Do both TSG and Proto-oncogenes have to suffer mutations to cause cancer? I'm having a conceptual nightmare trying to understand when a group of cells may become cancerous and the more resources I consult the more confused I seem to get.

In order for a cell to become cancerous, does it have to mutate to knock out tumour suppressor genes and have a proto-oncogene become an oncogene?

I'm  currently working on the basis that that is the case, or at least that a mutated TSG on its own will not cause uncontrolled division.  However wikipedia seems to suggest that an oncogene alone can cause uncontrolled division with a functional TSG in place.

It could be a flaw in the idea I have that tumour suppressor genes only trigger apoptosis once a cell has started to divide rapidly, are they actually carrying it out to a regular schedule independent of oncogene presence?

The typical idea is that several "hits" are required. The difference between proto-oncogene and TSG is mainly in their heritability - TSG mutations are usually recessive (because a heterozygote will still express sufficient suppressor, e.g. p53) whereas proto-oncogenes are dominant (if a consitutively active agent e.g. Ras is present, it doesn't matter if the other allele is under normal control).

A single "hit" in this way (TSG or proto-oncogene) may just cause the cell to die, which isn't a bad thing (in fact, TSG such as p53 often work by inducing apoptosis because proliferative errors make them accumulute). A tumour only results when a single cell accumulates sufficient mutations and genomic damage to gain a reproductive advantage over the cells in its vicinity.

However, you are asking about cancer, which is not simply a tumour. Tumours are any sort of abnormal growth, i.e. neoplasms, but they can be benign! This means they stay in their tumour capsule, do not grow at a fast rate and do not invade or metastasise other tissues. The distinct characteristics that define a cancer are very well-known and were published in a well recognised paper by Weinberg & Hanahan, 2002, "The Hallmarks of Cancer".

The six primary hallmarks of cancer. The first two are the ones most people know, but the other ones are just as essential for

Independence from external growth signals: Cancer cells produce their on autocrine growth factors or have mutated signal pathways active without GF receptor stimulation (Oncogenes).
Resistance to anti-growth signals: Cancer cells do not respond to growth-inhibitory factors from outside or inside (Tumour suppressor genes).
Evasion of apoptosis: Cancer cells resist signals which cause normal cells to die (apoptose) (these are also tumour suppressor genes).
Limitless replication / Evasion of cell senescence: Apart from stem cells, all normal cells can only replicate their genome a certain number of times before the ends of the chromosomes known as telomeres are too short, disintegrate and cause the cell to enter senescence or die. Cancer cells express telomerase, which extends telomeres and maintains replicative potential.
Sustained angiogenesis: Tumours and cancers form massive cell heaps. Tumours may stall growth because blood vessels do not grow into the heap and supply the cells with the nutrients needed to proliferate. Cancer cells have found a way to induce blood vessel growth (VEGF) and sustain it in order to maintain nutrient supply.
Invasion and metastasis: This is the crucial, most distinguishing difference between benign neoplasm (tumour) and malign neoplasm (cancer). Cancer cells degrade the extracellular matrix around them (by secreting metallo-matrix-proteases, MMP), which allows them to move away from where they are and invade into neighbouring tissues. They can also spill into blood vessels this way (especially if the neoplasm is well-vascularised thanks to hallmark number 5), where they can travel to other sites in the body and grow new cancerous tumours in other locations.

There are four more emerging hallmarks and enabling characteristics (immune evasion, inflammation induction, modification of energy metabolism, genomic instability), which allow better cancer growth and make a cancer more dangerous if it acquires them, but these are outside the scope of this answer.


Can the body of any organism on Earth live without impairment both in vacuum, and within Earth's atmosphere? I know from reading that a human in vacuum needs a space-suit to survive.

Is the body of any organism on Earth capable of living equally in vacuum, and on/below Earth's surface within the atmosphere?

Remarkably, Tardigrades are multi-cellular animals which can survive the vacuum of space.


Is it possible to make a cancer cell that doesn’t encode any neoantigens? The cell still has mutations, but those mutations only occur in the noncoding sequences, such as promoters, which drives over expression of proto-oncogenes and downregulation of tumor suppressor genes. So the cell will proliferate uncontrollably, but won’t express any neoantigens.
Will such cell be invisible to our immune system?

Immunosurveillance of cancer cells is predicated upon multiple "signals" derived from the cancerous cells and their microenvironment.

I should point out tumor mutational load (Figure 1). A sort of take-home point here is that certain indications have less mutations and thus less neoantigens than others. You also have to take into consideration the stage of the tumor, though. Stage IV tumors have amassed more mutations than stage I/II.

Figure 1. Mutational prevalence by indication. A higher prevalence predicts a higher neoantigen frequency or mutational load for that cancer histology. (1, 2)

It's interesting to point out the bottom part of figure 1 where the authors of a separate review note for us where it's believed the disconnect between traditional checkpoint blockade immunotherapy and CAR-T immunotherapy exists. Just to educate a bit on the subject, checkpoint blockade targets T cells, the drivers of antigen-dependent cell killing. T cells naturally infiltrate the tumor as it develops and attempt to mount an attack. One of the methods tumors use to evade T cell killing is through persistent antigen, expression of inhibitory receptors and secretion of inhibitory molecules. Checkpoint blockade immunotherapy uses antibodies against the inhibitory receptors such as PD-1 (Opdivo, Keytruda), it's ligand PD-L1, CTLA-4 (Yervoy), Tim3, Lag3, and so forth. This attempts to lift the dampening effect these receptors have on T cells so that they may resume killing. The T-antigen-dependent paradigm is also supported by such publications which look at checkpoint blockade in the setting of clonal T cell diversity and confirm that (1) a diverse repertoire of T cell clones result in successful checkpoint blockade, and (2) enrichment of certain clonotypes within the repertoire, presumably the antigen-specific clonotypes, further indicates a response (3).

So below that are indications circled in red, notably the histologies with a low neoantigen frequency. The idea behind CAR T cells is that I can take advantage of T cell biology, notably that T cells recognize antigen with a receptor and kill the target cell. So just backing up to checkpoint blockade immunotherapy real quick, say a patient has melanoma which can consist of 1000s of mutations and 100s of neoantigens. There is a greater chance that an infiltrated T cell has specificity for any particular antigen. So how about a glioblastoma patient? They may have 10-20 neoantigens, or as you said they may have no neoantigens, at least none that their T cells are specific against. So checkpoint blockade may not be so effective. CAR stands for chimeric antigen receptor. It's essentially a monoclonal antibody against one target connected to a linker connected to the intracellular domain of a T cell receptor. Hematologic malignancies such as NHL like diffuse large B-cell lymphoma are commonly targeted for a B cell receptor known as CD19. So all you have to do is make your CAR CD19 specific and transfect the T cells with it in place of their own T cell receptor or TCR. So the basic process behind CAR is I isolate your T cells as with leukapheresis, lentivirally transfect with my anti-CD19 CAR, expand, and infuse. There are two CD19 CAR T products with great response rates on the market (Kymriah, YESCARTA). The whole reason these are good is because we can direct them to whatever antigen we want (of course be careful about self-antigens, see autoimmunity).

Figure 2. Schematic of CAR T cell therapy. (4)

The CAR T approach is in fact because the neoantigen load is low or non-existent, which is problematic for un-modified T cells, and thus problematic for standard-of-care treatments like checkpoint blockade.

As such, there are other ways, and other cells that can handle some of the abnormalities presented by tumors as a whole. This includes the presence of danger/damage-associated molecular patterns (DAMPs) and the regulation of surface receptors, for example, NK receptor ligands such as MIC.

The way DAMPs work is that a milieu of molecules are secreted by cells that are damaged or transformed, signaling cells of the innate immune system. One of the issues is that the DAMPs promote an inflammatory environment. This means that yes, you get immune cells checking out the situation, but that some of these are good immune cells and some are "bad" (myeloid-derived suppressor cells (MDSC), tumor-associated M2 macrophages (TAM), or T-regulatory cells (Treg)). These dampen the immune response both through inhibitory cytokine release like IL-10, and expression of inhibitory receptors like PD-L1.

Figure 5. The molecules secreted by the inflammatory tumor microenvironment both help and hurt the immune response. (5).

And then the idea behind NKR ligands is pretty straightforward: Natural killer (NK) cells patrol your body routinely for abnormalities and are licensed to kill cells that are abnormal. For example, all nucleated cells express class I major histocompatibility complex (MHC-I) on their surface. Some receptors like MIC are also present on the cell surface that engage receptors on the NK cells like NKG2D in distress. So what do cancers do? They sometimes express truncated and thus inactive MIC, express no MHC but also express inhibitory receptors to NK cells, and so forth.

Everything is summed nicely in the following figure on cancer immunoediting (Figure 7). Note that while things are working normally, the immune system can handle the tumor load. As the scales tip, and this could be for example, your T cell response edits out an immunoantigen but doesn't take care of the whole tumor, resulting in growth that those T cells no longer respond to. As this happens, the cancer becomes increasingly invasive.

Figure 7. Cancer immunoediting. (7).

So just to clarify at the end, there probably isn't a case where the immune system isn't responding at all unless you had chemotherapy that destroyed your immune system. Inflammatory environments alone are sufficient for your immune cells to at least check out the tumor. In fact, and I cant find the paper now but I'll try, investigators even found naïve T cells in the tumor microenvironment simply due to the inflammation. We could also get into "hot" and "cold" tumors, but that's out of scope here (take-home point, cold tumors aren't inflamed and are known to contain less immune infiltrate). I used immunotherapy as a vehicle to get my point across, note that this answer isn't about immunotherapy but rather about immune escape and mutational load theory.


Did Darwin explain why he believed that domestic dogs descend from several distinct species of ancestor? Charles Darwin begins his book Origin of the Species (1859), in which he argues that species evolve as a result of variations caused by natural selection, with a chapter about variations that have occurred not naturally but under domestication. There he writes

  I may, without here entering on any details, state that, from
  geographical and other considerations, I think it highly probable that
  our domestic dogs have descended from several wild species.

