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How does evolution produce complex organs
I've been wondering lately how evolution manages to produce complex organs. It is pretty obvious to me how evolution would select some minor traits like size, resistnce to illness or climate. There is a mutation where some organisms are slightly different and better traits are selected. However I cannot imagine how an organism will mutate to have lets say lungs at once and unless organism has a functional organ there is no reason for the trait to be selected. So how does evolution produce complx organs?

The answer is 'gradually'. All other answers will be longer ways of saying the same thing.

This is, fortunately, not true. See Evo Devo below.

It is true, there is no sudden transition from no organ to a complex organ. It happens gradually.

You might find some relevant material if you search for "What use is half an eye", the classical question about how complex systems can evolve. Typically the answer is along the lines of "from smaller systems which in themselves are useful or at least not impeding".

@Armatus if this was an answer I would mark it as accepted. Found really simple explaination here - http://www.dbskeptic.com/2008/07/06/what-good-is-half-an-eye/

@Stilgar: Nice article, though I think it's worth mentioning that the human eye has not evolved from this line ;) The mammalian eye develops as an outgrowth of the brain whereas the given examples all develop first and then attach to the brain (according to biology year 12 which may have been wrong of course)

Still it make sense to me (as total Biology noob). First some tissue forms that works in some very basic way and then it evolves to form an organ.

Watch The Christmas Lectures by Richard Dawkins, here https://www.youtube.com/playlist?list=PL24C9639BE2DD4223 In one of them he shows how an eye can evolve incrementally. You don't need much biological training or knowledge to appreciate them.

you may be interested in cloacal breathing in turtles and things called swim bladders. both are ways incomplete lungs can be useful.  There is no such thing as an irreducibly complex organ.

The best introduction to evolution of complex phenotypes via master control genes is Endless Forms Most Beautiful: The New Science of Evo Devo and the Making of the Animal Kingdom by Sean B. Carroll. You might also want to have a look at a more recent Evolutional developmental biology (Evo Devo) book like those you get when searching for "Evo Devo" in Google Books.
In summary, it is possible for a mutation to change a shape by changing the spatial distribution of a transcription factor during embryo development. What's more, by changing the distribution of two mutually dependent factors, formation of any shape is possible if the distributions overlap. Such transcription factors are highly conserved in evolution and the most important cause of the endless forms we see.

Excuse my ignorance but I have only studied high school biology 15 years ago and in another language. If I understand your answer correctly it is possible for a mutation to create a functional organ at once?

No. You said above there are always small steps, and I said this is not true. The shape of an organ, when it is already evolved, can change drastically because it is determined by processes that are very sensible to the environment and to some mutations.

PS. There are indeed mutations that can 'create' a functional organ at once, because there are mutations that can make organs disappear. Just do the reverse change. I know the reverse would be near impossible in evolution.

This is a bit too simplistic. For sure we did not get from unicellular organisms to organisms with a stomach, hearth and lunghs just with a couple of mutations. Several small adaptive steps exist in the middle.

This is a strawman argument because I never stated that, either.

Just because the inverse of something is true, does not make that thing true. Organs disappearing with a single mutation is not evidence that they could ever have evolved with one.

And complex phenotypes are not equivalent to organs - do you have an example of an organ which evolved as a result of a master switch?

@rwst: -1, if your intention was not to state that then you have not really answered the question... You may want to quote relevant extracts from the books you refer to, in order to improve your answer.

Part of organ complexity is shape, and that can well be changed with a single mutation or even small change in environment. The question isn't about lungs popping into existence. It's about lungs with all their complexity, and part of that can change drastically. As you're not inclined to accept anything from me, I will close this now

@rwst: I am very sorry that you are taking this so personally. The only thing I am interesting into is to have a good answer, I don't care who writes the answer. The OP states: I cannot imagine how an organism will mutate to have lets [sic] say lungs at once so it is clear that he is asking for how lungs popped into existence, not how they were modified from a previous existing respiratory apparatus.

Yeah I am interested in how organs pop into existence. I am fully aware that they have been changed and improved slowly over time but unless they somewhat worked from the start evolution would not select for this trait

@rwst it's not a personal attack, it's just that the interesting point you've made (that complex phenotypes can appear rapidly in evolution due to master switches) does not demonstrate that organs arise suddenly, but that they can change form quite suddenly. It doesn't answer the question. It remains that gradual accumulation of small changes still accounts for evolution of the molecular networks which might be rearranged by a master switch mutation. For what it's worth, I do think your answer was interesting :). Please don't stop contributing just because of this.

-1 While certainly relevant, I don't think this answer is actually answering the question. Will undo if improved of course :)


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A timeline of the odds for survival for fertilized eggs and fetuses
I'm looking for data to build a timeline of the odds for survival of a fertilized egg, i.e.,

What are the odds it'll last a week?
What are the odds it'll last a month?
2 months?
(and so on until)
What are the odds of it being born?

I am interested in the odds with the usual level of care in an industrialized nation (and a mother that is not trying to abort the fetus).

Not exactly what you are looking for, but kind of related: http://4dpiecharts.com/2012/06/15/how-long-does-it-take-to-get-pregnant/

here I found an answer. Not sure how accurate is is, though.
Data seems to be from the US
Here is a rewrite of parts of that article:

266 days before birth, all we have is a fertilized egg.  (~33% chance of living birth).
The odds are calculated using data from in-vitro fertilization, and the next stage is 66%.
In in-vitro, some 50% of the eggs cannot fix to the uterine wall
262 days before birth, the egg has implanted (~66% chance of living birth)
After implantation, there is still a decent chance that the embryo will be aborted (and maybe the woman will not even know that she was pregnant).
Half of the embryos that die from here on will die because of chromosome abnormalities.
241 days before birth (~88%)
178 days before birth, entering the second trimester (~97%)
At this stage, problems are more likely to stem from the mother, not the fetus' genome. Problems with the cervix, the uterus or the placenta are (some ?) likely causes of death.
89 days before birth, entering the third trimester (~99%)
At this stage, doctors will consider the fetus a patient, and treat it if needed.

Maybe you could summarize a little bit the content of that page, in case it went down in the future.

source: Stack Exchange

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

sort: votes


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Where can I find histograms and tables of prevalence of mutations in cancer?
At some point in the past I found a cancer portal site which had aggregated data for the relationships between various mutations and their prevalence in cancer types and tumor data. The data was presented in various pleasantly coloured interactive histograms and you could search per-gene or per-disease.
However after spending a few hours, I cannot find the site again. Though I have found many sites with a great deal of data and nice visualizations.
The nearest looking site, was this one:
http://plugins.biogps.org/data_chart/data_chart.cgi?id=673
But that doesn't have the level of detail that I remember.

Perhaps you mean COSMIC? The EBI Gene Expression Atlas also has pretty charts, but now mutations.

Your description sounds a lot like the International Cancer Genome Consortium's website. Choose a cancer and click your way to "Project Data" and you'll see some nicely covered histograms describing disease prevalence. You can also get mutation data among other things
Another good bet is the cBio Portal. If you click on "Data Sets" at the main page, you can choose a cancer and get various data in the "Study Summary" section including the prevalence of mutations within the study dataset.

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


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How does the brain instinctively know the math behind Newtonian Physics?
A 10 year old child does not have the intellectual power to accurately calculate the energy required to throw a ball an arbitrary distance. Yet they are able to accurately throw a ball at a distinctive target.
Similarily, we often "instinctively" know an approximation of the amount of energy and force required to accomplish certain tasks, even considering that many of us have minimal knowledge of the mathematical complexity behind the tasks.
How does the human brain know the values of force, energy etc. required when accomplishing certain tasks, while being ignorant of the mathematics behind the Newtonian Physics of the task? Is it just a game of "guess and check"?

A 10 year old child does not have the intellectual power to accurately calculate the energy required to throw a ball an arbitrary distance... says who? The fact that he is indeed able to seems to say the exact contrary.

Also, remember that the laws of physics exist and work independently from the fact that one knows them (in fact the old "bumblebee should not fly" story is just a myth).

@nico It would unreasonable to expect a 10 year old of average intelligence to be able to create a mathematical model of a a ball thrown - a concept taught in highschool. I do not understand your second comment. Could you clarify it?

You don't need to generate a complex mathemathical model in order to throw a ball. A toodler can do it. You just try and try and you learn. A 10 year old may not be able to tell you that a 45° angle is the optimum to have a long throw, but he can easily realise that when he throws balls at that angle (even if he does not quantify it exactly) they go further away. Think of walking: most of us do it with no issue. Almost noone, however, is able to do a correct mathematical/physical model for standing and walking.

The second comment was just a reference to the old myth that -according to the laws of physics- bumblebees could not fly. However, as they don't know these laws they continue to fly with no problem. Of course this is false: you don't need to know the laws of physics in order for them to work (and for you to make use of their effects).

I agree with @nico, a child does have the intellectual power to calculate trajectories and launch energies, and they develop the ability through trial and error. Your question is backwards - the brain doesn't know the math until it explictly learns it, and you don't need math to interact with physical systems, only to describe them in the abstract.

Anyway, to get into the biology of "how the brain knows" you may start reading about proprioception.

Forget 10-year-old children. Pigeons literally have a pigeon brain, yet they can integrate complex ODE systems in real-time.

I'd advise that Farhad also reads about neural networks (the computational algorithms). Even a small neural net is capable of astonishing things, after it has learned them.

I think this question makes much more sense, and will receive a better answer at CogSci.SE

Trial and error.
The CNS is very much a living, changing organ system - much more so before you are an adult. While you are a child your neurons fire, muscles contract, and force is exerted on objects - then your CNS modifies itself (either through redistribution of neural contacts or growth of new neurons spurned by chemical changes) to account for the results.
This is why "practice makes perfect." As you continuously perform a task, like throwing a ball, your body is keeping track of the results. Did X muscle fibers contracting in Y muscles overshoot your buddy? You register the failure and compensate by utilizing X-N muscle fibers that contract in Y muscles until you consistently satisfy your goal.
Your CNS is keeping track of everything, all the time. There isn't a single instant in your life - asleep or awake - that's not being monitored, so your body has copious amounts of data to work with when making its estimates.
This is also why simulations take time to adapt to, even if the person is fully aware of the basics behind the physics involved.

