Molds associated with Aflatoxin? I've been reading how some molds may be carcinogenic. In particular, molds associated with the fungus metabolite, Aflatoxin.

Are the types of mold that produce this toxin, present in buildings/showers/domestic environments, or do they only grow on food-stuffs?

Strictly speaking the common bread mould Rhizopus sp. does not produce aflatoxin.
The fungus Aspergillus flavus which belongs to the class Ascomycetes secretes aflatoxin. It attacks cereal grains , legumes, tree nuts. The fungi are green in colour and 'mould' like in appearance.
The fungus attacks the food stuffs and storage grains. So under favourable conditions it may grow in your store room if it finds food for its growth. Also Aspergillus can grow at temperatures as high as 48°C and even at low temperatures like 5-8°C.

Edit: On being asked for sources I include some which strongly support my claim
1. For suitable conditions of growth of the fungi visit https://en.m.wikipedia.org/wiki/Aspergillus_flavus and read under the Environment heading.
2. Visit https://bioweb.uwlax.edu/bio203/s2013/ernst_ale2/habitat.htm and read from " Aspergillus flavus is omnipresent " upto " Aspergillus may also grow on or inside walls in homes, especially if the house is damp or has been damaged by flooding. "
3.https://www.moldbacteria.com/mold-types.html this site provides a list of different fungi found in our homes. Here you can find Aspergillus flavus to grow in flower pot soil. Moreover other species of Aspergillus are found in kitchens and bathrooms.


Why do red muscle fibres have more mitochondria than white muscle fibre but less ATP than White muscle fibres? This is a question given in my Anatomy book and I am really confused because logically the substance which have more mitochondria should have more ATP as mitochondria is the power house of cell.But the question contrast the logic.

This is because of the difference in mitochondrial protein expression of red and white muscle fibres. There is difference in posttranslational modification, which leads to functional difference as red muscle contraction is slow, and white muscle contraction is rapid.

Metabolic control in mitochondria contributes in speed of activity and cellular energy production. So, these differences effect the cellular energy levels in both white and red muscle fibres.

Following factors also contribute to the ATP production:
White muscle mitochondria have higher proton leak.
Red muscle contain high palmitic acid and oleic acid, but white muscle possess more phosphate ions.
Collagen and elastic fibers are largely distributed in red muscle mitochondria, whereas high titin levels and densely packed sarcomeres are present in white muscles. Whereas high levels of long sarcomeres are present in red muscles.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118618/

https://www.hindawi.com/journals/bmri/2018/5816875/


Decomposition Rate of A Body In A Wet Environment I have a photo of a decomposing dog which is in a water logged environment. My peers and I are debating how long that body has been decomposing. They are saying it is at least a year old. I however think it's much more recent (1-3 months).

My understanding is that when a body is put into a wet environment either partially submerged or fully it speeds up the decomposition process provided the water is not lacking oxygen such as if it was deep on the ocean floor.

The carcass has its skull fully decomposed, which I think is due to the bacteria rich water having more access to surface area through the various orifices and also the skull having much less flesh than the rest of the body.

The torso looks for the most part intact, and I don't see any bloating from gas buildup (not sure when and how long such a feature would be present), and there appears to be a pink area which could be muscle.

Would these features be typical of a recent death in this type of environment or am I overlooking some other important processes that could be speeding up or slowing down the decomposition?

Photo (image unboxed in case graphic for some viewers)

It depends on the temperature of the environment as well. In the heat of summer and in a watery environment, I can verify through unfortunate personal reference that stuff can decompose very quickly. I honestly didn't look at the image, but judging by your description it can't have been there a year. There would be nothing left. Hungry bacteria and decomposers would have left nothing but bones by then. I would say your guess is more on target.


Why is exercise good? The fact that exercise is healthy is a bit counter intuitive to me. If we have any machine, a car for example, the less we use it the longer it lasts. Then how is it that using our body to do sports, to a reasonable amount, lead to longer or healthier life?

My guess is that lack of activity might resemble starvation no matter how much food we consume. Then the body instead of repairing itself tries to save energy as much as it can. Are there any other ideas to explain why exercise is good?

As jamesqf points out in comment, "the less we use it the longer it lasts" isn't always true even of machines. Sometimes if a machine isn't used, the moving parts start sticking together through rust or other decay processes, which does not happen when the machine is used and the moving parts move regularly against each other.

Another example that comes immediately to mind is a hybrid car, which needs to be driven regularly or the battery runs out. Granted this doesn't affect the car's longevity (I think?), but it is another example where use maintains functionality better than disuse does.

This is even more true when we actively maintain machines, fixing them as they break, replacing parts, oiling, etc.

The key point here is that decay is inevitable. It is a law of thermodynamics, and it doesn't care whether something is in use or not. Granted, things will sometimes decay faster if they're used, but not always, and they'll always decay either way. The only way to forestall decay is active maintenance. This isn't contradictory with decay being inevitable, because you can actively maintain something only for so long (it takes work and energy).

This is relevant to biological system because that is how our body works: it is constantly self-repairing and self-maintaining, for the length of the person's life. One reason we die is that it stops doing so as efficiently as one ages. But as long as we are living, these processes mean our bodies aren't a static object: they are a dynamic system that is constantly reacting to outside and inside stimuli. And that system, including the self-repair mechanisms, are set up such that they work best within a certain range of motion and activities. It so happens that range doesn't include "no motion or activities". Likely because we evolved as an active species, so being able to function efficiently when active is useful, and some of the things that make us able to function efficiently when active can cause some harm when we aren't. For example, we store fat in order to use it when food isn't available and as fuel for effort, but if too much of it accumulates it has effects on hormones and inflammation that our bodies don't deal with well. Another example is how our muscles waste away when we don't use them; this is useful for an active species that needs the muscles it uses and shouldn't waste energy and protein on those it doesn't, but an inactive species might be better off conserving its muscles through periods of inactivity, so that they would still be capable of moving well those rare times they do need or want to.

Having said that, look at high-level athletes getting injured, getting early arthritis, etc... It is possible to exercise more than the body's self-reparation abilities can handle, and that also leads to health problems down the road.


