text:
Why do living fossils like crocodiles remain so constant and not evolve?
Crocodiles have supposedly remained unchanged for millions of years, and several other species are considered as "living fossils". How do such species remain so constant over time given that they will have had so much time to accumulate new mutations?

I'd add that although they may appear morphologically the same as their ancestors they may well be substantially genetically different. "Unchanged" on the surface does not necessarily mean the same under the hood.

Molecular evolution != phenotypic evolution!

Evolution is a process of change by four mechanisms; mutation, migration, drift, and selection.
You are correct in thinking that, because crocodiles have been around for a long time, they could have accumulated many new mutations in that time, relative to other more recent species. However, mutation is only one of the important mechanisms underlying evolution.
How different are ancestral and modern crocodiles?
It seems the appearance of crocodiles has been fairly unchanged since their occurrence ~85 million years ago (mya).
How can they remain so unchanged?
Genetic variation may have been low in the ancestral population, this would reduce the potential for evolutionary change, as most change would have to occur through new mutations. It seems the populations of ancestral crocodiles were quite small, such that a genetic bottleneck may have occurred (which would reduce genetic variation). Mutation rates seem to be relatively low in crocodiles (also see here) which would reduce the rate at which novel mutation occurs, reducing the potential for evolution.
Note that many mutations will be neutral in their effect (or "synonymous") so won't have an obvious phenotypic effect, so there may be substantial evolution at the genetic level despite the phenotypic similarity.
Low rates of evolutionary change could suggests some other things may have also played a factor. Given that the populations have been through multiple genetic bottlenecks, genetic drift could have slowed down rates of evolution eroding genetic variance, removing rare mutations from the population.
If selection has been fairly constant over time then there is less chance that changes will occur. If selection were to change and favour new adaptations then these are likely to spread, but if selection remains fairly constant over time then it will continue to favour the same mutations. After a long time of consistent selection it is likely that most mutations will be deleterious (have a negative effect) and be removed from the population by selection. Darwin suggested that living fossils could occur because the environment they are in has remained fairly constant (from this link).

When the species is not affected by disease, The species has masterd the environment and the mutations should entirely cease. The salt water croc has a incredible immunity and a wide variety of food

@TheVoid - diseases have basically no effect on mutations. What are you even talking about?

@Davor-spontanious new mutaions that suddenly show up in slight steady numbers are signs of a upgrade to better the species evolve in other words, Should I provide a link to show the strength of a crocodiles immunity from disease and infection?

@TheVoid Mutations don't happen on purpose, they just do. They are not trying to make any species better.

The quality of a crocodiles immune system won't have any effect on mutation rates. If the immune system is very well adapted then most mutations will be deleterious and selected away, but mutations will still occur

I think The Void wants to say that a perfectly (as far as biologically/physically possible) adapted species won’t change because all mutations would only yield a disadvantage (so there would be no permanent mutations). Because of that there would even be a strong selective pressure against mutations once a species has reached that point.

that point is made in my answer I think "After a long time of consistent selection it is likely that most mutations will be deleterious" - it relates to fisher's geometric model of adaptation

Crocodylomorpha were actually once a lot more varied than they are today, so their group isn't immune to change or evolution.

The tongue in cheek answer is to say, there were a lot more forms of crocodile in the past so chances are the single form we see today would look like one of them!
A better answer is: Species often evolve to fit a niche, they become specialised in their form both externally and internally. As long as this niche stays the same and neighbouring niches remain filled, the species will only become more suited to its niche. Over time you'd expect new mutations which made an individual fitter to become rarer, or have a smaller impact on survival so be selected for less strongly, thus the longer a niche exists, the more stable the form of animals living in it will become.

Looking at adapting to niches from the other side, we could ask why dolphins look so much like ichthyosaurs.

I particularly like your first paragraph in your "better answer" - it's a good clear and simple summary of the effect of constant selection! (+1) Do you he any references and links to external material to add so people can follow it up with further reading if they want?

@rg255 Unfortunately I didn't have any particular papers in mind when writing that answer, I could probably dig out my old uni notes and find the lecturers references if you were really interested?

I think in the case of crocodiles in particular, this is a question of body type. Crocodiles have fixed jaws, meaning that they have lost the mechanism used to move their lower jaw from side to side. This simplification means that they can exert a huge amount of power, making it a great adaptation for their particular strategy of hiding in water and ambushing large land mammals that drink from it.
However, it also means that it's very hard for them to adapt to any other niche. Anything that would require eating smaller prey, or eating on land, would be untenable, because crocodiles can't chew. (Instead they close their mouth and rotate their whole body in the water to rip chunks of flesh off.) They can't easily re-evolve the ability to chew, because the mechanism needed to do that is pretty complicated, so their fixed jaw is more or less "locked in" evolutionarily.
So crocodiles have remained constant because they are very well adapted to a particular niche; because they've lost features that would allow them to adapt to other niches; and because the niche they occupy has been around for a very long time.
Personally I think these are the primary reasons. The low mutation rate mentioned in the other answers seems to me more likely to be effect than cause. If you are very tightly adapted to a particular niche then there is less advantage in genetically exploring other possibilities, so the descendants of individuals with lower mutation rates would have an advantage over those with higher mutation rates. This would provide an evolutionary pressure for a low mutation rate, which might explain the observation. (But this last paragraph is speculation on my part. I work on modelling evolution and I know that this kind of selection on mutation rates can occur, but I have no evidence at all about whether it happens in crocodiles.)

I think the "fixed jaws" argument is a weak one: if they evolved jaws which are more fixed then they can evolve ones that are less fixed, and you're whole answer hinges on that argument. You also have no sources and say nothing direct about genetic drift or consistent/variable selection (niche stability). As it stands this is a very opinion based answer and has questionable scientific content.

@rg255 to answer your first point, it's typically much easier to lose complex features than to evolve them in the first place. E.g. vertebrate eyes evolved only once but have been lost but have been lost many times. (I don't know if a species exists that is known to have lost its eyes and then un-lost them, but I very much doubt it exists.) If the developmental pathways responsible for the jaw hinge mechanism have been lost they are very unlikely to reappear. On your second point I can only plead guilty to the lack of references, but I did mention the other two things, albeit briefly.

(The reason I only covered them briefly is that you already covered them in your answer. This was only intended as a complement to yours.)

Well, two things.
First the assumption that creatures that are living fossils are strong as a species isn't strictly true. Evolution; especially in relatively long-lived animals like crocodiles and sharks (compared to dogs, houseflies, j-walkers, etc.) is such a long process. It isn't factually verifiable that they are doing well as a species, only that they are in a stable food chain.
Second; and User23715 raises all these point, animals that aren't exposed to evolutionary motivators (mutagens, predation, and habitant change) won't have as much genetic divergence. A crocodile won't benefit from a Darwinian advantage if it doesn't provide enough of a survival advantage to eventually fuel a divergent evolution. Any dominant trait needs to be aggressive enough to stay dominant. In a simple dominant-recessive model it would need to be twice as potent for hundreds of generations (close to 2000 years for crocodilian life spans and birth rates).

Welcome to Bio. Could you add sources to your claims?


text:
5-HTTLPR polymorphism and Depression
I am reading about the biology of depression and came across something I can't understand. Here is the thing:
Lesch K-P, et al. (1996) say that people with short alleles of 5-HTTLPR are more prone to anxiety and depression. Pezawas (2005) also say that short allele carriers have worse anterior cingulate cortex - amygdala connectivity, which is observed among MDD patients. This, however, doesn't make much sense to me, since I'd expect people with short allels to have underperforming serotonin transporter - and isn't it overperforming serotonin transporter that contributes to depression by preventing serotonin transmission by sending it back to the presynaptic neuron? So, wouldn't you expect people with long alleles then to be prone to depression more?
To complicate things further, Willeit et al. (2008) do say that enhanced 5-HTT is observed in Depression. And enhanced 5-HTT would be found in people with long 5-HTTLPR?
So my questions are:

Do I understand it right that Willeit's (2008) results contradict
Lesch (1996) and Pezawa's (2005) results?
To the best of today's knowledge, is it the people with short or
long allels who are more prone to Depression? If the answer is -
with short, could you please clear up my confusion about it (see 2d
paragraph)?

I hope my question makes sense.
References:

Lesch, K., et al.(1996). Association of Anxiety-Related Traits with
a Polymorphism in the Serotonin Transporter Gene Regulatory Region.
Science, 274, 1527-1531.
Pezawas, L., et al. (2005). 5-HTTLPR polymorphism impacts human
cingulate-amygdala interactions: A genetic susceptibility mechanism
for depression. Nature Neuroscience, 8(6), 828-834.
Willeit, M., et al. (2008) Enhanced serotonin transporter function
    during depression in seasonal affective disorder.
    Neuropsychopharmacology, (33), 1503-1513

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text:
How does the body switch between aerobic and anaerobic respiration?
Lets take the case of a person doing heavy exercise. Aerobic respiration is taking place, but oxygen is about to be finished up. Glycolysis occurs, Krebs cycle finishes. Now NADH and FADH2  enter electron transport system (ETS) to form ATP, but at the last step, cytochrome c oxidase cannot get oxygen as it just finished up. Now, what happens to the ongoing ETS? Does it go in reverse order and then arnon cycle to get back Acetyl co-A and respire anaerobically, or does this process get paused and respiration switches over to anaerobic mode till oxygen supply is replenished?