First of all a little detail : laws of physics describe what is going on, they are not what is actually going on. Beeing able to make nearly precise predictions about the outcome of a certain action is what those formulas are about, as well as getting a feeling of how and why it actually happens this way. I would bet that neither Newton nor Einstein or any great head of physics ever tried to predict a real life action by the mathematics they know.
The key to understand how organisms predict actions is heuristics. So you and any organism on earth uses other intuitively calculated values for predicting actions. You can easily predict that every object you throw in the air will fall to the ground whether you are a physicist or not.
Prof. Gigerenzer explained this phenomena at this presentation at 36:50 unfortunately this is in German, but maybe the pictures he shows help a little bit. https://youtu.be/IderadHRCu8
An easy example: a dog that is trying to catch a thrown freesbee in the air does not know anything about mathematics.  But dogs actually seem to be pretty good at predicting where a freesbee is in a good position to get caught while it is still in the air. How they do this? A dog is focusing the freesbee at a certain angle to themselve at which it would be good to get caught when they are close enough. They then ran fast or slow, always keeping the same angle, not the same distance, to the freesbee. No matter the parabola of the freesbee as long as the dog keeps the angle all is fine. When the freesbee comes close enough to get caught, the dog bites and catches the freesbee.
Do we do unconscious mathematics? Yes kind of easy sensoric heuristics. Do we do unconscious mathematics like physics? Definetly not, as I said Newton and others are formulas that work well to EXPLAIN what happens, they are not what is actually happening.

+1 for the first sentence. Exactly what I was going to comment.

And just to be different.
You are looking at 30 million years of evolution and natural selection to be able to gauge distance and relative position in 3 dimensional space accurately. The penalty of making a mistake is death by falling out of a tree.
http://anthro.palomar.edu/earlyprimates/early_2.htm
As for throwing... that is another 3 million years of evolution on how to use such a tool. The penalty for missing a target... well I am guessing it is to be eaten or have your child eaten by one or more predators.
https://en.wikipedia.org/wiki/Oldowan
Humans are good at throwing things... better than good. Human can throw fast and accurately. Our shoulder joints have undergone natural selection such that humans have weird shoulder blades compared to other great ape.
http://www.natureworldnews.com/articles/16572/20150909/ape-human-evolution-more-clues-revealed-shoulders.htm
If there was enough selection pressure to reshape the shoulder of an ape to enable it to throw rocks (projectiles) fast, I am sure that was equal pressure on the software side to make sure said rock hits its intended target.


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Is the theory of evolution being disproved by bats?
For some species the Darwin's theory evolution makes perfect sense. I can easily imagine how, for example, the giraffe has evolved to its current appearance: the natural selection was favoring individuals that could consume more vegetable food from trees using longer necks, and some individuals were getting at birth necks longer than average by pure genetic randomness and the long neck trait was being propagated to descendant individuals by means of genetic inheritance. I have no problem with understanding this kind of evolution.
Now let's have a look at the bat and its relatives. The bat is one of the few mammals that have something to do with flying and the only one that took flying to the bird level. Paleontologically, first mammals date to the dinosaur era and initially looked similar to the present-day shrew (which looks much like a mouse). The question is: how in the world prehistoric mouse-like creatures could grow wings over time? It impossible to believe that some mouse-like individuals were getting wing-like limbs by mutation and the "wings" were growing out accompanied with the knowledge of how the "wings" can actually be used. Ok, then maybe first wings were tiny moth-size wings and then grew larger? But where natural selection would come into play in this case? Such mouse-like individuals would have no advantage over their wingless relatives and thus would not be able to transfer those wing-growing genes to their descendants, quite the contrary, such individuals with useless mutations that interfere with their ability to walk would be suppressed by natural selection and therefore "weeded out".
So what is the story behind the bat's wings and is the Darwin's theory really able to support it?

Darwin's theory was flawed and that's not a secret, but the contemporary theory of evolution is about as accepted as it gets. Species or traits which pose a challenge to it are nowadays more commonly regarded as a case which will be solved sooner or later (possibly by fossil findings) rather than a potential proof against the theory.

Please don’t cross-post. – If you’re unsure which site to post on, discuss this on the meta sites. FWIW Skeptics is a better suited site. A biology website is probably not the best place to question the basic tenet of biology, much like the Christianity Stack Exchange will not accept discussions about the non-existence of god.

@KonradRudolph: the cross-post looks like it may be closed as off-topic there.

http://www.sweary.com/dailyfun/wp-content/uploads/giraffes.jpg

@Mechanicals How do you figure that out? Two mods (me included) have commented saying that it’s on topic.

That's weird.  I added a comment here yesterday and it seems to have been deleted.  Is that possible?

Is the giraffe example accurate? Was reaching higher food sources indeed the mechanism driving the evolution of longer necks?

@DanielStandage... Maybe: http://www.wired.com/wiredscience/2010/09/giraffes-necks-for-food-or-necks-for-sex/

Never really fond of scientific fundamentalism  all theories are in need of continual questioning to keep them relevant. Socratic biology was at least as accepted for much longer than Darwin. In any case beginners often find that evolution in general is a lot more robust than it appears at first. This is not a difficult question.

Theory of evolution is not being disproven by anything and therefore it must not be being disproven by bats.

@Jerry yes, it is possible, in short if comments are straying too far away from the question they are pruned.

I think bats would actually be a good place to look to study evolution. Bats make up 25% of all mammal species, so there is a lot a diversity there. That diversity is direct evidence of evolution and speciation.

Take a look at this little fellow:

It's a flying squirrel — a shy little nocturnal rodent which lives in trees and, despite its name, does not actually fly.  It does, however, have a skin membrane called a patagium between its fore and hind limbs which allows it to glide from tree to tree and thus evade ground predators.
It's not hard to see how the flying squirrel's patagium may have evolved: after all, ordinary squirrels, to which the flying squirrel is indeed related, also spend most of their time in trees and avoid the ground, often performing quite impressive leaps to cross from one tree to another.  With sufficient pressure to minimize time spent on the ground, any little morphological changes that allowed longer leaps would be favored by natural selection.
Indeed, there are plenty of other groups of mammals which have independently evolved very similar adaptations to gliding.  Given how many small arboreal mammals there are, this is perhaps not surprising.  What's special about bats is not the fact that they possess flight membranes — it's that they're the only group of mammals, so far, to have taken the next step to actual powered flight.

Gotta love the way you started your answer. Thanks.

So basically, once trees evolved, birds (and bats) were inevitable.

I think sugar gliders (and the like) are different in that their skeletons dont indicate that they are gliders. The bone structure of bats have clearly evolved i.e. in forming elongated fingers to fit their wings.

try "flying" lemurs then, sugar gliders would the very start of the adaptations. you can also look at onychonycteris a late bad ancestor with short fingers compared to modern bats but far too long to serve any other function.

Check out this famous paper by Gould and Lewontin, the Spandrels of San Marco.  It's essentially a criticism of your question as it's not really the right question to ask.  You're engaging in what they call "adaptive storytelling".  The truth is that barring fossil intermediaries it's almost impossible to infer how a species transitioned from primitive ancestors.  Secondly you're assuming constant selective pressure over time. It certainly can be the case that traits evolve in certain environments but are conserved over time despite no longer serving their original function (why do flightless birds have feathers still? etc.).

Penguins would be pretty cold without their feathers.

Perhaps you didn't realise that bats' wings are equivalent to the front limbs of other mammals? They aren't extra limbs, just adapted ones, and the wings are formed from flaps of skin between the 'fingers'.
Taking that into account, I don't even see how anyone can think this is a challenge to the theory of evolution. It's obvious that increased skin webbing between fingers, eventually combined with increased finger length, provides an adaptive benefit to tree-dwelling small mammals. Initially it gives increased air resistance to allow controlled falling, then to allow gliding (like in flying squirrels), and in the most extreme cases to allow flying.
These kinds of questions are always about a failure of imagination, or a misunderstanding of the basic facts, and never about the theory of evolution being wrong. (edit: that doesn't mean the theory of evolution can't be challenged - it is a theory - but that this isn't a valid way to challenge it).

+1, I agree completely with you but I would remove or rephrase the last sentence. The theory of evolution is our current accepted model for the evolution of species. It is a scientific theory and hence it is falsificable. Maybe 500 years in the future strong evidence will have shown up that will make us rethink our current theory of evolution, much like some of Darwins' original points are now being refined. Assuming that any questioning of a scientific theory stems from misunderstanding it and that the theory cannot be wrong makes it become something more like a religious dogma.

By 'equivalent' you mean 'homologous', right?

@nico I certainly didn't mean the theory of evolution is immune to testing or falsification, but that saying 'I can't imagine how X trait evolved, therefore the theory is wrong' are not valid challenges to the theory. My answer was more of a grumpy tirade than a proper answer :)

@Mechanicalsnail yes, but given the asker thought bats' wings were an extra limb, I went for non-technical vocabulary.

@RichardSmith-Unna: I think the technical term for the OP's line of reasoning is Argument from Personal Incredulity.


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What is itching?
What exactly at the molecular level is itching? What physiological function does itching serve, if any? I cant remember the reference but a PLCb3 null mice lost the itch phenotype, so presumably it is mediated by the Gq-PLCbeta pathway through a cell surface GPCR. Since a physical action of scratching relieves it, could it be a case of a mechanosensitive channel at work?

I have seen two answers posted and then "disappear" after a couple of days.. Can someone tell me whats happening or was I dreaming? :-)

one was just a link to the wikipedia page about itching, was deleted by a mod as it was not an answer. The other was deleted by the owner (see my comment in the current answer).

