transmitted genetically to its offspring?
I understand that a behavioral tendency for stress acquired through evolutionary time can be transmitted from parent to child, but I'm wondering whether a trait not present before can be transmitted between 2 generations.
For example many studies claim that offsprings of holocaust survivors inherit psychopathological disorders. I'm wondering how this inheritance could occur genetically given such a short time period?

You may want to have a look at: http://biology.stackexchange.com/questions/2875/can-rats-pass-on-memories-of-a-maze-to-their-offspring and http://en.wikipedia.org/wiki/Epigenetics

I think this is a duplicate of the question @nico mentions. In particular, the answer there completely solves this question.

This is a perfectly good question, but my answer linked above is relevant. The short version: it's not genetic; stress is transmitted hormonally from mother to child.

“many studies claim” – do you have any reference for that? This sounds very dodgy. Some naive epigenetics studies claim similar results for mice but their interpretations are simply not backed by the data.

@KonradRudolph he's right that many studies claim increased stress-related disorders in Holocaust survivors' offspring. I'll write up a full answer and include some. The key point is that none of those studies claim it's a genetic effect; that was an assumption of the asker.

Vote to reopen - whilst the other question is similar, there are specific features related to the human case which warrant a separate answer (which I was just about to post when the Q was closed!)

I want to say no, because parents can't pass down their behaviors genetically their children can have their own way of behaving.

Strictly speaking no. There are ideas about cultural inheritance though that seem relevant here: see http://www.ncbi.nlm.nih.gov/pubmed/11425279.  Cultural inheritance theory uses the plasticity of the human brain as the evidence for the underlying genetics of culture.  I.e. we aren't born with the ability to speak English because our parents learned it but we have an the underlying brain structure that is controlled by genetics to learn cultural traits.  It seems far more likely that the phenomenon you describe with holocaust survivors is more related to some environmental effects (from their parents) than anything genetic.  In the comments stress hormones in pregnant mothers were mentioned.  Any impact these have on the offspring are not truly "genetic", they're termed "maternal effects" in the evolution literature.  In fact most selection studies go to great lengths to control for them or eliminate them.  They aren't truly genetic because these traits would never get passed down to the grandoffspring of the original mother.

I am just repeating @emhart answer but wanted to highlight the semantic.
There are several ways an individual can inherit from its parents.

Genetics

Through transmission of DNA. An acquired trait cannot affect DNA sequence directly and therefore cannot be inherited genetically by the offspring (this sentence is the answer to your question). Note however, that the environment in which an individual is found and the amount of stress an individual is experiencing may affect its mutation rate. But this has nothing to do with transmission of an acquired trait.

Non-genetics (or "environmental in the broad sense")

Environmental in a very narrow sense. For example, a dam that a beaver transmits to its offspring, a good habitat that the parents had to fight for. Note in the broad sense, any non-genetic inheritence should be considered as being part of the environment. Environmental change that an individual has caused (niche construction) of fighted for can potentially be inherited by the offspring
Cultural. For example a language, a method to hunt seals or a method to clean potatoes. Cultural modifications acquired by an individual can potentially transmitted to the offspring
Epigenetics. It includes any modification over the DNA and histones and any content of the egg. Something an individual has lived can affect the types of epigenetic modifications that a parent can transmit to its offspring.

Genetic and epigenetic characteristics can be exclusively transmitted from parent to offspring (setting aside horizontal gene transfer and transduction), while environmental characteristics and cultural characteristics can potentially inherited between any two individuals. In the field of population genetics, the ratio of the phenotypic variance that is due to (additive) genetic variance over the total phenotypic variance in a population is called heritability (in the narrow sense).
There are plenty of important keywords in my (and @emhart's) answer. You might want to have a look at the wikipedia entries for all these concepts. You might also want to have a look at this answer.


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What is the biological mechanism linking temperature and probability to be infected with a virus?
It is common knowledge that when you're cold you could get a cold.
What is the mechanism linking temperature and viral infection?

There's some information on that in this question on Skeptics.SE

Wow that seems like a really bad idea for a stackexchange site.

@Uri What do you mean by that? “a really bad idea for a stackexchange site”

skeptics stack exchange overlapping with everything

It is common knowledge that when you're cold you could get a cold.

This may be a nice illustration why we need to be wary of “common knowledge”.

What is the mechanism linking temperature and viral infection?

