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Energy released during the production of ATP?
When glucose is used during aerobic and anaerobic exercise, how much energy is expended or required?
During aerobic exercise:
$C_6H_{12}O_6 + 6 O_2 \to ATP + H_2O + 6 CO_2$ + energy
During anaerobic exercise:
$C_6H_{12}O_6 + 6 O_2 \to 2 C_3H_6O_3 + 2 ATP$ + energy
For each of the reactions above what is the value of the '+ energy' part?

where did you get this from? i am pretty sure the ATP is the energy, isn't it?

@TanMath I guess "energy" here refers to heat loss, besides the "useful" energy capture in the form of ATP?

Your formulas are not correct: there is no O2 involved in the anaerobic case, and for the aerobic case there is a coefficient N before ATP, typically around 25--35. Please edit.

This is difficult to answer exactly since the thermodynamics of cellular metabolism are not well understood.
These are spontaneous reactions, so there is certainly a loss of Gibbs' energy $\Delta G < 0$; this energy corresponds to your "energy" term on the product side of the reactions. For the anaerobic case (glycolysis) a balanced reaction formula is
Glucose + 2 ADP + 2 Pi $\rightarrow$ 2 Lactate + 2 ATP + 2 H2O
Details like phosphate (Pi) and water is important here. Now, if we know the free energies $G$ of each substrate and product, we can calculate the $\Delta G$ as the sum of the products' energies minus the sum of the reactants. Unfortunately, this energy $G$ is hard to get at. It depends on a number of things, like the molecule structure, concentration, temperature and the pH and ion strength of the solution. These things are not exactly known, so the answer will be uncertain. This is actually an active area of research, and sophisticated methods have been developed for calculating $G$. One of the best are from a groyp at the Weizmann institute in Israel, and is available at http://equilibrator.weizmann.ac.il
If we assume all concentrations to be 1mM, this method gives $\Delta G = -118.7$ for the glycolytic reaction above. This is the energy lost (mainly as heat) in the reaction. For comparison with energy captures by ATP, we can break up the reaction into two parts and calculate
Glucose $\rightarrow$ 2 Lactate $\quad\quad\quad\quad\quad \Delta G = -206.7$
2 ADP + 2 Pi $\rightarrow$ 2 ATP + 2 H2O $\quad\quad\Delta G = 87.0$
which sums to -118.7, as expected. This tells us the fraction of the Gibb's energy captured as ATP is 87/206.7 = 42%, while 58% is lost as "heat". So glycolysis has an efficiency of 42%. (For comparison, a combustion engine is somewhere at 15--20%.)
The aerobic case is more difficult, because the stoichiometry is not even fixed: the number of ATP molecules actually obtained from 1 molecule of glucose depends on the efficiency of the respiratory chain, on cytosolic NADH oxidation, and otherthings. But let's say we get 30 ATP. Then
Glucose + 30 ADP + 30 Pi + 6 O2 $\rightarrow$ 6 CO2 + 30 ATP + 36 H2O
has $\Delta G = -1608$, which can be broken up into
Glucose + 6 O2 $\rightarrow$ 6 CO2 + 6 H2O $\quad\quad\Delta G = -2913$
30 ADP + 30 Pi$\rightarrow$  30 ATP + 30 H2O $\quad\quad\Delta G = 1305$
So here 1305/2913 = 45% of the energy is captured. So in this sense, glycolysis and respiration are similar in efficiency. Varying the number of ATP changes this value; try it! Of course, glycolysis can only partially oxidize glucose (into lactate), while respiration achieves complete oxidation to CO2, extracting much more energy.
Again, these values depends heavily on concentrations of metabolites inside cells, which are not well known. Try changing them at the equilibrator web site and note the effects! Unfortunately, many biochemistry textbooks present values of $\Delta G$ assuming reactants at 1M (!) which is completely irrelevant to actual conditions in living cells.

In biology, anaerobic respiration is a way for an organism to produce usable energy, in the form of adenosine triphosphate, or ATP, without the involvement of oxygen; it is respiration without oxygen. This process is mainly used by prokayotic organisms (bacteria) that live in environments devoid of oxygen. Although oxygen is not used, the process is still called respiration because the basic three steps of respiration are all used, namely glycolysis, the citric acid cycle, and the respiratory chain, or electron transport chain. It is the use of the third and final step that defines the process as respiration. In order for the electron transport chain to function, a final electron acceptor must be present to take the electron away from the system after it is used. In aerobic orgainisms, this final electron acceptor is oxygen. Oxygen is a highly electronegative atom and therefore is an excellent candidate for the job. In anaerobes, the chain still functions, but oxygen is not used as the final electron acceptor. Other less electronegative substances such as sulfate (SO4), nitrate (NO3), and sulfur (S) are used. Oftentimes, anaerobic organisms are obligate anaerobes, meaning they can only respire using anaerobic compounds and can actually die in the presence of oxygen.
Anaerobic respiration is not the same as fermentation, which does not use either the citric acid cycle or the respiratory chain (electron transport chain) and therefore, cannot be classified as respiration.
Aerobic Respiration
Aerobic respiration requires oxygen in order to generate energy (ATP). Although carbohydrates, fats, and proteins can all be processed and consumed as reactant, it is the preferred method of pyruvate breakdown from glycolysis and requires that pyruvate enter the mitochondrion in order to be fully oxidized by the Krebs cycle. The product of this process is energy in the form of ATP (Adenosine Triphosphate), by substrate-level phosphorylation, NADH and FADH2.
Simplified reaction: C6H12O6 (aq) + 6 O2 (g) → 6 CO2 (g) + 6 H2O (l)
ΔG = -2880 kJ per mole of C6H12O6
The negative ΔG indicates that the products of the chemical process store less energy than the reactants and the reaction can happen spontaneously; In other words, without an input of energy
The reducing potential of NADH and FADH2 is converted to more ATP through an electron transport chain with oxygen as the "terminal electron acceptor". Most of the ATP produced by aerobic cellular respiration is made by oxidative phosphorylation. This works by the energy released in the consumption of pyruvate being used to create a chemiosmotic potential by pumping protons across a membrane. This potential is then used to drive ATP synthase and produce ATP from ADP. Biology textbooks often state that 38 ATP molecules can be made per oxidised glucose molecule during cellular respiration (2 from glycolysis, 2 from the Krebs cycle, and about 34 from the electron transport system). However, this maximum yield is never quite reached due to losses (leaky membranes) as well as the cost of moving pyruvate and ADP into the mitochondrial matrix and current estimates range around 29 to 30 ATP per glucose.
Aerobic metabolism is 19 times more efficient than anaerobic metabolism (which yields 2 mol ATP per 1 mol glucose). They share the initial pathway of glycolysis but aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation. The post glycolytic reactions take place in the mitochondria in eukaryotic cells, and in the cytoplasm in prokaryotic cells.
Thus,more energy is released during Aerobic Respiration than Anaerobic Respiration.


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Whole Genome Sequencing and Chromosome Counts
In general, do standard whole genome sequencing techniques rely more on known chromosome counts, independently arrive at chromosome counts, and/or not directly address issues such as base number, aneuploidy, and polyploidy?
For example would have normal whole genome sequencing techniques detected that humans have 46 rather than 48 chromosomes?
Maybe a better way to put this question would be as follows:
Given the whole genome sequence for humans and a belief that chimpanzee had 46 chromosomes would whole genome sequencing of the chimpanzee most likely say
1) Here are the sequences for those 46 and by the way there was material left over.
2) Here is the best representation of all the chimpanzee's DNA mapped onto 46 chromosomes.
3) Here are the sequences for those 46 and chimpanzee's appear to have 48 chromosomes.

What Biomed_guy says is basically the answer, I just wanted to clarify a bit. When you sequence DNA, you do something during the preparation of your DNA library to turn it into small fragments if it isn't already, like shearing the DNA. This gives you very small pieces of DNA that should still be quite unique when matched to reference genome.
But as previously answered, the determining factor for how DNA is then mapped is the reference genome you are using. So the answer is what you state in both 1 and 2. When trying to figure out what DNA you have, you start with a reference sequence which is all of the genomic DNA 'layed out' so that your fragments can then be compared against it and matched to a best fit region based on matching sequence. Anything that does not match the ref genome gets dumped into a 'junk' output file.
So conceptually, many gene sequences are highly conserved between humans and chimpanzees. This would mean that you could successfully align your sequences fragments to either genome. Importantly, this is number of chromosomes agnostic. It is the genes that matter.
Imagine that if Ras, Myc, and Erk are all on human chr 12 in humans, but split up in chimps so that Ras is on chr 12, Myc on Chr 13, and Erk on Chr 24, this would make no difference when you map back to the genome assuming the genes are conserved between human and chimp. If you have a sequenced fragment from human Myc that is the same as Chimp Myc, it would align to a location on chr 12 if you use human DNA as ref, or it would align to a location on chr 13 if you use Chimp as ref. Make sense?

I'm pretty sure that it relies on a reference genome. As in, since the original human genome sequencing, most of the techniques used today rely on that original construction (with modifications).
That's how people use it to detect copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) with these sequencing techniques (and aneuploidy as well).
The reads from the sequencing run are compared to the reference genome and if statistically significant differences in the number of reads are seen, then they are noted as differences in the genome. If there is extra unmapped DNA, then it would likely just not know where to put it and call it "extra material".
So #1.

You understand, it's not that chimps have lots of extra DNA that humans do not, they have two chromosomes which are fused in humans.
Theoretically, discrepancies between the reads and the reference could be discovered.  Practically, with current short read technology, it would be difficult to sort out a discrepancy that involved a region of the genome that was repetitive, which the telomeres of the chimp 2A and 2B and the telomeric-like sequences in the regions where those fused in humans, would be.