Just for the record: as a comment to one of the deleted answers I linked to this article: The neurobiology of itch - Ikoma et al., Nat Rev Neurosci 2006. I think it could be a good starting point for an answer (I do not really know the subject and at the moment do not have much time to write a proper one, but I thought I would put the link again here)

Regarding physiological function. I was always of opinion thst purpose of itching reflex is to drive away insects that are drilling or biting or clinging to hair or skin. Given that insects transmit diseases and damage skin, the reflex makes perfect sense. It works for me :-) as it works for dogs, cows, etc.

Like all tough questions, this one has no well understood answer.  Itching "is one of the most poorly understood sensations."
The obvious facts: The urge to scratch part of your skin is the result of stimulus of the skin which causes some of the nerves to register an irritation (you can get an itch in internal organs too - which sounds excruciating).
Biochemically, following the effects of poison Ivy oils, the cathechols break down to orthoquinones and may stimulate local mast cells to release histimine.  So in this case you can see that itching, like many irritations are linked to the immune system which is highly variable from one individual to another, as such it is still a bit of a black box.
The histamine pathway is well studied and histamine stimulates an ion channel protein in nerve cells called TRPV1, which is also known as the capsaicin receptor, which means it is also related to sensing heat.  This explains why itching can be relieved (temporarily) by exposing the skin to water that is as hot as the patient can stand without burning them.  This is one of the ways pain and itching are highly intertwined.
Still, not all itching is stimulated by histamine release; that isn't the whole story.  Antihistamine allergy pills don't help itching.  Other nerve channel proteins can be activated to stimulate itching.  One example found in an itchy mutant strain of mice is TRPA1, and maybe the G protein coupled receptor, Gastrin Releasing Protein Receptor (GRPR). Its hard to imagine that there will not be more mechanisms discovered later.
Mediated both by immune systems and nerve cells, which literally have a mind of their own and whose signal processing is highly individualized and sensitive to local conditions in the body make itching a fairly mysterious phenomenon.  Its also likely that itching can be entirely initiated as a mental condition (Pruritus), so it is not entirely a biochemical phenomenon, which only serves to illustrate the point I guess.

Don't forget to mention that certain drugs can make people itchy, complicating things further.

i'll just +1 you for mentioning it  :)

It has also been related to nociceptive receptor based pathways too! That related the inflammatory pain and nociceptive pain pathways in a weird and interesting way!


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Evolution of long necks in giraffes
In this question, the OP uses giraffe necks as a supportive example of evolution. Is the mechanism described in this post accurate? At some point, I thought I remember hearing that giraffes did not evolve long necks to reach higher food resources, but instead longer, stronger necks gave some sort of mating advantage (male competition perhaps?).
Is there a consensus in the scientific community as to evolutionary mechanism(s) that contributed most to the evolution of long necks in giraffes?

That was Lamark's postulate: http://evolution.berkeley.edu/evolibrary/article/history_09

There seems to consensus that it is not competition for tall food.  Giraffes actually often feed on resources that are lower than their maximum possible height.    See:
Simmons, R. E. & Scheepers, L. 1996. Winning by a Neck: Sexual Selection in the Evolution of Giraffe. The American Naturalist 148: 771–786
This paper put forth the idea that sexual selection is the reason behind long necks.  The idea is that longer necked males are dominant.  But this  theory has also been questioned.  See:
G. Mitchell, S. J. Van Sittert, J. D. Skinner. 2009.Sexual selection is not the origin of long necks in giraffes. Journal of Zoology 278, Issue 4: 281–286
So in the end there's no clear consensus.  Some papers have returned to the theory of competition for research in the past few years.To put it simply, no there is no consensus.

Competition for research? Giraffes must be more advanced than I've been giving them credit for!

Lol, yeah, that's awkwardly worded I suppose.  I meant returned to the theory of competition as a topic of research :)

Long neck might have started for food gathering... but once necks became long enough, it would have been useful for males to fight with. Hence the selection pressure on the neck changed.


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When is the lactase in lactose-free milk active?
Recently we have started suspecting that one of our children has hypolactasia (lactose intolerance), and so accordingly I have had my first exposure to lactose-free dairy- and dairy-like products. In addition to soy milk and almond milk, we have recently purchased actual dairy milk that was labeled lactose-free. This gave me the impression that they had used some process to remove the lactose, but looking at the ingredients more closely, it seems that they simply added lactase enzyme to the milk to assist breaking down the sugars.
My question is this: when is the lactase enzyme active? Does the lactase activity begin right as it is added to the milk, or will it not become active until ingested?
Essentially, I'm wondering if this type of milk can/should be used in cooking or baking. High temperatures will certainly denature the lactase enzymes in the milk, but if the lactose has already been broken down, this shouldn't be a problem.

Having done an inordinate number of rather mind-numbing A.S. practicals involving milk and enzymes the year before last, in my experience lactase always began breaking down the lactose immediately and converting a boiling tube worth of milk in less than 50 minutes at below room temperature.
To further allay your concerns, this website suggests that most Lactose Free milk has undergone UHT treatment - therefore cooking shouldn't be a problem as the enzymes have presumably been added before the pasteurisation, and are therefore denatured - I can't see why you'd then go to the extra trouble of adding the lactase aseptically after pasteurisation; and if the lactase shows in the ingredient list it presumably wasn't done with immobilised enzymes in the factory.

I would just add that lactase has an optimum temperature of action of 25 °C and an optimum pH of 6. So, for sure the stomach (very low pH) is not the good place for it to function.


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Exactly which amino acids are phosphorylated in higher plants during state transitions?
I know it is usually stated as the threonine residue near the N-terminus of either light harvesting complex (lhc) b1 or lhcb2, but if this is somehow lost, say in a mutant, is the system flexible enough to compensate by phosphorylation at another site such as a serine residue or will state transitions just cease?

The protein in question from Arabidopsis has this UniProt entry. In the comments you read: The N-terminus of the protein extends into the stroma where it is involved with adhesion of granal membranes and post-translational modifications; both are believed to mediate the distribution of excitation energy between photosystems I and II. As known PTMs we have (see Sequence Annotations) Threonine-38 and Arginine-36; below you can see known mutations. My guess, though, is that they are a few years behind and so it's better to look at recent work.
Let us then take the PMID 11113141 referred to in the above entry and see the citing papers, e.g., via CiteXplore where I see at least a few relevant references on the topic of LHC phosphorylation. If there were a review, it would be listed there. Apparently, there is also a plant phosphorylation site database PhosPhAt which might help, see PMID 22723801.
In summary, not much is known, lacking even a single review on the subject.

is the system flexible enough to compensate by phosphorylation at another site such as a serine residue

If we are just talking about substituting a residue, I think that functionality would be dependent on the associated kinases. Perhaps the plant phosphorylation database rwst mentioned could be of help?
According to my biology book (S377 Book 3), threonine-serine kinases can usually phosphorylate both residues due to their similarity. There are also tyrosoine kinases, and hystidine kinases; the latter occurring in plants only. The book states that these are the only residues that are known to be phosphorylated. It is uncommon for a threonine-serine kinase to be able to phosphorylate tyrosine, but some rare kinases can do both.


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Plumage as indicator of health in birds
Anybody know which traits of bird plumage are accurate indicators of a birds health? For example feather coloration, feather brightness, amount of feather wear, number of feathers, moult timing, moult duration etc.

This resource provides a short list of which general components of plumage are good indicators of a healthy bird.

Your pet's plumage should be. . .
Soft - feathers should be strong, yet flexible.
Smooth - no rough feather shafts; no uneven or split edges
Glossy - sheen extends over the entire coat
Full - thick, where it needs to be
Vivid - color should be deep, bright and uniform
Clean - free of dust, dander, waste, or soil
Parasite-Free - no lice or mites

Also, this website page discusses the signs of malnutrition or disease in plumage in more detail.
Stress bars, dark lines which transect a feather, are directly caused by an inefficient absorption or lack of required nutrients. Stress bars can be found on all feathers during the period of malnutrition, and remain even after this period.
Assymetrical moulting is also a sign of bad health. There should not be any bald patches present during the moult.
The resource states that if a moult is delayed due to malnutrition, an incorrect photoperiod or a metabolic problem, plumage will become depigmented. However, the appearance of "dirty" feathers can also be due to overpreening or damage done to feathers by physical contact.
Finally, a change in the usual plumage color of the bird in question is indicative of a lack  or oversupply of a particular nutrient.


text:
How are synaptic vesicles brought to the synapse?
I'm reading about how synaptobrevin is used to identify synaptic vesicles for tethering near the synaptic cleft. Since neurons have a synapse and dendrites, I'd like to know how exactly  the vesicles get moved from the Golgi to the synapse.
As far as I can tell, they are transported along microtubules by dynamins as opposed to floating freely in the cytosol (correct?). If so how do the dynenins identify synaptic vesicles - would they form a SNARE complex that gets released near the synapse or by some other means?

In eukaryotic cells you can assume most things not to be floating freely. Enzymes and smaller molecules just diffuse, but all organelles and even big proteins are in constant contact with the cytoskeleton. (Source: Conversations with lecturers)

Or the membranes, of course.

You are looking for a review on vesicle cargoing along the cytoskeleton. This open access article is the most recent I found on the subject.
From the abstract:

How synaptic cargos achieve specificity, directionality and timing of transport is a developing area of investigation. Recent studies demonstrate that the docking of motors to their cargos is a key control point. Moreover, precise spatial and temporal regulation of motor-cargo interactions is important for transport specificity and cargo recruitment. Local signaling pathways Ca2+ influx, CaMKII signaling and Rab GTPase activity regulate motor activity and cargo release at synaptic locations.

M. A. Schlager, C. C. Hoogenraad: Basic mechanisms for recognition and transport of synaptic cargos. In: Molecular brain. Vol. 2, 2009, p. 25. DOI:10.1186/1756-6606-2-25. PMID 19653898. PMC 2732917.

Nice review. Although it is quite unlikely that that link will be removed... could you improve the answer by quoting relevant passages or summarizing the important information?