Why only female mammals have well developed mammary glands? In course of evolution (possibly), mammary glands became vestigial in male mammals, but became fully developed in females. Is there any plausible explanation for this characteristic?

It comes down to investment in offspring. Males invest little in offspring only a little sperm whilst females have to develop the more expensive egg and the energy used through its development. In the mammalian line, this investment has increased in amount, initially through viviparity and then through the secretion of feeding fluids.

In species, such as humans, where there is a lasting pair bond and both male and female invest in rearing the young then I suppose there could be a situation where it makes equal sense for both males and females to nurse - although the cost of mammaries on other functions may favour specialisation anyway - but remember that, in many mammals, it is the mother alone that rears the offspring.

You may also find the answer to this question useful: Do any birds beside the family Columbidae (or any reptile or mammal) feed their young “Crop Milk”. What I hadn't realised is that there actually two species of bats where the male lactates.


How can I produce milligram quantities of an isotope-labeled DNA oligomer? I'd like to produce a specific DNA sequence on a milligram-scale and 13C15N-label it. The sequence is around 35 nucleotides long, so chemical synthesis is out due to the exorbitant costs.

I'm also only interested in the single-stranded DNA, so a method that produces double-stranded DNA without any way to easily separate the strands would also not be useful.

What methods are there to produce labelled DNA that fulfill these requirements?

You can also design a plasmid that has your 35mers and raise the bacteria with isotopic carbon and nitrogen C13 acetate and N15 ammonium sulfate will work with E coli in a minimal medium.

this is not cheap, but the cheapest available sources of the isotopes can be used.


More entropy: Atom or Macromolecule? A question that appeared on my last exam was :

  Which of the following has greater entropy A) An atom B) A
  macromolecule

The question doesn't specify anything else(i.e. type/size of atom or macromolecule). The macromolecules we learned class were proteins, sugars, nucleic acids(DNA/RNA) or lipids. What is the correct answer and why(hypothetical calculation, if possible) ?

Ahh entropy. The bane of many undergraduates. You won't need a lot of mathematical rigor needed to solve for absolute entropies in most biological fields so it's best to think of it abstractly.

Consider the atom. What can it do? Well if you remember from chemistry class, it can bounce around a process we call translate, and the electrons can basically switch spins. For the most part, if you had a single atom alone in the universe, that's all it could do. Move around and have its electrons switch states. It's best to think of these as "states" of the atom.

Let's see, the atom can move in the X direction and be in spin up. It can move in the x and y direction and be spin down...etc. But the point is, there is not a whole lot the single atom all by it's lonesome can do.

On the other hand, if we start adding other atoms to the mix, say across chemical bonds, then they can start to do more. If two atoms are bonded, they can stretch and contract (vibrational states), they can rotate around each other, and they can do everything the atom can do as well.

As you can see, there a lot more "things" or "states" that the two atoms can be defined in at any one time. They can be rotating one direction, vibrating in one way, moving in another... etc etc...even this sentence seems to be getting more chaotic! And that is really all entropy is. Adding up more and more ways for matter to get into all these possible configurations.

So the answer to your question is the macromolecule. It has tons of atoms and bonds. An uncountable number of ways to rotate, translate and vibrate, and be struck with photons, and emit light, and do all kinds of chaotic "stuff" (you can count it actually, it's just really hard).


why does blood when oxidized over time become bluish green? Oxygenated blood is bright red and deoxygenated blood is dark red or brown.

If you take oxygenated blood and leave it in the air it will turn dark red, then brown, then finally a bluish green from exposure to atmospheric oxygen.

Why does it oxidize this far to get a copper oxide color to it after it has passed the phase where it is the same color as iron oxide? Why doesn't it stay at the iron oxide color?

Apparently there is a rare condition, sulfhemoglobinemia in which sulphide ions or H2S combine with the haem group in haemoglobin, causing a greenish colour. This can be related to certain drugs being present in the blood.

See here for an example in which surgeons discovered dark green blood in their patient.


Is it appropriate to say "selection of" or "selection for" an allele that evolves by genetic hitchhiking? In terms of Sober's selection of/selection for distinction, is it appropriate to say that there was selection of or selection for an allele that evolved by hitchhiking?  I am inclined to say selection of.  Is that correct?

The expressions "selection for" and "selection of", their definitions and their usage have been subject to a number of semantic issues throughout the literature. Good and Griffith (1995) is a good read on the subject.

I would argue that neither "selection for" or "selection of" is appropriate to use in the context of genetic hitchhiking because, in this context, by definition, the increase in frequency of an allele is only due to a different locus nearby that is under selection. So an allele that evolves due to hitchhiking is not directly under selection and only changes frequency indirectly due to nearby selection on a linked site.


Does the order of amino acids matter in making up a protein? For instance, if a protein is made of 2 amino acids, that is, AB, would the same protein form if the order of combination of amino acids become BA? If yes, would the behavior of interaction of that protein change? For instance, if AB interacted with another protein XY, would BA interact with XY in the same way?

Yes.

The 'order' of amino acids is the protein sequence, also known as the primary structure. A peptide (short protein) with sequence XYXYXYXYX is very different from XXXXXXXYYYYYYY.

Your example is a bit trickier, since it seems like AB should be roughly equal to BA. However, each amino acid has two ends - the amino and carboxyl - and so a dipeptide like this is more like NH2-A-CONH-B-COOH with a peptide bond in between.

The really tricky question is : are two sequences 'the same' if they are different by just one or two letters. In other words is AAAAAABAAAAAA different from AAAAAACAAAAAA - and this is the study of mutations of proteins.

There is a lot more to say on this topic, of course.


Are there neuron mediated reactions faster than reflexes? I'm interested in how fast the human body can respond to a stimulus.  I know the fastest reflex, the blink reflex, operates around 100ms from stimulus to reaction.  I also know that the blink reflex is known as the fastest reflex in the human body.  My interest is in the fastest responses to stimuli I can find in the body.

Are there any faster responses to stimuli within the human body which use neurons but are not categorized as a reflex (due to some technicality), meaning they could be faster than the fastest reflex?  To the best of my understanding a reflex is defined by the use of neurons to convey the information, I'm just wondering if there are any grey areas which don't qualify as a reflex but may be faster.  I don't want to potentially write off an entire class of neurological behavior in my research simply because I stopped at the blink reflex.