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Can flow cytometric analysis differentiate between a parent contributing longer chromosomes versus multiple smaller chromosomes?
For flowering plants, can flow cytometry of seed from muti-generational interaction of two species and their offspring help us decide if wide differences in genome size for the two species and their offspring is a function of differences in chromosome count versus chromosome length?
Flow cytometry of seed allows us to examine the contributions by the 2 parents to the resulting offspring from generation to generation.
The basic premise is flow cytometry scores for the offspring of "triploid" intermediates would distribute differently if the issue was length versus count. Fine distribution would indicate "aneuploids" because of counts whereas wide distribution would indicate length because length differences are concentrated in only a few chromosomes.
This basic premise proved faulty since flow cytometry scores indicate fine distribution (genome size scores reflecting every potential aneuploid between triploid and tetraploid) but documented chromosome counts indicate the issue is length.
What are the normal distribution patterns in terms of genome size for multigenerational offspring between 2 species having wide differences in chromosome length?
.

This is not a homework assignment. This question is motivated by actual flow cytometry results from a large number of samples for a large group of closely related Rhododendron species. I have been unable to find any good information on how the barriers to species interaction differ when the issue is chromosome number versus chromosome length. If there are straight forward textbook answers to this question, I would love to be guided to resources that provide insight to the answer.

I would recommend that you mention the flow cytometry protocol that you used (PI staining??). You need not elaborate on how you ruled out endoreplication. Just a short summary is enough. Focus on your main question.

@WYSIWYG How can a question be off topic as a homework question when I have not taken a biology course since freshman year high school 1966? I do not know this biology forum well enough to say this question is not off topic but this is not a homework question and the question is motivated by actual flow cytometry findings for Rhododendrons on 2 different continents.

Please see our homework policy. Homework does not just mean homework in a course. For any problem, research or otherwise, the OP should show some effort towards the answer. I see that you have edited to add your effort but your question is too long and is difficult to read. Please retain only relevant sections and then this post can be reopened.

@WYSIWYG  Have focused attention to the basic premise of why I incorrectly thought flow cytometry could address the question of length versus count. Appreciate your efforts to refine this question to address the question of what is wrong with that basic premise,

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How do we know Denisovans had 46 Chromosomes
What allows sequencers to conclude that Denisovans had 46 chromosomes rather than merely knowing Denisovans had the crossover material arranged in 48 or say 44 chromosomes?
See http://genetics.thetech.org/ask-a-geneticist/denisovan-chromosome-2
What I am asking its what allows sequencers in this case to make an inference to an actual number of chromosomes (packaging) rather than the mere presents of corresponding DNA?
In the article above, interbreeding was rejected as a sufficient condition for inferring equality to humans in chromosome number and the author points to a man in China known to have the same cross over (fusion) known in humans and only 44 chromosomes indicating having the cross over that reduced 48 to 46 is also not a sufficient condition for concluding 46.

We know Denisovans interbred with other members of the genus Homo, therefore they must have had the same number of chromosomes. Individuals with different numbers of chromosomes cannot interbreed.

The referenced link says "As of now we don’t know have any hard DNA evidence for how many chromosomes Neanderthals had.   We are guessing that since humans and Neanderthals probably had babies together that they shared the same number of chromosomes.  But this doesn’t necessarily have to be the case." so this is not the reason for the inference of 46 for Denisovans.

@MattDMo People with Trisomy 21 are fertile, although at a much lower rate than in humans with the standard set of 46 chromosomes.

John, I think the answer is that without having a living cell that we can perform a karyotype on, we cannot know for sure. That being said, telomeres and centromeres are highly conserved, so if you're sequencing a female specimen, and it gives you 23 sets of centromeres and 46 sets of telomeres, then I would say that it would be safe to make the educated guess that the individual had 2n = 46.

Also, Svante Pääbo's group at the Max Planck Institute were the ones to publish the Neanderthal Genome, so you may want to take a look at their peer-reviewed publications to see if they address this issue.

@AMR I would agree that 46 would be a very good educated guess especially if the other choice is only 48.

File under tl;dr... but this may be a good starting point. http://rstb.royalsocietypublishing.org/content/royptb/370/1660/20130387.full.pdf . This article may get more into the technical aspects http://www.genomebiology.com/2010/11/5/R47

@AMR I don't have a reference at the moment, but I would imagine that people with trisomy 21 are only fertile if the fertilizing gametes have 23 chromosomes, so it all depends on how the extra #21 segregates during meiosis.

@MattDMo Actually no. Without reproductive aid, IVF and screening, there is a 50% chance that the offspring will be afflicted. Afflicted males tend to have very low fertility rates, but it is unclear if that has to do with problems with sperm production or just a lack of sexual activity, though there are cases in record of afflicted males fathering offspring. Afflicted females have fertility rates 30-50% that of unafflicted females. So while fertility is much lower than the general population, it is there.

@MattDMo Now if you wanted to make the case that Denisovins and modern humans couldn't produce offspring because the cell surface receptors that mediate gamete fusion were incompatible, that I would go along with. I think that the lethality with additional chromosomes comes from "dosage" problems and whether or not enhancer/promoter regions were preserved and TFs responded to the same chemical signaling and could bind to the DNA to drive transcription.


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Partial Contribution By One Parent
For flowering plants, what might cause the genome size of offspring from a cross between 2 diploid parent of differing genome size to reflect only a partial contribution by the larger genome size parent?
Many hybridizers of Rhododendron attempt wide crosses between two sections of the genus. In some cases the resulting hybrids show physical characteristics of both parents. However, flow cytometry indicates that instead of the offspring being half the sum of the 2 parents genome sizes the genome size is actually twice the genome size of the smaller genome size parent.
See Evergreen azalea X deciduous azalea
Can a successful cross result in a reduction in normal contribution of one of the diploid parents after fertilization?

We have seen instances where the genome size of the offspring are significantly less than the genome size of either parent.


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Differing Flow Cytometry Genome Sizes and Sexual Mating Implies Differing Chromosome Counts
Do the fundamental principles of genetics strongly suggest the following is a derived conjecture?
If 2 flowering plant species A and B have widely differing genome size (at a minimum a 50% difference) based on flow cytometry and normal successful sexual mating of A and B is indicated based on the flow cytometry measured genome sizes of the embryo and endosperm of the seeds produced by crossing A and B, then A and B differ in number of chromosomes to a degree indicative of ploidy level differences.
Corn, Cotton, and Rice are three genus where large genome size differences do not mean differences in chromosome counts.
The Vireya in the genus Rhododendron are a group that have large genome size differences between species where multi-generational hybrids between such species appears to be possible at least in some cases. Documentation suggests that all Vireya have the same chromosome counts indicating diploids.

It is not clear to me what you are asking. Clearly there are examples in D. melanogaster, C. elegans, and Z. mays where an autosome contains a relatively large contiguous block that is a tandem duplication. This type of genetic rearrangement would have to increase the length of the autosome. As long as the breakpoint does not inactivate an essential gene, and as long as the increased copy number of the affected genes is not lethal, the heterozygotes and homozygotes would be able to reproduce with the wild type.

I will investigate these 3 examples. I did not realize that autosomes can be widely unequal and normal sexual mating is still possible if the difference in length of the autosomes is due to tandem duplications.


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What cells would have the CD3 marker on them (other than T-cells)
Do you know of any peripheral blood mononuclear cells that would express any amount (beit low or high) of CD3 on their surface (other than T-cells)?

CD3 is initially expressed in the cytoplasm of pro-thymocytes, the
  stem cells from which T-cells arise in the thymus. The pro-thymocytes
  differentiate into common thymocytes, and then into medullary
  thymocytes, and it is at this latter stage that CD3 antigen begins to
  migrate to the cell membrane. The antigen is found bound to the
  membranes of all mature T cells, and in virtually no other cell type,
  although it does appear to be present in small amounts in Purkinje
  cells. This high specificity, combined with the presence of CD3 at
  all stages of T cell development, makes it a useful
  immunohistochemical marker for T cells in tissue sections. The antigen
  remains present in almost all T-cell lymphomas and leukaemias, and can
  therefore be used to distinguish them from superficially similar
  B-cell and myeloid neoplasms.

Source: http://en.wikipedia.org/wiki/CD3_(immunology)

Purkinje cells are neurons rather than peripheral blood cells

As you know CD3 is

a protein complex and is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains.

Natural Killer (NK) cells have been shown to express CD3 epsilon proteins, but not CD3 delta or gamma.
Also on a side note, there are several other non peripheral mononucleated cells besides Purkinje cells that can express CD3, but mostly in pathological circumstances. For instance Warthin-Finkeldey cells, also known as polykaryocyes, display CD3, although the origin of these cells is not certain (they might be multinucleated T-cells).
(PS: If you want more information on CD3, I found this site very interesting.)


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Is plastic just as good for you as corn?
To specify, I mean plain corn-on-the-cob, not anything processed like corn flakes.
Since one of the main important functions of corn is that it's not digestible, and therefore helps with digestion by loosening feces, would that make it just as beneficial as chopping up and eating a plastic bag?

This question appears to be off-topic because it is not biologically relevant.

Corn is digestible. Plastic is not.

corn cobs are not really digestable, but that still doesn't make plastic good for you

@MikeTaylor then please point me to the most relevant SE

Sorry, I do not know of an SE forum that fits.

@shigeta We digest corn cobs when we eat baby corn. Pigs can easily eat and digest corn cobs. Corn cobs are part of corn silage, which after fermentation is consumed and digested by cows and other farm animals. But still, none of this makes plastic any more nutritious or good for you. :)

the word 'you' seemed to imply human consumption, but it does seem like you have a response started here...

why isn't metabolism biology?  I just don't understand what some people think biology is.

I think I was the first vote to close this question but after considering comments by @shigeta I've voted to reopen and will submit an answer soon.

@shigeta Thanks for your comments. They gave me something to think about.