Thanks for the link, looks like it's Rab GTPases that attach them to microtubules.


text:
Free-flowing cells and those that are stuck together?
I've been thinking about the development of an embryo from the zygote stage.
How is it that when cytokinesis takes place at that stage, the cells all stick together in a little ball, but later in life, some are not bound to others (red blood cells, sperm cells, etc.)?
In other words, how is it that some cells are stuck together and some are separated? How does this property develop?

Cell-cell adhesion is a well-regulated mechanism, cells don't just stick together randomly, this interaction is mediated by specific molecules on the cell surfaces. The responsible proteins for that are the Cell Adhesion Molecules (CAMs) like integrins, cadherins and selectins. Which of these CAMs are present on the surface of a cell determines if those cells will bind to each other or not.
Cells can change their ability to adhere to each other or the extracellular matrix by expressing or not expressing different kinds of these molecules.
You can find a lot more information about this topic in the cell-cell adhesion chapter of "Molecular Biology of the Cell", available on the NCBI homepage.


text:
Is it possible for a substance to be absorbed by the hair or the scalp?
I've heard that the aplication of Monovin A in the hair would allow it to grow faster. Monovin A seems to be only A vitamin, according to the first website.
Could the application of A vitamin in the hair make it grow?
I'm thinking it's not very probable that applying it to the hair and the scalp would affect the hair growth. References will also be useful.

They have a lot of hair growth questions over at skeptics but not this one.

I've thought about asking this on Skeptics, But I believed here would be a more adequate place.

As to the subject line, yes, lipid substances or any non-polar small molecule will enter the skin cells and the body below. The reason is because cell membranes simply consist of fatty substance that behaves like a solvent for other lipids.
As to the specific question about this product, Monovin A. This is a veterinary product and the producer, Laboratórios Bravet, intends it to be injected into animals in case of a vitamin A deficiency. The main ingredients is a retinol ester in the amount of 2,000,000 IU (which usually means retinol equivalents in this respect).[1]
Indeed, retinol is a lipid and long-chain esters like retinol esters are non-polar, too, and can readily be de-esterified by esterases, making vitamin A (=retinol, retinal, retinyl palmitate, retinoic acid) immediately available to the surrounding cells and, via transport in the blood stream, to the liver, which is the body's store for it. Daily doses of 25,000 IU are known to be toxic when administered over a long time. Doses of 50,000 IU can be dangerous over weeks. In general, it appears that single high doses are better tolerated than long over-exposure.[2][3] So, do the math and dilute the stuff such that you get at most one hundredth of an ampoule, else...
Now the effects. Indeed, hair loss is one of the symptoms of heavy vitamin A-deficiency, and logically, that symptom can be cured with vitamin A. That does not mean that more results in more. While retinoids are important therapeutic agents for the management of many skin diseases, notably acne vulgaris, psoriasis, ichthyosis, and palmoplantar keratoderma, there exists something like retinoid-induced effluvium which is a side effect of such medication with tretinoin (ATRA).

Retinoid-induced hair loss (telogen effluvium) is among the most
  frequent and psychologically most distressing adverse effects of
  retinoid therapy, which results in premature termination of a
  clinically desired and often highly effective systemic therapy with
  retinoids.[4]

Since ATRA is readily produced from retinal, its concentration would be expected to be up, even if the original stuff was retinyl ester. In summary, I would expect no effect, or even hair loss, for you don't simply put such potent stuff on your head and elsewhere, and have no reaction from the body.
[1] http://www.bravet.com.br/pr-ceg-monovina.asp
[2] Vitamin A: Toxicity from Supplements In: Medical Sciences Bulletin 1995; Pharmaceutical Information Associates, Ltd.
[3] Hartmann S, Brørs O, Bock J, et al.: Exposure to retinyl esters, retinol, and retinoic acids in non-pregnant women following increasing single and repeated oral doses of vitamin A. In: Ann. Nutr. Metab.. 49, Nr. 3, 2005, p. 155–64. doi:10.1159/000086879. PMID 16006784
[4] K. Foitzik, T. Spexard u. a.: Towards dissecting the pathogenesis of retinoid-induced hair loss: all-trans retinoic acid induces premature hair follicle regression (catagen) by upregulation of transforming growth factor-beta2 in the dermal papilla. In: The Journal of investigative dermatology. Vol. 124, Nr 6, June 2005, p. 1119–1126. DOI:10.1111/j.0022-202X.2005.23686.x. PMID 15955085.

Great answer! I'm amazed that you posted some references. +1


text:
Is there a way for a 19th century scientist to prove that the octopus doesn't revive?
Say a sophiscated scientist in the 19th century noted that applying soy sauce on a dead octopus leads to movement of the legs, as a result of the voltage differences resulting from the salt in the soy sauce. (For example, see this video)
Is there a way for that scientist to prove, using only the methodologies available at that time, that the decapitated octopus doesn't regain the functions that a octopus brain normally has, for even a few seconds, when the soy sauce is applied?

I'm not sure what you mean by delude by medicine.  If you can clarify that, don't hesitate to add it back in, but I don't think it was adding anything to the meaning.  Also, this has nothing to do with bioinformatics.

Unsure if this is suited for this site. It's really a history question.

@LanceLafontaine - Nope, this question is really about how could a scientist use less advanced techlogy to conduct a experiment to develop advanced result

Although a proper theory of action potentials was not developed until the beginning of the 20th century, Galvani's experiments date back to the 18th century...

@nico - But that might lead some realigous group think the brain function is come from the heart...

@Victor: Galvani's experiments were done on frog legs, I don't think the heart was present.

Yes. The scientist could cut a small piece of the octopus's tentacle and perform the experiment again. If the same result is observed, no other organs are involved.


text:
Is there a program that simulates biology on a molecular level?
Is there a computer program that simulates biology on a molecular level? Software that has rules that simulates the rules of molecular-biology?

What do you mean by "simulates biology on a molecular level"? There are definitely 3D molecule viewers, as well as programs for organic chemistry mechanisms, but not something that encompasses every detail of all living processes ever.

I am currently working on a numerical model that simulates an evolving population by simulating the molecular interaction regulating gene expression.

There is a recent paper that introduced the first molecular-level whole-cell simulation.
Karr, J.R., Sanghvi, J.C., Macklin, D.N., Gutschow, M.V., Jacobs, J.M., Bolival, B., Assad-Garcia, N., Glass, J.I., & Covert, M.W. (2012). A whole-cell computational model predicts phenotype from genotype. Cell 150:389-401 DOI: 10.1016/j.cell.2012.05.044
The authors combined 28 different sub-modules of various biological processes from the literature. Each one operates at the level of macromolecules, although models them in different ways: some by ODEs, some by logic; some by agent-based approaches. If you want to fool around their code is available online and I wrote a basic introduction/summary of the paper.
Here are some related bio.SE questions motivated by that model:

Short-term Lamarckism in asexual single cell organisms
Computational/mathematical models for predicting phenotype from genotype
Macromolecule levels in daughter cells after fission

Just a very important note, seen what the OP is asking. Simulating one cell is great, but it does not in any way mean that we can currently simulate an entire organism with that same level of detail.

You might want to check out agent based modeling if you're up to programming your own model. NetLog  might be able to help you.

@RichardErickson I am not sure who your comment is directed at, but I think people would struggle to implement models like Karr, Sanghvi et al. in NetLogo. I think it is also a bit misleading to suggest that a completely novice modeler (of the sort that will be just starting with NetLogo) will be in a position to program their own model at the level of detail of Karr & Sanghvi.

NAMD is a molecular simulation software system with an extensive, active community of researchers
https://www-s.ks.uiuc.edu/Research/namd/
it has a slick visualization package called VMD
https://www-s.ks.uiuc.edu/Research/vmd/

I think this is a good answer, more useful than mine. But could you make it a bit more self-contained by saying a bit more about NAMD and maybe including an example reference where it is used in the literature? And why you think it's visualization package is particularly slick.


text:
Salmon returning to lay eggs
To spawn, salmon return to the river in which they were born. Is it because the individuals remember the specific river, or because populations are genetically conditioned to follow specific environmental cues that guide them to the specific river?
In other words, if a salmon is artificially taken to lay eggs in a different, ("wrong") river, will its progeny return, when grown, to the river where they were born, or that where their mother was born?
If salmon that was grown in a fish-farm is taken to the sea, does it return to a river? How does it choose which?

Answer
The mechanism for salmon natal homing isn't exactly known, but there are really two good hypotheses out there.

Salmon have an extremely good sense of smell. One hypothesis is that they retain an imprint of their birthplace's odor, and manage to recognize it again at a later time (as explained by this article).
Another hypothesis: the Earth's magnetic field guides the salmon to their birthplace via geomagnetic navigation. They then use chemical cues to recognize the stream in which they were born (supported by this scientific article).

These hypotheses were mentioned in this Wikipedia article. Note that there was a third pheromone-related hypothesis which was disproved (as shown here).
I would say that both memory and "genetic conditioning" could potentially be factors in how these animals perform this natal homing, among other things. However, it is difficult to pinpoint which one if any, because neither hypothesis has yet to be confirmed, and both function on completely different mechanisms. Not to mention that we can't tell what exactly a fish is thinking, and also what chemical we're looking for, if there is one.
Finally, for your personal information, salmon aren't the only animals to do this: sea turtles return to their birthplace as well.
TLDR: If a salmon was displaced right before birth, or birthed in a pool, I would imagine it returning to that particular location at sexual maturity.

References

Lohmann, K. J., N. F. Putman, and C. M. F. Lohmann. “Movement Ecology Special Feature: Geomagnetic Imprinting: A Unifying Hypothesis of Long-distance Natal Homing in Salmon and Sea Turtles.” Proceedings of the National Academy of Sciences 105, no. 49 (December 5, 2008): 19096–19101.

Dittman, A., and T. Quinn. “Homing in Pacific Salmon: Mechanisms and Ecological Basis.” Journal of Experimental Biology 199, no. 1 (January 1, 1996): 83–91.

Black, Geoff, and J. Dempson. “A Test of the Hypothesis of Pheromone Attraction in Salmonid Migration.” Environmental Biology of Fishes 15, no. 3 (1986): 229–235.