This isn’t clear. There are a few proposed mechanisms but a likely explanation is: “there is no mechanism” – and the assumed correlation between cold temperature and catching a cold might be nothing more than an illusion – a form of confirmation bias.
In fact, we don’t even know for sure that the cold season coincides with cold temperatures.
On the other hand, a 2007 review [1] found that

… most of the available evidence from laboratory and clinical studies suggests that inhaled cold air, cooling of the body surface and cold stress induced by lowering the core body temperature cause pathophysiological responses such as vasoconstriction in the respiratory tract mucosa and suppression of immune responses, which are responsible for increased susceptibility to infections.
   [emphasis mine]

So according to their results, potential mechanisms which link temperatures and viral infection are indirect:

The lowered core body temperature would imply, in my interpretation, that the body has to expend more energy to maintain its temperature, and hence less energy to power its immune system (which is expensive).
Lack of respiratory tract mucosa removes an important physical barrier between the environment and the body, and allows pathogens to enter the body with much less resistance.

[1] Mourtzoukou & Falagas: Exposure to Cold and respiratory tract infections, in Int J Tuberc Lung Dis. (2007), pp 938–943

The John Tesh Radio Show (not sure how credible) also mentions that communicable disease, such as a cold, tends to spread easier because we tend to pack more densily in warmer places like homes and buildings.


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Why does the sex of the parent species determines the species of a hybrid offspring
I've read a little about hybrid animals, and have been amazed by the fact that the sex of the parent species determine the species of the offspring, in some hybrids.
A male horse and a female donkey will give birth to a Hinny, while a female horse and a male donkey will give birth to a Mule.
The same goes for tigers and lions, male lion and a female tigress will give birth to a Liger, while a male tiger and a female lioness mating will result in a Tiglon
I thought that the only difference between the male and female reproductive cell's DNA code is the X-Y chromosome that determines gender, not differences that can define the phenotypical result of the offspring. Why does this happen?

Excellent question. Unfortunately, I am guessing that the answer is simply “because we defined it that way”, rather than a biological insight. Species are usually defined in terms of the possibility of interbreeding, which isn’t relevant here (hybrid offspring is usually sterile).

@KonradRudolph, but species are not defined just for the fun of it (I guess, I don't really know), they are defined because there are significant differences between two animals, and in the case of those two interbreeding, those differences are consistent with the gender of the parent species. In other cases, like the different types of Zebroids (Zebra and donkey/horse/pony hybrid) that doesn't seem to be differentiated by parent species gender. (http://en.wikipedia.org/wiki/Zebroid)

@Ilya Melamed: there is no strict definition of species... and anyway hybrids are NOT defined as separate species, but as the cross of two different ones.

@nico, maybe I'm using the word "species" wrong, I use it in its layman definition, as "different types of animals". The meaning is, as I said, that significantly different animals are born from the same parent animals, and that the change is consistent with the gender of the different parent animals. If you can think of a better term than "specie" please edit the question to bee more accurate.

I thought that the only difference between the male and female reproductive cell's DNA code is the X-Y chromosome that determines gender, not differences that can define the species of the offspring. Why does this happen?

Well that is not the only difference, there are certain characters that are only transmitted by one of the parents.
First of all you have to think that the zygote (the cell deriving from the fusion of two gametes) contains the nucleus of the egg and of the sperm but the cytoplasm of the egg only (or at least in great part).
One thing that is present in the cytoplasm are mithocondria, which contain DNA, called mtDNA. mtDNA is therefore transmitted only by the mother (at least, in most species). Therefore a hinny will have donkey mtDNA, while a mule will have horse mtDNA.
Furthermore, cytoplasm contains transcription factors and various proteins that will influence the subsequent development of the zygote into an embryo and, again, these are maternally derived.
Another thing that changes is that there are certain genes on nuclear DNA which are expressed in a single-parent manner. That is, you have 2 copies of these genes, called imprinted genes, one from the mother and one from the father but only one of these copies -that of the mother or of the father, depending on the gene- will be expressed.


text:
Shortest strings not present in the human genome
What length are the shortest strings of DNA not present in any known person's genome, and what are they?
And is there a database online by which I could find this out?

Just for my personal curiosity... why? Anyway, the fact that not everyone's genome has been sequenced may pose a problem

I was about to write a description of how to find this out yourself but after closer reflection, this sounds hard. Essentially you’d have to build a dynamic programming solution but the solution will still have an exponential runtime with a huge exponent in the length of the result string (which we don’t know).

I would love to see an actual algorithm for this. The answers so far are tempting but remain quite theorethical

@KonradRudolph can you turn that into an answer and expand on it? Sounds interesting but I'd love to know why it would be that hard and what that solution would look like.

@Richard Actually, Ilmari’s algorithm would work in linear time. My approach was approaching the problem the other way round because I assumed generality, whereas Ilmari (correctly) assumes that we can give an upper bound on the length of the non-present infix, which allows the usage of look-up tables. My approach would have iterated over the whole search space of all possible k-tupes for k=2… (which is exponential) and check whether each of those exists a pre-built index of the genome.