The part of the corn kernel that is visible in human feces is the outer coat of bran called the pericarp (see this image). This is a common structure in cereal grains like corn and wheat.  However, the bulk of the corn kernal is starchy endosperm, which is readily digestible by humans and provides carbohydrates and vitamins A and C.  The non-digestible (by humans) pericarp does help to keep fecal material soft.
Plastic bags do not provide those same benefits. Studies on human consumption of plastic bags are lacking, for obvious reasons.  However, marine organisms like sea turtles unfortunately consume large amounts of plastic debris (Derraik 2002). Bugoni et al. (2001) found that plastic debris caused mortality for 13% of the green turtles in their study. A review of 408 leatherback sea turtle autopsy records by Mrosovsky et al. (2009) found plastic inside 34% of turtles. The mortality in the sea turtles may be due to the accumulation of plastics in the gut which can block movement of food, alter feeding behaviors, and prevent absorbtion of nutrients.
If humans were to consume chopped up plastic bags, the evidence suggests that instead of receiving the same benefits as we do from whole kernal corn we are much more likely to be harmed. Eat your corn, recycle your plastic.
Literature Cited
Bugoni, L. et al., 2001. Marine debris and human impacts on sea turtles in southern Brazil. Marine Pollution Bulletin 42: 1330-1334.
Derraik, J.G.B. 2002. The pollution of the marine environment by plastic debris: A review. Marine Pollution Bulletin 44: 842-852.
Mrosovsky, N. et al. 2009. Leatherback turtles: The menance of plastic. Marine Pollution Bulletin 58: 287-289.


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How do rodenticides with delayed effect work?
Most modern rodenticides are claimed to cause death no earlier than several days after ingestion.
That's quite strange - once a chemical was ingested it will be absorbed in the digestive system and enter the blood stream and rapidly spread around the body (something like within ten hours - that's what most human medications claim in pharmacokinetics sections of their manuals). I'm pretty sure a rodent is very similar to a human in terms of digestive system functioning.
Then how do rodenticides not kill the rodent earlier than in several days after ingestion?

Not sure about the specifics of rodenticides but you should take into consideration that a drug may not be directly bioavailable. It may be given as an inactive form which is metabolized to the active form. It may be retained in adipose tissue and slowly released. Also, the effect which may be fairly rapid, but not immediately fatal. If I remember correctly rodenticides are often anticoaugulants, so the effect may not be immediatly obvious.

These poisons prevent recirculation of vitamin K and thus formation of prothrombin which is essential for coagulation of blood and are required for maintaining the integrity of capillaries. The depletion of vitamin K is slow and in a couple of days internal hemorrhage occurs extensively and the animal dies of shock. Early recognition of poisoning in humans and other animals can easily be treated with administration of vitamin K.
http://en.m.wikipedia.org/wiki/Rodenticide


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What's the use of DNA sequencing results?
Suppose I sequence DNA of some organism (a human perhaphs) and now I have the entire DNA "string" - the sequence of nucleotides.
What's the use of that? It's just a "string" where nucleotides encode something but I have no idea what they encode specifically. So to me it looks like some raw data, just represented as a sequence of elements.
How is having the entire DNA sequenced useful?

Whoa, quite a complex question. I’ve tried to restrict my answer to a single example (not very successfully).

Just to clarify the question: are you asking what the "man of the street" can learn by having his genome sequenced or are you asking what a team of scientists can learn by sequencing the genome of a species?

@nico: I guess what I ask is "what's the use of the sequence when you don't know which part does what".

It's just a "string" where nucleotides encode something but I have no idea what they encode specifically.

It sounds like you are describing a computer program, represented by a string of bytes on the hard drive.
Unfortunately, the analogy breaks down very quickly because DNA is vastly more complex and a lot of aspects are still poorly understood.
But the basis is the same: a string of symbols encodes information. In the case of DNA, different parts encode different things in a different manner.
The elephant in the room are of course coding sequences: stretches of DNA, contained in so-called “genes” – which code for proteins and other stuff.
Coding sequences use a fairly simple encoding schema that’s known as the genetic code, decoded in 1961. The genetic code has the nice property of being (almost) universal across all species, and easy enough for a child to understand:
Three consecutive DNA base pairs form a codon. Each codon stands for one amino acid (except for a special “stop codon”). Amino acids form so-called polypeptide chains – proteins. There are codon tables, just as you have manuals for assembly mnemonics in computing:

Unfortunately, it’s not trivial to know where genes are on the genome. Just by eyeballing the sequence there is nothing to distinguish one stretch of DNA from its surrounding. But there are certain recognisable stretches of DNA (“motifs”) which we can use to locate genes and other interesting regions.
Grossly simplified, a gene is preceded by a promoter region which is highly conserved between species (but gene-specific). Once you’ve identified one species’ promoter, you know it for other species. Furthermore, all promoters share highly similar elements, for instance the TATA box – literally the occurrence of “TATA” in the genome.
Of course, just looking for occurrences of “TATA” would yield vastly more spurious hits than actual promoters but combined with other information you get a gene model – a statistical machine which can tell you with high confidence where on a genome the genes are located.

Once you have found the genes in a sequence which you can trivially translate to amino acid sequences, you can try to form inferences about the function of the proteins (a protein’s function is an almost-direct consequence of its sequence). Unfortunately, discovering the function of a protein from its sequence alone isn’t possible but we do know the functions of many proteins.
When we now look at a genome and find a mutation in a protein-coding gene we can infer that the function of this protein is probably modified. Most mutations are so-called deleterious mutations (e.g. by deleting a single nucleotide you get a frame shift in the codons, and all the subsequent codons no longer make sense), meaning that they destroy the protein’s function.
Other, much rarer, mutations modify the protein’s function, making it more or less efficient, or giving it another function altogether.
In the simplest case (but these are rare), a single such mutation can explain a complex phenotype. This is known as a Mendelian trait and can be used to explain a phenotypes such as eye colour, but also hereditary diseases.
Usually, though, it is merely one of many adjusting screws which skew your susceptibility to a certain phenotype in one direction. For instance, you might be slightly more susceptible to breast cancer or diabetes.

This is one use of the DNA sequence, there are many more; in the last decade, we have realised that regulation of gene activity plays a much larger role than anticipated, and most research today looks at regulatory patterns on the DNA level. This is also done with sequence data, but there doesn’t appear to be a simple schema analogous to the genetic code to understand regulation. Instead, it’s a complex interplay of many completely unrelated mechanisms.

By the way, this doesn’t even touch on RNA-seq and ChIP-seq which technically are also sequence data results but with a twist.

There is a whole lot you can do with genome sequences, I'll focus on a specific example here.
A gene encodes for a protein, but as long as you have only the DNA sequence of that gene you can't easily find out what exactly the protein that is encoded by the gene does. There are ways to predict certain characteristics of the protein, but you really want to have large amounts of the protein itself to be able to examine it in detail.
Having the sequence of a gene allows you to put that gene into other cells, often bacteria but also yeast cells, insect or mammalian cell lines. Using those you can then mass-produce the protein, purify it and start to study its structure and function.
Getting the protein without a sequence means you need to extract it from whatever organism produces it. This is only feasible for proteins that are produced in very large amounts, and even then it probably means you'll have to process a large amount of material to get enough protein. Having the sequence available enables us to study a lot more different proteins than we could by purifying them from their original source.

As the others mentioned, identifying and annotating protein coding genes is an important part of any genome sequencing project. However, there are a variety of other things you can do with a complete genome sequence. You can annotate other types of features, such as transposable elements and repetitive sequences, you can sequence mRNA and map it back to the genome to get a measure of gene expression for a particular tissue, and you can look for variations in the genome such as single nucleotide polymorphisms (SNPs), copy number variations (CNVs), and other large scale variations. If other related genomes are available, there are a lot comparative genomics questions you can ask about large-scale conservation (synteny), DNA substitution rates, relative DNA composition, etc. We are really just beginning to scratch the surface as to the wealth of information a genome contains and how that information is biologically processed.


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What is "transcribed strand"
This is an excerpt from a paper:

T>C mutations at NpTpN trinucleotides, also found in hepatocellular carcinomas, shows strong transcriptional strand bias with more T>C mutations on the transcribed than untranscribed strands

What exactly is meant by "transcribed" strand: the sense strand or the template strand ?
I tried looking up for it but couldn't find any definition.

I think it should be the template strand .

i too guess that but am looking for a reference that defines so.

I also found this term being used in one of the leading A Level textbooks.

@biogirl which one?

In my opinion they should mean the template strand, and they probably do. Perhaps if we had a link to the paper we could have examined the language more closely.
Here is a paper which uses the term in that sense:

Mugal, CF et al. (2008) Transcription-Induced Mutational Strand Bias and Its Effect on Substitution Rates in Human Genes. Molecular Biology and Evolution 26,131-142

In the abstract (which I have linked to) the authors make a clear reference to the transcribed strand in contrast to the coding strand (i.e. the strand of DNA with the same sequence as the RNA transcript):

All three [mutational rates] considered are found to be on average higher on the coding strand and lower on the transcribed strand...

There are also definitions confirming this at this Wikipedia page.

Remember that DNA is double stranded and each strand has a chemical direction.  Genes are read by the ribosome in the 3' to 5' direction so that the DNA 'forward' direction is defined in this direction.  This is the direction of transcription.
Each segment of DNA can therefore be read in 2 directions.  In the direction of transcription each T will have an A on the other strand.  So each letter in the direction of transcription will not be the same if you read the other strand.
Transcription (that which is transcribed) refers to the ribosomal read strand.
Hope this helps.

I understand that.. But when the authors say "transcribed strand" do they mean the strand that RNAPol reads or the strand that is actually in sense with the transcript ?

transcription (that which is transcribed) is the ribosomal read strand.  i'll put that in the answer too...