I think both @David and @SatwikPasani have given nice answers, but none of them seems complete and involving all details. So I am posting another answer which involves much of the required details for benefit of readers as well as myself.
The simplest answer would be that cell switches from aerobic to anaerobic respiration via allosteric inhibition of enzymes from product build-up. The details, in a stepwise manner, go as follows:

In the absence of oxygen, mitochondria activate a factor known as hypoxia-inducible factor-1 (HIF-1)1. HIF-1 helps in slowly shutting down the electron transport chain. This happens as HIF-1 induces subunit switching from cytochrome-c oxidase subunit 4 isoform 1 (COX4-1) to COX4-22. Also, HIF-1 induces activation of micro-RNA 210 (mir-210)3, which blocks expression of iron-sulfur cluster assembly proteins ISCU1/24, which are required for the function of complex I5, COX106, aconitase and subunit D of succinate dehydrogenase. Apart from this, in decreased levels of O2, nitric oxide (NO) causes inhibition of respiration and even cell death7. Also, nitric oxide synthase is a target of HIF-18. You can understand this by this diagram9:

Now, shutting down electron transport chain causes accumulation of NADH (and FADH2) in the mitochondrion. This build up, in turn, shuts another process known as malate-aspartate shuttle (MA shuttle), which is essentially a process to indirectly transfer NADH from cytosol to mitochondrion since mitochondrial membrane is impermeable to NADH10. Now, since malate-aspartate shuttle is not working anymore, thus NADH remains in the cytosol. See this through the diagram below:

Another point is that accumulation of NADH in the mitochondrion shuts down krebs cycle. It is so because two of the main enzymes, isocitrate dehydrogenase and $\alpha$-ketoglutarate dehydrogenase, both of which require the presence of NAD+ to function, are inhibited by the presence of NADH11. Also, aconitase and succinate dehydrogenase are inhibited by mir-210 as already discussed. Thus, inhibition of krebs cycle occurs, which leads to accumulation of acetyl-coA. See the diagram below:

Now, accumulation of both NADH and acetyl-coA inhibit the activity of pyruvate dehydrogenase12, which leads to accumulation of pyruvic acid in the mitochondrion. This is also clear from the above diagram.
Now, since pyruvic acid is not being metabolized, it is hence no more transported from cytosol to mitochondrion. Transportation of pyruvic acid from cytosol (after glycolysis) to mitochondrion (for krebs cycle) requires mitochondrial pyruvate carrier (MPC). Now, presence of malate is shown to promote the activity of MPC13. But since krebs cycle has already stopped, so no more malate is being produced. Also, since malate is not metabolized through MA shuttle (see second point), so it travels back into the cytoplasm (or is not produced at all). Thus, activity of MPC is significantly reduced. Apart from this, $\alpha$-keto acids are known to inhibit the activity of MPC14. Thus, due to accumulation of $\alpha$-ketoglutarate (which is not metabolized by $\alpha$-ketoglutarate dehydrogenase, see third point), activity of MPC is further reduced. Because of these effects, pyruvate remains in the cytosol. See the following diagram for clarification15:

In the last step, accumulation of pyruvic acid as well as of NADH in the cytosol together promote anaerobic respiration since in this process, NADH is converted to NAD+, which is possible due to the presence of NADH. This is also helpful since it not only helps in decreasing the accumulation of cytosolic NADH, but also in metabolizing the NADH generated from glycolysis. Finally, the complete process can be visualized by the following diagram:

P.S.: However, accumulation of lactate does not happen (i.e. a question like What if excess lactate inhibits anaerobic respiration? would not make sense) because lactate is readily removed from the cytosol to outside the cell so that it is transported to the liver, where it is converted back into glucose. This process is known as Cori Cycle16. See this diagram:

Bonus: A novel research has concluded that extracellular acidosis (induced by release of lactic acid), causes a dramatic increase in efficiency of ATP production by mitochondria during hypoxia(!). Under neutral hypoxia (without acidosis), mitochondria get fragmented and lead to impaired ATP production, causing cell death. But under acidosis-hypoxia, mitochondria become unusually elongated (by inhibiting DRP1-mediated mitochondrial fission17 and inducing mitochondrial fusion via Stress-Induced Mitochondrial Hyperfusion (SIMH) pathway18), cristae get remodelled through OPA119 which protects and maintains ATP production in the cell in hypoxia. See this diagram:

Since the whole process is reversible (by bringing extracellular pH to neutral), thus a dynamic equilibrium can be attained in cells with high oxygen demand, like neurons, through which cell can maintain high ATP production even in hypoxia.
References:
 1. Giancarlo Solaini, Alessandra Baracca, Giorgio Lenaz, Gianluca Sgarbi, Hypoxia and mitochondrial oxidative metabolism, Biochimica et Biophysica Acta (BBA) - Bioenergetics, Volume 1797, Issues 6–7, June–July 2010, Pages 1171-1177, ISSN 0005-2728, http://doi.org/10.1016/j.bbabio.2010.02.011.
 2. Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129: 111–122, 2007
 3. Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell 35: 856–867, 2009
 4. Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL, Loscalzo J. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab 10: 273–284, 2009
 5. Puissegur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand K, Cardinaud B, Hofman V, Fourre S, Magnone V, Ricci JE, Pouyssegur J, Gounon P, Hofman P, Barbry P, Mari B. miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ. 2010. October 1
 6. Chen Z, Li Y, Zhang H, Huang P, Luthra R. Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29: 4362–4368
 7. Lee VY, McClintock DS, Santore MT, Budinger GR, Chandel NS. Hypoxia sensitizes cells to nitric oxide-induced apoptosis. J Biol Chem 277: 16067–16074, 2002
 8. Jung F, Palmer LA, Zhou N, Johns RA. Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes. Circ Res 86: 319–325, 2000
 9. Wheaton WW, Chandel NS. Hypoxia. 2. Hypoxia regulates cellular metabolism. American Journal of Physiology - Cell Physiology. 2011;300(3):C385-C393. doi:10.1152/ajpcell.00485.2010.
 10. Wikipedia contributors. "Malate-aspartate shuttle." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 7 Mar. 2017. Web. 7 Apr. 2017.
 11. Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 17.2, Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled.
 12. Budde RJA, Fang TK, Randall DD, Miernyk JA. Acetyl-Coenzyme A Can Regulate Activity of the Mitochondrial Pyruvate Dehydrogenase Complex in Situ. Plant Physiology. 1991;95(1):131-136.
 13. Mowbray A. Evidence for the role of a specific monocarboxylate transporter in the control of pyruvate oxidation by rat liver mitochondria. FEBS Lett. 1974;44:344–347. doi: 10.1016/0014-5793(74)81174-9
 14. Halestrap AP, Brand MD, Denton RM. Inhibition of mitochondrial pyruvate transport by phenylpyruvate and alpha-ketoisocaproate. Biochim Biophys Acta. 1974;367:102–108. doi: 10.1016/0005-2736(74)90140-0.
 15. Schell JC, Rutter J. The long and winding road to the mitochondrial pyruvate carrier. Cancer & Metabolism. 2013;1:6. doi:10.1186/2049-3002-1-6.
 16. Wikipedia contributors. "Cori cycle." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 28 Feb. 2017. Web. 7 Apr. 2017.
 17. Smirnova, E., Griparic, L., Shurland, D. L. & van der Bliek, A. M. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol. Biol. Cell 12, 2245–2256 (2001).
 18. Tondera, D. et al. SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J. 28, 1589–1600 (2009).
 19. Frezza, C. et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126, 177–189 (2006).

I think using end-product inhibition to illustrate the possible allosteric inhibition of early enzymes in aerobic respiration is misleading because 1. it would be the initial reactant (not the final one) — pyruvate that would build up, and 2. There is no evidence that pyruvate inhibits any of the key enzymes here. The NADH/NAD+ ratio might have an effect on pyruvate metabolism, but it is generally other compounds such as citrate that are the regulatory molecules, and these do not fit into that simple reaction pathway model.

The simple answer to your question is that in the absence of oxygen the electron transport chain stops. (It can't go backwards, that would generate oxygen.) However your assumption that it stops at the last step is incorrect, all the cytochromes are converted to their reduced form, and there is feedback that diverts the NADH elsewhere.
The situation is complicated because it depends what tissue you are talking about and what sort of exercise and what is the fuel for respiration. However let us consider the skeletal muscle at the start of a non-sprint run. Let us assume that it will be using glycogen as a source of fuel, which is converted to pyruvate and NADH. The pyruvate will enter the tricarboxylic acid (TCA) cycle in the mitochondria and be oxidized there and also produce metabolites. The NADH from glycolysis (produced by reducing NAD+) will enter the mitochondria and be oxidized; however it does not enter directly but via a shuttle, one of which — the malate-aspartate shuttle, show below — will be considered in a more detail lower down.
Now let us suppose there is a sudden need to sprint so that the muscle cannot get sufficient oxygen to deal with the NADH produced in glycolysis. What happens? The key event is that pyruvate is oxidized to lactate. Why? Not because lactate is useful, but because this is an anaerobic means of oxidizing the NADH back to NAD+ to allow glycolysis to continue and ATP to be produced at the substrate level.
Why doesn't the NADH keep going into the mitochondria (where it would be wasted as the electron transport chain has stopped)? Because the shuttle stops — in the case of the malate-aspartate shuttle mitochondrial malate dehydrogenase stops converting malate to oxaloacetate, malate builds up and therefore the malate transporter stops bringing malate into the mitochondrion.

This can be understood at the most general level by the fact that if NADH in the mitochondrion cannot be oxidized it will accumulate, hence slowing and eventually arresting the malate dehydrogenase reaction by simple mass action.
In fact Nature generally uses more sophisticated regulation that allows switch on and switch off to be performed more rapidly and completely, most notably by allosteric regulators. In the case of malate dehydrogenase the situation is not really clear, but there are reports that suggests citrate is an allosteric activator of the enzyme in some tissues (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131027/). The concentration of citrate falls as the TCA cycle stops because of the lack of NAD+ (this is because TCA cycle intermediates get tapped off for other purposes) so the activating effect of this intermediate would be removed.
(There is another shuttle for reducing power that my be more important in skeletal muscle. This is the glycerol 3-phosphate shuttle. However as this requires the oxidized form of FAD directly in the mitochondrial membrane it will clearly shut down in anoxia.)
The net result is that the NADH stays in the cytosol to be oxidized by pyruvate in the lactate dehydrogenase reaction.
This can only happen if the pyruvate stays in the cytoplasm and does not move to the mitochondrion. Obviously the lack of NADH to reduce it to acetyl-CoA in the pyruvate dehydrogenase reaction would cause its concentration to build up in the mitochondrion and reduce transport across the membrane by simple mass action. However it is likely that the specific mitochondrial pyruvate transporter is regulated by metabolites which change their concentration under these conditions. The evidence here is indirect as the transporter was only identified and cloned in 2012.

Nice answer, though some more explanation to "Because the malate-aspartate shuttle is subject to regulatory control" or diagram or at least a reference would be highly appreciated :)

The malate-aspartate shuttle and its regulation is a big topic. You can find more about it at https://en.wikipedia.org/wiki/Malate-aspartate_shuttle. Pasani has gone into regulation in more detail. For those not familiar with the molecular details  of allosteric regulation, try https://en.wikipedia.org/wiki/Allosteric_regulation.