I think you can count their possible length with statistics. I think finding them is impossible, because you cannot check the DNA of every living person... There are highly variable regions in the DNA, so in theory every combination van happen there... I think the shortest region - if there is such a thing - will be related to some functional stuff about DNA regulation (not my favorite topic), and it will be lethal if present. E.g. it will break chromosomes, or do some other fancy stuff...

Sequences that don't appear in a genome are called "nullomers".
That article claims that there are no 10bp sequences that don't appear in the human genome, and 80 11bp sequences that don't, citing this paper.

This is just about the protein coding region, but good point, there are diseases caused by specific DNA sequences. E.g. fragile X syndrome.

The human genome contains less than 416 base pairs, so, even after including a factor of 2 for the two strands and another to allow for some genetic variation, there must certainly exist some 17-base string not found in either strand of the genome.
Now, 417 bits is two gigabytes, which fits easily within the memory of a typical desktop computer these days, so a simple and efficient algorithm for finding such a string would be to set up an array of 417 bits, initialize them all to zero, and then simply iterate over the entire genome (including all known variations), taking each 17-base subsequence (and its complement), mapping them to base-4 integers and setting the bits in the array at the positions given by those integers to one.
Once you're done, any remaining zero bits will correspond to strings not found in the genome.  More to the point, the longest consecutive block of zero bits will give you the shortest base string not present in the genome.

simply iterate over the entire genome (including all known variations):  simply is not really the word I would have used but still...

@Ilmari: What you find with your method is those 17-sequences not in one human genome. But the question was about any known person's genome.

@rwst: The method I described can just as easily process multiple genomes, or fragments of genomes, and find those k-mers which are not present in any of them. I'm sure there are other complications one would need to deal with to apply it to actual genome data, but this should not be a major one.

@nico There are special data structures for this which do make it as simple as iterating over a single string (except that for each position you don’t have a single 17-mer starting there, but a list of 17-mers).

this is a good answer - there are certainly some 17mers that do not show up in the human genome. its certainly not possible to say that a given 17mer doesn't show up in any human genome, at least until we have sequenced every cell in every human being's bodies (non germline mutations happen too often).  That sounds hard.

This is why DNA PCR primers are about 20 bases long, helps ensure uniquiness. Also puts the melting point at a more reasonable temperature.

This actually wouldn't be too difficult to find. A common algorithm in genome assembly first takes stretches of DNA and finds all the substrings of length k that are present. (These are known as k-mers and the algorithm then builds the assembly based on how k-mers overlap.) So, given a genome(s) it's not that difficult to find all the k-mers of a certain length.
As Ilmari's answer points out, there are definitely 17-base k-mers that don't exist in a string of DNA the size of the human genome. Given the amount of repetitive content present in actual genomes, the actual shortest string will almost certainly be less than 17 base pairs.

Even if you give such a string you will never be 100% sure that you covered all human genomes, as asked.


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What is the difference between naive and adjusted p-values in a GWAS study?
What is the difference between a naive p-value and an adjusted p-value in the results of a GWAS study? See from this paper:

After Bonferroni adjustment, a single gene, DCTN4 (encoding dynactin 4) on chromosome 5q33.1, was significantly associated with time to chronic P. aeruginosa infection (naïve P = 2.2 × 10−6; adjusted P = 0.025; Supplementary Fig. 1).

Why did they even report it? Because the adjusted isn’t below their significance level? Well, tough luck!

Agree, including the unadjusted p-value is just waving around a big red herring.

Hummm, do you think they included the unadjusted p-value because the adjusted p-value is not very good?

No idea. For the normal 5% threshold, the adjusted p-value is actually still significant. I’ve seen several times that an unadjusted p-value was reported in papers without any explanation why that was done. Maybe the researchers just report what the software gives them without questioning whether it makes sense.

I suspect one of the reasons to report the unadjusted value is, as I allude to in my answer, many papers are now simply using a non-0.05 cutoff point instead of using some sort of multiple comparisons adjustment (which have their own issues). The unadjusted answer allows for comparison with those studies - I don't actually think its a red herring.

There’s an XKCD comic which explains the problem. Unfortunately, that comic is too big to post here. Briefly, a p-value of 0.1 says (roughly) that there’s a 10% chance (0.1) of the observed result being as extreme1 as it is simply due to chance (sampling variation from a population), assuming the null hypothesis is true.
Often, 5% is more or less arbitrarily chosen as “cut-off”: results with p-values below that (which occur by chance 1 time out of 20) are called significant – results above are insignificant.
However, this directly implies that when doing multiple studies, say 20, there’s a very high chance of getting a “significant” result by pure chance, without there being a real effect.
GWAS studies essentially perform experiments on many (hundreds or thousands) of factors simultaneously. Therefore, reporting the pure p-values would be very misleading since there would be a lot of spurious results with “significant” p-values. The probability of getting one or more spurious hits is called the familywise error rate (FWER).
The FWER can be reduced by adjusting the p values, for instance by performing the Bonferroni correction. The resulting p-values are quite a bit higher, which reflects the reduced certainty that the result is due to chance, i.e. the reduced significance.
It doesn’t generally make sense to report the unadjusted p-value. It was probably reported here because correcting for FWER is quite conservative (i.e. it trades a low false-positive rate for an increased false-negative rate) and the authors feared that the adjusted p-value looked less impressive than it should. This involves a fair bit of interpretation.