The ancestry of the subspecies Canis lupus familiaris is a controversial topic, but I have not found any papers which argue that it descends from several wild species. When the view is that the subspecies descends from two separately domesticated strands of ancestral wolf - East Eurasian and West Eurasian - the strands are not, as far as I am aware, referred to as separate species, but even if they were, two is not "several".

I appreciate that in a book on natural selection Darwin does not wish to spend more than a chapter on selection under domestication, but does he explain elsewhere his detailed reasons for his conclusion?

"Does (Darwin) explain elsewhere his detailed reasons for his conclusion?"

Yes. After Origin of the Species, he wrote a whole book, The Variation of Animals and Plants under Domestication (1868), which begins with Chapter 1.I on "Domestic Dogs and Cats".

He writes that "we shall probably never be able to ascertain their origin with certainty" and then gives detailed sources for both sides of the argument. It's Pallas against De Blainville.

  Firstly, the great difference between the several breeds; but this
  will appear of comparatively little weight, after we shall have seen
  how great are the differences between the several races of various
  domesticated animals which certainly have descended from a single
  parent-form. Secondly, the more important fact, that, at the most
  anciently known historical periods, several breeds of the dog existed,
  very unlike each other, and closely resembling or identical with
  breeds still alive (...)

  (A)t a period between four and five thousand years
  ago, various breeds, viz. pariah dogs, greyhounds, common hounds,
  mastiffs, house-dogs, lapdogs, and turnspits, existed, more or less
  closely resembling our present breeds (...)

  As long as man was believed to have existed on this earth only about
  6000 years, this fact of the great diversity of the breeds at so early
  a period was an argument of much weight that they had proceeded from
  several wild sources, for there would not have been sufficient time
  for their divergence and modification. But now that we know, from the
  discovery of flint tools embedded with the remains of extinct animals
  in districts which have since undergone great geographical changes,
  that man has existed for an incomparably longer period, and bearing in
  mind that the most barbarous nations possess domestic dogs, the
  argument from insufficient time falls away greatly in value (...)

  The existence of a single race, remarkably constant in form during the
  whole Neolithic period, is an interesting fact in contrast with what
  we see of the changes which the races underwent during the period of
  the successive Egyptian monuments, and in contrast with our existing
  dogs. The character of this animal during the Neolithic period, as
  given by Rutimeyer, supports De Blainville's view that our varieties
  have descended from an unknown and extinct form.

At this point it's not looking good for Pallas. But Darwin continues:

  (W)e should not forget that we know nothing with respect to the
  antiquity of man in the warmer parts of the world. The succession of
  the different kinds of dogs in Switzerland and Denmark is thought to
  be due to the immigration of conquering tribes bringing with them
  their dogs; and this view accords with the belief that different wild
  canine animals were domesticated in different regions (...)

  The main argument in favour of the several breeds of the dog being the
  descendants of distinct wild stocks, is their resemblance in various
  countries to distinct species still existing there.

Moreover,

  (s)everal canine species evince no strong repugnance or
  inability to breed under confinement; and the incapacity to breed
  under confinement is one of the commonest bars to domestication.
  Lastly, savages set the highest value (...) on dogs: even half-tamed
  animals are highly useful to
  them: the Indians of North America cross their half-wild dogs with
  wolves, and thus render them even wilder than before, but bolder: the
  savages of Guiana catch and partially tame and use the whelps of two
  wild species of Canis, as do the savages of Australia those of the
  wild Dingo. Mr. Philip King informs me that he once trained a wild
  Dingo puppy to drive cattle, and found it very useful. From these
  several considerations we see that there is no difficulty in believing
  that man might have domesticated various canine species in different
  countries. It would indeed have been a strange fact if one species
  alone had been domesticated throughout the world (...)

  If any wild canine species had distinctly exhibited the tan-coloured
  spots over the eyes, it might have been argued that this was the
  parent-form of nearly all our domestic races. But after looking at
  many coloured plates, and through the whole collection of skins in the
  British Museum, I can find no species thus marked. It is no doubt
  possible that some extinct species was thus coloured (...)

  The belief that our dogs are descended from wolves, jackals, South
  American Canidae, and other species, suggests a far more important
  difficulty. These animals in their undomesticated state, judging from
  a widely-spread analogy, would have been in some degree sterile if
  intercrossed; and such sterility will be admitted as almost certain by
  all those who believe that the lessened fertility of crossed forms is
  an infallible criterion of specific distinctness. Anyhow these animals
  keep distinct in the countries which they inhabit in common. On the
  other hand, all domestic dogs, which are here supposed to be descended
  from several distinct species, are, as far as is known, mutually
  fertile together (...)

  Pallas assumes (...) that a long course of domestication eliminates that
  sterility which the parent-species would have exhibited if only lately
  captured; no distinct facts are recorded in support of this
  hypothesis; but the evidence seems to me so strong (independently of
  the evidence derived from other domesticated animals) in favour of our
  domestic dogs having descended from several wild stocks, that I am
  inclined to admit the truth of this hypothesis.

  There is another and closely allied difficulty consequent on the
  doctrine of the descent of our domestic dogs from several wild
  species, namely, that they do not seem to be perfectly fertile with
  their supposed parents. But the experiment has not been quite fairly
  tried; the Hungarian dog, for instance, which in external appearance
  so closely resembles the European wolf, ought to be crossed with this
  wolf: and the pariah dogs of India with Indian wolves and jackals; and
  so in other cases. That the sterility is very slight between certain
  dogs and wolves and other Canidae is shown by savages taking the
  trouble to cross them.

Concluding:

  Notwithstanding the difficulties in regard to fertility given in the
  last two paragraphs, when we reflect on the inherent improbability of
  man having domesticated throughout the world one single species alone
  of so widely distributed, so easily tamed, and so useful a group as
  the Canidae; when we reflect on the extreme antiquity of the different
  breeds; and especially when we reflect on the close similarity, both
  in external structure and habits, between the domestic dogs of various
  countries and the wild species still inhabiting these same countries,
  the balance of evidence is strongly in favour of the multiple origin
  of our dogs.

In short the main support for multispecific origin is that different breeds of the domestic dog, differing from each other in many physical respects, are very ancient and they are similar to wild species in the same geographical areas.


PCR and Semiconservative replication Why does PCR use heat as opposed to helicase like in semi-conservative replication in order to separate the double DNA strand?

Simply because it is ways more practical and there is no need to use a helicase. Heating is fast and convenient and denaturation is reversible. Also all the DNA is denaturated, so afterwards, primers can bind to their target sites, setting up the start point of the polymerase.

If you want to do this with and helicase, you need to make sure that you have a heat stable polymerase (at least at 72°C), you need to have the right places on the DNA unpackaged and finally, you need two enzymes in the reaction (which is more expensive than just having one).


Are unilaterally deaf people able to determine where sound comes from? My question is on people deafened in one ear, but normal hearing in the other.

Time and level differences between the two ears are only part of how the human body can localize the source of the sound. So what other factors are there and are they enough to help accurately determine the location of the sound for unilaterally deaf people ?

From what I could gather, there is a decent amount of variability in the ability to detect which direction sound is coming from in unilateral hearing impaired people. It would appear that some people have severely impaired localization skills, akin to someone with an earplug in one ear, but others can use their monaural hearing cues to better locate sound.

Monaural cues seem to be based on the structure of the outer ear as well as how the sound bounces off of the head and shoulders.

http://www.sciencedirect.com/science/article/pii/0378595594900531

http://en.wikipedia.org/wiki/Sound_localization#Monaural_cues


Why don't the heads of phospholipid bilayers repel hydrophobic molecules? What I Think I Know: Hydrophilic and hydrophobic things repel each other. Since the cell membrane contains hydrophobic tails, it is difficult for hydrophilic molecules to pass through the cell membrane.

Question: Why don't the heads of phospholipid bilayers repel hydrophobic molecules? In other words, if the phospholipid membrane has both hydrophilic and hydrophobic portions, why do only the hydrophobic portions act as repellents?

Stipulation: I need a quotation from a textbook, university, or other credible source.

Evidence of Prior Research:

Why lipophilic molecules can pass phospholipid bilayer, in spite of 2 hydrophilic layers?: This question has a comment that links a graph from a textbook. I can't understand the graph by itself. There are no other references.

Understanding what passes through and doesn't pass through the plasma membrane: All references discuss the topic, but none answer the question.

I understand that this topic is addressed quite frequently, but the question I'm asking is never answered. Texts tend to say something like, "Ions can't get through the core because of their charge" and completely gloss over the concept of lipids getting through the heads. Please don't dismiss this as a homework question that I didn't take the time to research. This is my second try asking this question (on this site); I have spent hours trying to find an answer.

Your question is rooted in a misundertsanding of the hydrophobic effect. Hydrophillic and hydrophobic molecules do not repel but, rather, attract one another through van der Waals interactions. The tendency of hydrophobic molecules to aggregate in aqueous solution (ie the hydrophobic effect) is, instead of some repulsive force, actually driven entropically. I don’t think I will go into this in detail since it has been explained well in many places. That said, it is also explained very poorly in many places (which I suspect you have encountered). I recommend this website to learn about it and other intermolecular interactions.

Once you have a firm grasp on that, consider that in order for a hydrophobic molecule to reach a plasma membrane, it must already be solvated by water. The transfer of a hydrophobe from one hydrophillic environment (water) to another (head groups of the phospholipids in the plasma membrane) should be energetically negligible. The limiting step for passive diffusion across a membrane is transfer from the hydrophillic environment of the phospholipid head groups to the hydrophobic environment of their tails. In fact, the rate of diffusion across a plasma membrane increases with hydrophobicity.