In response to your request for more detail of the malate-aspartate shunt I have provided a diagram of my own which provides this but still focuses on what I think are the key points, that net movement of NADH into the mitochondrial matrix and the role of mitochondrial malate dehydrogenase. I prefer my revised answer to the merged answer as I feel it is more focussed. I'll comment on that answer.

Nice question. Now a perfect answer should include all the regulatory steps involved in this transition (a lot) and all the places where a change of metabolic fluxes occur. But, the question can be answered in essence at least, by a very simple model.
Assume that no other regulations act except direct enzymatic feedback inhibition. This means that substrate being acted upon by an enzyme converting it to a product will stop being acted upon when the concentration of the product rises. Now, for the case in question. Lack of oxygen means that cytochrome c cannot work. Hence, it's substrate will accumulate, which is the product of the preceding enzyme, which will be blocked leading to the accumulation of its substrate and so on. This "waterlogged" system will continue leading to metabolite accumulation till pyruvate starts piling up. Now this pyruvate piling does something different because it had two enzymes that could act upon it. The other enzyme, which converts it to lactate does not have this feedback blockage and hence can function. So, the pyruvate is now converted into lactate, which requires NADH, and hence allows glycolysis to proceed (because the formation of NADH was an indispensable reaction in glycolysis), and hence, you have the anaerobic shift. Lactate doesn't pile as it has a favourable muscle-blood gradient and is quickly transported out the cell, and also because it has to pile up significantly before the enzyme forming it is back-logged.
Now, to add the other regulations. What all other regulatory factors do, is to enhance this waterlogged feedback. Instead of the product piling up to a huge amount before the enzyme is inhibited, these regulations will allow a smaller pile-up to produce the feedback inhibition. So in essence, you can view the shift as a simple consequence of blocking the enzymatic chain at a particular level.

A good source of basic biochemicl information is Stryer online at NCBI: http://www.ncbi.nlm.nih.gov/books/NBK21154/ . It's an old edition and you can only search it (not browse it), but the information and presentation is of a high standard.

I think the treatment of pyruvate build up here is a little simplistic as it neglects the movement of pyruvate between cytosol and mitochondrion and the role of the mitochondrial pyruvate transporter.

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text:
Is there evidence to suggest that nutrients in vitamin capsules are not as readily absorbed as the same nutrients in whole foods?
I recently fell ill with a cold, and began to take a vitamin C capsule each day to help my immune system. When I noticed no change in my condition, I began to incorporate an abundance of citrus into my diet instead of taking the capsules. When I ate the citrus my condition began to improve markedly.
The ingredients listed by the vitamin manufacturer are:

Ascorbic Cellulose Gel
Hydroxypropyl Cellulose
Croscarmellose Sodium
Stearic Acid
Magnesium Stearate
Silicon Dioxide

Not excluding the possibility of coincidence, I was was intrigued. Has evidence been published to suggest that nutrients in whole foods like vitamin C in citrus fruits are more readily utilized in the body than nutrients in vitamin capsules?

That's a coincidence. If you had eaten the fruits first and the pills then, you would probably see it the other way round. The body does not decide between vitamins coming from fruit or pills.

I concluded that that was most likely, though the hypothesis occurred to me that whole foods contain secondary nutrients that encourage uptake or utility of primary nutrients. I'm not making any assumptions, just asking if anyone has tested that hypothesis.

Colds generally last a limited amount of time so your recovery probably has more to do with your body's natural response than any vitamins, synthetic or food-based.

Like the question,  but,  as you and others have already pointed out, your sickness scenario is likely due to coincidence.

Vitamin C bioavailability
According to the review Synthetic or Food-Derived Vitamin C—Are They Equally Bioavailable? (Nutrients, 2013), the bioavailability of vitamin C from foods and supplements is similar:

...all steady state comparative bioavailability studies in humans have
  shown no differences between synthetic and natural vitamin C,
  regardless of the subject population, study design or intervention
  used.

and, according to Institute of Medicine (in the US):

The type of food consumed has not been shown to have a significant
  effect on absorption of either intrinsic or supplemental vitamin C.

Vitamin C supplements as prevention for common cold
Vitamin C supplements, even in doses 200+ mg/day (more than 3 x recommended dietary allowance - RDA) do not likely help in common cold:

This review is restricted to placebo‐controlled trials testing 0.2 g
  per day or more of vitamin C.
  Twenty‐nine trial comparisons involving 11,306 participants
  contributed to the meta‐analysis on the risk ratio (RR) of developing
  a cold whilst taking prophylactic vitamin C.
  The failure of vitamin C supplementation to reduce the incidence of
  colds in the general population indicates that routine prophylaxis is
  not justified. Vitamin C could be useful for people exposed to brief
  periods of severe physical exercise. (Cochrane, 2007)

To get 200+ mg vitamin C from citruses, you would need to eat at least 3 oranges or 7 lemons.
Considering the above evidence, the improvement of cold symptoms was likely a natural process.
Bioavailability of other nutrients from foods/supplements
There is no general rule to say that nutrients from foods or supplements are absorbed better or worse; it can depend on a specific food and a specific supplement formulation.
Iron:

In our in vitro model, naturally iron-rich mineral waters and
  synthetic liquid iron formulations have equivalent or better
  bioavailability compared with ferrous iron sulphate tablets. (European Journal of Nutrition)

Iron-fortified foods:

Bioavailability of fortification iron varies widely with the iron
  compound used (56), and foods sensitive to color and flavor changes
  are usually fortified with water-insoluble iron compounds of low
  bioavailability. Iron compounds recommended for food fortification by
  the World Health Organization (WHO) (56) include ferrous sulfate,
  ferrous fumarate, ferric pyrophosphate, and electrolytic iron powder.
  Many cereal foods, however, are fortified with low-cost elemental iron
  powders, which are not recommended by WHO (57) and these have even
  lower bioavailability (AJCN, 2010).

Magnesium:

The results of serum and urine analysis indicated that Mg
  bioavailability was comparable for mineral waters with different
  mineralization levels, bread, and a dietary supplement. (Tandofline,
  2017)

Mg supplements comparison:

Studies on the bioavailability of different magnesium salts
  consistently demonstrate that organic salts of magnesium (e.g., Mg
  citrate) have a higher bioavailability than inorganic salts (e.g., Mg
  oxide) (Nutrients, 2019)

Potassium:

The bioavailability of potassium is as high from potatoes as from
  potassium gluconate supplements. (AJCN, 2016)

In conclusion, even if most studies mentioned in this answer suggest that nutrients from foods and supplements are equally bioavailable, you need to check specific supplement formulations, for example, iron from many fortified foods and magnesium oxide can have poor bioavailability. Anyway, the studies show that most people with normal blood nutrient levels do not need dietary supplements (Int J. Prev. Med., 2012 ; Annals of Internal Medicine, 2014).

The answer probably varies for different nutrients.  An informal article by ConsumerLab.com indicates that many vitamins are better absorbed from natural sources, but a few are actually more readily absorbed from supplements.
Looking at Vitamin C specifically, a 2013 review article by Carr and Vissers concluded as follows (emphasis mine):

Overall, a majority of animal studies have shown differences in the comparative bioavailability of synthetic versus food-derived vitamin C, or vitamin C in the presence of isolated bioflavonoids, although the results varied depending on the animal model, study design and body compartments measured. In contrast, all steady state comparative bioavailability studies in humans have shown no differences between synthetic and natural vitamin C, regardless of the subject population, study design or intervention used. Some pharmacokinetic studies in humans have shown transient and small comparative differences between synthetic and natural vitamin C, although these differences are likely to have minimal physiological impact.

In other words, with vitamin C natural and synthetic sources appear to be equally bioavailable for humans.  The authors do note that "Although synthetic and food-derived vitamin C appear to be equally bioavailable in humans, ingesting vitamin C as part of a whole food is considered preferable because of the concomitant consumption of numerous other macro- and micronutrients and phytochemicals, which will confer additional health benefits."
References:

Carr, Anitra C.; Vissers, Margreet C. M. (2013). "Synthetic or food-derived vitamin C—Are they equally bioavailable?". Nutrients 11 (5). pp. 4284–4304. doi:10.3390/nu5114284. PMC 3847730.

This is not a coincidence.  Food-sourced vitamins are prized because of being in bio-available form, soluble and absorbable.  The only way to make a vitamin more absorbable is to deliver it elementally, with no digestion required at all.
The best absorption rates are through sublingual administration of elemental sprays, no additives,no fillers, nothing except what your body needs for maintenance and repairs. There is a 2011 review of research here:
http://www.ijplsjournal.com/issues%20PDF%20files/nov2011/10.pdf

I don't think IJPLS is a real peer-reviewed journal, they are published by a sketchy open-access publisher and they list a fake impact factor on their website.

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


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Why were the earliest humans hunter gatherers instead of fruit eaters living on trees?
How is it that the earliest humans who evolved from primates (who live on trees and mostly eat fruit) became hunter-gatherers (which seems like a harder, more stressful and more dangerous way to find food)?

Perhaps because living in trees and eating fruit rather limits you to living in places where there are fruit-bearing trees.  Becoming a hunter-gatherer allows a species to greatly expand its range.


text:
What is positive and negative supercoiling?
Is the following correct?
Positive supercoiling  = the coiling of DNA helix (B-DNA) on itself during intesified coiling of the two DNA stands in right handed direction
negative supercoiling  = the coiling of DNA helix(B-DNA) upon itself during uncoiling of the two DNA strands performed in left handed direction?
I'm a little confused.

Think of positive supercoiling as twisting the loop clockwise from the top, while think of negative supercoiling as twisting the loop counterclockwise from the top.

Positive means left handed or clockwise supercoiling. It results due to overwinding of dsDNA and thus relieve the torsional stress. Whereas the negative supercoil is just the opposite of the earlier.

The image from the web book seems to be contradictory with the text and the video.
(a) is a left handed helix, so is negative supercoil, (b) is a right handed helix, so is positive supercoil.
Cheers

According to this powerpoint from the SIU School of Medicine:

Right handed supercoiling = negative supercoiling (underwinding)
Left handed supercoiling = positive supercoiling

And from this Boston University webpage:

If DNA is in the form of a circular molecule, or if the ends are rigidly held so that it forms a loop, then overtwisting or undertwisting leads to the supercoiled state. Supercoiling occurs when the molecule relieves the helical stress by twisting around itself. Overtwisting leads to postive supercoiling, while undertwisting leads to negative supercoiling.