1 extreme = different from the expected result under the null hypothesis

I would have liked to +2 this: +1 for an excellent, precise answer and +1 for xkcdification.

I'd argue this actually belongs on CrossValidated.
Essentially, the problem is one of how a GWAS study is conducted. By looking over an entire genome for associations, you're actually conducting thousands or millions of experiments, not the single experiment most statistics were designed to handle. As such, you're going to find many results that meet the traditional threshold for "significance" purely by chance.
Early genomics studies had this problem - they'd generate tons of false-positives, and because of the numbers involved, their very small p-values would give an incorrect perception of the precision of their results. One way to handle this is to adjust for multiple comparisons to essentially penalize the p-value to enable you to still use the p < 0.05 threshold.
Another very common choice is to recognize that 0.05 is something of an arbitrary boundary, and simply choose a much, much stricter criteria for significance. This is, as far as I'm aware, what most state of the art GWAS epidemiology studies do.

Indeed. Bonferroni p-value correction simply divides the desired confidence (usually 95%: 0.05) by the number of independent tests performed - this gives you an adjusted 95% cut-off for significance. Alternatively, the Benjamini-Hochberg method actually adjusts the individual p-values after you have performed all your tests (see the "False discovery rate" wiki http://en.wikipedia.org/wiki/False_discovery_rate)


text:
Is there a biological basis to physical attraction?
Is there something encoded within us that makes us attracted to, e.g., someone

taller or shorter
with blonde or brunette hair
with green or blue eyes?

Or, is this phenomenon completely based on our social/cultural environment?

There is no way currently to tell us the exact meaning of the genetic code; Ask this question in 30 years and you may have the answer. AFAIK it is based off the environment as even different environments cause epigenetic changes in the expression of genes,

Yes, there is a biological basis. Your examples seem a little social/cultural to me, though. In any case, here are some examples I came across. One study that showed that women's hormones rose in response to smelling male sweat.  There's also a large psychological component that, for example, shows people find symmetry important in beauty.
A review discusses various aspects of facial beauty, and mentions that several studies have shown certain physical attractiveness standards are common across ethnic groups. It also mentions another study that shows how women are more attracted to a "masculine" face during the high-risk phase of their menstrual cycle.

Just to clarify, there are cultural biases as to what traits are attractive at the moment or given your own genetic make up when the specific traits mentioned in the question are considered.

@shigeta I agree, and I didn't mean it to sound like attraction was completely biological, just that there is some biological part of it. The examples I chose (or at least the first and last ones) were intended to highlight interesting and bizarre findings that caught my attention. I wrote it at work, so I probably didn't do a good job of writing it up...

i like your answer - just wanted to add a footnote... sometimes when I am abroad I'm struck by how movie stars we might view as 'on the chunky side' are the biggest hits there....


text:
How to quantitatively measure work done by a biological system?
Thermodynamic efficiency can be expressed as the ratio of Work done(W) to Energy invested (Q).
Thermodynamic efficiency= W/Q

How can one measure work done by a biological system?

Shouldn't this be W/Q? If Q/W then "thermodynamic efficiency" is very high when you do little work but put in a lot of energy. Doesn't seem very efficient.

Measuring the work done by a biological system seems pretty impossible. Imagine how many different ways one cell of your body uses energy (ATP). You can't really measure all the work done by every cell on a macro scale. Metabolic efficiency has been defined as... "health". That seems just a little ambiguous. That's why we use things like averages to determine if energy use is normal or not, such as in metabolic age.
In short, work is a more tangible term in discrete physics examples, but there is so much complicated energy use in biological systems that total systemic work can't be easily defined.

Just like with work in non biological systems, one needs to consider the path that the system takes. The definition of work for a process depends on a path. As well, different types of potential energy can be equilibrated for different systems.
So what's your system? Let's say a plant is in a sealed system, with a movable piston. It starts with a small amount of CO2 gas and a lot dissolved in solution. Then the plant is placed in a light source, which can enter the closed system and drive photosynthesis. As the plant makes oxygen it comes out of solution and increases the volume/pressure of gas in the system. As a result, the photosynthesis could do work against the piston. Then, since the energy inputted from the light source can also be readily estimated, the thermodynamic efficiency of "driving a cylinder using photosynthetically derived oxygen gas."

all_licenses: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/


text:
What is the lowest common denominator of cancer?
What is the lowest level attribute that all cancers share? Also, what is the highest level attributes that all cancers share?