Is there any relationship between heartbeat rate and life span of an animal? Is there any relationship between heartbeat rate and life span of an animal?

Do they belong to a cause-and-effect relationship or are they both caused by some phenomenons or a common cause?

Interestingly there is a inverse negative correlation between heart rate and life span, meaning the faster your heart rate is, the shorter is your lifespan. See this figure (from the paper 2 cited below):

When the authors plotted the approximately total heartbeats vs. the lifespan, the amount of total heartbeats was in a pretty narrow corridor:

So it seems that at least the hearts in mammals have a maximum number of strokes they could do. The obvious question what causes this phenomenon is not really answered.
Since the metabolism of small animals is (compared to their weight) higher and also their oxygen consumption is higher because of that, it is hypothesized that this causes more reactive oxygen species and related damage which subsequently leads to an earlier death.

See the references for more details:

Rest heart rate and life expectancy.
Heart rate, lifespan, and mortality risk
Oxidative damage to DNA: relation to species metabolic rate and life
span


Are there known downsides to removing UV mutation hotspots to prevent some skin cancers (Genetic sunblock)? Khavari et al. recently demonstrated that a significant fraction of  one of the major forms of skin cancer (cutaneous squamous cell carcinomas) are associated with a mutated KNSTRN gene (a protein associated with the kinetochore). They identify a specific region of the gene as being a hotspot for UV induced mutation and suggest that these mutations may be an early event in the development of this type of skin cancer.(1)

Abstract from their nature paper (paywalled):

  Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo. These findings suggest a role for KNSTRN mutagenesis in SCC development.(2)

My question:
Scientists could theoretically alter the nucleotide sequence of the KNSTRN gene to remove the mutation hotspot, potentially lowering the incidence of this type of skin cancer. But are there any downsides to doing so? Are there any cases where a UV mutatable hotspot has shown to have some useful function in a cell or organism?

Thanks!

http://www.sciencedaily.com/releases/2014/09/140907181722.htm
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3091.html

Short-wave UV light (UVB and UVC) causes transition mutations at dipyrmidine sequences (ref.). In the work presented on KNSTRN quoted by the OP the authors report that 19 from a panel of 100 squamous cell carcinomas (SCC) contained a mutation in KNSTRN (and furthermore three of these contained no other mutation across the six genes that were analysed (Fig. 1b)). Normalising for ORF length this makes it the 3rd most recurrent mutated gene. It would seem therefore that it a fairly important mutagenic target. In a broadened set of SCCs they found a total of 29 KSTRN mutations, and of these 13 were Ser24Phe (TCC>TTC) mutations, which they refer to as a 'hotspot'.
Accepting the arguments in the answer from @Chris it is still interesting to consider how one might remove such a hotspot. The normal amino acid at this position is a serine. Here is the human codon useage for ser, obtained from here:

TCT 14.6%
TCC 22.0%
TCA 15.0%
TCG  6.0%
AGT 11.9%
AGC 19.4%

It would seem therefore that it would be theoretically possible to edit the Ser24 codon from the UV-sensitive TCC to AGC, essentially eliminating this 'hotspot'.
This, of course, doesn't answer the question - are there downsides to this? I already selected a synonymous codon with a similar frequency of useage so that shouldn't be a problem. However here is an example of a synonymous codon substitution which has an effect upon splicing of the LMNA gene resulting in muscular dystrophy, and the paper cites several other examples of this. (I haven't actually checked to see where the Ser24 codon lies in relation the exon-intron boundaries in the KNSTRN gene.) No doubt there are other mechanisms by which my proposed edit could have unwanted effects. It would have to be tested carefully, and so we come back around to a cost-benefit analysis - would it be worth developing this editing idea (even if it were feasible as a therapy) given that there are clearly many paths to SCC not involving this specific mutation.


Like Mother Cape Buffalo,do remaining mammal mother species also try to protect their babies from being eaten by predative animals? Some statistics say that on earth there are approximately 5500 mammal species.I have seen a video of Mother Cape Buffalo protecting it's calf from being eaten by predative animals.Like Mother Cape Buffalo,do remaining mammal mother species also try to protect their babies from being eaten by predative animals?

There is quite a bit of evidence showing that mothers of a number of mammalian species will sometimes kill and eat their own young.  E.g. https://www.nationalgeographic.com/news/2014/3/140328-sloth-bear-zoo-infanticide-chimps-bonobos-animals/


Could hydrogen replace oxygen in cellular respiration? I was wondering what oxygen actually does in the body. I have seen a few answers to other questions that involve the electron chain and I am really not sure what that is. So I was wondering what oxygen does and could hydrogen do the same thing as a substitute?

No, hydrogen could not replace oxygen because it has entirely different characteristics. The most important one is probably its electronegativity - oxygen 'pulls' electrons much 'stronger' than hydrogen.

Basics: Reduction potential

Oxygen is the so-called terminal electron acceptor of the electron transport chain in eukaryotes. You can see "reduction potential" as a kind of stored "energy" which molecules have, similar to the power stored in batteries (very similar actually). To make this text a bit shorter I'll call it "RP" from now on.

One maybe confusing detail is that a substance with low RP has "more energy" than a substance with high RP, so it is the opposite way of thinking.

In very generalised terms, metabolism means that molecules with a low RP (glucose) are oxidised (burned) and turn into molecules with much higher RP (CO2). Coupled with this, a different molecule with very high RP (oxygen) is reduced and becomes a molecule with slightly lower RP (H2O). (You may have heard this before - it's called a redox reaction.) *

The important part is that the RP "released" by the oxidisation (burning) is larger than the RP "taken up" by the reduction. The surplus leaves as energy - heat and light if you just burn the glucose. This is a spontaneous process, meaning it will occur just by itself - even if it takes a long time if nobody drops a match on it.

The idea of metabolism is to let that process happen - but use as much of the energy it releases as possible. This works by not just letting it burn, but intercepting that burning process at different stages so that at each step a bit of the RP can be taken off and stored in something else. This "something else" is NAD which I'm sure you've encountered before. Each step that glucose is burned down, another bit of NADH is made, which then has a respectable reduction potential.

NADH (leaving out NADPH here which is a bit different) is channeled into a process called oxidative phosphorylation which retrieves the reduction potential in an actual form of energy.

Basics: Terminal electron acceptor

Finally, the reduction potential I've been talking about all the time is really just electrons, involved in bonds which are "happy" to react. Passing down the reduction potential as I've explained is really a passing down of electrons into more and more stable, less reactive bonds. That's why it's called "electron transport chain". At the end of oxidative phosphorylation, those electrons are dropped onto O2 and make it into H2O. That's why O2 is called the "terminal electron acceptor".

Why Hydrogen can't replace Oxygen

Now to come back to why hydrogen cannot perform oxygen's function in our body. We use glucose as our source of reduction power and oxygen as our terminal electron acceptor. O has a high electronegativity (3.5) so it pulls electrons strongly towards it. H's electronegativity is only 2.1, so it's much weaker. O as a terminal electron acceptor works because it pulls them much stronger than H when they bond, so an O-H bond is almost like giving oxygen an electron. In order for hydrogen gas (H2) to perform the same function, it would need to be possible to drop electrons onto hydrogen in a bond where it pulls them much stronger than the other partner. They do exist, and such compounds are called hydrides. But the catch is: unlike H2O, these are normally strong reducing agents, meaning that hydrogen would rather not be in that bond. This not a feasible option for cell respiration, at least in humans, because it requires a lot of RP input. Making oxygen into H2O does not require a lot, it's a very cheap electron acceptor.

I hope I was able to put this in understandable terms. Let me know if I need to clarify anything.

--

*It works with other molecules than glucose->CO2 / O2->H2O too, many prokaryotes do that and in fact that's how batteries work


Why don't intelligent animals like primates use plastic bags? I'll be honest here. Although this is a serious question, what made me wonder about it is this comic from Wumo:

This question is not specific to monkeys. It applies to animals that live with or sufficiently close to human dwellings and would be able to observe our habits daily. I'm not referring to training animals.
Even among animals that have an opposable thumb like ours but different HAR regions, the use of tools seems to be too primitive. Chimps have been known to re-use tools and even cumulative cultural evolution is documented. Whales have been hypothesized to have high intelligence (although not necessarily) due to larger brains containing more spindle neurons. But I couldn't find any info on whether whales use tools (Dolphins are said to use sponges though).

On considering if mirror neurons were helping chimps copy each other and use tools, I found that the very existence of mirror neurons in humans is under question.

So if a chimp can use simple tools, what prevents them from looking at us and imitating our use of something as simple as using a plastic bag or a crude tray to carry a bunch of fruits? Is there a gradation of complexity of tool use that various brains can process? A reason that no matter what happens, a chimp would not be able to imitate our use of tools? Could this be compared to how aged people are unable to learn how to use a smartphone or computer no matter how many times it is explained to them (or even how young people fail to understand pointers and recursion)? Perhaps the ability is related to an animal's capability to form new neural connections of a certain type?

Training an animal like Jack the baboon is different from what I'm asking.

Some examples of primates trying to carry many fruits.

Bags are not that useful if your are not human.

Most primates are too small to get any benefit from it, the bags are too large and would drag on the ground or get snagged on branches, even chimps and gorilla don't have enough ground clearance to not have this problem. Primates have been known to play with plastic bags, but they would not provide much benefit. A primate would need to carry the bag around for hours to fill it and wait before they could eat anything from it, all the while dragging it and hoping it did not tear. Upright humans are the only primate built to carry things long distance, a bag would not help other primates much.

Most primates are frugivores, carrying around extra fruit is not actually very helpful, most primates live near their food sources. Not to mention getting fruit in a tree into a bag is rather difficult task. Carrying around fruit is not very helpful because many primates have a different and much better way of storing ripe fruit in other primates AKA food sharing. Most primates will call other primates of the same species to ripe fruit since sharing in this way means they are more likely to have other primates share with them, thats far better food security than carrying around some extra fruit. It is also a lot easier to call many others to you than carry enough for everyone else.