A reflex as fast as the blink in a neural circuit:

I would consider suppression of outer hair cells in the cochlea to be a reflex; the faster component of this reflex is about the same as the blink reflex, around 100 ms. The hair cells themselves aren't considered neurons, but the pathway that suppresses their motility certainly is.

A much much faster non-neuronal "reflex":

That said, the outer hair cells themselves also dance along quite fast in response to sensory input, even faster than the typical hearing range for humans, faster than 20kHz! In some ways, this is a reflex because you are taking sensory (specifically, auditory) information and turning it into a motor response, but all the "action" is taking place within one cell, and it isn't a neuron.

A more classical reflex that is substantially faster than 100 ms

Reflexes in the periphery can be much faster than 100 ms. The myotatic reflex, or stretch reflex, can be as fast as 30 ms in the knee - this is the reflex that is tested when a physician smacks you on the knee with a hammer (used as a test of spinal and peripheral nerve function, not as a punishment). It's likely there are other stretch reflexes that are faster just because distances to the spinal cord are shorter, but these might be more difficult to test (in this paper they report latencies as fast as 20 ms).

Eyeblink reflexes can also be faster than 100 ms!

For example, see this paper: strong auditory stimuli evoked blinks within about 20ms!

tl;dr: I'd check your source that 100 ms is the fastest reflex! I stuck with mostly human examples here (some of the hair cell work is in other mammals), but you will find even faster reflexes if you look at smaller organisms, such as insects.


Is there any evolutionary reason for why some organisms (wrasse) change their sex in adult stage? In San Francisco, I saw this fish:

and quoting the aquarium's page:

  Part of the wrasse family, the California sheephead is a protogynous hermaphrodite. Simply put, all sheepheads are born as females, but eventually transform into males. Due to hormonal changes triggered by environmental and social cues, this fish can go from a reproductively-functional female to a fully-functional male.

I have never heard of something like this for any organism. Is this behavior unique?

But the real biology question is why they do that and not simply retain one gender throughout their life? In other words, what's the evolutionary advantage of such a weird approach?

This is an interesting question.  This strategy is common among wrasses, but the Labridae is a rather huge family.  I found this article here that I think may help answer your questions:  http://faculty.sites.uci.edu/johncavise/files/2011/03/299-SexDev-herms.pdf


Vitamins — how did they get their names? There are several types of vitamins. A,B,C,D,E,H,K,P, etc. How did they get their names?

They were more or less named in the order that they were found.  Letters F-J are skipped because many of those were reclassified or later found not to be vitamins.  The K comes from the German word for Koagulation because the vitamin is involved in the coagulation of blood.

The discovery dates of the vitamins and their sources /
Year of discovery   /Vitamin    Food source

1913 Vitamin A (Retinol) Cod liver oil
1910 Vitamin B1 (Thiamine)   Rice bran
1920 Vitamin C (Ascorbic acid)   Citrus, most fresh foods
1920 Vitamin D (Calciferol)  Cod liver oil
1920 Vitamin B2 (Riboflavin) Meat, dairy products, eggs
1922 Vitamin E (Tocopherol)  Wheat germ oil, unrefined vegetable oils
1929 Vitamin K1 (Phylloquinone)  Leaf vegetables
1931 Vitamin B5 (Pantothenic acid)   Meat, whole grains, in many foods
1931 Vitamin B7 (Biotin) Meat, dairy products, eggs
1934 Vitamin B6 (Pyridoxine) Meat, dairy products
1936 Vitamin B3 (Niacin) Meat, grains
1941 Vitamin B9 (Folic acid) Leaf vegetables
1948[42] Vitamin B12 (Cobalamins)    Liver, eggs, animal products

There are many different B vitamins, water soluble, because many vitamins previously given different letters where later found to be part of the B complex. For example H is now B7.  Additionally, many letters, such as P, are no longer classified as vitamins.

More information can be found on this Wikipedia page.


Distance between species Is there an on-line database that will enable one to find the genetic distance between two species?

I'm vaguely aware that there are various metrics used that may give different results, but I'm looking for a database that can be used to derive any of these metrics.

Unless someone has already done the work to determine genetic distance between the two species you're interested in, unfortunately the answer is "no, there is no such database".  If representative members of the two species have had their DNA fully sequenced, any of the relevant metrics (e.g., those described in Wikipedia https://en.wikipedia.org/wiki/Genetic_distance) can be used to calculate a value for the genetic distance.  But it's important to keep in mind that "genetic distance" is a pretty vague notion when talking about different species.  There are all sorts of epigenetic factors and gene rearrangements that can play important roles in determining the developmental and phenotypic differences between species; and those factors won't show up in most methods for calculating genetic distance.


Can plants survive indefinitely without external supply of gases at compensation point? During photosynthesis, there is a point at which the light intensity is such that the rate of photosynthesis exactly matches the rate of respiration called the compensation point. What this means is that the plant can essentially utilize the $\ce{CO_2}$ produced during respiration for photosynthesis and the $\ce{O_2}$ produced during photosynthesis for respiration. But, does this mean, that a plant which has been given an initial supply of $\ce{CO_2}$ and $\ce{O_2}$ and then subsequently put into another gas (still in compensation point light intensity), say nitrogen, can survive indefinitely? (or as long as it's life span).

If the plant is growing the system will fall out of equilibrium due to more carbon going into biomass than oxygen.


Differentiating Taenia solium and Taenia saginata Infections I have been told that both are spread by pigs and cattle, respectively. I would like to know the complications caused by Taenia solium and Taenia saginata. Also elaborate how dangerous is one as compared to the other, as well as preventive measure.

I googled , and found no relative comparison between these two.

Thank you.

Taenia solium is more dangerous:

  T. saginata is relatively innocuous, since only the intestinal tapeworm phase occurs in man, whereas infection with T. solium has major health effects due to extraintestinal infection by the larval or cyst phase in the CNS [1].

The most feared complication of Taenia solium is cysticercosis. Taenia saginata can lead in extreme cases to intestinal obstruction.