What I'm trying to establish on this post is.. What do all cancers have in common? Even on the lowest level.

The answer is the question. If you can state the question with sufficient clarity, the answer can always be found. A thorough comprehension of carcinogens is but the start of prevention. The essence of Genetics is necessary to even start. We first seek also what is common that avoids cancer. To what extent is transmittal possible by plants, the animal kingdom, as well as the variety in mankind? Aging, timing, the critical factor of timeliness and thermal genetics are but a partial segment of immunity or cure. There is a huge gap between Cancer Research versus cancer treatment. Genetic pronenes

Hanahan and Weinberg's "Hallmarks of Cancer" articles should answer your question.
Their original, highly cited (14k+ citations), [Six] Hallmarks of Cancer article list these six common attributes of all cancers:

Sustaining proliferative signaling
Evading growth suppressors
Activating invasion and metastasis
Enabling replicative immortality
Inducing angiogenesis
Resisting cell death

The new article, Hallmarks of Cancer: The Next Generation includes additional "emerging hallmarks" and "enabling characteristics" (Figure 3) common among cancers:

The capability to modify, or reprogram, cellular metabolism in order to most effectively support neoplastic proliferation; and
The ability to evade immunological destruction, in particular by T and B lymphocytes, macrophages, and natural killer cells.

I would say angiogenesis, is Cancer's weapon of choice, please see this talk at TED

Cancer is such a diverse group of diseases that they really only share one commonality, unregulated cell growth with the potential ability to invade or transfer to other tissue types.
Many types of cancer share certain characteristics and can thus be grouped, but as a whole the only characteristic all cancers share is that they are classified as cancer. That classification is based on a number of markers and evaluations used to differentiate between benign and malignant neoplasms. Malignancy is determined by an expert pathologist who uses these markers and evaluations to determine his or her diagnosis based on experience. Some examples of indicators are circumscription, pleomorphism, presence of a capsule, nuclei number and morphology, amount of cytoplasm, number of mitoses, size, depth, particular gene mutations and so on. Even with all of these indicators, it can't be known with certainty beforehand whether or not neoplasms will metastasize.

Could you define your terms a bit more? How do you define levels?
The most common trait shared by cancerous cells is a regulatory malfunction somewhere. Whether it's a failure to regulate apoptosis, failure to recognize boundaries composed of regular cells, or failure to enter states of the cell cycle - a metabolic process somewhere goes awry, which leads to the unwanted proliferation of the cell and its daughter cells.
It was recently discovered that some (but not all) tumors spring from a set of "cancer stem cells" which originally incurred the mutation and serve as the epicenter. They have the capacity to regrow tumors if they are not destroyed or harvested during treatment.
I think the "highest" level trait they all share is that all cancers are unwanted. Other than that, cancers vary so widely that there's practically no universals between them that I'm aware of.
However, I'm not an Oncoligst or a researcher.

A reference would strengthen this answer, especially if you aren't familiar with the field. Although you are right: "cancer" is very much a blanket term for anything uncontrollable division of cells, whatever the cause.

There definitely has to be an upstream factor that drives ALL cancers.  The fundamental common denominator of all cancers is growth and survival, basic life processes.  If you can figure out what ultimately drives these processes, you can figure out what ultimately drives ALL cancer types and subtypes.  Cancer is just diversified growth.  With an open toolbox to employ.  All cancer cells originate because of one point factor, one switch point that alters their developmental trajectory.  There are lot of variables it could be.

All cancers are very different, even when they are the same type of cancer. Breast Cancer, for example, falls into ER+, HER+ and Triple Negative subtypes, all which have different survival outcomes and response to therapeutics.  We didn't realise the extent of diversity until we started to analyse the tumours at a higher level of resolution.
That being said, there can be some common pathways that are affected. p53 mutations tend be common in all cancer types, RAS, EGFR  are some examples. When we analyze the details at the genomic level(SNP level,Copy Number variants, insertions-deletions), mutations can be very variable, but as you zoom out we see that they target similar genes and furthermore similar pathways.
But recall: people used to die just of fever back in the day, we know now that fever is a symptom not the disease. Technology will allow us to understand whether Cancer is just a catch-all, or whether they are actually different diseases.