The primates in your pictures are zoo primates which are both extremely bored and often very anti-social due to being raised in isolation. They might get some benefit, but they are not going to do well in the wild, and no zoo in its right mind is going to give its animals plastic bags.


System biology and evolution: Book-recommendations I have relatively good knowledge in evolutionary biology and in population genetics. I am getting more and more interested in the evolution of ...

genetic developmental processes
gene interactions
gene expression
plasticity
intrinsic or cellular noise
mutational robustness

It seems that i am getting increasingly interested in a field that is in between population genetics and system biology. I know very little about system biology.

Can you please give me some recommendations for books (and other readings such as reviews) that talk about the evolution of those processes that are usually studied by system biologists? I am much more interested in a book that presents concepts and methods than a book listing empirical observations. Also, I am not interested in medicine but in biology.

Here there are a couple that I own:

The "classic" from Uri Alon touches many of the topics you mention. It is easy to read and goes relatively deep into the methods. There seems to be a new edition (if you search it in Amazon it will pop up), but it was planned for last year's April and then delayed so no so clear when will be actually published. For the original one: Amazon link

Title: An Introduction to Systems Biology: Design Principles of Biological Circuits
Year: 2006
Author: Uri Alon
Publisher: Chapman & Hall/CRC Mathematical and Computational Biology

The other book is this textbook "Systems biology" by  Edda Klipp and others. I attended a talk by Edda Klipp two years ago and she seems to be doing interesting things. This book is more general, covering, somewhat superficially, many topics. It can be good to get a general idea on the field. Amazon link.

Title: Systems Biology Paperback
Year: 2009
Author: Edda Klipp, Wolfram Liebermeister, Christoph Wierling, Axel Kowald, Hans Lehrach, Ralf Herwig
Publisher: Wiley-Blackwell

There are many others (see Amazon results here). Maybe other members can comment on some of the other titles.


Hypersensitivity Simultaneously in Ear canals I got experimental data where hypersensitivity (i.e. tonic pain when touching ear canal) was recognised for about 100 minutes.

I do not know which type of hypersensitivity is this one.
IgM can reach ear canal, I think (not sure) - it is just in the limit.
If IgM cannot reach ear canal, then the hypersensitivity must be caused by

humoral immune system

which is responding slowly to the trigger.

It is proposed that this cannot be contact dermatitis because

the reaction happened simultaneously in both ear canals

after irritating ear canals with plastic the subject is not allergic.
Irritation was also a selected signal which resulted in the dynamic cycle of bass music by Beats earphones.
It was studied the effect of the specific signal with bass music on the movement on the inner membrane on the subject with problem in maintaining the inner physiology of ear itself (also repeated cycle of ear infections during childhood).

Can IgM reach ear canal?

The hypersensitivity was simultaneous in both ear canals.
I did not know before that you can get hypersensitivity reaction in ear canals and also simultaneously.
I think hypersensitivity is not in normal condition.
There must be some etiological factors (probably neuronal) that can cause it.

There are other organs which can have hypersensitivity too.
So I started to think what is the trigger of hypersensitivity.

My conjecture is about Secreted substances of endothelium (EDRF, EDCF).
There are three types of substances secreted by the endothelium

NO
Endothelium hyperpolarising factors
Endothelins

NO is the most important one.
But what is its role in the hypersensitivity of ear canal is unknown to me.

What is the mechanism of hypersensitivity of our body and particularly in the ear canal?

This answer is based on embryological studies and is limited.
I will extend it later when understand better.

Sensory areas

maculae acusticae - walls of utricle and saccule (this most probable area)
cristae acusticae - change in body position

Nerve

vestibular fibers of cranial nerve VIII (TODO each branchial arch has a nerve - how these differentiate between different arches?)

Embryonal Ganglion

statoacoustic (spinal) ganglion (19.5 C Fig)

Embryonal ganglion splits into two

cochlear portion
vestibular portion

which supply sensory cells of organ of Corti, and those of the saccule, utricle and semicircular canals, respectively

Branchial Arches

Each arch has a vessel, cartilage and nerve.
The task is to understand which part of embryonal ear is able to start hypersensitivity reaction.

Middle ear

Tympanic Cavity and Auditory Tube

origin endoderm (1st pharyngeal pouch) - malleus and incus
malleus - 2nd a.a.a.

Eardrum or Tympanic Membrane

ectodermal epithelial lining at bottom of auditory meatus
endodermal epithelial lining of the tympanic cavity
intermediate layer of connective tissue (See Langmans' Fig 19.9B). TODO this part is superficially covered in Langmans.

Auricle

6 mesenchymal proliferations at dorsal ends of 1-2 a.a.a.

TODO I must look again embryonal slides of ear to see where the nerves occur first and how they develop.

Sources

Langmans Medical Embryology, 12th ed, 2011
My notes of Embryology classes, Spring 2014 (I did not have all my notes now so must study these things again after holiday)


Why do some grasshoppers have a black exoskeleton? What species of grasshoppers have black exoskeletons? Is there a scientific difference in species between field crickets and grasshoppers?

Field crickets are rather distinct from grasshoppers. Although both groups are in the Order Orthoptera, grasshoppers are insects of the suborder Caelifera and field crickets are in the family Gryllidae of the suborder Ensifera.

For a discussion on insect coloraiton, see here.

If you'd like a specific species ID, please provide more information as requested in the comments.

Generally, field crickets are black, red or brown in color.

However, some species of grasshoppers are likewise black:

For example: Romalea species such as R. microptera and dark nymphs and morphs of R. guttata

Finally, here is a simple checklist of some typical differences between grasshoppers and crickets.


Is this basic gene diagram correctly labeled? I keep seeing this gene diagram, and I am not sure how to interpret it. I don't know what this diagram is called or where it was first depicted, but in the second picture, I have labeled it with what I think are the correct regions.

Unlabeled

Labeled

If the labels are correct, does this mean that an open reading frame (and consequently, the CDS) does not have to begin at exon 1?
If the labels are not correct, could you make some suggestions on how to fix the mistakes or point me towards some resource for interpreting this diagram?

My professor got back to me and said my diagram is correct -- and that allows me to answer my second question: an ORF does not have to begin in the first exon.

(The UCSC Genome Browser uses a similar format to display genes.)


Advantages of bisexual reproduction over asexual one toward species promotion? Are there any advantages of bisexual reproduction over asexual one towards species conservation and promotion? Do animals that have two or more sexes have more chances to reproduce?
Does anybody had a quantitative account of this fact?

Those are very good questions. Unfortunately answers are not easy and ask for writing a lot! But maybe someone else will give it a try and make it better than I can. Note that the evolution of recombination and of sexual reproduction are not quite the same thing. Also, evolution of sexual reproduction is not the same than evolution from various reproductive system. Finally there are also questions concerning the evolution of sexual determination system. You might have more chance to get useful answers  by splitting up your question and to ask for evolution between different reproductive system. Hermaphroditism vs Bisexual reproduction. Asexual vs sexual. And finally on another post you may add the "conservation" part of your question.

What do you mean "animals that have two or more sexes"? Do you mean hermaphrodites?

You may have a look to other posts on this sites that discuss the question. I don't think there is one post yet that really goes in depth though.

I think that would be great if someone could post an easy-to-read source of information on the subject. Here is one but it is in french only. This presentation by Sally Otto will probably interests you.

Some hints in very short: One issue with hermaphroditism is selfing and its associated concept inbreeding depression. For conservation purposes, note that if one beneficial mutation occurs (at any locus) before another beneficial mutation had time to reach fixation, then  the frequency of one of the two beneficial mutations will necessarily goes to zero. You may be interested in the two-fold cost of sex. Müller's ratchet is also a concept you may want to learn about. There are several very interesting quantitative models on the subject and it is still an ongoing debate. You may be interested in the work of S. Otto and B.& D. Charlesworth. You may be interested in E. Charnov's book although it is a bit old now.


What does "cellular" mean in this context? I came across a confusing word when I was reading a Scientific American story, “Controversial Spewed Iron Experiment Succeeds as Carbon Sink” (by David Biello). It goes like this:

  “One key to the whole experiment’s success turns out to be the
  specific diatoms involved, which use silicon to make their shells and
  tend to form long strands of cellular slime after their demise that
  falls quickly to the seafloor.”

I'm wondering what “cellular” means in this context. Does it mean “of (diatom) cells” or “porous”?

Could someone kindly enlighten me on this?

My understanding is that the slime in question is formed of the bodies (the cells) of the dead diatoms. Where does porous come into it? Is it mentioned in a previous sentence?


If a cell has two different GPCRs, how does the cell differentiate between the phosphorylation cascade caused by each? In my biochem course, we learned that GPCR receptors trigger a phosphorylation cascade, with the end result being a large amplification of the signal in the form of cAMP. We never studied any particular GPCR individually, but we were told that GPCRs always end in the formation of a large amount of cAMP, which will go on to phosphorylate key targets that achieve the end result.

My question is as follows: If there are two GPCRs on the same cell membrane (let's say GPCR-A and GPCR-B triggered by substrates A and B respectively), how does the cell "know" which GPCR triggered the phosphorylation cascade if the end result is the same (large amount of cAMP). In theory, couldn't substrate B bind to GPCR-B and cause a phosphorylation cascade identical to that of GPCR-A, thus triggering GPCR-A's cellular response?

Is there some deeper specialization/uniqueness to each type of GPCR receptor that we didn't cover in my course? Does each GPCR produce a slightly different cascade that ends in something similar, but not exactly cAMP? Or is there some restriction, like each cell limited to only one GPCR (I would find this surprising, if this is the case)?

First, it would be an oversimplification to say that GPCRs act only through increases in cytosolic cAMP. This is true for receptors coupled to Gs proteins, but there are other G proteins like Gi, Go and Gq which act differently [1].