Preventive measures:

improved hygiene
adequate thermal processing of meat [2]
preventing contamination of animals (pigs and cattle) [3]

Differential diagnosis:

PCR [1, 4]
Hematoxylin-Eosin Staining [1]

References:

Mayta H, Talley A, Gilman RH, Jimenez J, Verastegui M, Ruiz M, Garcia HH, Gonzalez AE. Differentiating Taenia solium and Taenia saginata infections by simple hematoxylin-eosin staining and PCR-restriction enzyme analysis. J. Clin. Microbiol. 2000 Jan;38(1):133-7. PubMed PMID: 10618076. Cited text is from full text article available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC86038/
Wikipedia contributors, "Taenia saginata," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Taenia_saginata&oldid=618599196 (accessed July 28, 2014).
Wikipedia contributors, "Taenia solium," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Taenia_solium&oldid=618599210 (accessed July 28, 2014).
Luis Miguel González, Estrella Montero, Leslie J. S. Harrison, R. Michael E. Parkhouse, and Teresa Garate. Differential Diagnosis of Taenia saginata and Taenia solium Infection by PCR. J. Clin. Microbiol. February 2000 vol. 38 no. 2 737-744


Bimodal frequency distribution of size of protein loops The graph of number of amino acid (AA) residues in a loop Vs the frequency of their occurrence in proteins largely follows a tending-to-zero pattern. However, there appear to be some specific number of AAs where the frequency suddenly drops, leading to bi- or multi-modality in the plot. Is there some molecular explanation for this, or is it just an artifact?

I’ve attached the figure from a paper with a different research question but the same graph(Figure 2), albeit more detailed. (The same graph can be found in Brandon and Tooze (fig.2.8).) In the paper from which this is taken “A loop structure was defined as any region between two regular secondary structures that was at least three residues in length.”

A curve of this type, showing a bi- or multi-modal distribution,
  suggests two or more constituent species
  in the population. In this case this is borne out by further analysis
  in the paper of different types of secondary structure components
  anchoring the loop, the peak at low numbers of amino acids reflecting
  the loops connecting β-strands in anti-parallel β-sheets.

The second frame (B) of Figure 2 is shown below (dashed line):

Anti-parallel β-sheets are abundant in proteins, and in many — although not all — cases adjacent strands are connected by short (four- or five-amino acid) loops such as the β-turn, the β-hairpin or the β-bulge loop.

Repeating small loops are especially well illustrated in β-sheets displaying β-meander:

The β-meander motif from the outer surface Protein A

Examples in larger domains of the β-barrel and immunoglobulin type also show some larger loops.

Beta barrel of green fluorescent protein, showing loops at end of strands

Immunoglobulin domain of PDB 5IML showing β-sheet with loops connecting strands


What's it called when a male seahorse gets "inseminated"? I am looking for the scientific term for the process where a male seahorse receives eggs from the female. For example, we usually say, "the male inseminates the female with sperm." What is the correct term to use for seahorses? Would you say "the female inseminates the male with eggs", or is another term more appropriate?

Short answer
I think that "egg deposition" by means of the female "ovipositor" seems the most commonly used terminology.

Background
A cursory Google search yielded quite a few alternatives, ordered here from the most fancy to the least:

...that are deposited directly into the brood pouch ... (Look et al., 2007)
...transferring their eggs directly into the male brood pouch... (Masonjones & Lewis, 1997)
...the female injects her eggs into the male’s pouch using her penis-like ovipositor
...once all the eggs are inserted

References
- Look et al., J Exp Biol (2007); 210: 432-7
- Masonjones & Lewis, Copeia 1996; (3): 634-40


How can birds keep their eyes moist during flight? Mammals have an upper lid and small mass  of tissue in the upper corner known as nictitating membrane. This helps keep the eyes clean; birds can moisten their eyes in flight using this membrane without blinking. How does this work?

Because the nictitating membrane secretes a fluid that is resistant to evaporation. Therefore, birds need not blink their eyes during flight.


What is this? In Florida. Found in plant bed under rosemary tree that gecko' enjoy hiding aloe plants also growing. Species identification of round soft outer shell

I only know this because I have seen them before in the tropics, but this is probably Clathrus ruber (Wikipedia).  So interesting!

EDIT: Also mentioned in these questions 1 and 2 so perhaps this will get marked as a duplicate.


Are specialized cells considered to have life? A common definition of life, including the one in Biology SE Life requires physical entitites to have the capability of being able to reproduce.

A process defining organisms that grow and adapt to stimuli while
maintaining a state of organization and energy production and being
capable of reproduction.

Under this definition one could think that a specialized cell like a bone cell or a skin cell doesnt have life. But also, a common definition of cell, including the one here in Biology SE says a cell is

the smallest unit of life.

So, my question is, are specialized cells which dont reproduce supposed to have life? This question came up to me thinking of other living organisms which have tissues which seems to be inert and survive hundreds or thousands of years (ie, wood, bones, etc.)

Life is defined in many ways.
Common definitions are usually simplified definitions. Under some definitions it would be "life" under others it would not be. But it doesn't matter. The problem you are having is thinking definitions of life are anything more than artificial categorization. Really there is no difference between living things and the rest of chemistry, or at least there is a smooth gradient connecting them, but we humans can't easily think that way, so we create descriptive but imperfect definitions to help our thought processes. There is a lot of gray area for any definition of life, and you have found one.


Biochemistry Question: Antibodies I'm doing conceptual questions in preparation for a Western Blott and needed clarification on a specific question:

Is it possible/ will your Western blot work if you use a primary antibody (say generated in mice) and use a secondary antibody (generated in goats)? Would this combination still work with the western blot? At first glance, I'd say no but I'm still looking into it. Any clarification would be greatly appreciated!

As others pointed out, the question is not clear.. but yes, in general you use a primary antibody recognizing your peptide of interest, e.g. an antibody made in mouse, and then a secondary antibody recognizing your primary antibody, in this case an anti-mouse. The secondary antibody will obviously be made in a different animal than mouse (e.g. in goat), because mice cannot develop anti-mouse antibodies!
I hope I understood your question.


Why "Having chlorophyll without photosynthesis is actually very dangerous" and "like living with a bomb"? The Phys.org article Scientists discover first organism with chlorophyll genes that doesn't photosynthesize says

"For the first time scientists have found an organism that can produce chlorophyll but does not engage in photosynthesis.