Mites are one of the biggest major causes of diseases including cancer. It's known that's mites change th1 into th2 effectively compromising the immune response. Scabies (scarcoptes var homis) is NOT the only mite that can infest a human being. In fact there s 250 mites that can.
This is an area that needs to be collaborated with veterinary medicine.
I think the rise of cancer in the UK over past years will correspond to the increased trend over recent years for designer dogs. There's zero awareness to general public about mites and majority of people do not realise small caged animals or birds require to be treated also.
There's plenty case studies and peer approved papers that highlight the diseases alternate mite infestations transmit yet the medical community are not being educated in this area.
As a point of interest I find it difficult to understand why the UK government are giving drug addicts and alcoholics an additional £20 per week for the keep of the addicts dog. To my mind it's blantanly obvious these people are not responsible enough to regularly worm or treat for parasites I  these animals. Perfect way to spears the disease. Look at studies on stray dogs abroad and wild animals and birds. Whether mites have always been in the environment I believe the assumption they are self limiting is utterly ridiculous and wrong.  Mites are a hugely under researched area and there is conflicting references with authors giving the wrong information which they cannot prove. The evidence is there to say alternate mites or pseudo scabies acariasis can host swap can complete their life cycle on the alternate host.

Link to papers?

Can you please add some references to back up your claims?


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What is the concentration of ATP in an average cell?
Can someone give me some references showing the average concentration of ATP in a cell?

The concentration of ATP depends strongly upon cell type, its current activity (for muscle, neuronal and secretorial cells). Besides, the local concentration of ATP in certain cell areas (mitochondria, near myosine heads, near membrane, in synaptic vesicles) might be orders of magnitude higher than that in other parts of cytozole.

Do you have a reference to an estimate of the ATP concentration in mitochondria?

Answer
This article covers the energy charge and ATP concentrations of an array of muscle cells from many different organisms. Since many factors come into play (amount of glucose available, rate and regulation of glycolysis and cellular respiration, use of energy in metabolism, etc.) it is expected for the ATP concentration within the cell to vary significantly. The ATP concentrations reported span from approximately 1 to 10 mM.

References
 - Beis, I, and E A Newsholme. “The Contents of Adenine Nucleotides, Phosphagens and Some Glycolytic Intermediates in Resting Muscles from Vertebrates and Invertebrates.” Biochemical Journal 152, no. 1 (October 1975): 23–32.

Muscle cells generally need much more ATP than any other cell in order to to relax. The concentration in other cells (for example neurons) can differ significantly from these values.

Alternatively: http://bionumbers.hms.harvard.edu/search.aspx?log=y&task=searchbytrmorg&trm=atp+concentration&org=
As LanceLafontain answered, most of the numbers fall within the range of .5-10 mM

Both answers have 10 mM as upper limit, but why is there a discrepancy in the lower range? 1 or 5? That's quite a big difference IMO.


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In cancer, why do cells duplicate themselves?
In regards to cancer why do cells replicate themselves? If it's a mutation, what kind of mutation would this be classified as?

I would rephrase the beginning of the question, if you agree. Right now it seems a bit "backwards". Cancer is defined as an uncontrolled growth of cells, so there is no specific reason (finality) for cancerous cells to grow. When a mutation causes cells to grow in an uncontrolled manner then you have cancer.

This article covers some of the key issues of cancer in layman's terms.
Essential, cancer is caused by multiple mutations in key regulatory genes which function in maintaining the cell cycle. This provokes uncontrollably rapid cell division, with only furthers the problem with genetic mutation. Here are some quotes from the article to strengthen your understanding in cancer cell mutations.

Image source

The cells become progressively more abnormal as more genes become damaged. Often, the genes that are in control of DNA repair become damaged themselves, rendering the cells even more susceptible to ever-increasing levels of genetic mayhem.
[...] Most cancers are thought to arise from a single mutant precursor cell. As that cell divides, the resulting 'daughter' cells may acquire different mutations and different behaviors over a period of time. Those cells that gain an advantage in division or resistance to cell death will tend to take over the population. In this way, the tumor cells are able to gain a wide range of capabilities that are not normally seen in the healthy version of the cell type represented.
[...] Mutations in key regulatory genes (tumor suppressors and proto-oncogenes) alter the behavior of cells and can potentially lead to the unregulated growth seen in cancer.

Hallmarks of Cancer: The Next Generation is by far my favorite article at the moment explaining cancer in-depth. I'd recommend reading through it.
The cells replicate themselves, without regard for normal cellular restriction, due to a number of mutations that accumulate:

So our cancer cells are evading apoptosis. P53 might be knocked down, so cell cycle arrest cant occur, but what about when Akt is constitutively "ON"? Normally P53 can induce apoptosis via the following mechanism:

And as it turns out, Akt inhibits apoptosis in the following manner:

So the cells really aren't dying. What about replicative aging? We find cancer cells have telomerase activity which essentially makes them immortal.
There's also evidence to support regulation of pathways which promote epithelial-mesenchymal transition in tumor cells, and promote invasiveness and cellular motility in most cases:

For the sake of a short response that isn't a wall of text/images, this is a broad survey of some relevant cancer pathways which essentially make cancer what it is. It's more complex than this, but if you put in some research given these hallmarks of cancer, the answers are there.