And finally from wikibooks:

Positive and Negative Supercoilings

Positive supercoiling is the right-handed, double helical form of DNA. It is twisted tightly in a right handed direction until the helix creates knot.

Negative supercoiling is the left-handed, double helical form of DNA.

Although the helix is underwound and has low twisting stress, negative supercoil's knot has high twisting stress. Prokaryotes and Eukaryotes usually have negative supercoiled DNA. Negative supercoiling is naturally prevalent because negative supercoiling prepares the molecule for processes that require separation of the DNA strands. For example, negative supercoiling would be advantageous in replication because it is easier to unwind whereas positive supercoiling is more condensed and would make separation difficult.
Topoisomerases unwind helix to do DNA transcription and DNA replication. After the proteins have been made,the DNA template supercoils by the force to make chromatin. RNA polymerase also influence DNA strand to have two different supercoiled directions. The region RNA polymerase has passed forms negative supercoil while the region RNA polymerase that have not passed forms positive supercoil. By these processes, supercoils are generated.

In the following image from web-books:

 (a) Positive supercoils (the front segment of a DNA molecule cross over the back segment from left to right). (b) Negative supercoils.
This video, titled "super coil (positive and negative) formation of DNA" should help you visualize this.

@SanjuktaGhosh Does this help clarify it for you at all?

I read this topic from a book which cleared my doubts and your answer reassured it.Thank you.


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What is this animal that hides in dustlike structure?
I'd like help identifying the species of animal in these two photos. There's some dust(or dust-like substance) with something alive inside of it (possibly a larva or I don't really know what to call it). This appeared in a couple of hours in the wall. Please, try to even just guess what this could be (I can't think of anything!). Very odd...
I don't even know what tags I hsould use for this!
Thanks in advance

new photo

How big is it? Where do you live? It's very hard to see any animal in the photos, but for example Case Bearing Moth larvae use fibers to make the "case" that it lives in. Or maybe a carpet beetle larva that happened to hide in this dust.

it's a bedroom. there's a dust around in a room(I cleaned a lot), but when I just came there's was a very big humidity in the air(you know, the smell of it...). It's one of my relatives home and I'm very disturb about it.

I think it might be a moth larva. And I really don't think one larva is reason to be worried! Just remove it and keep an eye out for more of them, in dust or perhaps wool materials.

I've been here for three days now, and noticed this yesterday... I removed three of them(yesterday) and today more two. while I was gone(for about 2-3 hours outside to travel in the city) this one appear... that's why I'm worried :/

Sorry to hear that (even if it's still not an outright infestation). I'm no expert, but I would recommend more vacuming, removing of materials that they like, and if they keep coming, googling for clothes moth pest control.

Where in the world is this, what's the nearest City?

This might indeed be a moth larvae. If you already found six, there might be more. Moth larvae generally eat something organic like plants, cotton or wool. Search for this source, it might be a plant, carpet, curtain, cloths, etc.

Related: https://biology.stackexchange.com/q/28479/16866

There's a lot of animals that do that: https://fr.m.wikipedia.org/wiki/Fichier:Reduvius_personatus,_Masked_Hunter_Bug_nymph_camouflaged_with_sand_grains.JPG

This is likely a case-bearing clothes moth (Tinea pellionella).
Though more information and a better image would aid in confirming that to be the case.
Here are some pictures:


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What are the dangers related to keeping a human brain alive outside of a human body?
I am interested in learning about the feasibility of keeping a human brain alive outside of a human body.
The question: What obstacles do we need to overcome to be able to keep a human brain alive outside of a human body?
The problems I am taking into consideration are:

connecting nerves with an artificial skeleton, (no need to connect spinal cord?)
delivering signals to the brain to avoid sensory deprivation?,
keeping brain in a "healthy state" as long as possible,
augmenting and stimulating brain,
connecting the brain to external devices without hurting it,
maintaining blood supply,blood transfusion problems (allergic reactions and hives, fever, hemolytic reactions, iron overload etc.)
can a brain be in a sleep mode? keeping brain in a "work" mode,
can a brain function without hormones?,
can we copy a brain?,
can we grow a brain? part of a brain?,
regenerating brain, slowing down the process of brain degeneration,
does the brain need bone marrow to properly function,
maintaining cerebrospinal fluid supply.

I asked this question on Quora, https://www.quora.com/What-must-be-the-conditions-to-keep-a-brain-alive-outside-of-a-body

What dangers are you talking about?

What the dangers (with explanations) related to keeping a human brain alive outside of a human body. I want to understand them better. What are the reasons that we still cannot make a human brain live outside of a human body? I want a "big" answer.


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Irradiation positive effect on humans?
In research paper Euphytica 135: 187–204, 2004 it is written that:

434 mutant varieties of rice have been released with improved characters such as semi-dwarf height,
  early  maturity,  improved  grain  yield,  disease-  and
  cold-tolerance, and improved grain quality. Of these,
  225 (56%) were induced with gamma rays, 16 with X-
  rays, 7 with fast neutrons and 12 with other radiation
  sources

So I can see that irradiation may have positive effects on plants' genome.
Is there any information that mutations induced in this way in humans were beneficial for them? Can irradiation have positive effects on your body?

Regarding your first question, I don't know of any instance in which irradiation was used to select for a beneficial trait in humans. I italicized 'used' because I think that you could argue that naturally occurring sources of irradiation have led to the selection of traits that protect us from radiation damage.
That might sound like a bit of a circular argument, but keep in mind that in the case of the rice you mention, the discovery of beneficial traits came at the expense of a lot of dead rice that suffered deleterious effects of radiation. Unfortunately, the deleterious effects are a lot more likely to occur than than any really useful ones.
That leads to your second question. Conceivably, radiation could lead to a beneficial mutation. However, there are some pretty big caveats with that. First, in order for it to be beneficial, this hypothetical mutation would have to occur very early on in development, otherwise it would be limited to, at best, a handful of cells, probably in your skin, which would just get sloughed off anyway. So the second caveat is that in order for such a beneficial radiation-induced mutation to occur in the right place at the right developmental time, it would have to penetrate all the layers of your mother's genetic material that separate your fetal cells from the outside world without losing the energy needed to damage your DNA.
I couldn't tell you what sort of radiation might be capable of pulling that off with what probability of success, but my guess is that it's really unlikely.


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The properties of benign tumours
Do benign tumours have no functioning apoptosis mechanisms ? If so what stops benign tumours from excessive growth? Also can a benign tumour have a functioning apoptosis mechanism?

To rephrase ; 'Does a benign tumour have no working apoptosis mechanism?' If they have no self-destruct mechanisms what stops them from excessive growth?

If a benign tumours genome is analyzed would this give clues as to how it has no functioning apoptosis mechanisms yet it doesn't grow or metastasize ?

Benign tumors can absolutely have mechanisms available to them to commit to and carry out apoptosis.  An example of this would be benign prostatic hyperplasia, in which the balance of apoptotic and proliferating cells is offset, but apoptosis is still occurring, simply at a lower comparative rate than the proliferation.
Benign tumors can therefore be caused either by excessive proliferation or inadequate cell death; evidently, a complete failure of programmed cell death in many tissues would result in a tumor, benign or no.

Source:

Kyprianou N, Tu H, Jacobs SC. Apoptotic versus proliferative activities in human benign prostatic hyperplasia.  Hum Pathol. 1996 Jul. 27(7): 668-75.


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Can we study all the genes of one human being?
Considering the fact that a new-born child gets 23 chromosomes containing DNA and genes from each of his parents and then 23 chromosomes from those 46 chromosomes of the new-born child will be transmitted to his child, I am wondering do all the people have the same 46 chromosomes or all have different chromosomes ( that's another thing that some genes present in the DNA of chromosomes don't express themselves. Of course, they are present there, no? )
If all of us have same chromosomes then can we study those genes present in 46 chromosomes to find out ALL the characters one person can have?


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Why can one swim longer underwater by blowing out air?
I am a human. I take a deep breath. I swim underwater... After some time, I need to blow out some air. I blow out some air... By doing so, I can swim underwater longer. Blowing out some air gives me more time underwater. Why?
Apparently, dolphins encounter this phenomenon too.

"I am a human" congrats! As for the question, most probably because blowing out air decreases your buoyancy, I've never heard of such a biological response which helps us to swim longer by blowing out air. Dolphins should encounter it too as laws of physics apply on everyone.

Please add a citation regarding your dolphin statement. It would also be nice to see some primary literature where this was tested in a vigorous way, not just your personal experience.

Whales blow out when they surface. Hence the fountain of air/water known as the 'blow'.

@another — Blowing out some air gives me more time underwater.

This is purely a psychological response, and it does not help in decreasing the speed of CO2 level rise. As CO2 level in your blood rises, you instinctively want to breath out the 'bad' air and breath in fresh one. The latter is impossible under water, but the former eases you psychologically a little; you have "started doing something" with your predicament of high CO2 level.
Most freediving courses (as well as my own experience - humble as it is) suggest not to have the last breath substantially larger than your normal one; this comes from people who train to achieve 6-7 minutes dives, so I would assume they meticulously tried various methods.
The key here is not to have a victory over physiology; the key is psychology. Most people fail at diving because they unnecessarily get into a positive feedback loop: they get excited, their brain and muscles become even more active, they produce more CO2, brain receives information about rising CO2 in blood, and it becomes excited even more, produces even more CO2, etc, etc, until a panicked diver surfaces or inhales water. Without such unnecessary excitation, each moderately healthy human would be easily physiologically capable of 3-4 minute dives.
My take is the amount of air you have in your lungs should be primarily the amount that eases your psyche the most and helps to stop needless stress.

The problem is with the high carbon dioxide, not with the low oxygen. Humans don't have oxygen detectors, so we can't respond to that. Humans have carbon dioxide detectors, so we do respond to that.

Very interesting answer! Before apnea diving, taking a last BIIIG breath seems the logical thing to do, in order to have as much oxygen as possible. Why doing otherwise?

Can you please explain "the problem" after taking more air than "the optimum"? Thank you!