I don't understand how those two hypothesis answer the question. They provide a mechanism for how to find their way back, but it doesn't answer if a given salmon has a genetic predisposition for going towards a certain spawn-site smell or if it remembers it from its' hatching. Both mechanisms could be consistent with either of the OPs interpretations (although the memory version makes more sense), can you explain why you think both these mechanisms operate interdependent of memory or genetic conditioning?

Hmm, I can see what you mean. I've edited the answer slightly. Please let me know if I've solved the problem or what else can be changed. :)

It would be rather difficult for a released salmon to return to its birthing fish farm. :-)

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


text:
What is the frequency of double-hets between parent and child?
Say both parent and child are genotyped for all SNPs. In this setup we are only looking at variant positions between one parent and child - so neither parent nor child are homozygous reference (no AA/AA) in the millions of positions we are studying.
Assume all variants are biallelic and there is no de novo mutation (no AA/BB or BB/AA)
P    C
AA   AB
AB   AA
AB   AB
AB   BB
BB   AB
BB   BB

What is the fraction of AB/AB among these possibilites?
We are looking at all positions in the genome so the minor allele frequency (MAF) of B allele varies. You can choose whatever B frequency you like.

I'm a little confused: are the genotypes in the rows representing different loci or just different potential, non AA/AA scenarios of one locus?

Potentials. I am going to go with 1/6, regardless of B's MAF.

I don't understand the question. You say so neither parent nor child are homozygous while in your example you have examples where one of the two or even the two are homozygous. Then it is unclear what you mean by no AA/BB or BB/AA. I suppose the / notation separate one parent genotype from the child genotype. I don't know if you're assuming sexual reproduction and talk only about one parent or not. I think you want to assume that all A alleles are at the same frequency. In the same time you seem to say the MAF varies, however you say the "MAF of  B" varies which makes little sense.

For the above reasons, I am voting to close as unclear (four years after the question has been posted :) )

by no AA/BB or BB/AA I mean if the one parent we know about is AA we never BB in the child.

"I don't know if you're assuming sexual reproduction and talk only about one parent or not."
because often we only have access to one parent


text:
Assembly of metagenomic data
I'm trying to assemble metagenomic data that comes from termite guts. The sequences comes from SOLiD and no paired, so the reads are extremely short (25bp).
I have tried multiple assemblers (CLC, velvet, metavelvet, Meta-IDBA) but all produce few contigs (15 contigs, 1000bp average). The contig output is scarce considering the amount of raw data (5 Gpb).
Has anybody has any success in a task such as this?.
Thanks.

Not sure there is a lot you can do. 15 contigs of 10kb do seem awfully little, though.

This depends on your coverage and the number and relative proportion of species in the mixture.  this seems unlikely to produce results unless the protocol biases the library (rRNA universal primers for instance.)  I think at 25 bp sequences, even 30x coverage would not give full assembly sequences. Typically I believe 25 bp reads are only used to resequence close variants from similar or reference genomes.

The protocol have not been biased, that would be the correct approach. I was just hoping for some new point of view. What do you think about comparative assemble against some other assembled metagenomic data set to compare?. Thanks

Metagenomic data are tricky as novel organisms can't be identified.  But since you are in a bit of a jam you might try blatting your 25mers against a library of a few thousand bacterial genomes (as many as you can get a hold of) and you would get some idea of the distribution of the species in your sample, though rigorous identification would be some work....

Thanks, I was planning to do something like that. I think I'm going to try against some of the known bacteria of termite guts.

yup - better than nothing - plus the reads that do not form alignments will give you some idea of the novel content you are missing....


text:
Is the EC50 of an activating protein for an enzyme a good indicator for the binding affinity Kd?
We work with a membrane protein system where measuring the affinity between the enzyme and the upstream activating protein has been difficult, and when measured in detergent solution, it is almost 100 fold lesser (ie ~100nM) whereas the EC50 in an enzymatic assay using vesicles in ~1-2nM. Would it be reasonable to say that the "real" affinity is ~1nM than 100s of nM based on the biochemical assay?
Alternately, is there a documented system where a huge discrepancy exists between measurements from direct binding and biochemical assays?

You can certainly get massive differences between EC50 and affinity. This is especially true for cell-based assays and membrane protein systems.
The reason why is because the appropriate time scales to achieve binding equilibrium (hrs for nM affinity, days for picomolar, feptomolar affinity according to back of the envelope calculations) may be and likely will be different from the appropriate time scales of activation, endocytosis, degradation, etc. Furthermore, you can have avidity effects that would not be apparent in a dilute membrane assay compared to a cell's surface. It could very much be that the dominant terms in mass transport change depending on the geometry and antigen density and while I'm not entirely sure bout vesicles vs. emulsions it is true for cancer models. Theoretical analysis of antibody targeting of tumor spheroids: importance of dosage for penetration, and affinity for retention.

Case study number I: hGH:hGHR interactions have been extensively studied and high affinity hGH have been produced. However, none of the variants showed improved EC50. It turns out that the binding was primarily influenced by the off-rates which were so slow, that affecting those values did little to the kinetics of the system. Growth Hormone Binding Affinity for Its Receptor Surpasses the Requirements for Cellular Activity
Case study number II: CEA-antibodies have been affinity matured to have pM activity compared to the wild-type nM affinity. However, the antibody had minimal effect on tumor uptake. As CEA gets endocytosed on the order of 30 minutes, all of the antibody was simply getting endocytosed rather than acting as an inhibitor. Directed evolution of an anti-carcinoembryonic antigen scFv with a 4-day monovalent dissociation half-time at 37°C.
(edit)
I realized that this answer is more applicable to IC50s vs. the EC50 experiments described above. However, many of the points remains. The Km between a substrate and its enzyme is a thermodynamic property where as the EC50 also has dynamic factors that may influence its measurement.
I would also add that simply adjusting the pH 2 units may result in a 2 orders of magnitude change in activity.
(edit2)
A further point to make about enzymatic assays is that from an observation of Michaelis-Menten kinetics, the KM of the reaction isn't the KD of the enzyme but alternatively the effective binding constant.
Recall that:

If there is a non-trivial kcat comparable to the dissociation rate kr, the enzyme will have an effective half maximal concentration that is significantly higher than the Kd. There are multiple ways how your assay can result in the discrepancies that you're seeing. The first would your strategy in measuring your EC50. If one is an enzymatic readout and the other is a binding readout, you would naturally have very different results.  Alternatively, the enzyme in the detergent system may be catalytically more active than the vesicle system resulting in a higher effective KM. Again, the pH thing.
Finally, there is always that awkward moment when you realized that you might accidentally have measured a titration curve rather than a binding curve.

bobthejoe: I like the detail in your answer, especially the hGH example is very surprising. However, my question pertains to comparing affinities and EC50 measurements, both being derived from in vitro assays with purified proteins. I would think the avidity argument might hold, especially when the same system were compared in a vesicular environment versus detergent solution.

bobthejoe, just thought I'd say this: You've laid out really well why interpreting Km is not always trivial. Exactly why I chose to focus on EC50 (with the trivial(?) assumption that substrate far exceeds enzyme concentration). I'm going to accept your answer, given the richness of detail that you've laid out!

In what follows I am going to attempt to answer your question using a specific example of  (competitive) reversible activation, and I hope to show what a misleading parameter EC50 can be.  (Rate law derivation is an area of interest, hence the long-winded answer).
It can of course give information, but IMO it needs to be used with extreme care.
I am restricting my comments to the case where A is a reversible activator and where  [A] >> eo and [S] >> eo.  (All constants are defined below).
In short, I am not treating irreversible activation, and I am not treating the case where A is considered a tight-binding activator (so that [A] ≈ eo). In other words, I am making the steady-state approximation (Briggs & Haldane, 1925)
Consider the following simple mechanism for activation in a single-substrate enzyme:
A Mechanism for Competitive, Reversible Activation

The substrate (S) cannot bind to the free enzyme (E) unless the activator (A) is present.  That is, only the activator can bind (reversibly) to E, and the substrate binds (reversibly) to the EA complex.  Reaction occurs within the EAS complex (giving EAP). Dissociation of product (P) from EAP gives EA.
The (steady-state) initial-rate law for the above mechanism is the following:

As stated, all constants are defined below and follow the usual definitions in enzyme kinetics.  I'll mention just one here: KA is the dissociation constant for the activator, and has units of concentration.
I derived these equations using a computerized version of the King & Altman method (King & Altman, 1956), but it is not difficult to do. It was pure laziness that prevented a 'first principles' derivation. Rate law derivation is treated in depth in most books on enzyme kinetics and good accounts may be found in Segel (1975) and Cornish-Bowden (2004).
One can now make the following points

There is no activity without A (as one would expect).
When [A]  >>  KA, the rate law becomes identical with the Michaelis-Menten equation (as one would expect).
The equation is similar to the case of competitive inhibition, but (note subtle change) with (1 + KA / [A]) substituted for (1 + [I] / Ki)
One can consider this mechanism an example of competitive activation

Defining

νiexc     =     the initial velocity when A is in vast excess [ie setting [A] equal to ∞ in eqn (1) ].
EC50    =     the concentration of A that gives νi equal to νiexc / 2 (half-maximal activation)

allows the following two equations to be derived:

Setting the left-hand side of the above equal to 2, and solving for [A], gives the following all-important equation

One can now draw the following conclusions

When [S] = KSm

In words, when the substrate is present at a concentration equal to the Michaelis constant the value of EC50 is half the value of KA!.
When [S] >> KSm

When [S] = 10 x KSm, for example, EC50 is one-tenth the value of KA, and when  [S] = 100 x KSm the figure is one-hundreth.
When [S] << KSm

Thus, for a competitive activator, it is only when [S] << KSm
that EC50 gives a reasonable estimate of KA.
The substrate concentration in a 'normal' enzyme assay will probably be equal to or greater than the Michaelis constant (in order to 'see' activity), and thus EC50 will be an underestimate of KA.
If the substrate is present at a 'saturating' concentration (say 10 x KSm) then one is in real trouble.
However, this is not the only consideration.  As well as being substrate-concentration dependent, the manner in which EC50 depends on [substrate] depends on mechanism.
As briefly discussed below, the competitive activation case is analogous to that of competitive inhibition. However for uncompetitive inhibition the Ki (inhibition constant) is only equal to IC50 (the concentration of inhibitor giving half-maximal inhibition) at high substrate concentration! (see Naqui, 1982). By analogy, one can conclude that the same is true of uncompetitive activation.
It is very difficult to see how EC50 can be of any practical use, except perhaps when the mechanism of activation is known.  At the very least, conclusions drawn from EC50 data should otherwise not be considered definitive.
In addition, I have discussed the only the case of a single-substrate reaction.  Two-substrate reactions have the potential for even greater complexity.