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What causes mutations in regulatory genes?
In detail, what causes mutations in regulatory genes?

This question is just too vague, there is nothing special about regulatory genes with respect to mutations.

nothing causes mutations in any specific genes.  mutations actually occur as the result of random processes and can mutate any given point in the genome.  mutations may be found more often in some genes or regions of the genome more often because they have a positive selective force that gives them more staying power in the gene pool over time.
Its better to think of it this way: mutations happen everywhere, but they stay in the gene pool more often if they do something useful.  Genes are the active portions of the genome so mutations in genes are more likely to stay around.

Not entirely true;multiple well defined mutational processes that have very specific mutational signatures; for example a large subgroup of APOBEC family of cytosine deaminases specifically mutates cytosines that are preceded  by a 5' Thymine and are followed by A/T/C ; Also - the probability of mutations in various regions of the genome can vary by covariates, which is used in the MutSig CV algorithm to estimate mutation frequencies in genes under conditions of null selection.
See http://www.nature.com/nature/journal/v500/n7463/full/nature12477.html for how processes determine mutations.

I wish to add that my point was that non-selective forces can still result in variations in the frequencies of mutations at different genomic loci. Also, some mutational processes are associated with the generation of very specific oncogenic mutations; Recently my group showed that the activity of APOBEC enzymes was strongly associated with a preference for a certain PIK3CA mutation hotspot instead of another that is equally potent, due to the presence of a target sequence motif in that hotspot.
http://bit.ly/1pdgKzS

interesting @AnkurChakravarthy - mind outlining how much more likely such hotspots are than the background here for the record?

OK - in the case of PIK3CA mutations the two hotspots that are equally potent in terms of selection during tumorigenesis generally occur at a 1:1 ratio across cancers overall, but in those tumour types with high APOBEC activity, the correlation between the activity of the enzyme in the genome and a preference for the hotspot containing the sites it recognises was 0.7 (Spearman's Rho) - suggesting that the process was dictating enrichment for mutations in one hotspot over the other, independent of selection.


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How realistic is to use DNA for long term storage?
This is mainly a followup question to the recent paper Next-Generation Digital Information Storage in DNA.
Personally, while I agree about the data density of the format, I can't help point out the large issues with the inability to rewrite and recopy the data efficiently and potential issues regarding the "immutability" of the data. I'm curious about other takes on the publication and whether or not the stability of the DNA as well as the "writing" inefficiencies are better than I'm believing.

http://the-scientist.com/2012/08/16/dna-data-storage/, for the lazier.

My own view is that while reading DNA has advanced (and is still advancing) immensely, but writing is very much a work in process and still has a long way to go. As for stability/fidelity, I don't think there is a problem, considering that the Neanderthal genome was sequenced and it was stored in less-than-perfect conditions.

I can at least answer the question about the stability of the stored information. With my colleagues, I worked for several years to estimate the rate of DNA degradation at room temperatures. Our results showed that the information could  be retrieved after 100,000 years storage.

Did you publish the research?  Could you link to it?

Hi Jerome. Given the source of the studies, it's probably not published.

I seem to recall a recent report that DNA had a half-life of 517 years. I don't know the conditions under which this was tested. I'll look up the reference and post it here.

EDIT: 521 years, radiocarbon dated from bone fossils, specifically measuring mtDNA. (http://rspb.royalsocietypublishing.org/content/early/2012/10/05/rspb.2012.1745). That said, dried DNA is orders of magnitude more stable at room temp than solubilized DNA, so the longevity of DNA for storage, when the conditions are not specified, can vary widely.

Further more, Harvard researchers have used DNA to encode 700 TB of binary information into a single gram of dsDNA. http://hms.harvard.edu/content/writing-book-dna


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Why don't flies avoid the motorway?
Flies have a short lifespan, therefore evolution should technically happen over a shorter period of time (years).
Flies die all the time from getting hit by cars on the motorway.
Those flies that don't go near the motorways have a greater chance of reproducing.
If this was an advantage (motorway avoidance = not dying), shouldn't more and more flies be avoiding the motorway?
Cars have been around since, roughly ~1950. That's 60 years.
Why don't flies avoid the motorway?

Again, this kind of question is down-voted? As with this question there is an answer! In fact this is a semi-duplicate?

I agree and upvoted, though it might be nice if we had an FAQ as this sort of question pops up regularly...  evolution and biology is hard to get an entree.