I didn't say that taking more air causes a problem. The problem is the instinctive need to breathe. It is triggered to get carbon dioxide OUT (you produce it), not because you need more oxygen IN. The focus is usually on decreasing the carbon dioxide production.

But, in order to avoid having too much CO2, we can blow CO2 out, so the CO2 detectors won't ring too soon?

I try to find the reasons for the 2nd paragraph of your answer: "suggest not to have the last breath substantially larger than your normal one".


text:
Why is an excess number of eosinophils consistent with a violent allergic reaction?
What roles do eosinophils play in allergic reaction?

The primary function of Eosinophils is to releas digestive enzymes and destroy extracellular parasites, but they also contain pro-inflammatory molecules and cytokines in their granules.
Eosinophils play an important role in late response inflammation. The primary inflammation is caused by degranulation of improper hyperactivation of mast cells when they encounter antigen/allergen (They have IgE bound to their receptors on a membrane). They release cytokines as IL-4 and IL-13 which recruit Th2 lymphocytes. Th2 lymphocytes release i.e. IL-5 which attract eosinophils.
Eosinophils release the content of their granules, which can degrade the tissue on an organism. Their cytokines attract more WBC - eosinophils (macrophages, TH2 lymphocytes and mast cells) and since this process is not controlled, they accumulate in tissues and it can lead to allergic reaction.
Good book contemplating this topic


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Anatomical differences between herbivores and omnivores
What are differences of herbivores vs omnivores? I do not mean dietary differences (obviously), but physical ones.
E.g., afaik herbivores have a much longer digestive tract than carnivores; then there is the difference in teeth, possession of carnivorous instincts or lack thereof, etc.
But where is the distinction between herbivores and omnivores? Is there a clear distinction at all, or is the border between the two groups somewhat fuzzy? Or are omnivores merely herbivores who are less picky?
EDIT
As pointed out in the comments, the last sentence seems to ask for dietary differences. It is not meant to; the only difference I am aware of is dietary, so it asks whether there are any anatomical distinctions, or the dietary is the only one. I.e. are they anatomically similar, and not distinguishable in the same way herbivores and carnivores are; hence are they herbivores that simply do not mind eating non-plant based food in a while?
I hope this serves to clarify.
EDIT 2
I realize that this question is quite broad, so while I am trying to get a good view of the bigger picture, partial answers will be more than welcome!

at first you're asking about anatomical differences, but your last paragraph seems more focused on the dietary behavior for which you said you were not asking about. If this is not the case, please clarify your question.

@theforestecologist I just did, I hope this clarifies!

This is a bit broad. Teeth, gastrointestinal differences (not alike in all herbivores), hooves/claws, eyes, etc, not to mention instincts... it's pretty broad.

@anongoodnurse I realize that it is. However, I lack the knowledge to narrow it down. Also, I am basically interested in the big picture, i.e. pretty much anything having an impact on how they feed.

@foaly Instead of making additional sections like EDIT1 or EDIT2 while retaining the original content, please actually edit the question so that it becomes short and precise.

@WYSIWYG For exactly that purpose I did not. The question is still correct and as precise as I can make it without wordy explanations. If anyone feels uncertain about it though, there is a clarification below in the edits. ;)


text:
Why is competitive inhibition reversible?
My Biochemistry book mentions that 'competitive inhibition' is a reversible form of inhibition. But given that the inhibitor is blocking the active site and prevents an enzyme-substrate complex to be formed, how can it be reversible?

Not all competitive inhibition is permanently irreversible. Only substrates which bind covalently are irreversible. Something like Narcan(Naloxone) is a competitive antagonist, but it is not permanent.

A competitive inhibitor typically competes for the active site with the substrate. In this textbook case, binding of a competitive inhibitor is reversible, because it binds to the active site of the enzyme, but is also released, making way for the substrate to bind. The affinity of the substrate, as well as its concentration determine the amount of inhibition (Berg et al., 2002).
An irreversible inhibitor may covalently bind to the active site, permanently disabling the enzyme (McDonald et al., 2012).
References
- McDonald et al., Enzymes: Irreversible Inhibition. In: eLS. John Wiley & Sons Ltd, Chichester (2012)
- Berg et al., Biochemistry. 5th ed. New York: W H Freeman; (2002)

In light of this meta post, this might be the single greatest answer of all time. I had a good laugh.

@canadianer thanks :-) It was a bit of an over-reactive response to someone claiming the answer was undersourced (a whole string of comments has been deleted since). Admittedly, it was indeed undersourced, but to me its contents are common knowledge and I didn't even bother to source it. Well, after it had been scrutinized even in a meta post, others began to interfere, mainly long-term residents here who knew I was probably among the last deserving to be blamed for not sourcing his answer :) Eventually it lead to the above result....

The high number of upvotes is totally not representative of its quality, it's just that people appreciate the principle of sourcing answers to that extreme point where it becomes just plain silly :)

@xusr thanks for your input. It sounds like you could write an excellent answer. In the meantime, I have adapted the wording of my answer above to reflect your thoughts. My approach was to give a schoolbook answer to a schoolbook question. Nothing more, nothing less.

It's water under the bridge, but if I were writing a schoolbook answer I would have included a diagram and an equation. School books are the most highly reviewed and edited form of literature. The publishers stand to lose a lot if they get things wrong in a very lucrative corner of the market.


text:
Do pharmacodynamics and pharmacokinetics of the drug in animals are the same as in human?
I'm trying to understand the purpose of different clinical trial phases, and the following question comes into my mind :

Do pharmacodynamics and pharmacokinetics of the drug in animals are the same as in human?

The reason I asked this question is that our professor said that pharmacodynamic and pharmacokinetic studies are performed during pre-clinical studies (in animals), as well as during clinical trial's phase 1. The answer I was thinking about is that animal's physiology cannot be the same as human's physiology, thus, pharmacological profils should be different.
I just want to know more about this and feed my curiosity.

Drug metabolism in humans is different than animal models.
Here is one example: http://www.ncbi.nlm.nih.gov/pubmed/17125407
The link is a review where they compare different animal models to humans with a focus on CYP enzymes commonly involved in drug metabolism.  While they describe similarities, they note:

CYP2C, -2D and -3A show appreciable interspecies differences in terms of catalytic activity and some caution should be applied when extrapolating metabolism data from animal models to humans

Essentially your instincts that different species have different pharmacology is accurate and based on the many genetically-based differences in the drug processing machinery.
Similarly, there are differences in drug metabolism between humans with different genetic backgrounds, which is the basis for pharmacogenetics (https://en.wikipedia.org/wiki/Pharmacogenetics).
More recently, differences in gut microbes have also been raised as contributory factors (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529681/).  In this case, identical twins with different diets could conceivably have different pharmacokinetics.

Tying this all back, the reason human drug trials are needed is because animal and tissue culture models are necessary, but insufficient to predict drug efficacy or safety.

So, what is the purpose of pharmacodynamics and pharmacokinetics studies on animal if the drug metabolism is not the same as in humans? can't we just wait until the study is performed during clinical trials?

Is the same article on CYP enzymes, the authors also describe similarities, so the animal models do provide some insight into how drugs might behave in humans.  More simply, would you volunteer for a phase 1 drug trial for a drug that has never been tested on any living creature?

You are correct.  The pharmacokinetics are different, but also quite similar.  The good thing is that we know what most of those differences are and can account for them when we scale models from animal species to humans.
Conducting pharmacokinetic studies in animals before conducting studies in humans is necessary and useful for a few reasons.

The Dose-Toxicity relationship can be assessed.  We will also get a better idea of what specific toxic effects to look for.
Scaled physiologically-based pharmacokinetic models appropriately predict pharmacokinetics in humans from animal data.
Variability can be assessed (i.e. if I administer a certain dose, how much variation can I expect in concentration profiles for a group of individuals?)

Physiologically-based pharmacokinetic models use a bottom-up rather than a top-down approach to modelling.  This approach allows accurate interspecies scaling simply by changing the system parameters according to the species of interest.  To begin, a virtual animal or person is created with organ volumes, blood flow rates, enzyme activities, etc. as defined in literature.  These are the system parameters.  Next, drug-specific parameters (solubility, charge, partition coefficients) are determined from literature or experimentally where possible.  Finally, all processes which are theorized to affect the drug's absorption, distribution, metabolism and excretion are described with a system of ordinary differential equations, using the system and drug-specific parameters. Any unknown drug-specific parameters can be fitted to animal data at this time.  It is useful to be able to determine estimates for drug-specific parameters with animal models that can be later applied to human models.
The model is validated by comparing the model simulations with actual experimental data from animals (Animal PK Trials!).  If the model makes accurate predictions, all we have to do is change the system parameters (organ volumes, blood flow rates, enzyme activites, etc.) from animal values to human values, while keeping the drug-specific parameters constant, and the system of ODEs will make a good prediction of the pharmacokinetics in humans.  Of course, this is a simplified methodology.  Occasionally the model equations or drug-specific parameters must be changed between species to account for some physiologic differences.  This process is called interspecies scaling and considerable research efforts have been put forward to standardize it.
These conclusions can be used to find an ideal First-in-Human dose.  PBPK modelling gives great insights into more than just First-in-Human trials.  Pediatric and Geriatric simulations are also very useful.  By changing the system parameters from adult to pediatric or geriatric (recognizing that humans change a lot with age), we can make guesses about the doses that are safe for children or the elderly.  The FDA now requires PBPK modelling to be done for its submissions.  All of this starts with animal PK trials.

great answer - if you could add some links to some of the terms, etc it would greatly strengthen it - thanks for your efforts!

Sorry I'm new, what audience should I be writing for w.r.t the terms that I define

that's a great question Poly... I usually err on the side of too many links to terms, helpful pages, etc - even if the links are just to a wikipedia type page with a very basic definition. The community is broad - with undergraduates all the way up to biomedical and other scientific faculty at academic universities throughout the world. I think most of the time you can tell the level of detail necessary based on how much detail or level of sophistication that the individual asking the question uses - hope that helps! Welcome to the Community!


text:
How can dopamine modulate synaptic strength?
Does dopamine act on G protein coupled receptor, leading to more Ca2+ channels on the postsynaptic knob?
Also, how is the specificity of the location (of the brain) that dopamine acts on controlled? Or is it controlled at all? Is this chemical associated with addiction?