Illustrative Example (Competitive Activation)
Let's take an example, and check some conclusions:

kfcat   =   1000 s-1
eo   =   1
KSm    =   10 µM
KA      =   50 µM

It may be calculated that:

When [S] equals  10 µM (ie when [S] is equal to KSm) and when [A] is 'saturating' (for the sake of argument set equal to ∞) the velocity is 500 µM s-1 [from eqn (1) ].
From eqn (2), the concentration of A required to achieve half this value (half maximal activation) is 25 µM (EC50 equals 25 µM)
This value can be directly calculated from eqn (3)
When [S] equals  100 µM (ie [S] equals 10 x KSm) and when [A] is 'saturating' the velocity is now 909 µM s-1 [from eqn (1) ].
From eqn (2), the concentration of A required to achieve half this value  is now only ~4.5 µM
This value can be directly calculated from eqn (3) [EC50 equals (50 / 11) µM]
When [S] equals  1 µM (ie [S] equal to one-tenth the Michaelis constant) and when [A] is 'saturating' the velocity is now only ~91 µM s-1 [from eqn (1) ].
From eqn (2), the concentration of A required to achieve half this value is ~45.5 µM (now almost equal to KA)
This value can be directly calculated from eqn (3) [EC50 equals (500 / 11) µM]

Reversible Inhibition & IC50.  A Brief Comment
There is nothing much new in any of the above. In the field of enzyme inhibition, the inadequecies of IC50 (the concentration of inhibitor giving 50% inhibition) and the relationship to the Inhibition constant are well-known  [see, for example,  Chou (1974), Segel (1975), Naqui (1982) & Tsou (1987)], but (it seems to me) often ignored.
The paper of Naqui gives a very succinct analysis of the situation and the pdf is freely available to all.
Reversible inhibitors may be divided into four classes, depending on the pattern of inhibition: competitive, uncompetitive, non-competitive and 'mixed' (see Naqui, 1982, and references therein).
In all cases except non-competitive inhibition, Ki ≠ IC50, and IC50 is substrate- dependent.
(Non-competitive inhibition is the 'fluky' one where it just so happens that the catalytic constant and the specificity constant (kfcat / KSm) are changed to the same extent or, to put it another way, the slope and intercept of a Lineweaver-Burk plot (it just so happens) are changed to the same extent)
For an uncompetitive inhibitor (as stated) the IC50 only equals Ki at high substrate concentration (see Naqui, 1982).
Like the case of competitive activation, IC50  equals Ki for a competitive inhibitor only at low susbstrate concentrations (see Naqui, 1982).
'Mixed' inhibition is even more complex, and the inhibition constant may be greater than or less than IC50 depending on experimental conditons (see Naqui, 1982).
Great question, BTW.

Addendum
As I have derived the full form of the rate law (as opposed to the initial-rate law), it is probably worth posting it. The initial-rate law is obtained from this equation by setting [P] equal to zero.

Kinetic Constants defined in terms of Rate Contants
Rate constants are numbered (as subscripts) from species, to species, with numbering as in diagram.
Thus the rate constant k1,2 is that from E (species 1) to EA (species 2).

Catalytic Constants

Michaelis Constants

Specificity Constants

Activation (Dissociation Constant)

Kinetic Constant Definition

ν     velocity
νi   the initial velocity
KSm    the Michaelis Constant for S
KPm    the Michaelis Constant for P
kfcat   the catalytic constant (in the forward direction)
krcat   the catalytic constant (in the reverse direction)
Vmax    the maximum velocity, equal to kfcat eo
eo   the total enzyme concentration

KA      the dissociation constant for (activator), equal to k2,1 / k1,2, with units of concentration (Molarity, say) [rate constants are numbered from species, to species, numbering as in diagram].
νiexc    the initial velocity when A is in excess ([A] = ∞).
EC50   the concencentration of A that gives νi equal to νiexc / 2 (half-maximal activation)
[A]     The initial concentration of activator.
[S]     The initial concentration of substrate.

The rate law and the diagrams were obtained using Mathematica.  For Matematica at SE see here

References

Briggs, G. E. & Haldane, J. B. S. (1925). A note on the kinetics of enzyme action.  Biochem. J. 19, 338 - 339.[pdf]
Chou, T.C. (1974) Relationships between inhibition constants and fractional inhibition in enzyme-catalyzed reactions with different numbers of reactants, different reaction mechanisms, and different types and mechanisms of inhibition. Mol. Pharmacol., 10, 235-247 [pubmed]
Cornish-Bowden, A. (2004). Fundamentals of Enzyme Kinetics. 3rd edn. Portland Press Ltd, London.
King, E. L. & Altman, C. (1956). A schematic method of deriving the rate laws for enzyme-catalyzed reactions.  J. Phys. Chem. 60, 1375 - 1378. [ACS site]
Naqui, A. (1982). What does I50 mean? (1983)  Biochem. J.  215,  429-430 [pdf]
Segel, I. H. (1975). Enzyme Kinetics.  Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. John Wiley & Sons, Inc., New York.
Tsou, C. L. (1987) The screening of enzyme-targeted drugs.  Bioessays, 6, 237-238. [pubmed]


text:
Why are pilots under the illusion of gaining altitude without doing so?
We had a lecture about the balancing systems of the body (mainly the otolith organ / semilunar canals) in which a case was described where a pilot crashed into a ship. He was supposed to keep his altitude and had not been looking at his instruments, but was guiding the plane by feeling.
However, he was under the illusion that the plane was gaining altitude when it wasn't and so steered it downwards, dropping and eventually crashing into a ship which happened to be at that particular spot that moment.
Since the otolith organs detect de- and acceleration in all directions (that just comes from how the mechanism works), if the pilot was flying at steady altitude, why would they signal that he is rising?
(Will add an article later if I find one.)

See this link. It provides a great overview. The answer you want is in the otolith section. To paraphrase, it states that our otolith organs are designed to help us lean forward while running to maintain our center of gravity when in motion; however, in a plane this reflex can backfire by causing a pilot to believe he is going straight when in actuality he may be going downward.


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How do parasitic fungi sense optimal fruiting conditions from inside the host?
Question is pretty straight forward. Are there generally any chemical cues?

In model fungi, the G protein coupled receptor Gpr1 is known to sense sugars and upregulate a cAMP linked PKA pathway, while in pathogenic strains, it senses Methionine. This probably is the environmental cue that sets off fruiting. There is a recently published extensive review too: Heterotrimeric G protein signaling in filamentous fungi

Reference

Li, Liande, Sara J. Wright, Svetlana Krystofova, Gyungsoon Park, and Katherine A. Borkovich. “Heterotrimeric G Protein Signaling in Filamentous Fungi.” Annual Review of Microbiology 61, no. 1 (October 2007): 423–452.


text:
Why does muscle tissue have relatively constant AMP + ADP + AMP?
I was going over slides of energy expenditure in muscle cells. It mentions that in muscle tissue, the cell's energy charge ([ATP] / [AMP]) is the principle factor controlling glycolytic activity, and also that glycolysis’ primary role here is to provide ATP for contraction.
However, the slides also mentions that "Keep in mind that [ATP] + [ADP] + [AMP] remains relatively constant in the cell over short time frames" with no further explanation. I was under the impression that ATP was actively consumed in muscle tissue during intense activity (which is why lactic acid builds up in muscles: oxidative phosphorylation can't keep up with your rate of energy expenditure).
Thus, my question is Are my slides wrong? During muscle activity, is there a general lack or constancy of ATP?

Adenosine triphosphate (ATP) is often thought of as the energy currency of cells. It is not "used up" per se, but energy is released from the conversion of ATP to ADP (adenosine diphosphate), and yet more can be obtained by removing another phosphate to make AMP (adenosine monophosphate).
Here's a chemical schematic of ATP, you can see the three phosphates to the left.

Your slides state that the amount of (ATP + ADP + AMP) remains constant in the muscle, which makes sense because ATP is not used up, but converted to ADP. So as cells use energy, they do not actually reduce the total concentration of (ATP + ADP + AMP). Energy is required to add the phosphates back onto an ADP or AMP molecule - the process is called oxidative phosphorylation in cellular respiration (although this is not the only way).
I hope I didn't misunderstand your question.

Ohhhhhhhhh, I think I may have just misunderstood the professor's wording in the slides. This makes total sense of course (and must be what the prof is referring to) but didn't occur to me. I was understanding that the concentration of EACH nucleotide remained constant (which is not so), and not the SUM of all three. Thanks for the epiphany :).

The pluses stand for addition, not "and".

In fact there is even a certain balance ATP/ADP/AMP + GTP/GDP/GMP + IMP/XMP as these are all interconvertible purine nucleotides.


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What is the life cycle of a wart?
There doesn't seem to be a lot of information available on research done on warts.  What is the life cycle of a wart?  How does it spread? -- specifically how does it recruit cells to spread it?  What is the life cycle of a PV-infected dermal cell?

This article has some good information. It's certainly more than I want to know about warts.

Isolated warts may remain unaltered for
  months or years, or a large number of new lesions
  may develop rapidly in a short period of time. The
  development of warts is not predictable.
  Approximately 65% of warts disappear spontaneously
  within two years. The patient’s age and number of
  lesions do not seem to affect the prognosis.