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text:
Better population models than the logistic equation
For modelling the population of a single species in a region, the logistic equation is used
$$ \frac{dN}{dt} =kN\Big(1-\frac{N}{K}\Big) $$
where $N$ is the number of organisms, $K$ is the carrying capacity, and $k$ is a constant.
However, for most real primary consumers, in the absence of predation, the population usually deviates from the standard sigmoidal curve in two ways

The population typically overshoots the carrying capacity before decaying again to the carrying capacity
The population usually oscillates around the carrying capacity, rather then remaining constant

Are there any better mathematical models for describing growth mediated by density dependent factors of primary consumers in the absence of predation?

You should explain what exactly do you mean by better

I agree with @WYSIWYG - this is opinion-based at the moment. Are you asking for models that can accomodate for your points 1 and 2? What other types of models have you looked at?

I don't see how using the world "better" is opinion based. The point of models is to accurately simulate real systems. By "better" I mean more accurate at producing the experimentally observed population versus time graphs, which display the points I mentioned above.

The thing is that many types of models can produce the type of dynamics that you describe. Whether they are suitable for a particular species depends on the biology of this species though, and you haven't included any information about the organism you want to model (prey/predator? generation length? discrete or continuous reproduction? etc etc). And whether something is "better" is rather opinion based, while "What types of models can accomodate for points 1 and 2 in the absence of predation, and describe a population with discrete reproductive events?" can be answered more easily .

I think "better" is pretty well defined in the question, and the edits presumably address the above concerns. Voted to reopen.

The accepted answer does not deal with the question as I understand it, which is whether continuous time models can display non monotonous behaviours (overshoots and oscillations being two examples). Note that one can give a pretty clear and complete answer to this question. OP: How comes?

I'm not explicitly interested in only continuous time models, but with any model than can accurately simulate an ecosystem. And in some ways, for organisms that have a well defined seasonal mating cycle, a discrete time model makes more sense.

All the more reason to make this explicit in your question from the start, don't you think? At the moment, said question only mentions continuous time models. (Unrelated: Please use @.)

It is not complicated to make your own model of population growth
You can make a model with any kind of function, it is not super hard. It just happen that logistic growth offer quite a good match to observations. You can have exponential growth, linear growth, quadratic growth, ...
However, there are more possible behaviours behind those models than what you think!
The behaviour that you describe is totally possible with a discrete time logistic model. In short, consider the recursion equation $n_{t+1} = f(n_t)$. Consider also $\hat n$ as being an equilibrium of your system (typically n=0 or n=k, where k is the carrying capacity). In other words, $\hat n$ satisfies the equation $\hat n = f(\hat n)$. And finally consider the statistics $\lambda$ which is equal to the derivative of $f(n)$ over $n$ evaluated at the equilibrium $\hat n$. If $\lambda < 0$, then you have oscillatory behaviour (and therefore overshoot) at the vicinity of the equilibrium $\hat n$. Using the correct parameters, the logistics equation gives you a lambda smaller than 0 (typically between $-1 > \lambda > 0$), and therefore you can have the oscillatory behaviour you describe.
If you have any trouble to make these basic analyses of those models, I strongly recommend that book.


text:
minimum ratio of the shortest isoform to the longest one derived from one same parent gene
I want to know what is the minimum percentage of the shortest isoform/transcript to the longest one that derived from the same parent gene? Does it have organism specificity? What is the function of the shortest isoform?
Because I want to filter the gtf file from cuffmerge. One consideration is that the very short isoform maybe artificial or random transcripts that should be filtered.
From this page 1, the CREB gene has been manually annotated and included a processed transcripts only 84bp, while the longest transcript of this gene is 8532bp. So the ratio is < 0.01; However, this transcript is not coding sequences. I also plot the minimum ratio distribution in human GENCODE v22 data.

1 vega.sanger.ac.uk/Homo_sapiens/Transcript/Summary?g=OTTHUMG00000097081;r=7:28724300-28726731;t=OTTHUMT00000327948
Best,
Pengcheng

maybe you are looking for proportion? That is ratio of isoform A to isoform B

thank you @aandreev, I have updated the content accordingly.

Splice product that short cannot be considered an isoform. If you are interested in splice products then you can have a look at miRNA arising from intron of the host gene.

@WYSIWYG thank you. I have disregarded the transcripts without annotated as "protein_coding". Yes, as you suggested, miRNA can be produced from intron, so the processed transcripts that detected in RNAseq potentially miRNA sequences.


text:
Is it possible for prion-infected meat to be processed safely (such as in Soylent Green) and still provide some form of nutrition?
I watched Soylent Green again today, and it's clear that our understanding of the health effects from cannibalism have improved since filming. Since then, we have now already experienced first-hand a localized epidemic as a result of the outbreak of Mad Cow Disease in the United Kingdom. Morality aside, any such product could cause the suicide of Humans as a species, due to the systemic spread of incurable and fatal disease from the ingestion of misfolded proteins.
It's already known that these proteins cannot be destroyed through the normal cooking process, and can survive temperatures of over 600 °C. I've read that it would require, by temperature alone, up to 1,000 °C to destroy prion infectivity.

Incineration of prion-contaminated material is considered the most
effective method of disposal. Combustion at 1,000°C can destroy prion
infectivity, however, low infectivity remains after treatment at
600°C. Despite its effectiveness, incineration may not be a
practical solution, such as during a large outbreak of BSE, scrapie or
CWD requiring a mass culling. Incineration of contaminated soil,
vegetation and farm infrastructure (paddocks, fences) to eliminate CWD
or scrapie environmental infectivity is also not practical.

I am not a biologist, and I don't know anything about food preparation or nutrition. But I am curious as to whether Soylent Green as a concept would even be possible. For example, if temperatures must reach the point of incineration, then any form of nutrition and other desirable proteins would effectively be destroyed as well. The remains would become carbonized, which wouldn't leave anything of nutritional value.
I thought about asking this as a science fiction question, as it is dystopian in origin, but I'm interested in the biology of the problem, as it exists in reality. I also think that it would be somewhat inappropriate to ask this on the nutrition stack exchange, for obvious reasons.

I believe your question is: "Is there nutritional value in protein after exposure to temperatures of 1000 C?" "Prion-infected" is the motivation for the 1000C figure, but otherwise is irrelevant to the question, isn't it?

Nitpicking, but what you refer to as a pandemic of mad cow disease (properly known as variant Creutzfeld-Jacob Disease or vCJD in humans and Bovine Spongiform Encephalopathy in cows) was only an epidemic (localized to one area rather than world-wide).

No.
There are two processes that we need to consider.
First off: incineration at 1000 C (1832 F) in an oxidizing atmosphere will result in almost total destruction of the material. Carbon based material, such as protein, will likely be mostly converted into CO2 and water (ignoring the amine groups, sulphur groups). Calcium based substances (bones, teeth) will be significantly damaged and some residual material will be deposited as ash, similar to the remains you get from a cremation. There is no nutritional value in these remains other than some mineral content, certainly no energy value (i.e. food value).
Secondly. Pyrolysis. In a non-oxidising atmosphere (anaerobic, or in the absence of oxygen), you get something called pyrolysis, which results in permanent chemical changes in the substances treated that way. I had a look through the literature for pyrolysis of meat and it is commonly used to dispose of remains from meat processing plants/slaughterhouses, especially meat-and-bone meal (the stuff formerly fed to cattle, causing the spread of Bovine Spongiform Encephalopathy in the UK). A common theme is that there are several remains from pyrolysis carried out at 500 C (932 F) - a solid material, a liquid oil, an aqueous phase, and gas.
Typical output (from A. Chaala and C. Roy1)

and in summary of outputs and uses (ibid):

The process generated oil, gas, a solid residue, and an aqueous phase. The oil, which exhibits a high heating value of 34.2 MJ/kg, can be used alone or mixed with petroleum products as a fuel in boilers or gas turbines. However, the presence of nitrogenated compounds may cause some environmental problems if the oil is used alone. The complex chemical composition of the pyrolysis oil allows it to be potentially used for various applications, for example, as a softener for polymer processing and as an additive for the fabrication of well drilling mud. The gas with its calorific value of 12.9 MJ/kg and the burnable aqueous phase can be cofired to provide heat to the vacuum pyrolysis reactor. The solid residue can be used as a fertilizer, a moisturizer, an adsorbent, a filler for road bitumen, or a solid fuel in cement kilns.

Long story short: no nutritional value left after heating to the sorts of temperatures used for destroying prions.
1: A. Chaala and C. Roy Environmental Science & Technology 2003. 37 (19), 4517-4522. DOI: 10.1021/es026346m. Reprinted with permission from American Chemical Society.

Removal of prions in organic material by thermal degradation completely destroys the organic material. However, prions can also be digested by some enzymes, particularly keratinase, under relatively mild denaturing conditions. The resulting short peptides would retain their nutritive value. From Enzymatic Formulation Capable of Degrading Scrapie Prion under Mild Digestion Conditions:

An enzymatic formulation combining N22 keratinase and biosurfactant derived from Pseudomonas aeruginosa degraded PrPSc at 65°C in 10 min to undetectable level

A study of protease digestion of infected brain homogenates under milder conditions (50°C and pH 9.6 for 2 h.) showed partial digestion of prion protein PrP reduced infectivity more than proportionally. From High CJD infectivity remains after prion protein is destroyed

In contrast to PK, NAP digestion left 0.8% residual PrP after 2hr, yet decreased titer by >2.5logs; few residual protein bands remained. FU-CJD infected cells with 10x the infectivity of brain by both animal and cell culture assays were also evaluated. NAP again significantly reduced cell infectivity (>3.5 logs).

Another study looked at the penetration of protease into actual meat and bone meal (MBM), which is the ground-up scraps of butchery refuse that was banned for use as livestock feed after the BSE epidemic in the UK. This study is the most relevant to preparing potentially prion-infected tissues for consumption, but they don't actually investigate changes in infectivity. From Diffusion of Protease into Meat & Bone Meal for Solubility Improvement and Potential Inactivation of the BSE Prion:

Results showed that surrogate distributed in bone particles was more susceptible to degradation than that in soft tissue particles. Three factors controllable by unit operations in an industrial-scale process were also tested. It was found that removing the lipid content and hydrating MBM prior to incubation both significantly increased the rate of surrogate degradation. In a test of particle size, the smallest collected diameter range demonstrated the largest degradation of the prion surrogate, suggesting milling would be beneficial.