It is referring to the new paper in Nature A widespread coral-infecting apicomplexan with chlorophyll biosynthesis genes (paywalled).

"This is the second most abundant cohabitant of coral on the planet and it hasn't been seen until now," says Patrick Keeling, a University of British Columbia botanist and senior researcher overseeing the study published in Nature. "This organism poses completely new biochemical questions. It looks like a parasite, and it's definitely not photosynthetic. But it still makes chlorophyll."
[...]
Chlorophyll is the green pigment found in plants and algae that allows them to absorb energy from sunlight during photosynthesis.
"Having chlorophyll without photosynthesis is actually very dangerous because chlorophyll is very good at capturing energy, but without photosynthesis to release the energy slowly it is like living with a bomb in your cells," Keeling says.

Question: Why is it that "Having chlorophyll without photosynthesis is actually very dangerous" and "like living with a bomb"?

Chlorophyll absorbs photons (light). The energy in the photon extracts an electron from a molecule of water. Electron transfer creates intermediate superoxide and hydroxyl radicals from the oxygen and hydrogen from the donor water molecule.

In normal photosynthesis, these radicals are quickly used to power the reduction of NADP to NADPH and the synthesis of ATP from ADP. NADPH and ATP in turn power the synthesis of sugars from carbon dioxide and water, via the Calvin cycle.

These radicals are highly reactive. If they hang around and don't get used properly in redox reactions, they will just as happily attack DNA, proteins, and structural lipids within the cell, and are therefore dangerous. In normal plant cells that get too much sun, for instance, free radicals can build up and cause cell damage.

My guess is that the author's "bomb" is made up of higher concentrations of these radicals within a cell with no apparent machinery to perform the downstream (photosynthetic) chemical reactions needed to consume them safely.

Edit

I skimmed the (sadly, paywalled) paper, and it sounds like my guess was right, that it is indeed these radicals that are the danger from having chlorophyll, with no light-independent (Calvin cycle) mediated reactions to safely consume the energy in them:

  Chlorophyll itself has no natural biological function outside of
  photosynthesis, so if photosystems are indeed absent, corallicolids
  must have evolved a novel use for either chlorophyll or its closely
  related precursors or derivatives. However, these molecules generally
  function in light harvesting, which would be destructive to cellular
  integrity without the coupling of the resulting high-energy compounds
  to photosynthesis. Other possibilities are functions in light sensing,
  photo-quenching or the regulation of haem synthesis, but these too
  leave open the question of what the cell would do with the highenergy end products.

What's not clear to me is that the genes that help generate chlorophyll are expressed, but the cells are unpigmented. I don't see any explanation where the chlorophyll and associated proteins are localized in the cell — seems like a missing part of the paper, or I missed that part when skimming. Or perhaps the organism has evolved interesting and novel ways to manage the damage caused by these oxygen radicals, or has other mechanisms for consuming them, yet to be identified.

Should motivate further research, especially if these organisms share ancestry with malaria and toxoplasmosis — there might be something interesting to learn that would help with eliminating these diseases. I imagine a biochemical "radical bomb" could be very handy for destroying parasites, if there was a way to expose them to light or some other source of photons; perhaps some drug therapies could target the relevant genes and induce the parasite to destroy itself. Interesting paper.


What's the difference between the spindle assembly checkpoint (SAC) and mitotic checkpoint complex (MCC)? Are the SAC and MCC two separate complexes? Does the SAC activate the MCC? Thanks

It can be helpful look into a few technical articles on the subject to clarify these ideas.

For example, this article has an abstract that lays it out quite nicely in the first 2 sentences of the abstract:

  In mitosis, the spindle assembly checkpoint (SAC) ensures genome stability by delaying chromosome segregation until all sister chromatids have achieved bipolar attachment to the mitotic spindle. The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chromosomes...

So the SAC is a human conceptual model of how cells prevent the improper onset of anaphase before chromosomes are set up properly for cell division. MCC is the actual protein complex acting as an agent to make the SAC happen in cells.

The SAC could be thought of as containing the MCC and any other agents that prevent improper anaphase until spindle assembly and chromosome bi-orientation is complete, but it is not a protein complex per se in the sense of a bunch of proteins that stick together for a specific molecular function.


How does horse extract the energy to needs from a relatively small digestive system? Recently I saw Inside nature's gaints episode on horse, and was fascinated about its internal organisation. And my question is that they have a very large lungs to accommodate, but a relatively smaller stomach. But other herbivores like the hippopotamus have a very large digestive system even though they need less energy than horse. How does horse manage this problem? How do they get that much of energy even though it had small digestive system and more over it is an herbivore?

The digestive system of a horse is by no means small:

They have 15 to 21 m (50 to 70 ft) of small intestine, with a capacity of 38 to 45 L.
They have a 1.2 m (4 ft) long caecum that holds 26 to 30 L.
They have 3.0 to 3.7 m (10 to 12 ft) of colon, capacity up to 76 L.
(Figures sourced from Equine Anatomy (Wikipedia))

Certainly horse stomachs are comparatively small as they are hindgut fermenters, but that is not where most energy and nutrients are absorbed. Some food passes from the stomach to the small intestines before it is fully digested, which enables more continuous eating to keep up with their energy and nutrition requirements. Most proteins, carbohydrates, and fats are absorbed in the horse's small intestine. Some nutrients are absorbed in the large intestine as well, see Is there nutrient absorption in the large intestine of hindgut fermenters?.

The hippopotamus is a pseudoruminant, having a 3 chambered stomach (unlike the 4 chambers of a cow). Hippos are therefore considered to be foregut fermenters, and are not comparable to horses. In terms its digestive tract, the hippo is much more similar to a cow than a horse.


Why do genitals feel frozen when freefalling? I don't want to add much more about that. Since childhood I noticed a chilling effect, even when doing rollercoaster-type activities.

Probably because the blood would be forced, physically, that is, by inertia to move upwards during free-fall, thus causing the genital's blood supply to become obstructed thus reducing their temperature and thus leading to the sensation of them being frozen as you described. Plus you might feel cooler all over your body due to the air flow against it and since your genitals wouldn't be as biologically favoured when your body's survival instincts for low-temperature environments kicks in you're body would probably reduce the blood flow to your genitals and other extremities favouring your vital organs such as your heart, lungs, brain, etc. with a greater blood supply to keep them warm and working.