Yes, dopamine receptors (D1-D5) are G protein coupled receptors,  which act primarily on adenylatecyclase (changing cAMP concentration, which activate proteinkinase A, which phosphorylates other proteins in turn such as CREB... you can find the pathway in the following article). D1 receptors activate adenylatecyclase, D2 inhibit its activity.
I wouldn't say it directly alters the Ca2+ channel concentration per se, the article says however it can modify their state.
According to this article, G proteins of these receptors could also have different effects (alternative effects through G-proteins such as activating phospholipase C, which results in IP3 formation which results in Ca2+ influx to cytoplasm from ER which acts on proteinkinase C) or new research suggest that it could also act through G protein-independent mechanisms via interactions with ion channels.

specificity of the location (of the brain) that dopamine acts on controlled?

The idea is that cells with certain neurotransmitter may induce growth of cells with same transmitter, thus forming specific circuits. I don't know however how specifically this happens and how the cells communicate to form specific connections (like dopaminergic connection from substantia nigra to basal ganglia) during development. I'd bet on some morphogenes. Someone else might know better :) .
Yes, dopamine is associated with addiction, as it's part of the reward system in brain. Many drugs inhibit its transport from synaptic cleft into the cells, which means prolonged activity, brain senses positive effects you can see when you've done something good (reward).

Thx that is an excellent detailed answer


text:
Are the words biology and Ecology ever interchangeable?
I often hear people use the word "Ecology" when i think they mean "biology." This got me wondering: are the words ever interchangeable, or are these people really just that frequently using the wrong word?
My understanding is biology is the broader study of life while Ecology is the more specialized study of life interacting with other stuff (life + earth).

You pretty much nailed it with your definitions. Good guess. Wikipedia should also be able to help you

Ah... So you've heard people to use words despite they don't know what they mean?


text:
Lizard species identification

I managed to photograph a lizard in Haruvit Forest, Israel. I would like to know - what lizard species is this? Size appr. 20-25cm

Could you estimate the size of the lizard?

Try to assign a size relative to something. for example, would the lizard fit in your hand, or it closer to the size of your foot?

About 20-25 cm.

This lizard is likely a Roughtail Rock Agama (Stellagama stellio or Laudakia stellio). They are colloquially referred to as hardon (or hardun) lizards.
According to Wikipedia:

Like many agamids, stellions can change color to express their moods. They bask on stone walls, rocks, and trees. They are usually found in rocky habitats, and are quite shy, being very ready to dive into cracks to hide from potential predators.

More from natureisreal:

The most commonly seen local lizard where I live in central Israel is probably the roughtail rock agama (laudakia stellio stellio), known locally as a hardon or hardun. They are rather sinister looking with rough dark armoured skin, but perfectly harmless. If frightened they run away and hide in the crevice of a rock or tree, inflating their skin and opening their mouth wide to wedge themsevles into the space, making it impossible to dislodge them. Sometimes I see a large dark male surveying his territory from the top of the nearby water tower.More usually they are to be seen during the warmest times of day sunning themselves on rocks, to the extent that it seems that each rocks has its own resident hardon, and believe me, this country is full of rocks, and that makes for a lot of these lizards...


text:
Do animals have different taste preferences within the same species?
Humans (especially children...) seem to dislike certain foods or drinks, that other humans seem to like. Common examples are coffee, french cheeses, olives, milk, fish and cabbage. Are there examples of animals either wild or in captivity that show the same behaviour? For example a group of primates that eat something except one or two members of the group? And if so, any clues to the evolutionary aspects of such preferences?

Certainly.  Just for an example, one of my dogs likes carrots and apples, the other won't touch them.

In captivity this seems to be observed quite often - almost every pet holder (at least the ones that live with at least two pets of the same species) will confirm this. In my cats, for example, this also is not restricted to taste but also includes smell. Generalising this to wild living animals and an evolutionary perspective is really interesting. Good question!

Yes. Intra-species variation in food preferences has been observed in

Rabbits (Bilko et al. 1994)
Copepods (Rieber 1982; Berghe and Bergmans 1981)
C. elegans (Abada et al. 2009)
Earthworms (Bonkowski 2000)
Butterflies (Jermy et al. 1968)
Beetles (Sarker et al. 2013)

I am sure most pet owners will find the existence of this variation quite intuitive. No too cats have the same food preferences.
Why such variation exist?
I can think of several possible (non-exclusive and non-exhaustive) reasons for why such variation exist?

Individuals compete. If preferences vary, it allow specialisation (inspired from @John's comment)
Phenotypic variance (whether genetic, environmental or other) is not necessarily maintained by some kind of balancing selection. You may observe purely neutral variation in preferences.
Genetic variance can explain variance in food needs and therefore it is good that preference can be plastic
Same as above but for environmental reason. Say, an individual may have different need based on its environment.
One must learn to recognize good food. There might be a tradition among family of liking specific types of food.

Thanks for the links, fascinating (+1). Do you have any ideas about the evolutionary aspects?

if your taste varies a little bit from your main competitor (others of your species) you are likely to find food they have overlooked, several variations on taste is more evolutionarily stable than just one species wide preference.

@RHA see edit in my answer

Thanks, as your answer is the best of all given, I am inclined to accept it ;-)


text:
Why is down syndrome more common than other trisomies?
Why is Down syndrome more common than say trisomy 18? Is chromosome 21 easier to replicate? Or is it because those babies are more viable?


text:
What is two-start or zigzag model of 30 nm chromatin fibre?
I read some webpages describing the two-start model but could not get it. I'll be obliged if someone helped me understand the topic.
The websites I have been through are:
1.http://www.nature.com/nrm/journal/v13/n7/fig_tab/nrm3382_F4.html
2.http://www.mechanobio.info/topics/synthesis/go-0006323
3.http://www.fastbleep.com/biology-notes/41/118/1272

What do you mean by two-start model? Maybe it would be easier to answer, if you explain your question a bit better.

@Chris Two start model or Zigzag model is a model which explains the structure of 30nm chromatin fibre other than the solenoid model.

From the MB Info Wiki you linked:

In the one-start solenoid model, bent linker DNA sequentially connects each nucleosome cores, creating a structure where nucleosomes follow each other along the same helical path [4, 7]. Alternatively, in the two-start zigzag model, straight linker DNA connects two opposing nucleosome cores, creating the opposing rows of nucleosomes that form so called “two-start��? helix.

This means that in the one-start model each nucleosome is connected to the one adjacent to it, and this is a continuous cycle. Meaning that it is more like a phone chord.
The Zig-Zag model instead proposes that each nucleosome is connected to the nucleosome approximately opposite to it (parallel), and is a pattern that is continuous through out the chromatin fiber. This is more complicated to understand but imagine it being more like lacing on a shoe.It goes from a hole on one side to a hole on the other side parallel to it but not in the same plane as itself.
To move to the third nucleosome (and pack as tightly as possible) instead of it being directly below the 1st one it is slightly off to the side and not exactly parallel to the 2nd nucleosome.
However the 4rth nucleosome will be exactly parallel to the 3rd, and thus the same amount of degrees off-center from the 2nd nucleosome as the 3rd nucleosome is to the 1st, maintaining the pattern.
This forms a more 3-D tubular strucuture than an actual shoelace on a shoe would (which is more flat like a plane but serves for visual cue).
A 2D step-by-step representation of this would be like the image below:

Here is a model of final figure I made to help explain this:

In the MBI figure each "Green" nucleosome is connected to an opposite slighty lower "Purple" nucleosome and that purple one is connected to yet another green one that is slightly off center to the first green nucleosome:

In Theory (Not sure if correct):
This may mean that when this fiber "unwraps" it would act less like a spring coming undone(where the whole structure would start to unravel due to how it's linked) and instead each sequential nucleosome being pulled away from the fiber after the one its connected to has moved and experiences full tension.
For the ZigZag model imagine you take a piece of paper and fold it many times as if it were an accordion. Then hold the paper folded up in one hand. Take your opposite hand and pull the paper from one end slowly unfolding it. You'll notice that each fold comes out sequentially while the rest of the structure stays intact until the fold before it flattens out so the tension can pull it. At least that is what would happen in my mind. I could be totally off base.


text:
Do goosebumps always appear in the same spots on the skin?
Often one gets goosebumps when one is cold. I am curious whether the precise location of the goosebumps on, say, one's leg changes from occurrence to occurrence or not? In case if their precise locations are always identical is there anything particular about those locations that differentiate them from other parts of one's skin?
Thus the question: do goosebumps appear at the same spots on one's body every time or their exact location changes?

Goosebumps are caused by the contraction of the arrector pili muscles, which are attached to hair follicles. Accordingly, they appear at the same spots on one's body every time.


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Is it possible to derive the Michaelis-Menten equation under conditions where the product formation is reversible
Text books etc generally derive the Michaelis-Menten equation for the irreversible case i.e $$\ce{E + S <=> ES -> E +P}$$ I can't see how to do it for the reversible case i.e  $$\ce{E + S <=> ES <=> E +P}\;$$ Is it possible?

The Michaelis-Menten equation is based on the explicit assumption that substrate is at a much higher concentration than the products. This is in fact what you have written and is true at the start of a reaction. At later stages it is generally not true and therefore the Michaelis-Menten equation no longer holds. If you ever do a biochemistry kinetics class you will always plot the initial rate of an enzymic reaction.

Now I understood what you mean to say. I was thinking you were referring to the first reaction of enzyme-substrate binding. Okay, there is no particular reversible conversion model that I have come across with but you can build a model based on a few assumptions. "Substrate concentration is much greater than the enzyme concentration" is true for the QSSA approximation. The original model used an equilibrium approximation which assumes that binding/unbinding reaction is much faster than the conversion.

No it is not possible to derive the equation for the reversible case. This is because the Michaelis-Menten equation is derived on the explicit assumption that the substrate concentration is much greater than the product concentration so that the back reaction does not occur. This is true at the start of a reaction in the lab when you add enzyme to your substrate. At later times when product builds up these conditions no longer hold and the M-M equation breaks down.
It is possible to derive a different equation for the reversible case (as some other posters do) but this begs the question of the importance of the Michaelis-Menten equation for biology. The poster seems to think that it is some universal truth, important in its own right or because it models the reaction in the living cell. I think this misses the point, which I think is as follows.