So, by grinding up everything into tiny pieces, removing the fat content, then treating with enzymes, it may be possible to reduce transmissions to levels that are acceptable in your hypothetical cannibalistic dystopia.

Good answer. However, you'd want to be pretty certain in your processing that you had gotten rid of all the PrP before consuming - undetectable in their sample doesn't mean that it would necessarily be eliminated completely, just to the limits of the assay! I'm guessing instead of Soylent Green you would have some sort of nice nutrient broth left over - Matrix style!

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text:
Parasitism and mimicry
I was reading this article which states this:

Classical Batesian mimicry, in which an undefended mimic evolves to
  look like a toxic model, is a parasitic relationship in which the
  mimic gains an advantage at the expense of the model

I don't understand why this mimicry is equivalent to parasitism. Do the authors call it parasitic because eventually it may cause threat to the model, as the predator learns that it is being fooled around ?
I don't see a clear and certain antagonistic relationship here. Can someone please explain.
EDIT
If it is the case that the mimic reduces the likelihood of the model being preyed then then outcome of this is dependent on multiple parameters.
The +/- effect of this interaction is not always certain (which on the other hand is usually certain in the case of a typical parasitism). The uncertainty can arise not just by evolution of the predator but by other factors such as population size and structure.
Considering all this is it correct to call a relationship as parasitism just based on one of the many possible outcomes ?

A parasitic interaction is when one species has a fitness increase (benefit) from the interaction while the other has a fitness decrease (cost). Note: you don't need to have physical contact to have an interaction. As soon as the presence of one specie influence the fitness of the other, it is enough to consider that there is an interaction.
In the case of Batesian mimicry, I think it is obvious to understand why the non-toxic species gain from this interaction. Let's imagine the toxic (model) species is blue. Predators learn to avoid blue species because they feel very sick right after eating it. In other words, the predators have a bad experience or even better we can say that the predator receives a punishment or a negative reinforcement (instrumental conditioning). In consequence the predator that got this negative reinforcement will probably avoid blue individuals in the future.
When a predator eats an individual from the mimic non-toxic species, he got a positive reinforcement. In consequence the predator learns that the prey tastes good and in consequence it is more likely to eat a blue prey next time it encounters one, which obviously has a negative impact on toxic model organism.
Now, I have two issues with this concept.

The interaction is not one-to-one and we can consider that the presence of a species that use Batesian mimicry influence the variance in fitness of the toxic species only if (actually you might argue differently by not assuming infinite population size) the distribution ranges are not completely overlapping or if there are some kind of population structure.
If the toxic species causes death to the predator, then the predators never get the opportunity to learn. But one can consider the same mechanisms at evolutionary timescale than at the time of the lifespan of the predators. It is also possible that the predators have higher cognitive abilities allowing them to gain insights concerning the toxicity of one species without having to taste it.

EDIT

What if predators can tell the difference between the two prey species?

Your point, if I understand it, is that if the predators manage to sense (or to evolve sensing) the two prey species differently (in consequence the non-toxic species does not mimic the other prey species anymore), then the toxic species will not suffer anymore from the mimicry. So in other words, mimicry is a parasitic interaction but predators might evolve ways to sense the two species differently in which case there would have no mimicry anymore. Note: the predator is more likely to evolve good sensing abilities if it forages on few species only.
I think your issue is that you should not consider a species to be mimicry if the predator can tell the difference between the two prey species. It is not to the human eyes that the mimicry makes sense but only to those of the predators. So, batesian mimicry is a parasitic interaction and if the predators evolve so that they can sense the difference between the two species, then there is no more Batesian mimicry and there is no more parasitic interactions between the two prey species.

Why do you say that  "physical contact" not necessary for two species to have a parasitic interaction?

The interactions between species are defined as follow:

The benefits and costs (harmed) are defined in terms of fitness. These definitions do not involve any physical interactions. And to the eyes of the evolutionist at least, that would not make much sense to add a notion of physical interaction into these definitions.

In the case of Batesian mimicry the ± effect is not always certain (while it is certain in common parasitic interactions)

The point is interesting. I think it just mean that the non-toxic organism is a facultative parasite (a species that can live with or without the parasitic interaction). Statistically speaking, if you have enough preys of each species and especially enough predators, then the consequence is certain.
Consider the common Ivy. It is a parasite of other plants but can also live on human-made walls in which case the negative effect on other plants is not always certain either. The difference between the Ivy and the non-toxic prey is that the fitness of the non-toxic prey depends on whether it parasites the other species while the Ivy is doing just fine on human-made walls.
You can think about the interactions between rabbits and wolves. They share a prey-predator interaction which is a special case of the parasitic interaction according to above diagram. In a particular environment the wolves might be absent and so predation does not occur, just like the non-toxic species might be absent species might be absent and so the parasitic interaction does not occur anymore.

Nicely summarized. But one doubt still remains. The +/- effect of this interaction is not always certain (which on the other hand is always certain in the case of a typical parasitism). The uncertainty can arise not just by evolution of the predator. As you pointed out it is also dependent on the population sizes and structures. Also a predator may not evolve and continue to be fooled.

another clarification.. i was discussing this with a friend and another point emerged: in the case of predator not updating its knowledge of a certain appearance associated with toxicity i.e predator still wont attack the mimic and the model both. In this case also the model is in disadvantage that it invests in production of toxin whereas the mimic doesnt. is this a valid point ?

I think you say: "If the predator, for some reason, cannot associate toxicity with appearance, then the toxic species pay a cost of producing the toxin while the mimic species doesn't have this cost." Yes! Note: there might have some cost for "looking" like the other species. And cost for displaying some shiny structure. Also, this interpretation might be a bit too simple. Producing toxin might be beneficial under kin selection if the survival of the predator is reduced so that it won't kill the brothers of the prey and stuff like that.

I meant that the predator has strongly associated the appearance with toxicity and will not attack the mimic. In this case the model produces color/pattern + toxin but the mimic just produces colors. So the model has an additional cost of living. But it is likely that there might be other confounding factors.

Ah ok. I missunderstood what you said. Well, yes indeed the toxic species would have an additional cost compare to the non-toxic prey species. I think that comparing their costs only make sense if these two species have a relatively high overlap of ecological niche (due to principle of competitive exclusion).


text:
How to avoid mutations when performing Gibson Assembly (or generating amplicons during PCR)
More often than desired (about 75 % of the time), when building plasmids via Gibson Assembly (~ 5 kb plasmids; from a maximum of 2 fragments) we obtain clones with several random point mutations all along the plasmid (from 1–3 point mutations to 6+ depending on the day, without specific region targetted).
Since we use the NEBuilder HiFi DNA Assembly kit and since there doesn't seem to be any specificity as of where those mutation are found, I suspect that they arise during the PCR reaction when producing the amplicons.
We use the Phusion High-Fidelity polymerase to generate the amplicons from ~1 pmol of template in 50 µL of PCR reaction (or split in 5 x 10 µL since working with reduced volumes seems to improve the efficiency of amplification) and 30 cycles.

Is this a normal/common issue or does this result indicate that something wrong is happening in our experiments?

And more importantly, any idea of how to prevent such problems?

I have in mind:

Reducing the number of cycles (how low can one go?) and/or increasing the concentration of template (related).
Changing polymerase (but for which one and shouldn't Phusion High-Fidelity be one of the best suited?).
Changing other parameters or conditions (but which ones?)

Any bullet-proof experience on that? Thanks
EDIT:
Changing the DNA polymerase from a Phusion HF to the Q5 suggested in the NEBuilder kit manual (suggestion that I had overlooked) completely solved the problem.
Rem 1: Mind that the elongation time must be slightly increased to amplify "long" fragments with Q5—probably a side effect of its higher proofreading ability. Whereas 20–30 s/kb is recommended, 120 s where not enough to amplify a fragment of 3.5 kb; an elongation time of 240 s—i.e. 60 s/kb—did work though.
Rem 2: In the past, amplification with the Phusion HF DNA polymerase did result in correct sequences in most of the cases, so I was surprised to have issues here. A possible factor that came to my mind afterwards and that could explain the apparition of mutations could be a low purification quality of the DNA preparation used as the template (leftover chemical contaminants). Although I have not (yet) tested and confirmed this possible explanation in my case.
I marked the answer from @markur below as accepted, as his/her suggestions (along with the accompanying discussion underneath) prompted me to go and read the original articles and then to read again more carefully the manual of the NEBuilder kit where the solution was.

Polymerases are never perfect. Mistakes can happen and are usually the reason why one always picks several clones and sends them off to sequencing. Phusion polymerase is advertised to contain 1 error in 6% of all PCR products (5000 bp, 30 cycles, HF buffer;  thermofisher error calculator). Companies always underestimate their errors, but in your case, having 6 point mutations in each clone is reason enough to optimize your protocol.
Changing the Enzyme will definitely have the greatest impact on your problem. Especially if it also includes changing the buffer system.
Phusion has been around quite a while, I'm sure that some companies did apply some optimizations trying to beat the competition (Kapa).
Another thing that came to my mind is that high magnesium concentrations increase the amplification rate, hence reducing corrective activity (aatbio). You might want to review your plasmid purification protocol to see if there might be salt contaminants (e.g. after EtOH precipitation).
Decreasing cycles also makes sense, and is definitely worth a shot.
Other aspects to try, if you're desperate:

Get a longer primer (~30 bp) and use a higher melting temperature to enforce strict and correct primer binding.
Getting fresh primers is also a good idea to avoid freeze/thaw damages
Use a fresh dNTP solution
Adding BSA is always worth a shot with PCR Farell 2012. Not just during the reaction, but also during storage to protect nucleic acids from freeze/thaw cycles Svec et al. 2013!
Check out thermofishers troubleshooting guide, there are some more ideas that might help!