There are many different types of warts and of HPV. Since warts cause a type of dysplasia their life cycle can be very variable and unpredictable.

Do you mind summarize some of the key points in the article. The link might die someday, and it'd just make a much more complete answer :).

Sure. I'm new to Biology beta. It seems to me that the nature of the site necessitates a lot of linking and referencing since there's no way to confirm someone's credentials. And even those with credentials need to cite their sources.

Welcome :). Generally, when making a claim, a reference is just customary. The edited answer is great though, +1.

Conner's response contained just the type of source material I was looking for.  Thanks Conner -- let us all +1 him.  Allow me to summarize the specifics of the article in relation to my question:
Transmission

PVs are transmitted through direct or indirect contact with an
  individual who has the lesion. Dysfunctions in the epithelial barrier
  by trauma, minor injuries or maceration cause loss of solution of
  continuity in the skin, thus allowing viral infection. After
  inoculation, the incubation period varies from 3 weeks to 8 months.
  Spontaneous regression is observed in most cases.

Infection

Infection begins when the PV reaches the cells of the basal layer;
  there is no viral replication at this location and the virus just
  keeps its genome by amplification of a low number of copies.

Replication

The replicative phase and protein synthesis occur in the suprabasal
  differentiated keratinocytes. Progression time and type of lesion
  correlates with the quantity of viral particles detected. Younger
  warts present a higher viral amount when compared to old warts.
  Plantar warts have a higher viral load than common warts. The center
  of the lesion appears to be the main site of viral concentration.

Latency

PVs appear to remain in their host for long periods of life. A variety
  of different types of PVs can be detected in random sites of normal
  skin in humans and animals. This reinforces that a latent life cycle
  is often a characteristic of these viruses.

Interesting Notes

There are no known PVs that infect more than one species.
To date, about 100 different types of HPVs have been fully characterized.
Human PVs does not grow on conventional culture media. The diagnosis of HPV infection is made by histopathology of lesions


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During human ageing, which immune cell sub-types are most affected?
It is now well established that human ageing is accompanied by an increase in systemic, low-grade (chronic) inflammation, sometimes termed inflammaging (Franceschi, 2007). This is in part due to more global changes to the body, including an increased number of senescent cells, but of interest to me currently is the change in the composition of the circulating immune cell sub-types that may either cause, or be affected by, the increase in 'global' inflammation.
I imagine the answer to this question is a study that samples individuals of different ages and separates the various leukocyte fractions. Using this it could be determined which immune sub-types are over-/under-represented in the aged, and at what age the changes occur (e.g. monocyte numbers may decrease from age 40, whereas neutrophil numbers may increase...). I have done some fairly extensive research, but have been unable to find a study that has done this - however it seems likely that it has been performed. Thanks.

From my Immunology notes:
*Decrease in hematopoietic stem cells resulting in a reduction of Affector cells. Erythroid and myeloid progeny cells don't seem to be affected.
*Fewer pro-B cells, resulting in fewer affector B-cells.
*Lymphoid progenitors in the bone marrow and thymus mature.
*Lymphocytes in secondary lymphoid organs.
For the Innate system:
*Neutrophils have a reduced capacity for Oxidative bursts, Batericidal activity, and Chemotaxis.
*Macrophages have a reduced capacity for phagocytic activity, oxidative bursts, and MHC II expression (which impairs their ability to present antigen and initiate CD4 Helper T-Cell responses).
*NK Cells have a reduced capacity for Cytotoxicity, proinflammatory cytokines and chemokines,and proliferation in response to IL-2. However, the total number of NK cells increases.
The sources: Both clinical (it was at a teaching hospital) and Aging and Immune System, Chapter 33 of the class text: Cellular and Molecular Immunology

Does the textbook give any information on the different stages of the decline? I.e. at what ages the various changes occur, whether the adaptive immune response is affected more-so? Thanks for the answer though - will have a look for that chapter.

30 and 60 were the major milestones mentioned in my notes, where an increased prevalence of cancers and diseases (respectively) become significant. However, that's probably due to the architecture of the studies the authors drew the numbers from and not any natural impetus.
My personal guess would be that after 30 it's just a downward sigmoidal curve without any "hard" ages that signify major shifts in immunological makeup.


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Athletes: nature vs. nurture?
Having watched a lot of olympians the last few weeks, I was struck by how many of them have actually spent their wholes lives/careers training for their one event (be in running a marathon, or throwing a javelin). This is of course unsurprising - a lot of people take their sport very seriously - but I wondered to what degree these athletes are predisposed to becoming atheletes, and to what degree they just 'happened' to end up doing it.
I've had a bit of a search around, but have been unable to find any studies (although there is an awful lot of media attention to the topic) that actually study the interaction between nature (genetics) and nurture (environment/training etc) in the context of top-end athletes.
It is quite clear to me that the answer is of course 'both', but to what degree? Have any common genetic variants/loci been identified, or is 'athleticism' a far too complex trait for this? Thanks.

All I can think of is http://abcnews.go.com/Health/MedicineCuttingEdge/story?id=7231487&page=1#.UCow92NYvis

@LanceLafontaine That is very interesting - I've seen the mutant animals before, but did not know there were naturally occurring variants in humans! These individuals would certainly be predisposed to become strong-men!

I'm wondering if there are currently or going to be Olympic "policies" against people like that. It's gives an unfair advantage (that's for sure), but it's not like it's anyone's fault.

@LanceLafontaine you have to remember there will be a gaussian distribution, and these people are just at the very tail of it. I imagine that most athletes will also be close to it, but with a not so pronounced phenotype? At what point labeling these 'extremes' as 'mutants' becomes acceptable, and deem them unsuitable to compete in sports is an interesting thought

The Oregon Project might also be interesting to look at, as a means to counter the seemingly 'superior genes' of the, say Kenyan, runners with high-tech equipment.

All these fantastic atheletes on the record breaking levels are a combination of hard work, good funding and a good genetic predisposition.  Swimmers have flexible joints, Lance Armstrong has an extra large heart.  You can train to increase fast twitch muscles and reaction times, but a few extra mutations in your favor makes the champion I think.  Horses have been bred to champions for centuries.  Human champions also need a genetic advantage.  This is just my opinion, but not so controversial in my opinion.

@shigeta I completely agree - there is definitely an element of nature and nurture in the predisposition and development of athleticism. I am interested to know of any scientific studies on athletes, and whether there is any enrichment for genetic traits, or environmental traits (other than the 'obvious' - training very hard. Although this is not always the case - Usain Bolt famously does not train as hard as his competitors. This is a good example of natural advantage).

@Luke good question. not my field, but i'd be interested to know if all these superstars would have donated their genetic material to a study....

@shigeta Yeah it would require that they participate in cohort studies, but it would be so interesting to know of any conserved traits between them (presumably they would mostly be cardiovascular? as the muscle groups, etc, would be sport-specific).

you have to be careful though - its likely the genetic and physiological traits are so complex that no single group will stand out.  it looks as if there are many ways to make a tall person, there are probably an infinite number of ways to make a great ball player/runner etc. @Luke

I wonder if a case/control genetic study would be informative here: obtain genetic information from athletes (cases) and compare against the same genetic marks in the general population (controls).

For all types of athlete, their ability is determined by both genetic and environmental factors (nature and nurture). The degree to which each contributes ultimately depends on the demands of the sport.
As an example let's compare basketball and golf.
Basketball is likely to have a strong genetic component because players tend to be exceptionally tall (average is over 2 metres and there are only a handful who have played NBA under 1.75m). Because height is strongly genetically (but not entirely) determined by the genes, they have a big influence on whether someone can poses the physical qualities to play in the NBA. However, a large part of their technical capabilities are due to their environment. If you give a basketball to someone who has played 2 games a week their entire lives and ask them to take 10 shots it is likely they would score more than someone who has never seen a basketball!
Comparing basketball to golf, there are all sorts of body types within the PGA tour, and they is no/few obvious genetic traits which golfers tend to have over other people. This would suggest that golfing ability is more affected by environment.
So an easy way to get a rudimentary test of genetic contributions to sporting ability would be to compare frequency distributions of focal traits in the athletes to distributions of regular people. Obviously the phenotypic trait you measure has both genetic and environmental contributions (e.g. childhood diet) which could affect them but it would be a good starting indicator which could give some candidate traits to test.
As a scientist I would also consider sequencing some athletes and some non athletes and seeing which genes the athletes have more often then the regular person's genome. However, such studies are likely to be complex - linking phenotypes (in polygenic traits) to the single allele variants relies on large sample sizes. Generally it will be more difficult if:

There is large variance in the trait
The gene has a small effect (see major and minor effect genes)

Both of these problems going to be positively correlated with the number of genes affecting a trait (how polygenic is it?) which for athletic ability is probably quite a substantial amount of genes.
EDIT:  Here are some possible studies for your further exploration of the topic-
Candidate genes for Specific Genetic Markers of Endurance Performance and o2max
Rowers have an excess of the ACE I allele
Elite Italian footballers with "explosive" leg strength also reveal ACE and other genetic markers
A precautionary tale about Genetic tests for athletic ability

I am thinking that another good example could be 'sumo wrestlers', who are also very different in body types to the average population.

here is a paper which finds a candidate gene for physical athletic superiority (http://www.springerlink.com/content/hwllqyy12x29tpde/) in a method similar to that which I suggested. However, I can't find anything suggesting a gene leading people to being predisposed to being an athlete psychologically. The genetics of behavioural psychology is incredibly complex and hotly debated, classic example being "the gay gene."

@Luke, does this answer your question?

Hi @rg255 - thanks for the information and your opinions, but I was hoping for links to studies (like the one in your comment) where authors have tested for genetic contributions. I am of course expecting a large environmental contribution, but as you suggest the genetic contributions may be sport specific (e.g. height-increasing alleles for basketballers, bulk-increasing alleles for sumo-wrestling... etc). When I have some time later I will follow-up the paper you have sent, as this is quite an old study and have been cited almost 200 times! Clearly some other studies too. Many thanks.