It originally was a prediction from, and hence a test of, the hypothesis that enzymes have a single active site at which the substrate binds and is converted to products.
It allowed two fundamental aspects of this enzyme model to be quantified: (i) the binding affinity of the substrate for the active site, as the inverse Km, and (ii) the catalytic efficiency ('smartness') as the turnover number or kcat, which is derived from Vmax (and enzyme concentration).
These enzyme constants can be used to address biological questions, for example whether an enzyme capable of a particular reaction in the test tube is able to account for the observed reaction rates in a tissue. Or whether the substrate you find the enzyme can use is likely to be the physiological substrate in a tissue.
It turns up enzymes that do not exhibit M-M kinetics, implying that some aspect of the model does not apply to them. This can be of mainly chemical interest (ping-pong kinetics and the like) or of physiological importance, as in allosteric kinetics (S-shaped rather than hyperbolic curve) shown by multi-subunit enzymes where the individual subunits show co-operativity, allowing more finely tuned regulation.
And if you do want to model reactions within cells, the kinetic constants can be of use. However as one is normally dealing with a chain of reactions in an open system the mathematics are complex (and nothing to do with the equation for a single reversible reaction in the test tube).

Most biochemistry students (and many teachers) would be hard pressed to explain why they should learn the derivation of the Michaelis-Menten equation. The answer is partly so they see that it is based on a particular model of the enzyme, but also so that they are aware of the assumptions on which it is based. Hence they need to be aware that the Michaelis-Menten equation is only true for initial rates of reaction, otherwise their determination of the practically and biologically useful Km and Vmax will be incorrect.

Well, I disagree.  I think the reversible case is almost always considered in enzyme kinetics, especially for more complex mechanisms, and then simplifying assumptions applied to the full rate law.  The equation for the reversible Michaelis-Menten equation is derived, for example, by Cornish-Bowden 'Fundamentals of Enzyme Kinetics', p 31 (of the first edition).  See Cook and Cleland for more details.

The Reversible Michaelis-Menten Equation (after Cornish-Bowden, Fundamentals of Enzyme Kinetics)$$ v = {{{{V_{s}^f}[s]\over{K_{m}^s}}-{{V_{p}^f}[p]\over{K_{m}^p}}}\over{1 + {{[s]}\over{K_{m}^s}} + {{[p]}\over{K_{m}^p}}}}$$

$ {V_{s}^f}$ is the maximum velocity for s (substrate) in the 'forward' direction, $ {V_{p}^r}$ is the maximum velocity for p (product) in the 'reverse' direction,   $ {{K_{m}^s}}$ is the Michaelis Constant for s, and   $ {{K_{m}^p}}$ is the Michaelis Constant for P.  Set [p] to zero to get 'classical' Michaelis-Menten equation.

It is always possible to derive some mathematical model given the right assumptions. You perhaps mean to say that the reversible case would not be compatible with the MM model. Well, of course because MM model assumes irreversible conversion. The assumptions are different altogether.

It is possible to derive AN equation to describe the reversible reaction, however that equation is NOT the Michaelis-Menten equation. The point about the Michaelis-Menten equation is not that it models reactions in the cell, but that it can be easily tested and fundamental properties of the enzyme calculated. These are important from a biological point of view. Writing equations to describe the reverse reaction may be an interesting exercise for a chemist, but has little biological relevance and I doubt is what the questioner had in mind.

@TomD. I had assumed from the other comments that Cornish-Bowden had done this, or even if the average chemist couldn't do it the modern mathematician (or his computer programs) could. But I don't really care. As my modified answer shows, I'm trying to point out the relevance of the 'text-book' M-M equation to the novice. If the poster was more interested in the chemistry or mathematics than the biology, I'm missing the target.

@TomD I just meant that Michaelis-Menten is a model. Any deviation from it is not a Michaelis-Menten model (we can say they are MM-like) but similar approximations can be applied, as you rightly put, in other situations. And actually my comment was intended for David as he is the one who was emphasizing of reversible case not being MM :P

@David Late to this thread, but it depends on whether you're referring to steady state (Briggs-Haldane) or MM equilibrium assumptions. It's perfectly ok to derive the reversible form using the steady state assumption. It's done all the time. For whole pathway models the reversible form is a decent approximation and far more realistic that the irreversible version.

@rhody — I bow to your superior knowledge on this. I am not an enzymologist.

The Reversible Michaelis-Menten Equation
An equation for the reversible form of the Michaelis-Menten equation was first derived by Haldane (1932, p 81), and the form shown in Eqn (1) was first given by Peller and Alberty (1953).
$$ v = {
  {{{V_{max}^f}\over{K_{m}^s}}\ s\ -{{V_{max}^r}\over{K_{m}^p}}\ p }\over{1 + {{s}\over{K_{m}^s}} + {{p}\over{K_{m}^p}}}}\ \ \ \ \ (1)$$

$v$ is velocity

$s$ is substrate concentration
$p$ is product concentration

$K_{m}^s$  is the Michaelis Constant for $s$
$K_{m}^p$  is the Michaelis Constant for $p$

$V_{max}^f $ is the maximum velocity in the 'forward' direction
$V_{max}^r $ is the maximum velocity in the 'reverse' direction

Setting $p$ to zero gives the more familiar form of the Michaelis-Menten equation (where $v_i$ is now the initial velocity)
$$ v_i = {
  {{V_{max}^f} s }\over{K_{m}^s + s}}\ \ \ \ \ (2)$$
Derivation of the Rate Law
How can Eqn (1) be derived?
This has been done by (among others) Cornish-Bowden (2004, pp 48 -52), and the derivation given below closely follows this source (with some help from  Wolfram Mathematica).
Let's consider the following form of the reversible single-substrate, single-product enzyme mechanism

A substrate $s$ may reversibly bind to $E$ (the 'free' enzyme) to give $ES$.  This in turn may be reversibly converted to $EP$, and reversible dissociation of product gives back the original form of the 'free' enzyme together with $p$.
The complexes $ES$ and $EP$ are sometimes called 'central complexes'
However, in order to simplify the algebra, I will derive the rate law for the following simplified (and unrealistic) mechanism containing a single central complex.

We need to be very, very careful here.  This simplifying assumption will not change the overall form of the  kinetic constant form of the rate law, that is both mechanism (3) and (4) will give rise to Eqn (1), but it will make the definition of kinetic constants simpler.
We must not assume that these simplified definitions necessarily apply to any realistic case. The definitions for $V_{max}^f$  (Eqn 10) and $V_{max}^r$ (Eqn 11), for example, contain a single rate constant but those for the mechanism of Eqn (3) are more complex (Eqns 15 & 16).
Thus statements such as 'for unit enzyme concentration, $k_{3,2}$ equals the maximum velocity in the forward direction' are fraught with difficulties. (It probably is valid to argue, at least for the type of mechanisms considered here, that 'for unit enzyme concentration, the maximum velocity cannot exceed $k_{3,2}$').
But we digress. Let's return to the derivation.

Let  $e_o$ be the total enzyme concentration
Let $x$ equal the  concentration of $ES$
The concentration of $E$ is therefore ($e_o$ - $x$)

In addition, let's make two fundamental assumptions (see here for a great elucidation of the steady-state method in enzyme kinetics).

Very soon after the reaction is initiated, a steady-state is established so that the rate of formation of $x$ equals the rate of breakdown of $x$.  This is the steady-state assumption. (What happens in the pre-steady-state period does not concern us here).
The concentration of $e_o$ is so low that formation of $ES$ and $EP$ may be ignored in calculating  substrate and product concentrations  (this also greatly simplifies the algebra)

The following differential equation, which describes the rate of breakdown of $x$, may now be written:
$$ {dx\over dt} =  {k_{1,2}\ (e_o -x)\ s + k_{3,2}\ (e_o -x)\ p - (k_{2,1} + k_{2,3})\ x = 0}\ \ \ \ \ \ \ (5)$$
Let's solve for $x$. I am going to be lazy here and allow Wolfram Mathematica to do the work.
(A more detailed version of the Mathematica notebook may be found here).

The above command produces the following output (how cool is that?)

Now let's define the velocity equation in terms of $x$, taking the reverse reaction into account
$$ {dp\over dt} =  {k_{1,2}\ x\ -\  k_{3,2}\ (e_o -x)\ p}\ \ \ \ \ \ \ \ \ (6)$$
We now need to substitute for $x$ in the above equation. Again, using Mathematica

Using substitution

the following output is obtained:

That is, the rate-constant form of the rate law may be expressed as follows:
$$ {dp\over dt} =  { {(k_{1,2}\ k_{2,3}\ s - {k_{2,1}\ k_{3,2}\ p)\ e_o}}\over{{k_{1,2}\ s} + k_{2,1}+ k_{2,3}+{k_{3,2}\ p}}} \ \ \ \ \ \ \ (7)$$
The 'trick' now is to define kinetic constants in such a way that the more useful kinetic-constant form of the rate law may be obtained.
Let's define the kinetic constants as follows
$$K_{m}^s = {{k_{2,1}\ +\ k_{2,3}}\over{k_{1,2}}}\ \ \ \ (8)$$
$$K_{m}^p = {{k_{2,1}\ +\ k_{2,3}}\over{k_{3,2}}}\ \ \ \ (9)$$
$$ k_{cat}^f  =  {{V_{max}^f}\over{e_o}} = k_{2,3}\ \ \ \ (10)$$
$$ k_{cat}^r  =  {{V_{max}^r}\over{e_o}} = k_{2,1}\  \ \ \ (11) $$
Dividing Eqn.(7) 'above-and-below' by ($ {k_{1,2}\ + k_{2,3}}$) gives the following expression:

Substituting the values of the kinetic constants into the above expression leads logically to the following kinetic-constant form of the rate law:
$$ v = {
  {({{k_{cat}^f}\over{K_{m}^s}}\ s\ -{{k_{cat}^r}\over{K_{m}^p}}\ p)\ e_o }\over{1 + {{s}\over{K_{m}^s}} + {{p}\over{K_{m}^p}}}}\ \ \ \ \ (12)$$
Kinetic Constants for the More Realistic Mechanism
The definition of kinetic constants for the more realistic mechanism of Eqn (3) are as follows: (see here for the Mathematica derivation).

In general,  different mechanisms may give rise to an identical rate law.
The following mechanism will also give rise to Eqn (1).