Important: Please verify that it's indeed the PCR reaction that's causing point mutations, and not the bacterial clones! Check that by re-amplifying the same plasmid with PCR without prior Gibson Assembly and sequencing the product like any other clone!

Thank you very much for your answer + the tips + the links. A question: do you have experience in Gibson Assembly? I am asking because I am also wondering how my experience compares with others (1st point in my question) regardless of theoretical error rates as advertised by companies.

I've done a lot of Gibson Assembly with a home made kit (preparation identical to the original publication), and although I don't have numbers, I can't recall random mutations being particularly common. Do you see any pattern to where the mutations most often appear? Is it anywhere in the PCR amplified fragments, or are they more common in the repair regions (fragment overlaps)?

@TheQuark - I did it a few times but I will ask some technical assistants if 1-6 random point mutations per 5 kb for each clone is common (I don't think it is). One clone should be "perfect".

Following these exchanges, see the edit in my original post.


text:
Are there irreversible metabolic reactions that can happen in opposite ways depending on the cellular conditions?
Irreversible reactions are thermodynamically irreversible, not microscopically irreversible. "Irreversible" here means the reaction happens "out-of-equilibrium". It is a macroscopic property.
Being (thermodynamically) irreversible doesn't mean that a reaction cannot be inverted if conditions (temperature, pressure, concentration of species) change so that the reaction then spontaneously proceeds in the opposite direction as in the previous conditions. In other words, a reaction can happen irreversibly (spontaneously) in one direction in given conditions, and happen irreversibly (spontaneously) in the opposite direction in other conditions.
Are there any known (reported) examples of metabolic reactions that are found to happen in opposite directions depending on the conditions in which a given cell or cell type is found, and that happen thermodynamically irreversibly in either case? I have found reactions that happen irreversibly in opposite directions in different cell types (although I am not sure the reactions are irreversible in the respective cases):

Lactate dehydrogenase catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+. It converts pyruvate, the final product of glycolysis, to lactate when oxygen is absent or in short supply, and it performs the reverse reaction during the Cori cycle in the liver.

Ref.: Lactate dehydrogenase (Wikipedia)
But I am wondering about a case where such inversion can happen in different conditions or states for a given cell or cell type.
[Note: see also the discussion in the comments for clarifications if needed.]

Reversibility of biochemical reactions
The general view of the way “irreversibility” is regarded in biochemistry is well summarized by the respected enzymologist, Athel Cornish-Bowden:

“Mathematically and thermodynamically there are no irreversible
reactions in chemistry, and all enzymes catalyse reversible reactions.
All reactions have finite standard Gibbs energies, which is just
another way of saying that they all have finite equilibrium constants.
Nonetheless, for an enzyme like pyruvate kinase, with an equilibrium
constant of the order of 105, one may feel that this is just a
mathematical nicety and that the thermodynamic necessity for the
reverse reaction to be possible has no practical consequences for cell
physiology, and in practice many metabolic reactions are
conventionally regarded as irreversible. This typically means that
they have equilibrium constants of the order of 1000 or more, though
when the mass action ratio in the cell also strongly favours the
forward direction a reaction with a substantially smaller
equilibrium constant than this can be regarded as irreversible.“

[my emphases]
The standard textbook example of this is the three reactions of glycolysis — hexokinase, phosphofructokinase and phosphoenolpyruvate carboxykinase — that are regarded as effectively irreversible, a view supported by the fact that gluconeogenesis (the overall reverse process to glycolysis) employs separate enzymes for these steps. To quote one such text, Biochemistry by Berg et al.:

“However gluconeogenesis is not a reversal of glycolysis. Several
reactions must differ because the equilibrium of glycolysis lies far
on the side of pyruvate formation.“

The text then elaborates on the enzymes and lists the standard free energy changes of the reactions they catalyse (ΔG0′) as in the table below, to which I have added the equilibrium constants (K′eq) calculated for the same ‘standard’ conditions.

Reaction
K′eq
ΔG0′ (kcal/mol)

Hexokinase
1.32 x 10–6
–8.0

Phosphofructokinase
1.25 x 10–5
–5.3

PEP carboxykinase
1.11 x 10–3
–4.0

The PEP carboxykinase value is consistent with the border value of Cornish-Bowden, above.
So, in my opinion, the question becomes whether there are any examples of reactions at this thermodynamic borderline that are reversed under certain physiological circumstances.
Examples of reversal of very thermodynamically unfavourable reactions
I feel that there are probably other examples I should know of, but will be happy to add any that others can supply to make a community answer. However at the moment the only one that comes to mind is the carbonic anhydrase reaction:

HCO3− + H+ → CO2 + H2O

which has an equilibrium constant of the order of 10–3. (I have found values of 1.7–2.7 x 10–3.)
The situation is complicated because of the equilibrium between bicarbonate and carbonic acid, and between dissolved and gaseous carbon dioxide. However, the striking fact is that in the tissues the enzyme catalyses the conversion of carbon dioxide produced in metabolism to bicarbonate:
Tissues: CO2 → HCO3−
whereas in the lungs the reverse occurs in order to allow the carbon dioxide to be removed from the blood:
Lungs: HCO3− → CO2
What drives the ‘unfavourable’ conversion of carbon dioxide to carbonate in the tissues? One factor must be the high concentration of  CO2; another must be the lower pH, which, of course, represents an increase in the concentration of hydrogen ions. Both of these are a result of oxidative metabolism in the tissues.
Footnote: Lactate Dehydrogenase
I see that the poster has edited his question to refer to lactate dehydrogenase. The value of ΔG0′ for LDH is –6 kcal/mol, so it falls into the ‘irreversible’ category biochemical reactions, although, strangely, this is seldom, if ever, mentioned. I don’t see what the poster has against this example. Liver cells can perform glycolysis and form pyruvate and they certainly convert lactate to pyruvate, so the same cell is subject to different circumstances (high blood lactate concentration v. low blood lactate concentration) when catalysing the reaction in opposite directions.

I think another aspect of biology/biochemistry that is missed by those coming from more of a chemistry background is the ability of biology to not only chain multiple reactions to make the "reverse of irreversible" more unlikely, but also to effectively make unavailable the products for reverse reaction by shipping them out to other compartments, sometimes seemingly for 'free' unless you consider a much larger thermodynamic problem. CO2 clearance is an example of one of these, taking advantage of cheap bulk gas flow and the low, biologically unsaturable environmental CO2 concentration.


text:
What chemical to use to recycle microplates used to grow bacteria
We grow bacteria (Escherichia coli) in polypropylene or polystyrene microplates with an optical bottom for some experiments (liquid culture).
I would like to try and recycle those microplates to be able to reuse them.
What chemical could be used? Ethanol, which I expected to kill the bacteria, doesn't work well as it leaves some deposit of bacteria aggregates. I was thinking about a chemical to lyse the bacteria, but I read here that it requires lysozyme to be efficient. I am rather looking for an inexpensive solution.

Would soap and hot water work? I assume you want to avoid scrubbing so as not to scratch the plates and change their optical properties

Are these in liquid culture or in/on solid media?  You could try NaOH and SDS - a la plasmid preparation lysis.

@acvill Thank you for the suggestion, I could try that. Indeed, we would like to avoid altering the optical properties of the optical phase.

@bob1 Yes, experiments are performed in liquid media (I have updated the question accordingly). The NaOH + SDS is a very good suggestion, thank you. I will try that.

Let us know how it goes by self- answering.


text:
Are SLC52A2 and GPR172A really the same?
The official HUGO gene nomenclature page says that GPR172A (Gamma-hydroxybutyrate receptor) and SLC52A2 (riboflavin transporter, member 2) are the same. The sequence reported by Andriamampandry seems to be the same, but I find no other evidence. Can anyone enlighten me?
(I'm wondering if I should add the SLC52A2 information to the GHB receptor Wikipedia page.)

This isn't a case of gene splicing causing different protein variants.  In the studies that identified these two functions (GHB sensitivity and riboflavin transport), they were using DNA derived from mRNA (cDNA), which means what was being expressed in their experiments did not have introns, so there was no chance for alternative splicing.
This gene has a weird history, here is the summary:
Takeda et al. 2002: Identification of G protein-coupled receptor genes from the human genome sequence
Takeda and co. download a copy of the human genome and translate it looking for GPCRs.  They look at all the ORF that DIDNT have introns: "We collected intronless open reading frames (ORFs), which were long enough to cover GPCRs from the human genome". They also only look at things with 6-8 transmembrane helices as determined by the prediction program SOSUI.  One of the GPCRs they found was named hGCRP41 (hypothetical protein similar to GPCR) accession number: AB083623.  They report it probably has 8 transmembrane helices, and 418aa.  This protein probably doesn't exist because they read straight through two introns in their analysis.  The protein also terminates in the middle of a frame-shifted exon.
Ericsson et al. 2003: Identification of receptors for pig endogenous retrovirus
Next, Ericsson et al come along looking for receptors for the pig endogenous retrovirus and find this gene.  They used cDNA to make a bunch of transduced cell lines that had difference human cDNAs expressed.  They found two related proteins that could serve as receptors to the pig endogenous retrovirus.  They named the first one HuPAR-1, which is 445aa long and has 11 transmembrane helices.  This is the length of one of the proper splice variants of this gene.
Andriamampandry et al. 2007: Cloning and functional characterization of a gammahydroxybutyrate receptor identiﬁed in the human brain
Andriamampandry is looking for gammahydroxtbutyrate (GHB) receptors by using cDNA and seeing which cDNA-transduced cells become sensitive to GHB.  They find two nice proteins that are sensitive to GHB, GHBh1 and C12K32.  GHBh1 is identical to HuPAR-1, it has 445aa and 11 transmembrane helices.  C12K32 is a frameshifted version of GHBh1 that is slightly longer, but has the same number of helices. They had previously found a 512aa ortholog in rats, in 2013.
Yao et al. 2010: Identification and Comparative Functional Characterization of a New Human Riboflavin Transporter hRFT3 Expressed in the Brain.
Finally, we have Yao et al, who searched for homologs to their Riboflavin transporters.  They found one in a cDNA library, and it was 445aa long.  But they noticed upon BLASTing it that people had been calling it a GPCR.  They point out that this is weird since it has 11 transmembrane helices, and go on to show that it is a Riboflavin transporter, concluding: "The molecular function of GPR172A has yet to be determined. We designated it hRFT3 (GenBank accession no. AB522904) based on its functional characterization as shown below."  This paper is in pretty poor form, because somehow they don't address the Andriamampandry paper which presented data supporting its function as a GPCR.