Why does flatulence vary in temperature and smell? Quite simply, why do some farts feel warmer than others?  Some feel regular, while others feel like lava.  What causes this?

If there is no real temperature difference, why do I perceive some to be warmer than others?  Does this contribute to the smell?  I've notice the hotter they feel, the worse they smell usually.

Kind of a bad question but I'm doing my best to answer.

First, the smell will depend on what goes in - primarily a function of what you ate, and conditions in your gut (including the mix of bacteria).

Next, if you ate something containing large amounts of capsaicin (the chemical that makes chili peppers spicy), it's going to "burn" on the way out. Overconsumption of capsaicin can irritate the intestines and cause diarrhea.


What kind of fish is this? I don't remember the full name but it started with Tiger name starts with tiger, forgot the rest, please help

It's probably a juvenile tiger loach, or tiger botia.

Adult Tiger Loach

Younger individual of another species

These fish are from the genus Syncrossus and the family Botiidae which include many common aquarium fishes. This genus comes from India, Myanmar, and Southern Asia.

These fish can grow up to 20-25cm (~10in).

Syncrossus species can be told appart using appropriate litterature. This specie sheet from seriously-fish is well documented and provide interesting links from further reading and a quick explanation of its taxonomy easily accessible for the average guy,


Gas from bacteria that's not methane Is gas produced by bacteria always mainly methane? Or, are there bacteria out there that produce some biogas composed mainly of hydrogen, natural gas, propane, butane?

Microbes can produce several gasses other than methane.

All microbes produce $CO_2$ through the oxidation of reduced carbon

Additionally some metabolic pathways produce other gases.

Photosynthetic microbes produce $O_2$
Sulfur reducing bacteria can produce $H_2S$ (as @ohcanada points out)
Denitrifying bacteria produce $NO$, $N_2O$, and $N_2$
Fermenters produce $H_2$ (as @mart indicates)

There may be others that I am not thinking of but these are some of the major players...


Advantages of Monogamy over Polygamy and Vice Versa In Nature? Some animals take on a single partner, possibly for life, while others have multiple partners over their lifetime, possibly even at the same time. What are the advantages to each approach, and how much is conscious choice verses instinct?

Polygamy spreads genetics further, but usually you trade that spread for care of the offspring.

Monogamy means less genetic diversity, but the offspring usually get more attention and care, meaning they're more likely to survive.

So it's more babies where more will die, or less babies that take more energy to grow and nurture but more likely to survive.


Why would eating the meat of cows fed with antibiotics trigger an immune response to the antibiotics? The document "Antibiotics and Antibiotic resistance" contains the following paragraph:

  The indiscriminate use of antibiotics in feed stuffs means that humans
  may receive unwanted doses of antibiotics in meats, eggs and milk.
  This exposure may cause the development of an immune or inflammatory
  response to the antibiotic so that the human cannot be treated with
  the drug at a later date. The practice has also resulted in the
  development of antibiotic-resistant strains of bacteria.

Here are my two questions that test general biology principles:

How can there be an immune response to an antibiotic?
I think that the answer to the first question will answer this one anyways, but for the sake of completeness: why would the immune response to an antibiotic prevent the antibiotic from being used again? (I may know how to answer this once I actually know what an immune response to an antibiotic looks like.)

It's difficult to know how to answer this question because it is unclear why you think that this might not happen.

As skymningen has said in comments, any foreign molecule is capable of acting as an antigen,  in principle. We know that people develop allergic reactions to penicillin. And if you do a Google search for immunoassay [insert name of antibiotic] you will probably find results indicating that there are commercially-available kits for assaying the antibiotic based upon antibodies directed against it.

It is however worth noting that these anti-antibiotic antibodies were certainly not raised directly by feeding, or even injecting, the antibiotic. This is because the immune system doesn't really respond to small molecules. If you want to make antibodies directed against a small molecule you have to tag it on to a protein - this is called haptenisation. Then some of the antibodies that develop against the modified protein will recognise the hapten (the small molecule). Another example of this is the development of immunoassay for steroid hormones.

So we have to imagine that a fed antibiotic enters the bloodstream and then reacts chemically with a blood protein - essentially the antibiotic has haptenised itself. I seem to recall reading that β-lactam antibiotics are fairly reactive against lysine residues. The propensity of different antibiotics to provoke an immune response may be simply a function of their reactivity.


Is there a system biology approach to compare pathways or famillies of proteins from an evolutionary point of view for the same organism? I would be interested to know if there is a method/analysis or a set of methods to compare two groups of pathways or families of proteins.

I would specifically be interested by a system biology approach which takes all the components of the pathway or family of proteins. I would like to know if there is a method which can not only compare the similarity, homology, divergence and convergence of a family of proteins (like ribosomal proteins) between species but also between groups in the same organism.

For example I would like to compare the molecular components of vesicular trafficking pathways to the molecular components of non-vesicular pathway in the same organism saccharomyces cerevisiae (yeast).

I would greatly appreciate your suggestions.

I am not sure that I completely understand, it would be a little easier if you described the problem you are trying to solve or what the motivation is.

However, I think that some of what you want to do can be accomplished by inferring gene/protein trees for each gene/protein of interest across different species (including paralogs, maybe?). This will allow you to see discordance or correlation of evolutionary rates of different genes/proteins across species.

THis kind of analysis is built into HyPhy, though I have never used it. There are also somewhat less involved methods for measuring distances between trees.

You might also be interested in protein co-evolution methods, depending on the question at hand.

Your mentioning systems biology methods suggests that you have something rather different in mind, as none of these things I suggest are really systems biology IMO, but I'm not sure what it would be. Possibly you are interested in integrating e.g. protein-protein interaction or metabolic network information as well, but that would probably involve something more homebrewed that might integrate some of these things.

Hope that helps.


Expression of plasmid genes Are plasmid genes always expressed? If so, then isn't a bacterium wasting it's resources in expressing genes (like antibiotic resistance) which are not required in "normal" conditions?

If not, then what triggers bacteria to express genes of recombinant plasmids? Can a bacterium survive in "normal" conditions if it is deprived of all the plasmids?