Now, a cell can have receptors coupled to many different G proteins. Vascular smooth muscle, for instance, has Gs, Gi and Gq-coupled receptors [2]. Further, a cell can have different receptors coupling to G proteins of the same type (e.g., hepatocytes have glucagon and beta adrenergic receptors [3], which both couple to Gs).

In such situations, the effects of different hormones add up. The final effect is a function of the total cytosolic concentration of second messenger (e.g., cAMP). Thus glycogen breakdown in a hepatocyte depends on the overall effects of glucagon and epinephrine [3]. The hepatocyte has no way of 'knowing' which cAMP molecule was formed by which hormone.

References

https://en.wikipedia.org/wiki/Heterotrimeric_G_protein
https://cvphysiology.com/Blood%20Pressure/BP026
https://www.nature.com/articles/emm2015122


Is it true that bees and wasps don't sting if struck by hand while they are in flight? Is it true that wasps don't sting if struck by hand while flying? I know of one person who claims to have done this at least 20 times and has never been stung. And out of curiosity (not that I'd want to kill them), what about bees?

I can confirm that I have often enough slapped a wasp or bee in flight without being stung. The reason is probably pure chance.

It is kind of like asking if a human can bite when slapped. If I come up to you and slap you, fast and hard, you will probably not be able to bite my hand because of surprise and the blinding speed with which I hit you. If, however, you happen to be talking to me and have your mouth open at the time, you might be able to pull off a quick bite.

In a similar vein, if I happen to swap a wasp (no anagram intended) and hit it on the sting, I will probably be stung. If I hit it on the side and move fast enough, I doubt it will have the time to reorient itself and sting me before my hand is gone.


What physics knowledge can be applied to biology of organisms and ecosystems? In the wiki page of Biophysics:

  Biophysics spans all scales of biological organization, from the molecular scale to whole organisms and ecosystems.

But after searching on the internet; the dominant application of physics in biology that I see is at the molecular scale. In the wiki page Mathematical biophysics, there is a lot of interesting information, but it is only about mathematical knowledge applied to biophysics, not physics itself.

What, if any, physics knowledge (based on principles and laws of physics) can be applied to biology in the sense of organisms and ecosystems?

This question is really asking for examples, and the list of ways that knowledge of physics can be used in biology could be very long. However, here are a couple of examples:

Systems ecology, especially with regard to energy and nutrient flow.
This type of ecology can be strongly influenced by physics. For one example see the book Theoretical Ecosystem Ecology: Understanding Element Cycles by Ågren & Bosatta (Ågren was originally a physicist)
Physical limitations to growth and transport
This can include for instance mechanical contraints on plant growth (see e.g. the book Plant Physics by Nicklas & Spatz), water transport in trees (see e.g. this BioSE question) or the biomechanics of movement (see e.g. Hudson et al (2012) on the speed and movement of cheetahs or Wikipedia: Biomechanics).
Allometric relationships between organisms, e.g. with regard to metabolism
To explain these types of relationships knowledge in physics is useful. See e.g. Kleiber's law for more.
MAXENT as a general approach to ecological patterns or to model species distributions
This is basically a tool lifted from physics that can be applied to ecological problems. There are many papers to look at, but Harte & Newman (2014) (Harte is another previous physicist) and Elith et al (2010) are two good starting points.
Dynamical modelling of populations and communities
This field use many of the same tools for analysis as physics, e.g. systems of differential equations. One of the pioneers in this field (among many) were Robert May (also started with a PhD in physics), and his classical book Theoretical Ecology: Principles and Applications is still a good starting point.
Energy harnessing and conversion by organisms
This can refer both to how organsims convert prey to energy (e.g. conversion efficiencies) and the physics of photosynthesis (which is an interesting intersection between physics and molecular biology). See Jang et al (2004) and O'Reilly & Olaya-Castro (2013) for examples of the how quantum mechanics can inform us about photosynthesis.

Hopefully this will give you a sense of some different ways that knowledge in physics can be useful for biology.


How does the immune system fight scabies mites? After a distressing episode involving my elderly mother and a nursing home, I've been reading up on scabies. It seems that in healthy people, the immune system limits the mite population to around 10 of the creatures at any one time; elderly and immunocompromised people can be infested by many more - thousands, even millions of mites (shudder).

So my question is, given that the mites burrow in the top, dead, layer of the skin, how does the immune system detect them and suppress them at all?
Conversely, if the immune system can limit the mite population so effectively, why doesn't it wipe them out entirely?

Found from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535073/

In addition to being a physical barrier, the skin is an immunological barrier63. The skin immune response is vital in wounding and infection and also modulates the commensal microbiota that colonizes the skin. Keratinocytes continuously sample the microbiota colonizing the skin surface through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), mannose receptors and the NOD-like receptors. These receptors recognize pathogen-associated molecular patterns (PAMPs) including flagellin and nucleic acids, as well as lipopolysaccharide from Gram-negative bacteria, mannan and zymosin from fungal cell walls, and peptidoglycan and lipoteichoic acid from Gram-positive bacteria. The activation of keratinocyte PRRs by PAMPs immediately initiates the innate immune response, resulting in the secretion of antimicrobial peptides (AMPs), cytokines and chemokines. Beyond effecting an adaptive immune response, AMPs also directly kill bacteria, fungi and enveloped viruses64. Therefore, there is a constant interplay among keratinocytes, immune cells and microorganisms that is modulated by AMPs, cytokines, chemokines and microbial peptides.

While mites certainly are not fungal, viral, or bacterial, you can extrapolate the mechanisms required to prevent mite infestation being similar to those referenced above. Hope this helps!


Height prediction based on genetics My height, as predicted by my genetics, is 156 cm whereas my actual height is 172 cm. What could be the reasons for this substantial discrepancy? Does it just mean I had very good nutrition as a child?

Sources of phenotypic variance

There is phenotypic variance in height in the human population. This phenotypic variance is in part explained by genetic variation, but there are also non-genetic variations, incl environmental variation (what you eat, your physical activity among many other things). See this post for more information.

Sampling error

On top of that, those measures of "genetic height" are based upon a limited number of SNPs and a limited number of individuals sampled. There is therefore a bit of room for a little bit of sampling error here. Note sampling error is not a mistake. It is just the fact that parameters estimated from a sample don't necessarily match perfectly the population parameters.

Training data set

Finally, the estimate is based upon correlation made from previous people. There might have a generational gap in height, typically present in countries that have recently largely changed their diets, such as many Asian countries.

For all of the above reasons, there might have a gap between your actual height and what has been predicted by some genetic testing. In short, yes your nutrition might part of the reason for this gap.


Where did the nondisjunction occur? A father with gene AC has a child with gene ACC. Where did the nondisjunction occur? (Meiosis I, Meiosis II, none of the above)

I do not know because both Meiosis I and II have the possibility of producing gametes with n+1. Is there something I'm missing here?

Think about what gametes the father could have given the child. If the mother contributed an "A", then the father gave two "C"s, if the mother contributed a "C" then the father contributed an "A" and a "C".

In meiosis I, the father's chromosomes duplicate, so he has AA and CC - normally, at the end of meiosis I, these would be pulled into separate cells, so one of the resulting cells would be AA (and then in meiosis II, split into two further cells both with one "A") and CC (which in meiosis II splits into two further cells both with one "C"). The final result would be four gametes (sperm cells), two with "A"s and two with "C"s.

Since this is tagged "homework" I'm not going to give the final answer - but think about what phase of meiosis would have to go wrong to create an "AC" sperm, and what phase of meiosis would have to go wrong to create a "CC" sperm.


evolution of advanced math ability I am trying to convince a friend that human beings evolved from primates, and he challenged me that advanced mathematical ability couldn't have been the product of mutation and natural selection because this ability wouldn't have conferred any reproductive advantage until the last few hundred years, and the process of mutation and natural selection would have taken much longer than this to produce the extensive genetic basis of advanced mathematical ability. How do we refute this?

Just to avoid misunderstandings
Just to avoid potential misunderstandings on your side, I wanted to talk about the saying that

human [are] evolved from primates

Humans are primates, so did our common ancestor with other primates.
Our ancestors are different from modern day primates. Chimps for example (which are great apes, like us) are not our ancestor more than we are their ancestors. We just share a common ancestor (who lived about 13 millions years ago).

Spandrel, exaptation and panselectionist arguments
Your are doing two mistakes. 1) The mistake of the spandrel (named after the title of the famous and old paper Gould and Lewontin (1979)) and the exaptation and 2) a panselectionist mistake.
1. Spandrel and exaptation
Spandrel

In evolutionary biology, a spandrel is a phenotypic characteristic that is a byproduct of the evolution of some other characteristic, rather than a direct product of adaptive selection

See also What is the “Spandrels” debate about?.
Exaptation

Exaptation [..] describe[s] a shift in the function of a trait during evolution.

While the existence of a spandrel in an evolutionary process does not necessarily cause the existence of an exaptation, but I will not go into these semantics details for simplicity.
Consider for example the two following wrong statements.

Birds have feathers to fly. It is impossible that birds evolved feather to fly because early feathers would have served no purpose to flight.

Bird feather actually probably first evolved for temperature regulation. Once this was done feathers were an exaptation for early flying tools.

Humans have nose to wear glasses. It is impossible that nose would have evolved because there was no glasses before

Noses evolved for another purpose and happen to be an exaptation for wearing glasses.

Humans have a big brain for advanced mathematical skills. It is impossible that humans evolved such big brains as such mathematical skills were useless in a time where we did not invent/discover much of the most basic math concept yet.

Humans evolved a big brain, mainly for social reasons incl. social hunting and social communication and probably because it was/is under sexual selection (see wikipedia > evolution of human intelligence). It just happen that logical reasoning, abstract thinking and other cognitive skills are an exaptation for advanced math skills.
2. Panselectionist view of evolution
I just want to highlight that there is much more to evolution than just mutations and natural selection. Not every trait has been selected for (otherwise we would not have any genetic disease).
On this subject, you might want to have a look at the paragraph Did you say Natural Selection? of this answer to Why don't mammals have more than 4 limbs? and to Why do some bad traits evolve, and good ones don't?