So this protein, in this specific spliced formation, has been shown to be a virus receptor, a GHB G protein-coupled receptor, and a riboflavin transporter.  It is very weird that it is a GPCR with 11 transmembrane domains... they very rarely have more or less than 7.  I'd wait for more studies to confirm both of these findings before I'd accept that this protein is an XXL GPCR moonlighting as a riboflavin transporter.

Its fairly common for a gene to have multiple names. I cant say for certain, but Jax and GeneCards also lists them as being synonymous so I would say its safe to say they are the same
http://www.informatics.jax.org/marker/MGI:1289288
http://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC52A2
Edit in reply to comment:
In higher level Eukaryotes the vast majority of genes have more than one isoform as a result of alternative splicing, and this can drastically change the protein sequence and function of that protein. So even if it comes from the gene, two different isoforms can have completely unrelated functions.
According to ensembl, this gene has 14 isoforms.
http://useast.ensembl.org/Homo_sapiens/Gene/Splice?g=ENSG00000185803;r=8:145577795-145584932
Of course there could also be some type of post translational modification that could also change the function, but Id say mostly likely if the same gene produces two different functioning proteins its because of alternative splicing.

the functions just seem to be so diverse that I have a hard time believing it... but you never know, I guess


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Serological assays not detecting native proteins
Is there anyone out there who has done much work with serological assays? We have antiserum for a manufactured viral protein but no luck so far getting it to detect native protein (unless today's attempt worked which we will find out tomorrow).
What are any common problems or possible considerations that we should bear in mind when testing?

It would probably help if you would add as much detail as possible about the specific assay you're performing. As it stands know you can only get very general advice, and the answerers have to guess the details.


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Earth overshoot day: is it a sound concept?
Today, August 8th, is Earth Overshoot Day (EOD) for 2016, the day when humanity supposedly has consumed the natural resources available from the planet for the year 2016; we're now running a deficit, somehow. At least if your believe the calculations of the Global Footprint Network (GFN), the think tank behind this concept. EOD is well reported by media every year, and perhaps it does some good as an ecology awareness thing. But is the idea scientifically sound?
EOD is based on the ecological footprint concept. The ecological footprint of a person (measured in hectares) is the area of the earth required to extract the natural resources needed to sustain that person: to grow crops, keep farm animals, obtain natural resources for consumables, etc. It's a very complex thing to calculate, and of course people argue about what the correct formula should be. One article by Willis Eschenbach (2010) goes into some depth and argues that the formula used by GFN vastly overestimates the footprint. I don't know who is right, but it does seem like the footprint is very difficult to estimate, so we should probably be careful with drawing strong conclusions.
But I have a more fundamental problem with EOD. Regardless of how it's calculated, the claim that we have today "overshot" our yearly earth-budget, at 8 months out of 12, means that we are consuming about 1.5 of the available food and natural resources available; or that the footprint of humanity is 1.5 Earths. This is not some kind of parable: GFN really claims that we have exhausted our natural resources, by a wide margin, and that this has been going on since the 1970's.
My question is, what are we all living on then?
As of today there should be no more food around, or any other natural-derived product for that matter. If GFNs estimate is correct, shouldn't humanity be long dead? Shouldn't we expect 1/3 of the earth's "surplus" population to die off pretty quickly? Doesn't the fact that we're not dead prove that EOD is wrong? Isn't it physically impossible for our total footprint to exceed 1 Earth?

EDIT: Nice to see that this question stirred a lot of debate! :) I think several answers bring up one key point that resolves the problem: GFN defines the footprint not as the actual area required for production at present (which must be < 1 Earth), but the area required for sustainable production (which is larger). Exactly how the sustainable area is defined is still mysterious to me, but I guess it is at least theoretically possible.

Why do you think humanity would be dead? I guess the point of the EOD is, that humanity now starts killing other species off, not itself. If we used up our resources, we now would be taking them from others. Taking more than earth can sustainably recover.

The point of EOD as I understand it is to present a bleak picture to the general public, so that they buckle up. Anyone who is a scholar or in one of the sciences or has pursued some sort of advanced education knows that calculating a foot print is very hard. Example, I am from India, where people routinely go hungry and die of hunger. Is it because India wants for food? No, we have been in surplus production for a long time, but the logistics is lagging behind.

@skymningen  I don't see how that's related to the ecological footprint of humans. If we kill/outcompete all other species in order to grab our require hectares, that's one thing. But as I understand it, EOD claims the footprint of humanity exceeds 1 earth, which seems logically impossible.  Are you saying that EOD includes the footprint of non-humans?

@KoustavPal   Yes, I understand that EOD can be a good move for ecological awareness, and might be motivated because of that. That's not my question, I'm wondering if the scientific underpinning is sound.

Scientifically, it isn't a sound concept. If I may bring a similar concept here. Consider Newtonian gravity versus Einstein's general relativity. Newtonian gravity describes gravity as best as possible for the average man's understanding, but it isn't the most scientifically accurate concept. General relativity though is scientifically accurate, but it is very hard to wrap your head around.

You've grossly misinterpreted it. Imagine a company that has a turnover of £1M per year. This would be the equivalent of the natural resources produced each year. Now the company spends £1.5M in a year. This would be the equivalent of using the natural resources produced for the year, the turnover, by August. However, the company has been around for 4.5 billion years and has some money in the bank becuase it was only recently that a stupid new CEO (humans) came in and started spending more money than they were making. The company's best hope is that the CEO dies before he destroys the company.

I also think your question is more philosophical. I say so because, to me you are asking when do we draw a line and say that the results are accurate. Accuracy for me is sufficient when the gain in accuracy would be 0.001 for another step in complexity. But I guess an astrophysics major would say, accuracy for them is sufficient when the gain is 0.00001 for another step up in complexity. So maybe this question belongs in philosophy

@rg255  Sure, that's one way to explain it --- that the Earth somehow has "reserves" that we can live off, but they are finite and will be used up. If so, then the footprint can be > 1 Earth for some limited time, until reserves run out. But what would those reserves be? I'm not an ecologist, so I'd really like to know. Perhaps you can write up an answer to explain?

@KoustavPal  No, this is not a question of accuracy. I'm wondering how the total footprint can exceed 1 Earth. That's a fundamental, conceptual problem, not related to accuracy of any estimate.

"EOD is well reported by the media each year" Really? This is the first I've ever heard of it.

Forests take many years to fully recover. If we use up the right fraction of forest land every year, we can continually utilize a different forest area without reducing total forest area. If we use a larger fraction, the world's forested area will get smaller every year, eventually effectively being wiped out. Using "1.5" as the excessive fraction, it means we use up half again as much forest as can naturally replenish itself "forever". It doesn't mean it's completely gone after 8 months; it means we use as much in 8 months as should only be used in 12.

@TylerH  Well, it is where I live (Sweden).  Perhaps not everywhere.

TL;DR: it's a simplified measure of sustainability, but accurate enough to be useful for public engagement
EOD is hosted and calculated by Global Footprint Network (GFN), an international think tank. The GFN estimates national and global net supply and demand for renewable resources, specifically:

food and fiber products,
livestock and fish products,
timber and other forest products,
space for urban infrastructure, and
carbon sequestration.

From the website:

Global Footprint Network measures a population’s demand for and
  ecosystems’ supply of resources and services. These calculations then
  serve as the foundation for calculating Earth Overshoot Day.
On the supply side, a city, state, or nation’s biocapacity represents
  its biologically productive land and sea area, including forest lands,
  grazing lands, cropland, fishing grounds, and built-up land.
On the demand side, the Ecological Footprint measures a population’s
  demand for plant-based food and fiber products, livestock and fish
  products, timber and other forest products, space for urban
  infrastructure, and forest to absorb its carbon dioxide emissions from
  fossil fuels.

The results are reported in 'global hectares', the area which would be required using global average productivity, to aid intercomparability.
The methodology was published in 2013 (Borucke &al 2013).
So, to answer the question in your title ("Earth overshoot day: is it a sound concept?"), data quality may be an issue (I haven't pored over the paper in detail) but the basic methodology is arguably appropriate for the question they're asking. The only issue I might have is that they effectively consider land and sea use to be interchangeable, but I'm not sure the alternative would be an improvement.
To answer the second part of your question ("what are we all living on then?"), it is possible to harvest more from a system than it can sustainably produce. Exceeding this harms the future productivity of the system. To take the specific examples named for EOD:

Overharvesting plant-based food and fibre products can result in soil acidification, soil erosion, and/or soil salinification;
Overharvesting livestock and fish products can result in overgrazing and/or overfishing;
Overharvesting timber and other forest products results in deforestation;
Using more space for urban infrastructure reduces the availability of land for the other examples on this list;
Producing more carbon emissions than can be absorbed by its forest leads to an increase in atmospheric carbon, resulting in climate change.

Ultimately, while 'Earth Overshoot Day' is a public engagement activity, there is a reasonably robust and transparent methodology behind it which is good enough for the job. Remember: all models are wrong, some models are useful.