"in the long run we're all dead men" - John Keynes
First is the fact that flies have adapted their way around cars long long ago by giving up longevity for faster breeding; flies are cheap and they just don't care if they get hit by a car.  The average flying insect lays large clutches of eggs - hundreds at a go is common.  See this reference on butterflies as an example.  In table 2 the potential fecundity (FEC) is I believe the number of eggs laid in a lifetime.  The smallest number is 53, the largest is 1500, the average is hundreds.  As long as one or two fly from each lifetime of breeding survives, the species holds on just fine, more and there is a population explosion.
Another side of the question is:

It would still be an advantage to be smart and stay off the road wouldn't it?  If they adapt so quickly why doesn't a mutant braniac fly come along that can see the cars and in short order all flies would have this trait... its just selection too, right?

The answer there is that not everything is available to adaption.   Flies could become that smart, heck maybe even smarter than us, but they have lots of pressure on them from many things they could do well, and their system is already doing many things very well enough for them to survive as they are without making such a large change that might require some short term disadvantages that prevent them from becoming entirely different animals.  The essay "why pigs don't have wings" is a pretty good reading for a longer more detailed answer.
Where I live its temperate and there is a good amount of water- lots of food and hospitable for all kinds of plants and animals can thrive here. On the hillsides where updraft currents blow flying insects.  The spiders 'figured this out' and the bushes and trees are often covered with cobwebs on this side of a house.  The flies don't avoid the wind just because so many of them are eaten - they would not themselves be able to mate or eat.
Note that the spiders haven't become 'smart' - just lucky to have landed in that area.  But then there are many many spiders there that they probably don't get a lot more food than a spider living on the other side of the house who has the only web for a space of several cubic feet.
Everything balances itself out in a competitive landscape because there are so many other living things ready to take advantage of a break like this.  Cars just aren't enough to budge the other things the flies have to watch out for. For more reading about how competition affects evolution read about the Red Queen and the Tangled bank.

Flies can and do evolve quickly thanks to a short generational time. However, your question seems to stem from a misunderstanding of what evolution entails.
Evolution occurs when the genome mutates. Why it mutates isn't particularly relevant, but a gene (or genes) mutates and as a result of that mutation a characteristic of the organism changes. It doesn't have to be a big change. Maybe a single protein somewhere operates 2% less efficiently, giving practically no outward signs of evolution. Sometimes it can be big - changes in coloration, changes in sensory perception, lifespan, etc.
In order for mutations (beneficial or detrimental) to have a significant effect across an entire population, the population itself has to be fairly small or the mutation has to give a large advantage over the old version.
Flies are not avoiding motorways because a mutation that specifically codes "AVOID CARS" is going to be very unlikely given that it would you would first have to encode what a "CAR" is in order to avoid it. That probably won't happen because on the time scale that evolution usually acts over very large populations (which flies have) we won't be driving cars by the time necessary for deaths due to cars has a serious effect.
Flies have huge populations and breed extremely quickly, so even if a few million are killed by cars, it doesn't put a dent in their population numbers. There's no reason for the change to occur. Combined with the extreme difficulty of actually encoding a gene specific to cars, the odds are it just won't happen in any realistic time-frame.

Wouldn't it be possible for the genome to mutate so flies avoid darker areas (i.e. black roads (not straight away but darker through generations)). These flies would be more successful. But I agree with your second point even if a few million are killed by cars, it doesn't put a dent in their population numbers

Sure, it's possible for the genome to mutate that way, but if you're just avoiding 'dark areas' then you're also avoiding natural 'dark areas' and not avoiding all of the light-colored roads made of concrete.
What's possible isn't so much the crux - there are very complex occurrences in the genome, but unless there's a big impact it's just not favored.

I second @Blundell here. There is no need for a concept of CAR in order to have a behavioural change that results in CAR AVOIDANCE. I think this is a misunderstanding of how evolution works (which I encounter in laymen very often) and downvoted this answer.

@luispedro: the essence of the answer does not change. You may not need to encode car, you may not need to encode car avoidance... the fact is: being smashed by cars is not really a big problem for flies, as the proportion of flies that dies like that is most probably very small. Actually, encoding for "avoid big objects that move" may even be negative, because, for instance, flies love to go on wild stinky animals... :)

@nico: Yes, the "irrelevancy" argument might be sufficient. That does not justify using a very wrong argument about how evolution could not generate a CAR AVOIDANCE behaviour. If that paragraph is removed, I will remove the downvote.

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


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Recommendation of a comprehensive book on the history of medicine
I was wondering if somebody could recommend a book on the history of medicine, be it comprehensive or an introduction to the history of medicine. I know there are a lot of medical books that cover this subject, but given that I have a limited amount of time for reading I was wondering which book would make the best use of my time.

While it's not meant to be a history of all of medicine, I thought the The Emperor of All Maladies touched on a good deal of the history as the author took us through how cancers were diagnosed and treated since long ago.
Great book, that was.

I enjoyed "Doctors: the biography of Medicine" by Sherwin Nuland
It is not comprehensive, but covers the major eras of medicine.
Im sure there are many others.