It would depend of the plasmid, the genes it contains and the promotors those genes have. Basically, regulation of extrachromosomal genes follow the same patterns of the rest. Bacteria, Archaea and some other organisms that can have plasmids will express the genes if the promotors of those genes are constitutive, or if they trigger by conditions that are present in a given moment. The degree of expression would be a function of the characteristics of the promoter and the number of copies of the plasmid. Finally, the number of copies of the plasmid would depend of its size and the characteristics of its replication origin.

Organisms can loss the plasmids if doing so don't suposse a negative effect (this is a big problem in industrial microbiology, since the recombinant strains may be unstable and reduce its productivity). In laboratory, a plasmid containing resistance genes towards an specific antibiotic would remain stable as long as this antibiotic is present in the media. The characteristics of its replication origin also play a big role determining the stabilty of plasmids. You can even select for the loss of plasmids, take the example of URA3 in Saccaromyces (not a bacteria, but the mechanisms are the same), wich can be used as a negative selection factor if the media contains 5-fluoroorotic acid.

So there's no particular advantage in expressing plasmidic genes all the time. When that happens, actually there exist an evolutionary pressure against the presence of the plasmid, and thus it trends to dissapear. Bacteria can survive without plasmids (with the exception of some that carry megaplasmids that acts more than little chromosomes. In some of this cases, the plasmid may contain genes for important methabolic pathways and other key elements of the cell, thought if the genes they carry are very importants, like polymerases or ribosomal RNAs, the term minichromosome is prefered). However, plasmids may contain genes that confer an important advantage to the population (like in presence of an antibiotic), and if so the plasmid spread. If at some point the ecological pressure cease, the plasmid would turn unstable again. Note that it's not impossible to have horizontal genes transfer between plasmid and chromosomes, and plasmids (alongside viruses and foreign transformed DNA) are important sources of new genetic material.


How to interpret dual luciferase assay result (RLU)? I performed a dual luciferase assay using pGL3 firefly luc as experimental reporter and pRL-TK renilla luc as internal control (Promega assay kit). I used a manual luminometer to analyze my sample. After that, I got following result:

Sample        RLU (LARII)                   RLU (stop & glo)

A               1978                               902

B               1702                               1101

C               1952                               980

As I am doing it for the first time, I cannot understand the result. I want to know, how can I interpret this result? There is no unit. RLU stands for relative luminescence unit; but what it actually means? What is the method to compare the results of different samples? How can I understand expression efficiency? I have read some papers but unfortunately my concept is not being clear.

Where can I find useful information and guidance about it?

Relative luminometer units (RLU) have no unit. They are the result of the luciferase reaction and proportional to the expression of the luciferase gene, meaning the higher the numbers are, the higher the expression is.

To analyze these numbers, you usually use a control, to which your samples are then relative to. So expression from your luciferase vector is 10x higher in the treated sample compared to the control for example.

As the RLU has no unit, it is hard to compare measurements directly. To overcome this problem, you can use a second luciferase reaction (the renilla luciferase) to be able to normalize between samples and to correct for transfection efficiency, but still, your values are only relative.

They are influenced but the kit you use for the measurement, the machine you use (so always use the same machine) and so on.

To normalize the values, you divide each firefly luciferase value by the value for the renilla in the same well. Ideally alls renilla measurements are the same (as you transfected the same amount of plasmid in each well, have the same number of cells etc., but if not, this corrects exactly this problem). You cannot calculate the transfection efficiency from this control.

To calculate the relative expression ratios between your sample B and the respective control A, you set the control to 1 by dividing A/A=1 (for example: A=10, 10/10=1) The relative expression of B is then B/A= relative expression (for example: B=5, relative expression: B/A= 5/10=0.5). In the example the relative expression of sample B would be half the one of the control.


Is the sense for salt depending on the electrolyte level in our body? I often noticed, after (heavy) physical activity like cycling, running, swimming or working an isotonic drink (to recover the electrolyte level) tastes less "salty" compared to when drinking it before the activity.

Is this possible or am I just hallucinating?

The object of this (if it's real) could be:

to save us of taking too much salt
to reduce the reluctance against salt if our body is undersupplied (with sodium ions)

My guess is, that the electrolyte or particularly the sodium (chloride) level in our body influences the cells/nerves that sense the taste for salt on our tongue.

Wikipedia says this:

  Salts, sweet, sour and umami tastes causes depolarization of the taste cells, although different mechanisms are applied.

So, I imagine it like this:

If there is enough salt in our body, the cells are saturated with e.g. sodium ions (higher polarization since there are more ions)
NaCl and other salts (probably KCl too) will then dissociate into Na+ and Cl- (etc.)
The Cl- will then attract more Na+ from the cells causing deplolarization
Our brain converts these signals into the proper perception

But maybe I'm just hallucinating... :)

Is this possible or am I just hallucinating?

Certainly possible, but I'd peg the mechanism closer to Sensitization or De-sensitization of the neurons involved so that when you finally ingest some salt the sensation is different. The sodium and chloride levels of the ingested material wouldn't have a direct effect on the level of De-/Sensitization, but rather how low your stores are or how long you've gone without.

  So, I imagine it like this....

What you broadly described is how regular sodium receptors work. They will work that way regardless of what you've been doing, and doesn't really explain an increase or decrease in your ability to taste salt - the signals will fire either way.

Check out the action of the Capsaicin receptor and how it changes sensitivity over short periods of time. I'm betting the phenomenon you're describing will be closer to this (an increase or decrease in the number of sodium receptors in response to the abundance of salts or lack-thereof) than an immediate mechanism from the drink itself.


How were the first primers made? I keep reading about how primers are useful in pcr -- they allow you to select a specific dna region. Similarly, in NGS or Sanger sequencing they give you a starting point. The primers I see are about 20-30 bases long.

However, how were the first primers developed? Somewhere, someone needed to come up with a 20-base sequence that bound to a specific part. Aren't there 4^20 such combinations? That's a lot of potential options to test.

How was that done?