For how long can influenza survive on a piece of paper? Consider the following hypothetical: A graduate student would like to return a set of assignments before a certain deadline, but she currently has the flu and may sneeze or cough while grading the papers at home. Under the assumption that she has just graded the papers but is still in possession of them, how long should she wait before returning them to the students? At what point does the risk of transmitting the flu to a student via paper become negligible?

Perhaps just eight to 12 hours.

  Both influenza A and B viruses survived for 24-48 hr on hard, nonporous surfaces such as stainless steel and plastic but survived for less than 8-12 hr on cloth, paper, and tissues. Measurable quantities of influenza A virus were transferred from stainless steel surfaces to hands for 24 hr and from tissues to hands for up to 15 min.

--Survival of influenza viruses on environmental surfaces.

Or, perhaps, up to 17 days, when in the presence of "respiratory mucus" (i.e. snot), although even then a couple days was more plausible. Note that this was on Swiss banknotes, which isn't standard paper.

  Influenza A viruses tested by cell culture survived up to 3 days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase in survival time (up to 17 days)....  When nasopharyngeal secretions of naturally infected children were used, influenza virus survived for at least 48 h in one-third of the cases.

-- Survival of influenza virus on banknotes.


Is the variance of a trait related to its rate of evolution? Posed with a question that has me stuck:

  Is increased variance of a phenotypic trait in a population associated with slower evolution of that trait?

I have to either 'disagree or agree' and argue my point. And I disagree. For this question, I think that if the variance of phenotypic trait has a genetic basis (additive genetic variance =/= 0) then increased additive genetic variance should speed up it's evolution. The greater the additive genetic variance, the greater the response to selection in the next generation. So increased additive genetic variance should increase the rate of evolution of that trait.

However, at the same time, if there is variation in a phenotypic trait but it does not have a genetic basis (narrow sense heritability is zero) and the basis for variation is due to an environmental, dominance, or interactive effect, then increased variation would have no effect in the rate of evolution. Or so I think. I'm not too sure how the rate of evolution would be affected in the case of a non-genetic basis of variation.

The question can be understood in different ways
Causality
I think the question is a bit unclear in using the term associated in terms of what is being causal. Is the interest to understand how do processes that affect speed of evolution also affect phenotypic variance or is the question `how does a change in phenotypic variance affect the speed of evolution.
What is meant by speed of evolution
Speed of evolution has no strict definition. Or rather it has two standard definitions and it can be measured in Haldanes or in Darwins (which are units).
Quite often by "speed of evolution" authors mean "response to selection over medium to long term" as for example in the wiki article for rate of evolution.
Below I am answering to two different questions.
How does processes that affect "speed of evolution" at neutral sequences also affect phenotypic variance
At neutral sequences, the rate at which mutations fixes is equal to the mutation rate (see this answer for explanation). And all else being equal (typically without changing the mutational effect), high mutation rate leads to high phenotypic variance.
How does a sudden change in the phenotypic variance affect the response to selection in regard to this trait?
I think you pretty much said it all. I will just rephrase what you just said with a few simple equations.
Breeder's equation and heritability
The response $R$ to selection $S$ is given by
$$R=S h_N^2$$
, where $h_N^2$ is the heritability in the narrow sense. This above equation is known as the breeder's equation and is a fundamental result from quantitative genetics. The heritability in the narrow sense is defined as
$$h_N^2 = \frac{V_A}{V_P}$$
, where $V_A$ is the additive genetic variance and $V_P$ is the phenotypic variance.
Partitioning phenotypic variance
So it feels like increasing $V_P$ would decrease $h_N^2$ and therefore the response to selection $R$, but that would be very naive as $V_P$ is not independent of $V_A$. It is quite standard to decompose the phenotypic variance into genetic ($V_G$) and environment variances ($V_E$) $\left(V_P = V_G + V_E\right)$. Of course in reality, we should take into account variance due to other factors such as epistasis or developmental noise for example and all of their covariances. The genetic variance can further be decomposed into additive genetic variance $V_A$ and dominance genetic variance $V_D$ $\left(V_G = V_A + V_D\right)$.
Interdependence between $V_P$ and $V_A$
$V_P$ is a function of $V_A$. So as currently stated, it is impossible to answer the question by a simple yes or no. The shortest correct answer would probably be "The response to selection will decrease if the increased variance is not (not mainly) related to increase in additive genetic variance".
To be perfectly accurate, let $\Delta_P$ be the increase phenotypic variance and $\Delta_A$ be the increased genetic additive variance such that $\Delta_P > \Delta_A$. All else being equal the increase in $V_P$ will cause faster response to selection if and only if $\frac{Va+\Delta_A}{V_P+\Delta_P} > \frac{Va}{V_P}$. Isolating the term of interest $\Delta_P$, we got
$$\Delta_P < \frac{\Delta_A V_P}{V_A} = \frac{\Delta_A}{h_N^2} $$
In other words, all else being equal, an increase of phenotypic variance of $\Delta_P$ above the original variance $V_P$ increases the response to selection if and only if this increase is lower than the increase in additive genetic variance $\Delta_A$ multiplied by the inverse of the original heritability (heritability before a change in phenotypic variance occured)."


Why does the sacrum fuse together? Everywhere I look describes how the 5 sacral vertebrae start fusing together during adolescence and are totally fused by the time you're 30 or so. But nobody seems to explain why this happens.

It seems like it would be disadvantageous for women, since presumably having a fused sacrum makes giving birth more difficult- apparently post-partum fractures are not uncommon (http://rheumatology.oxfordjournals.org/content/42/2/384.long). So why does it happen?

EDIT: Matthew McTernan gave a great answer, but I am greedy and would like to know more: Why does the sacrum only start fusing together in adolescence, and then finish in your late 20s - early 30s? Most major development ends in your early 20s. Does this have something to do with reproductive concerns? If so, why does it happen on the same timescale in men and women?

It isn't just humans that have fused sacral vertebrae. Animals on the phylogenetic tree ranging from Squamata (lizards), to Aves (birds), to even Monotremata (egg-laying mammals) all have fused sacral vertebrae. The fused vertebrae can serve as a stronger, weight-baring structures for animals that do land locomotion, including humans. Any bones that have evolved to withstand extensive force will also be thick or fused together: and example is the fusion of the radius and ulna in frogs. This fusion of bones allows for the forearms to withstand the force of landing after a large leap.

Photo references:

Bird Sacrum: http://www.discussfossils.com/forum/uploads/842/sacrum_2.jpg

Frog Radioulna: http://classconnection.s3.amazonaws.com/573/flashcards/4420573/png/appendicular_skeleton-frog-142D89D722717E64724.png


Does bleach destroy RNAse activity, and if so, how does it do it? I am working with RNA samples, and I'm trying to be very careful about RNAse contamination.

I have some questions about bleach, though. Some people say that a solution of bleach is enough to destroy RNAse activity, but is it really? How does it do it?

I'm not sure if wiping the surface using a solution of bleach would be enough to kill RNAse activity, or if it is necessary to use products such as RNAseZap or RNAseAway.

RNAses are enzymes, and there are various ways to inactivate them. Unfortunately, RNAses are rather stable proteins and autoclaving doesn't completely kill their activity. The common methods to inactivate are unspecific methods that will destroy any enzymes, either through covalent modification or degradation.

The most common methods for RNAse inactivation are:

Treatment with DEPC. This covalently modifies histidine and a few other amino acids, which will inactivate RNAses.
Heating to 200-250 °C for at least an hour, this is most commonly used for metal and glass equipment
Incubation with 1M NaOH for an hour at 37 °C, which will hydrolyze proteins

Using bleach is not a method I've used, but it should work in principle as hypochlorite will react with proteins.


Has DNA communication/interaction at a distance been empirically demonstrated? I recently had a discussion with a statistician in my school about memory. Among other things, he told me that it has been experimentally demonstrated that when one extracts DNA from any organism and then induces a stressful condition on that organism, the same effects on DNA can be observed both in that organism and the DNA sample that was extracted before the stressful condition. From what I could tell it is as if he was suggesting that DNA has some kind of a telepathic property that enables this phenomenon.

Now, I am not a biologist (and neither was he) but I am heavily suspicious of this idea. Also, when I asked him for a specific paper on that, he simply told me that there are many and that it is fairly easy to find them. However, my efforts to find anything on google scholar were fruitless so far.

So I want to know: Is such a thing possible and have there been any experimental studies on that?

No — typical DNA extraction will not preserve information about the biochemical state of the cell.

During the process of DNA extraction, proteins are removed and DNA from a population of cells gets precipitated. Then you dissolve the DNA. In this process native conformational state cannot be preserved.

However there are techniques (see this post) that can capture long distance molecular interactions of DNA (which reflects a conformational state). To summarize in a line, these techniques "lock" the DNA in its conformation and downstream steps are carefully done so as prevent loss of information.

Stress is just a kind of biochemical response. This technique can be applied to study long range DNA-DNA interactions for different conditions (for e.g. Developmental stages).

Stress can cause RNA in the cell to aggregate; however once you do the extraction you won't be able to know if it was aggregated in the cell before extraction.

An Analogy: Sugar can be anhydrous powder or can be crystalline. But once you dissolve the sugar in water, there is no way to know in what form it existed before dissolution.

Certain processes (epigentic mechanisms) can lead to methylation (sometimes hydroxymethylation) of DNA (at cytosine; Bacteria also have adenine methylation). These modifications can be detected in the extracted DNA by different methods; one of the common techniques employed for this is bisulphite-sequencing.

Final word: all these claims about molecules having telepathic memory is pseudoscience. There is no evidence whatsoever for such proposed phenomena.