@Luke there you go (see edit to answer) hopefully these will give you some help - looks like there are a few alleles that regularly come up in these studies (e.g. ACE I). Sorry it took a while to get around to it!

Mental aptitudes (which presumably are influenced by genetics) would also influence on athletic prowess both in the activity and in the training.  A highly driven, goal-oriented personality is more likely to train with firm intention.  A perfectionist is less likely to be satisfied with "good enough" performance--avoiding big fish in a small pond issues.  Aggressiveness and risk-tolerance are rewarded in some sports.  Social skills--e.g., reading and deceiving opponents and fostering teamwork--can also play a role.  Trusting one's training experts would also be important--autonomy is not good.

Yes, candidate genes like those found by these types of experiment could also be linked to mental attributes.

Two hints:

Do a google search for the ACTN3 gene (alpha-actinin-3)
Go to the fitness.stackexchange.com site and search for "fast
twitch" muscles, for example. There you'll find many similar questions
answered.

You can get an answer for you personally by genetic testing.
This is a quote from a genetic testing site 23andme.com (sorry it's behind a paywall). Note there are other companies who can do this equally well.

Genes vs. Environment
Athletic performance has different estimates of heritability,
  depending on what aspect one examines. For example, differences in the
  relative proportion of fast-twitch and slow-twitch muscle fiber are
  thought to have a heritability of about 45%. Although it is not yet
  clear whether ACTN3 genotype affects this proportion, it has been
  shown that the SNP in ACTN3 that we report accounts for about 2.3% of
  the variation in sprinting performance. However, at the molecular
  level, whether you have 0, 1, or 2 working copies of alpha-actinin-3
  is highly heritable. Lastly, muscle fiber only contributes a small
  part to your overall athletic performance. Other physical
  characteristics, such as lung capacity, and behaviors, such as regular
  exercise, also make important contributions to your prowess in sports.

This is considered "established research for 1 reported marker". It is still subject of much ongoing research, though.
So there you have it: around 2% of a difference in sprinting performance. For the general population this won't matter much. But for prospective professional athletes these 2.3% might matter a lot for developing the full potential of their athletic performance (assuming all other environmental factors, are of  equal top quality, e.g. technical equipment, coaching efficiency, etc)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255226/ - talking about genetic tests like the one for ACTN3 "this is a gross over-simplification of the science, according to many critics of these types of consumer genetic tests, including Timothy Caulfield, a Canada Research Chair in Health Law and Technology. “There are so many factors that contribute to something as complex as performance in sports that it seems ridiculous to narrow it down to this one type of genetic test,” he says."

so I'd suggest we can't call it a comprehensive test - individual loci only have minor effects on the overall ability.

@rg255: What the law school professor said is "I don't like questions like this narrowed down to 1 genetic test". That may be righteous, but I'm not narrowing it down. The original question asked for a quantitative estimation. Hence, the quote in my answer: we are talking about 2.3% differences here (which won't matter much for the general population) and the quote also says there are many factors.

I just don't think we can call it a comprehensive test

i removed the "comprehensive" word.

I meant to say that if you got a test result from any direct-to-consumer-genetic testing company, you'd also get a long reading list of science papers, probably carefully selected. Another aspect of "comprehensive" is the "established research" thing. The state of the science is that it's not a single geneticist who speculated about some ideas, there are many teams who have found similar results.

It's an interesting area of research - I just had a population genetics book discussion group for 2 hours and we talked about the difficulties in accurately connecting single allele variants to phenotypes particularly in polygenic traits. The finding of ACE I and ACTN3 could suggest that they are major effect genes. The ability to link a gene to polygenic phenotype depends on the strength of effect on the phenotype by the allele variant and the variance within the population for that trait.

I don't think this will ever be answered, mostly because studying the long-term effects of athletic training is very difficult. People constantly change their training methods, habits, and schedule, so controls are nearly impossible to construct.
My opinion, is that the nurture component is the strongest, because of the amazing plasticity of the body in response to stress: bones grow/reform differently, neural networks become trained, muscles change. Over many years these can be enormous. This is true of all humans, absent those with severe genetic faults.
Genetics probably has a stronger influence on the psychological traits which might induce someone to train so hard. Though parenting could certainly override this.

It is difficult but not impossible to quantify. Could you give us some solid scientific references?

I have no references because I don't think these data exist. Certainly you can get quantitative data, but it doesn't mean that it will be useful. My main point is that there are too many ill-defined variables that need to be tracked for many years. This is nearly impossible to do.


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How much energy does a cell expend maintaining its contents?
In software engineering, an analogy is sometimes made using biological cells. I would like to know whether it has basis in fact.
People say (Alan Kay was first) that "objects" in software should be like cells: separate from one another, communicating by passing messages. This separateness has been argued by saying that a cell spends much of its metabolic energy keeping its insides in and its outsides out. The implication is that programmers should likewise spend significant effort maintaining boundaries between parts of a system.
Is this actually true? What percentage of its energy does a cell generally spend maintaining its contents?
(My guess is that the answer varies wildly depending on the cell and its environment, but some ballpark example numbers would be nice.)

This could be a difficult question to answer, because where do you draw the line? Just the energy required to maintain the phospholipid bilayer? Or would the estimate also include the energy required to maintain the cytoskeleton? As you say, these components vary drastically between cell-types so an accurate estimate will be hard to come by. Arguably the majority of the cells energy is spent on maintaining the integrity of the cell - which includes all the component parts, without which the cell would not fully function and may not be as effective at maintaining its 'boundary'.

@Luke - unfortunately, I lack the knowledge to frame the question more precisely. Given the ambiguity of my question, an answer like "depending on the definition and the cell, a minimum of about %X and a maximum of about %Y" would be perfectly fine.

There's "more to it" than just that. Does the energy needed for transcription of the proteins that diffuse out of the cell count?

@NathanLong my apologies for not being very helpful, but the answer could surely be anywhere between ~5% and ~95% (extremes obviously), because it depends where the line is drawn. I will be interested to see what others put as answers though!

@LanceLafontaine - sorry, as I said, I don't know enough to answer that; please assume whatever seems most reasonable to you.

I'm going to take a stab at this.  Its a difficult question to get right, just to put is in the right mood here.
Lets leave energy out of this as the proper term is structure.  The cell is designed to compartmentalize itself to differentiate its own living tissue from other cells.
In this regard Alan Kay's analogy is pretty good.  In multicellular organisms, individual cells (mostly) each maintain their own DNA and energy storage, though they get their nutrients and energy from outside.  They create the organism as a whole by differentiation; each cell changes to take on a specialized role and depends on other cells to support it. E.g. in animals some cells/organs digest the food and distribute nutrients to the rest, others form the lung and help distribute oxygen and others scrub the blood of waste.
This is somewhat like good code design where functions are partitioned out into specialized parts of the software for the sake of maintainability and organization.
Somewhere after this point I think the analogy breaks down since after all the point of good coding practice is to organize the code for understanding within reasonable human conceptual limits.  The cells and how they organize themselves are still plenty mysterious to us as they have their own definition of roles and function much of which is still being discovered today.  For instance the many kinds of neurons in the brain and the sorts of structures they form are extremely diverse.  We have few organizing principles for predicting how many cell types would exist in a system and these only create partial answers.
After all its just an analogy...
getting close to an answer?

This is an old question by now, but thought I'd give it a shot anyway. I am guessing the "insides in and outsides out" refers to maintaining intracellular concentrations of nutrients and other important molecules.
The cell does spend a lot of energy to maintain high concentrations of amino acids and other key metabolites in the cytoplasm. The cell membrane is permeable to these molecules to allow uptake from the surroundings, but this also creates the problem that molecules are as likely to diffuse out as diffuse in. To maintain a concentration of any molecule higher than that of its surrondings, the cell must actively "pump" molecules inwards, which obviously costs energy. This goes on all the time; it's a constant fight against thermodynamics.
A number of active pumps exist in cells, and it's experimentally difficult to measure the energy consumption of all of them. One very important pump though is the Na/K-ATPase, which uses ATP (energy) to maintain sodium and potassium gradients across the cell membrane, which are in turn used to drive transport of other molecules. The energy requirement of the Na/K-ATPase is readily measurable; this review article estimates 19--28% of total energy consumption. This should be viewed as a lower bound.


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Why aren't mitochondria and plastids considered symbiotes of eukaryotic cells?
Mitochondria and plastids have their own DNA, their own membranes, and their reproduction is not tied to the reproductive cycle of the host cell. However, they are considered to be organelles rather than a separate species in symbiosis with eukaryotes. Granted, mitochondria and plastids are incapable of living outside their parent cells, and likewise eukaryotes are incapable of surviving without the help of mitochondria and plastids. But this is also true of many other symbiotic pairs in Eukarya. So where does the distinction lie? What makes mitochondria and plastids organelles rather than separate organisms?

Something to do with the lifecycle maybe? It is an interesting question. Perhaps it is because mitochondria are inseparably tied to the host cells mitotic cycle? A bacteria in a symbiotic relationship with a plant would have a distinct lifecycle... although I'm sure there would be examples where the distinction is less clear...

In my naivety I think that Richard Dawkins has given the perfect answer in the last chapter of The Selfish Gene. It’s indeed (solely, he argues) a function of their life cycle. Mitochondria may be able to reproduce independently, but their proliferation is bound to their hosts.

I would say it has to do with the amount of mitochondrial or sequence that has been transferred to the host genome. As a consequence of all this information stored in the host genome, mitochondria cannot reproduce without the host. In this way, they are not their own organisms, but rather organelles.
Over evolutionary time, the line between organelle and intracellular endosymbiont gets blurry, but in their current state, mitochondria are organelles.
The same goes for for plastids, in general.

I agree with this answer. Symbionts are distinguished as separate complete organisms in some stage, despite their need of other to survive.

Ninety percent of a mitochondrium's proteins are coded in the nucleus.