In fact, adding any number of central complexes to the mechanism of Eqn (3) will give rise to a rate law in the form of Eqn (1).
An Extension to the Michaelis-Menten Mechanism
Here is a mechanism that won't give rise to a rate law as shown in Eqn (1):

In the above mechanism, the form of the 'free' enzyme generated upon product release ($F$)  is different from that which combines with substrate ($E$), and emphasizes that we may need to take their inter-conversion into account in any complete description of a single-substrate, single-product enzyme (see Taraszka & Alberty, 1964).
The rate law for this mechanism contains an extra kinetic constant, here called $K_{sp}$
 $$ v = {
  {({{k_{cat}^f}\over{K_{m}^s}}\ s\ -{{k_{cat}^r}\over{K_{m}^p}}\ p)\ e_o }\over{1 + {{s}\over{K_{m}^s}} + {{p}\over{K_{m}^p}} + {{s p}\over{{K_{sp}}}}}}\ \ \ \ \ (19)$$
This mechanism could, for example, describe membrane transport where $F$ represents the carrier on the inside of the membrane and $E$ represents the carrier on the outside.  But it also could apply to any single-substrate, single-product enzyme. This again emphasizes the danger of over-simlification.
The rate law of Eqn (19) is well reviewed by Darvey (1972), and the pdf is freely available to all.
Final Thoughts ...
As the number of enzyme species increases, obtaining the rate-constant form of the rate law becomes difficult, as the equations very quickly accumulate many terms. Before the days of Mathematica and the like, enzymologists used the schematic method of King and Altman (1956), or one of its many variants, to obtain the rate-constant form of the rate law.
So what are the advantages of deriving the kinetic constant form of the full rate law?

If the reaction is demonstrably reversible, it may studied in both directions
For a multi-substrate enzyme, the product inhibition equations are easily written down.
It allows a relationship (or relationships) between the kinetic constants and the equilibrium constant to be obtained.  For the reversible Michaelis-Menten mechanism of Eqns (3) & (4), the Haldane relationship is as follows:

$$ K = {{k_{cat}^f\ k_{m}^p }\over{k_{cat}^r\ k_{m}^s }}\ \ \ \ (20)$$
where $K$ is the equilibrium constant for the reaction (Haldane, 1930)
References

Cook, P.F. & Cleland, W.W (2007) Enzyme kinetics and mechanism  Garland Science.
Cornish-Bowden (2004) Fundamentals of Enzyme Kinetics 3rd Edn. Portland Press (London)
Darvey, I. G. (1972) The application of product inhibition studies to one-substrate one-product enzymic reactions. Biochem J. 128, 383 - 387 [pdf]
Haldane, J.B.S (1930) Enzymes Longmans (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
Peller, L. & Alberty, R. A. (1959). Multiple intermediates in steady-state enzyme kinetics.  I.  The mechanism involving a single substrate and product.  J. Am. Chem. Soc. 81, 5907 - 5915
Segel, I. H. (1975) Enzyme Kinetics. Behavior and Analysis of Rapid Equilibrium and Steady-State Systems Wiley
Taraszka, M. & Alberty, R. A. (1964). Extensions of the steady-state rate law for the fumarase reaction. J. Phys. Chem. 68,  3368 - 3373.

Hey.. While you are at it, can you also try obtaining the rate as purely a function of substrate (by using the conservation relation). I haven't used mathematica.

The derivation for the equation mentioned by TomD in the comments:
$$ v = {{{{V_{s}^f}[s]\over{K_{m}^s}}-{{V_{p}^f}[p]\over{K_{m}^p}}}\over{1 + {{[s]}\over{K_{m}^s}} + {{[p]}\over{K_{m}^p}}}}$$
can be found here. This formula assumes a three step reaction. This equation uses product as a variable in the equation. Ideally, since there is no formation/degradation of the reactants/products (closed system), the product can be represented as a function of the other variables ($\ce{[S0] -[ES] -[S]}$). In short, the product formation rate can be simply represented as a function of the substrate concentration.
What I am going to show is not a full derivation but one approach that you can start with.
For this two step reversible reaction:
$$\ce{E + S <=>[k_1][k_2] I <=>[k_3][k_4] E + P}$$
You would have the system of ODEs:
$
\dfrac{d\ce{[E]}}{dt}=-k_1\ce{[E][S]} + (k_2+k_3)\ce{[I]} -k_4\ce{[E][P]}\\
\dfrac{d\ce{[I]}}{dt}=\quad k_1\ce{[E][S]} - (k_2+k_3)\ce{[I]} +k_4\ce{[E][P]}\\
\dfrac{d\ce{[S]}}{dt}= -k_1\ce{[E][S]} + k_2\ce{[I]} \\
\dfrac{d\ce{[P]}}{dt}= -k_4\ce{[E][P]} + k_3\ce{[I]}
$
Assuming QSSA for $\ce{[I]}$ (and hence also $\ce{[E]}$) and setting $\ce{[E]} = \ce{[E0] -[I]}$, you'll get:
$$\ce{[I]}=\frac{\ce{[E0]}(k_1\ce{[S]}+k_4\ce{[P]})}{k_2+k_3+k_1\ce{[S]}+k_4\ce{[P]}}$$
Since $\ce{[P]}=\ce{[S0] -[I] -[S]}$, the equation for $\ce{[I]}$ shown above, will become quadratic when you substitute this relation. This expression can be finally plugged into the fourth ODE to obtain the expression for the product formation rate, purely in terms of the substrate.
If you keep product as a variable then you can substitute the above expression for $\ce{[I]}$ in the fourth ODE.
$$V=-k_4\ce{[P]}\left(\ce{[E0]} - \frac{\ce{[E0]}(k_1\ce{[S]}+k_4\ce{[P]})}{k_2+k_3+k_1\ce{[S]}+k_4\ce{[P]}}\right) +k_3\frac{\ce{[E0]}(k_1\ce{[S]}+k_4\ce{[P]})}{k_2+k_3+k_1\ce{[S]}+k_4\ce{[P]}}$$
Some algebraic rearrangements will yield:
$$V=\ce{[E0]}\frac{k_3k_1\ce{[S]}+k_4k_2\ce{[P]}}{k_2+k_3+k_1\ce{[S]}+k_4\ce{[P]}}$$
Dividing both numerator and denominator by $k_2+k_3$ yields:
$$V=\ce{[E0]}\frac{\frac{k_3k_1}{k_2+k_3}\ce{[S]}+\frac{k_4k_2}{{k_2+k_3}}\ce{[P]}}{1+\frac{k_1}{k_2+k_3}\ce{[S]}+\frac{k_4}{k_2+k_3}\ce{[P]}}$$
This is the form of equation mentioned by TomD (just create new constants from the old ones).
For some more details have a look at this paper by Keleti [1] and the other papers citing it.

[1] Keleti, T. "Two rules of enzyme kinetics for reversible Michaelis‐Menten mechanisms." FEBS letters 208.1 (1986): 109-112.


text:
Mosaic segregation in C. elegans
How can mosaic segregation be used in C. elegans? Can it tell us where a given gene is expressed, or needs to be expressed for worm survival?


text:
Do animals get sick with hemorrhoids?
Do animals get sick with hemorrhoids ?
And why Humans are most affected of it ?
Is it because the gravity center of Humans is sittuated in the anal ?

Why are haemorrhoids more common in humans than in animals?
This is due to the majority of animals, including apes, are on all fours. Only the human species stands and walks straight up with two feet. Therefore, the blood in the body has enhanced arduousness in circulating and travelling back to the heart. A justification for the commonness of hemorrhoids in humans, is there is a higher frequency of blood congestion which then further leads to hemorrhoids.
There are animals which can get haemorrhoids

Cats
Dogs
Apes
Horses

The reasons and causes why animals can also get hemorrhoids is similar to humans, besides the structural reasons. This may include:
In Horses

The horse may strain while delivering young ones

When the bowel movements are disturbed, as in constipation, it leads to an increase in pressure applied to the rectum region. Unlike humans, the increased pressure from constipation does not come from straining to get the excrements out, but from the impaction of the excrements within the horse and the resultant pressure that causes.  This in turn leads to expansion of the blood vessels around the anus and this may cause hemorrhoids and eventually bleeding.

In cats

One of the main reasons behind the occurrence of cat hemorrhoids is heredity, which plays a major role in deciding who would and who would not get afflicted with this condition.
Diets low in fiber and liquid content are the main cause of constipation, which in turn leads to excess pressure being applied during defecation and straining when bowels are passed. Too much pressure in the rectum and lower abdomen causes blood vessels in this region to expand, thus leading to the creation of lumps called hemorrhoids.

There have also been some investigations in which haemorrhoids were induced by ligation of the inferior haemorrhoidal vein into apes. The outcome of this was that after a certain amount of days, there were hemorrhoidal piles in the anus in fifty percent of the animals. The outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering.
References:

"Horse Haemorrhoids, Horse Hemorrhoids, Horse Haemorrhoids, Horse Piles - Web. 01 Mar. 2016.
"Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, Sept.-Oct. 2006. Web. 01 Mar. 2016.


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How to generate simulated mass-spectrometry data for phosphorylated proteins?
I am trying to generate simulated MS data (Top-down and Bottom-up) for phosphorylated protein such as platelet-derived growth factor receptor (PDGFR-B). There are 10 tyrosine sites which are phosphorylated. Could you kindly tell me if there is any good software application to help me do that?
Also, how can I include in the input file (FASTA) that there are 10 modification sites on the protein sequence?
What are the parameters required to be set for top-down and bottom-up MS separately?

I know this is a two years old question... but I recently developed a web application which could be useful for you:
Prot pi
The Protein tool lets you simulate the mass spectrum of the intact protein, while the Peptide tool gives you the fragment ions of peptides. Modifications can easily attached to every site you want.

For peptides (bottom up) mMass accepts a sequence of interest and phosphorylated tyrosine can be specified as a modification after that. The program also performs in silico enzyme digests and in silico MS/MS fragmentation.
There are other tools that attempt to accurately mimic the intensities of the various fragments that could be generated.
The meaning of the final question is unclear. If you want to know which parameters to set for the in silico analyses you need to use those that match the sample processing and analyses that would take place in the real world. Sample processing and instrument setup are highly context dependent, there's insufficient information to help with those.
Obtaining good quality intact measurements from a protein the size of PDGFR-B would be a significant challenge.

Have a look at PeptideMass, you can choose to use the "post-translational modifications" option that will output the masses of phosphorylated (among other modifications) peptides.