What is the film that covers the tongue? What is the film that covers the tongue in the mornings, even after brushing the teeth and tongue the night before and why does it have color variations?  Do the different colors mean anything?

It isn't really a film. The tiny bumps that cover your tongue are called papillae, and are normally pink in color. However, they can become inflamed and white when irritated. The appearance of the white "coating" is caused by debris, bacteria and dead cells getting lodged between the papillae.

You may be breathing through your mouth when you sleep, which is drying it out. Bacteria may also still be the cause; you may not be brushing well enough or your toothpaste may not be correctly doing its job.

The color variations may be due to different types or amounts of debris, or the color may vary with different conditions listed here. Tongue color changes also often occur with glossitis (inflammation of the tongue itself).


How does an inhibitory synapse communicate to the cell body of a neuron? I picture a neuron as having multiple trees of dendrites attached to the cell body with a single axon leaving the cell body.  I believe the cell body near the axon root makes the decision to fire or not fire an action potential.

If the neuron has both excitatory and inhibitory synapses in the dendrite trees, how do these communicate to the cell body?
Does something like an action potential get transmitted down the dendritic trees to the cell body?
What is the difference between the excitatory and inhibitory signals that are transmitted?

An inhibitory synapse works just like an excitatory one!

When a presynaptic neuron fires it will release a neurotransmitter at its terminal(s). This neurotransmitter can be excitatory or inhibitory, the main excitatory one in the central nervous system being glutamate and the main inhibitory one GABA.*

GABA and Glu are far from being the only neurotransmitters in the brain, they're just a classic example, so we'll stick with them. When the neurotransmitter is released it binds to receptors on the postsynaptic neuron (provided, of course, that the postsynaptic neuron expresses these receptors).

Various GABA and Glu receptors exist, both ionotropic (i.e. channel-receptors that let ions flow through the membrane upon binding of the ligand) and metabotropic (i.e. receptors which activate an intracellular pathway that does not per se start the flow of ions, but that can induce it or prevent it indirectly).
For simplicity we'll stick to ionotropic receptors.

Glu binds to three types of ionotropic receptors: AMPA, NMDA and kainate receptors. These have different kinetics/properties, but the bottom line is that they let cations (positively charged ions, such as Na+ and Ca++) into the cell. When this happens a postsynaptic depolarization happens, which is named EPSP (excitatory post-synaptic potential).
So, if the resting membrane potential was, say, -57mV, it will become, for instance -52mV.
This means that, if the threshold potential for firing an action potential were -43mV the cell, which first needed a 14mV depolarization to fire now will need a 9mV depolarization.
If subsequent EPSP sum they can depolarize the cell sufficiently to reach threshold and let the cell fire.

This image from Wikipedia is quite self-explicatory: in this case 3 synaptic events generated 3 EPSPs that summed, making the cell depolarize enough to reach threshold potential, and generate an action potential, that will then propagate to the cell body.

GABA, on the other hand, binds to the GABA-A receptor, which is a chloride channel. In most cases, upon binding of GABA, GABA-A lets Cl- in the cell, effectively hypopolarizing it and generating an IPSP (inhibitory post-synaptic potential). The situation is the same (but opposite) to Glu, this time, though, the potential becomes more negative.

EPSP and IPSP can and do happen at the same time: as they can vary in frequency and intensity depending on the firing frequency and firing pattern of the presynaptic neuron, a pretty much continuous range of voltages can be achieved in the postsynaptic neuron.

Other controls over this process come from metabotropic receptors that can, for instance [de]phosphorylate (add or remove a phosphate group) ion channels modulating their permeability to ions or from the different kinetics of the different channels (for instance certain channels stay open for longer or open in a delayed manner etc), allowing for fine-tuning of the system.

*I am making a gross generalization here. A neurotransmitter is not excitatory or inhibitory per se, it depends on the context. For instance excitatory GABA synapses do exist.


What are ways to compare the "costs" and "gains" of food production systems? I'm looking for methodologies to compare the costs a food production requires with the gains it delivers (not in economic terms).

I'm aware of energy returned on investment. Are there other methods used in literature (also including qualitative approaches)?

To be a bit more precise (or rather unprecise?): Costs may include the input of fuel, feed, energy in general or - for me most interesting - the environmental burden to our environment (for example the carbon footprint) while gains should refer to the nutritional output of the product (energy, protein content, other (rare) nutrients).

The purpose is to link (or discuss) the burden of food production chains to their benefits but to find a unit that is quantitative comparable (except the pure energy content) doesn't seem so trivial - so I'm very happy with suggestions how to approach that - in the best case with a link to studies that employed the method.

Calories and dollars are the most obvious and straightforward, but including additional variables complicates the accounting. . A great paper that used energy has been updated in a more recent publication. Emergy is an interesting alternative.

Current work includes the Natural Captial project that "aims to integrate the values of nature into all major decisions affecting the environment and human well-being". Of course, this approach exchanges a simple currency for a more comprehensive one.

Climate regulating value is also a relatively straightforward and relevant currency that can be used to compare the value of food production systems.


When does one decide to refer to a virus as a new variant? I've read that SARS-Cov-2 has several variants, e.g.:

Can the U.S. keep Covid variants in check? Here's what it takes.
Novavax’s Vaccine Works Well — Except on Variant First Found in South Africa

When does one decide to refer to a virus as a new variant?

My research:

I looked at https://biology.stackexchange.com/questions/tagged/variant?tab=Votes
The question What determines when a virus becomes a “new strain”? addresses strain. Is strain the same as variant?

We use them as synonyms. However, variant is, in my view, more colloquial than scientific. Strains are in the literature often defined by their distinct genome compared to other strains of the same species (might be one base-pair substitution or more). In microbiology, including viruses, we often think of a strain as the proliferation of a single distinct DNA/RNA molecule.
https://www.sciencelearn.org.nz/resources/184-virus-strains


Why are bacteria and archaea in different domains? As I understand it, the main difference between the Bacteria and the Eucaryota domains are that eukaryotes have a nucleus and bacteria don't. I understand that bacteria and archaebacteria have enough of a genetic difference to be separate kingdoms, but why are they separate domains?

The reason that Archaea were determined to be a separate (and only the third) kingdom so late (1977 according to this reference) was because archaea often completely resemble eubacteria.  They are unicellular and have no organelles and appropriately they were grouped with other prokaryotes because of their morphology and cellular physiology.

But by the 1970s phylogeny becoming based on the sequence of DNA and RNA which were just becoming more available.  Based on a simple comparison of the sequences of 18S rRNA of 13 fungi, bacteria and archaea, Woese and Fox showed that the bacteria and the archaea were about as different from the eukaryotes than from the bacteria.  (see table 1).

Since then, the differences between bacteria and archaea have continued to be great.  The wikipedia diagram below is not to scale- the divergence of the three kingdoms is so far back that they pre-date the emergence of eukaryotes entirely. But you can see that fungi and other eukaryotes are more similar to archaea than the bacteria.

BTW, the idea that archaea are extremophiles is not entirely true - they are pretty much exclusively the only kingdom found in these conditions, but archaea have been found to coexist with bacteria and eukaryotes in the open sea and their detection heretofore in most environments may be only due to the fact that archaea are difficult to grow in the lab.

Just found this retrospective from Woese himself, who passed away recently.


What is meant by drug tolerance? What is meant by drug tolerance?

This question is in my biology textbook for IGCSE and I have no idea what drug tolerance is. It would be very helpful if someone could clarify. Thank you.

It basically means, that the body gets used to certain drugs and that you need to raise the dose to reach an effect. This is for example true for a number of anesthetics or pain medications as morphine.

Permanent application leads to a down-regulation of the drug receptor (for morphin this is the mu-opiod receptor) and the activation of counteracting signaltransduction pathways. To still get an activation you will need a higher drug concentration.
For more details have a look at these articles:

Opiate tolerance and dependence: receptors, G-proteins, and
antiopiates
Cellular neuroadaptations to chronic opioids: tolerance, withdrawal
and addiction


How does this headless fish still move? There is a (VIDEO) on Facebook where the fish starts to flail around despite no heart or internal organs.

What causes the fish to flail around the way it does?

My theories:

It is because of pressure causing the muscles to contract - much like when you leave your own hand loose and squeeze up your arm making your fingers curl.
It is because the nerves are still alive - much like how you can rub the fish heart the right way and cause it to beat again even though the fish is very much dead. (I watched my fifth-grade teacher do this in class)

It is a widely known spinal reflex arc which causes decapitated animals (even soldier without head) to move over some period of time after decapitation.

One of the arc representations:

see also The life after decapitation

additional video


What happens to IP3 molecules after release from IP3 receptors? IP3 molecules bind to IP3 receptors and open up the calcium channels on the endoplasmic reticulum. I am wondering what happens to IP3 molecules after they have been released from the IP3 receptor? Do they remain as IP3 molecules, or do they break down? Do they have any purpose after they have been released, and perhaps after been broken down?

All biomolecules are eventually broken down. This process is called turnover. Since inositol is a signalling molecule it is necessary to remove in order to terminate the signal, despite adaptive mechanism in the ER calcium channels.

IP3 is generally dephosphorylated by a family of phosphatase enzymes called inositol polyphosphate phosphatases. After dephosphorylation, the inositol can be recycled into the membrane by phosphatidyl-inositol synthase.

Reference:

The IUPHAR/BPS Guide to PHARMACOLOGY 1

1 I'm citing this website instead of a research article because apart from citing the original research articles, it also has other informative links about the enzymes and the substrate molecules. It is also from a very reliable source.


Which of the following demonstrates the pattern of development in Greylag Geese? Which of the following demonstrates the pattern of development in Greylag Geese? {Please give specific answers, which among the following gives the best available demonstration?, If needed, have a look at the Paragraph (Image Embedded)}

(A) Geese reared by humans cannot be taught to respond to its own species.