Thanks, this is very helpful. I will look at the Borucke et al paper. I take it that the key number is the amount of resources that can be sustainably produced. But I think that fits poorly with the "footprint" concept, unless you define it as the hectares required for sustainable production, not as the hectares required for actual production.

@Roland I'd say sustainability is implied in most similar questions. For example, consider "how much do you need to earn to rent a flat in London?" - most people would infer that the asker is interested in sustainable renting (i.e. a salary that would allow you to rent indefinitely), and wouldn't consider an answer that says 'you can rent a flat in London with zero income, assuming you're willing to eat into savings or go into debt" very helpful.

Yes, I understand you point, but I don't think that's so obvious in the case of the "footprint" idea, because "sustainable" is hard to define here.

Upvote for correct use of "pored over"

@Roland Why is it harder to define here? We have a source (the earth's resources) and a sink (our consumption of those resources). If the two are in long-term balance, we have sustainability.

@AkselA  I agree with that, I meant that it's hard to determine in practise what the conditions for long-term balance is.  At least I would think so.

@Roland - it certainly can be; model predictions can be based on incorrect assumptions (https://en.wikipedia.org/wiki/Maximum_sustainable_yield#Orange_roughy) and there can be hidden environmental impacts in supposedly sustainable systems (http://www.heraldscotland.com/news/11962874.Islanders_polluted_Utopian_idyll_for_centuries_Discarded_seabird_remains_responsible_for_heavy_metal_toxins_which_contaminated_the_soil_of_St_Kilda/). But in the case of arable production and commercial forestry I'd say it's quite well understood, and carbon sequestration rate estimation is getting better fast.

@Roland Ah, ok. arbivoral is pretty much on point in that case, but I might add that a certain amount of forecasting is also added to the models in some cases. The IPCC, for instance, when they propose what they consider to be a sustainable level of growth, the assumption that we become more energy efficient in the future is added in. There is naturally a lot of uncertainty associated with predictions like these.

I think that your question comes from a misunderstanding in the definition of the overshoot day, here is the definition in your question:

Regardless of how it's calculated, the claim that we have today "overshot" our yearly earth-budget, at 8 months out of 12, means that we are consuming about 1.5 of the available food and natural resources available; or that the footprint of humanity is 1.5 Earths.

And here is the definition from the website:

Earth Overshoot Day, falling on 8 August this year, marks the date when humanity’s annual demand on nature exceeds what Earth can regenerate in that year

(emphasize mine)
The difference is that you define resources as available while the website defines availability on a yearly basis.
Like you wrote, it's impossible to consume 1.5 Earths, that would mean that we harvested more fish than are in the ocean, for example.
But if we take it on a yearly basis (as the website do), it's easier to tackle that we harvest more fish each year than fish can reproduce and grow during the same time. So we are harvesting in the fish stocks that developed during the previous years.

Technically, an overshoot means the amount by which a certain dynamic variable shoots above its final steady state value. So, to know overshoot, you need to know the steady state. In this case, as you said, the steady state is just predicted and not really known.
Regarding your question:

what are we all living on then?

Assuming that the overshoot concept holds in this case then we are actually living on the available resources. However, if we are using more than a certain limit then we would deplete the resources in future. This will lead to decline in our population because we need resources to survive. Because of declined population, the resources would accumulate (because of the feedback) and we may finally reach the steady state via a damped oscillatory dynamics (compare with the fox-rabbit situation in the simple Lotka-Volterra models). There are other possible solutions too (sustained oscillations, extinction, etc).
Note that overshoot happens because of a delay and it would not happen (at least using deterministic models), if there is no feedback i.e. a fixed amount of resource is present and we just consume it.
Now, the main issues are:

How accurately do we know the rate and mechanisms of resource production?
How accurately can we calculate the steady state, or in other words, how accurate is our model of resource-population dynamics?

"Assuming that the overshoot concept is true, we are living on the available resources." how can we deplete food resources? Food production has a nonfinite limit (I mean a cap value which cannot be determined atm). How is it possible that we will exhaust natural finite resources such as iron? wouldn't we find newer sources with the advances of technology? We are already in the early stages of transitioning to renewable source. How is it that we will deplete available resources?

@KoustavPal As I said, there are many complexities. I am not commenting on whether whatever model is used, is correct. I am just explaining the concept of overshoot. However, food production is an easy concept that can be nicely explained using Lotka-Volterra. Renewable resources are resources that are formed constantly in nature. If the energy consumption rate is more than production, then the population will be affected again. In a timespan of million years even oil is renewable :P

That's a nice connection to dynamic systems. But this particular overshoot has been going on since at least the 1970's according to GFN ...

"Food production has a nonfinite limit" How can you say this? Food is not just agricultural. There are already the beginnings of protein wars (fighting over food from the sea.) Cod is a good example: cod populations are at record lows despite once being so plentiful that Explorers wrote that one could walk on the surface of the water (off Maine/Newfoundland) by stepping on the backs of cod. We are hunting many species to the brink of extinction. That's not non-finite.

@anongoodnurse when did I say "food production has a nonfinite limit". I didn't say anything like that. Extinction is one of the outcomes. I just said that to say something is an overshoot, you need to have an estimate of the steady state, given by some dynamical model. However, to account for extinction, you would need stochastic models. Deterministic continuous approximations work when the numbers are large.

@Roland I am not quite aware of how GFN estimate is calculated but technically an overshoot usually happens in feedback systems when one variable has faster rates than the other. So we could have overshot an estimate in 1970. However, the estimate should be based on a complex model that would account for all kinds of relationships otherwise you would not really know whether you have actually overshot or not. It is, however, always better to be cautious.

@WYSIWYG Koustav said it in the first comment, not you.

@WYSIWYG - Good grief, I forgot to use the @-user. That comment was not directed at you. Sorry!

Consider an investment earning interest x.
If I spend x dollars a month I cover the interest and will have spending money forever.
If I spend less then x the interest adds to the principal and the investment grows giving me potentially more interest to spend.
If I spend more than x I decrease the principal and so reduce the interest I get the next month. Even if I switch to only spending x I will still eventually run out of principal . To be stable I have to switch to spending x' a smaller limit.
They have modeled the whole earth as a group of investments and expenses using hectares as currency.
Note: in a mortgage when you are paying about 1/3 into principal you are about 2/3 through repayment. Counting  about 40 years to get here might mean maybe another 20 till we are "paid off" if a string of assumptions are true.

While it's not as direct an answer as some of the others, I find this metaphor to be extremely helpful in understanding the concept in clear mathematical terms.


text:
What is the difference between a "semi-contracted" muscle and a "contracted" muscle?
I read on http://www.spine-health.com/glossary/muscle-tension:

Muscle tension refers to the condition in which muscles of the body remain semi-contracted for an extended period.

What is the difference between a "semi-contracted" muscle and a "contracted" muscle?

If you consider the length of a muscle can vary from resting length to shortest length, my guess is that semi-contracted is somewhere in between. I believe that spine-health.com isn't being entirely clear with their definitions.

I think they're refering to rate coding and motor unit recruitment.


text:
Is there a standard reference for the importance of tumor heterogeneity?
In a recent post, Philip Gerlee highlighted the two biggest contributions of mathematical oncology to cancer research: (1) increasing focus on the progress of cancer as an evolutionary process, and (2) looking at the importance of tumor heterogeneity.
For the first point, the standard historical reference is: Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science, 194(4260): 23-28.
However, for the second point, although I am vaguely familiar with modern work, I don't know of a historical reference. When was tumour heterogeneity first recognized as important to cancer dynamics and treatment? Was this work related to mathematical or other modeling insights? If not, what is the first important mathematical (or computational) modeling work on tumour heterogeneity?

I more confident about the experimental evidence being older. The histological evidences are even presented in pathology books. The whole field of systems biology is relatively new- most cancer mathematical models have been published in the last decade only.
The oldest model that uses the concept of tumor heterogeneity is this- published in 1996. [ Based on google search ]

you might look for 'clonal selection' and cancer.  I've heard the term bandied around.

It's quite interesting that the first reference that come to mind is not a mathematical/theoretical one (which is, in all likelihood, going to be a lot older than the one I am going to mention) but a clinical one. That would be Gerlinger and Swanton and their paper in the New England Journal of Medicine.

This paper is quite recent. The concept of tumor heterogeneity was in discussion since long time back. I can't recall references but I have heard people talking in seminars about genome sequencing different regions of cancerous tissue to look for heterogeneity.
Histological evidences are even older. I guess pathology books also have it.

That paper is very well cited (over 1000 times!), but I agree with @WYSIWYG that 2012 seems too recent. Is there a richer history with Gerlinger and Swanton that you could expand on in your answer? Or did you intend this as a comment?

The idea of tumour heterogeneity has been around for a long time (look at the below review and the refs therein), but the underlying causes have been revised in the light of theoretical advances and the novel (Gerlinger et al.) genetic data.
Firstly genetic heterogeneity was largely believed to be the cause of genetic instability (an increased mutation rate), and hence being attributed to drift rather than multiple fitness peaks (i.e. selection).
Secondly there was no evidence to determine if the observed phenotypic heterogeneity (from histology slides) could be attributed to genetic changes, or if it was the cause of phenotypic plasticity.
Alexandrova, Tumour Heterogeneity, Exp. Pathol. Parasitol (2001).

Welcome to the site! Do you know any other sources for Alexandrova's essay apart from a dropbox link? I know a lot of people are unwilling to click those. Also, could you make your answer a bit more self-contained by taking a reference or two out of Alexandrova's essay for when you say "has been around for a long time", for example? That way people can have an idea of the timeline without having to leave this answer.

Actually it's a google drive link. In any case I uploaded it because I couldn't find a pdf of the manuscript anywhere. Do you know of a place that is considered "safe" in terms of downloading?