(B) The hatching at an advanced stage is critical for imprinting.

(C) The capacity to recognize an adult of its own species is necessarily inherited.

(D) Rearing by humans does not alter the object of the behavioral routine.

Option A: “Geese reared by humans cannot be taught to respond to its own species” is correct.
This is inferred from the 4th paragraph 2nd line: “When young geese are reared wholly by human beings it is towards humans that the young geese direct their behavioural routines”. This line clearly states that geese wholly reared by humans respond only towards humans. Also from the 2nd Paragraph 3rd line It is clear.
Option B: “The hatching at an advanced stage is critical for imprinting” is false.
Hatching at an advanced Stage is not shown by Greylag Geese, it is shown by Godwits. (3rd Paragraph, 1st & 2nd Line: The young of Godwits hatch at an advanced stage of development and soon after hatching can recognize the adult bird.) (So the fact is not conclusive from Behavioural Pattern of Greylag Geese) Imprinting can be shown by Greylag Geese, which do not have a prolonged period of hatching, and imprinting totally depends on whatever creature happens to be present at the right moment in their development.
Options C: “The capacity to recognise an adult of its own species is necessarily inherited” is false. According to the 2nd Paragraph, 2nd line: The capacities to recognise the right stimulus are not always inherited.
Option D: “Rearing by Humans does not alter the object of the behavioural routine.” is false, as shown in 4th Paragraph 2nd & 3rd line: When young geese are reared wholly by human beings it is towards humans that the young geese direct their behavioural routines.
Hence, answer should be A.

So Am I correct?

Your logic seems fine to me..

Option B: The hatching at an advanced stage is critical for imprinting.

This is wrong because Konrad Lorenz (who rediscovered imprinting)

  demonstrated how incubator-hatched geese would imprint on the first
  suitable moving stimulus they saw within what he called a "critical
  period" between 13–16 hours shortly after hatching (reference).

So saying that the hatchling should be at an advanced stage is incorrect.

Option C: The capacity to recognize an adult of its own species is necessarily inherited.

Again this is incorrect because Lorenz has also stated that

  The human-imprinted gosling will unequivocally refuse to follow a
  goose instead of a human, but it will not differentiate between a
  petite, slender young girl and a big old man with a beard (Lorenz,
  1965) (reference).

Also in this article it is implied that starlings that are imprinted to humans do not relate to its own kind.

Option D: Rearing by humans does not alter the object of the behavioral routine.

From the earlier findings, this is obviously false. Moreover a duck keeper has explained imprinting thus:

  An imprinted duck--a duck that was raised from the moment of hatching
  by a human and so views the human caretaker as a parent or equal--may
  become accustomed to riding in the car. Imprinted ducks might go
  camping with you (although you must keep them beside you at all times
  or in a crate) or go on play dates to a friend's house (you will not
  want to take them to a farm or a public pond where they may contract
  diseases). If your duck is in a diaper, you will need to change the
  diaper every hour or so (reference).

This shows clear behaviour changes.

Option A:  Geese reared by humans cannot be taught to respond to its own species.

It is mostly accepted that it is not with Lorenz himself stating that

  imprinting is irreversible. It is essential in learning that what has
  been learned can be either forgotten or modified (reference).

However there are claims to the contrary nowadays with it now firmly established that filial and sexual preferences are reversible (reference). Another interesting article by the American Psychological Association with a few links you might want to check out.

In conclusion, Option A could also have its problems with some response to its species possible, but overall it is the most and best plausible answer.

Dr Lorenz with his imprinted geese. Also a very interesting read (reference)


How to determine the most likely reading frame of a DNA sequence? This question is from a past exam paper for an introductory bioinformatics module. I'm a computer scientist doing biology for the first time.

"A short bacterial gene has been sequenced, giving the following DNA sequence. Write out the 6 possible reading frames for this sequence and indicate which is the most likely protein translation of this sequence. Explain your reasoning for picking the given translation, and write all the translations in single letter amino acid code form.

5' - ttattcatccgccagcgccatgcgcgccat - 3'  "

I think I understand the 6 possible reading frames: three from the 5' end starting tta, tat and att; and three from the 3' end starting tac, acc and ccg.

I could also write out the translations for a given reading frame with a codon usage table.
It's the most probable reading frame part I don't get. I thought perhaps I was looking for the longest open reading frame. I can only see one start codon (atg). What is the correct way to recognize the most probable reading frame?

I can't find this problem exactly on Biology Stack Exchange. I did find:

Help reading chromatogram

It made me wonder if I'm getting confused between "reading frame" and "open reading frame", this question only asks or the former.

Thanks!

This is what we classify as a homework question, but as it satisfies the criterion of the poster demonstrating an attempt to answer it, I provide the following suggestion of an answer.

I assume that as it appeared in an introductory bioinformatics module the exam question is just testing reading frames (obviously) and the punctuation of the genetic code. The meaning is not entirely clear, but as one reading frame would start with the initiation codon ATG/AUG (reverse complement of: cat - 3′)† and end with the termination codon TAA/UAA (reverse complement of: 5′ - tta) that will presumably produce “the most likely protein translation”.

This is reading frame F4 in the output from EMBOSS Sixpack, below, in which termination codons are indicated by an asterisk.

      L  F  I  R  Q  R  H  A  R  H                                   F1
       Y  S  S  A  S  A  M  R  A  X                                  F2
        I  H  P  P  A  P  C  A  P  X                                 F3
    1 ttattcatccgccagcgccatgcgcgccat 30
      ----:----|----:----|----:----|
    1 aataagtaggcggtcgcggtacgcgcggta 30
       X  N  M  R  W  R  W  A  R  W                                  F6
      X  I  *  G  G  A  G  H  A  G                                   F5
        *  E  D  A  L  A  M  R  A  M                                 F4

The conceptual translation, reading N to C, is MARMALADE, which is obviously meant to be humorous and suggests that it is indeed the intended answer.

Open Reading Frames

The poster asks for clarification of the difference between reading frame and open reading frame. There is a Wikipedia entry for open reading frame but I provide an explanation of my own to relate it to the example.

There are always six reading-frames for the conceptual translation of a piece of double-stranded DNA, as shown in the example.

I would define an open reading frame as one that is not excluded from being translated by the punctuation of the genetic code. It has the theoretical potential to be translated considering only the punctuation of the code, although it may not actual be translated. It can start either with the first AUG after a termination codon (even though it cannot be certain that this is the actual AUG used) or the start of a sequenced fragment of DNA (with the assumption that an AUG is possible preceding the 5′ end of the fragment). It can end either with a termination codon or the end of the sequenced fragment (with the assumption that a termination codon will lie 5′ to the end of the fragment).

By these criteria, reading frames F1, F2, F3 and F6, above are completely open (even though the internal methionine could theoretically be an initiation codon), F5 contains the open reading frame GAHGAGG, and F4 is a complete open reading frame, perhaps excluding the termination codon (depending on your semantic definition of the precise end of an open reading frame).

† Reverse Complement

If we take a section of DNA written in the 5′-to-3′ direction — according to standard convention — and use the Watson–Crick base-pairing equivalences (A=T, G=C) to generate the complementary strand, this will be in the 3′-to-5′ direction. For the strand in the question,

5′ - ttattcatccgccagcgccatgcgcgccat - 3′

the complementary strand is:

3′ - aataagtaggcggtcgcggtacgcgcggta - 5′

As shown above.

For ease of translation manually — and for any computer program that manipulates sequences — one needs to reverse this to the  5′-to-3′ direction:

5′ - atggcgcgcatggcgctggcggatgaataa - 3′

This is the reverse complement. Now the starts of the three reverse reading frames are easy to read as:

ATG...
 TGG...
  GGC...


What light intensity determines the start/end of a photoperiod in humans? I'm reading this article, which discusses the influence of Long Photoperiod (LP) and Short Photoperiod (SP) on melatonin production:
HIOMT drives the photoperiodic changes in the amplitude of the melatonin peak of the Siberian hamster[1].

I'm interested in knowing what light intensity is interpreted as the onset and end of a light-dark photoperiod.

The referenced article indicates that animals were kept in cages, with a pre-set photoperiod duration, this sounds to me like it was done indoors. If it has been done indoors, then artificial lighting was involved, and I would guess it was an on-off affair, rather than gradual change or jumps in intensity.

The reason why I'm asking is that I'm trying to understand the implications of this article for humans, who may wake up before dawn, and spend some time under artificial lighting of various intensity before sunrise, and continue to function after sunset. For example a person may be looking at a TV or a monitor, and I would like to get an idea if this "presence of light" is enough to trigger photoperiod-related changes in the brain. Is there some "critical" density (or density at a specific wavelength) of light that signals the start/end of a photoperiod?

Ribelayga C, Pévet O, Simonneaux V. 2000. HIOMT drives the photoperiodic changes in the amplitude of the melatonin peak of the Siberian hamster. Regulatory, Integrative, and Comparative Physiology, 278(5), R1339-R1345.

It isn't really a specific light intensity that an organism will interpret as the start of a photoperiod. Maynard Johnson reported in 1939 that intensity of light used had an effect on the rate at which mice would shift their circadian rhythms. So, brighter light has a stronger effect, but there isn't a cutoff point that I'm aware of. Johnson was using illumination as low as 2.5 foot candles, which is pretty dim. Aschoff and Pittendrigh did some more work on light intensity in the 50s and 60s, but I don't think anyone ever found anything resembling a cutoff point, only the degree to which intensity had an effect.

Computer monitors are pretty bright. Luminance rating is typically 250-350 cd/m2, which, for comparison with Maynard's experiment, is eqivalent to 23-32 foot-candles. http://computer.howstuffworks.com/monitor6.htm

Johnson, Maynard S. "Effect of continuous light on periodic spontaneous activity of white‐footed mice (Peromyscus)." Journal of Experimental Zoology 82.2 (1939): 315-328.