The MIT synthetic chemist Gobind Khorana won the 1968 Nobel Prize in Chemistry for his work which successfully was able to make chains of Ribonucleic acids.  The chemistry was difficult at the time but he won the prize for making specific sequences of RNA bases which were then fed to cells, resulting in specific amino acid chains, which ultimately deciphered the specific base to amino acid correspondence of the genetic code.

Khorana was only one of the chemists who worked on nucelotide synthesis, but the technique overall is simple and since nucleic acid polymers are only unbranched polymers,
any sequence combination is easily obtained.  Each sequential reaction adds one base.  Repeat the reaction as many times as needed.

The chemistry Khorana devised was refined and easily extended to DNA polymers since the linkages are identical, the difference between DNA and RNA is only a single alcohol (-OH) group, which is not directly involved in the bond between the nucleotide bases.

By 1983 when Kary Mullis concieved the idea of PCR, short sequences of DNA and RNA could be synthesized on commercially available machines.  In fact Mullis was responsible for just such a machine at Cetus Pharmaceuticals and had been trying to find a way to increase demand for his services.

The PCR oligos were the easy part of the operation.  To prove the concept, the team at Cetus used a conventional DNA polymerase and add it to the PCR mix after every cycle.  By 1986 the Cetus team had succeeded in performing PCR a heat tolerant DNA polymerase from Thermus aquaticus, a bacterium from a hot spring, which basically made it the technique we still use today.


Pedigree Diagram help I am asked to fill the genotypes in the spaces provided but looks like I am aving a little bit of trouble. can anyone help? thanks in advance!

Here are a few hints that might help:

Talking about Maria's pedigree:
Firstly, it seems as if you have mixed up with $X^a$ and $X^A$, see that the disorder is X-linked DOMINANT. Anyone with either heterozygous or homozygous dominant expression would have the disease expressed. So the first generation male should have a genotype: $X^aY$, because if it were $X^AY$ then Amelogenesis imperfecta would be expressed as his phenotype and the first generation female should have a homozygous recessive genotype. Also no child in the second generation would suffer from the same.
(NOTE: The one suffering from Amelogenesis in the second generation would have genotype $X^AY$)

As for Gunther disease, both the parent in the first generation should have a heterozygous dominant expression and the offspring suffering must have a homozygous recessive expression. And you can apply the same basics in Peter's pedigree.

I think this much should be enough to complete the task, but if you still have some doubt you can put it forward in the comments.


Under what conditions do laboratories have the need to perform both, colony counting and cell counting? It seems that the requirements to perform colony counting and cell counting in petri dishes are quite different. This is especially true, because colony counting can be done with the naked eye, even though it can get very tiring.

Since I am interested to find out what tasks most biological labs have to go through, I was wondering whether these two tasks might be requested by the same types of labs.

Any lab that would like to make the distinction between live and dead cells in a cheap way would use both techniques. You count colonies on petri dishes to get the number of living cells, and count in counting chambers under the microscope to get the total number of cells.

There are easier ways to do this though, for example using this: https://www.thermofisher.com/de/de/home/brands/molecular-probes/key-molecular-probes-products/live-dead-viability-brand-page.html in a flow cytometer. That's not that cheap though.


How do scientists decide which version of a polymorphism is the main one? This in fact has bugged me for years, but now I finally remembered to ask.

I suppose that if one variation is more frequent, it can be labeled as the default, but what about variations that are equally as common?
The example that I just saw, it seems that the frequency of both variants is the same, and yet somebody claims that G is the default and C is the polymorphism:
Polymorphism with genotypes CC, CG and GG occuring in 30, 40 and 30% of the control group, respectively http://hell.org.pl/~kamyk/stackexchange/Zorena1.jpg

Maybe it is possible to determine which one was first, but how? Is there ancient data about polymorphism frequencies?

[..] G is the default and C is the polymorphism

An allele (or just a nucleotide variant) cannot be "the polymorphism". There is polymorphism, if a given locus (or just a given nucleotide position) is polymorphic, that is, if as this position, there are different variants existing in the population. Therefore, an allele cannot be called polymorphism, only a locus can be called to be polymorphic and if a locus is polymorphic, then there is some polymorphism in the population.

I have never of people talking about the main or default variant. Do they use this word in the article you link? If yes, can you please indicate where?

Commonly, people talk about the wildtype versus the mutant variants. In this case, the wildtype variant is just the most common variant. Rarely I have seen people referring to wildtype variant when talking about variants that are at low frequency because the mutant is increasing in frequency and slowly reaching fixation. In such case, the wildtype mutant would correspond to the original variant at an arbitrary time point in the past but would not depend on the frequencies observed today.


Is it true that oral sex exists in non-human animals? For example, outside of humans, do other species of animals engage in oral sex, or any oral stimulation of others' genitals purely for pleasure, not any cleansing habits, etc.?

Basically, what I am saying is, is it true that oral sex, like in humans, exists in non-human animals?

Yes, it is true. Have a look at this post:9 Animals Who Are Into Oral Sex:

  A recent study of fruit bats found cunnilingus to be a major part of their repertoire. While following a colony of 420 bats roosting in a fig tree over the course of 13 months, researchers witnessed 57 incidences of sex — both oral and intercourse. The female bats who received oral sex before intercourse were found to last longer during copulation.

The paper they cite is this one.


Is it possible to have undamaged healthy cell, that is dead? I am trying to clarify my understanding of how unicellular organisms are alive, given my existing background (computational modelling, unrelated to biology). During my thoughts on subject I have came to a conclusion that any unicellular organism, given it's undamaged, and has enough resources (so it does not undergo autolysis), must be always alive.

Is my conclusion true? In other words, is it possible to have completely undamaged cell that appears healthy, but yet is dead? And by "dead cell" I mean a cell that does not move, does not consume any resources, does not respond to any external stimulus an alive cell would respond to, does not divide, etc.

There is a great bit on the podcast "The Infinite Monkey Cage" wherein Brian Cox recurrently asks "When is a strawberry dead?"

If you think about it, it is a difficult question: when a berry is growing on a plant, it is easy to say it is living because the cells are actively dividing and functioning. But when the berry reaches maturity, the autosomal cells no longer divide. This is called Programmed Cell Death or apoptosis. This is a physiological process. However, one could still argue the strawberry is alive in the sense that the seeds are still viable and can actively produce new strawberry plants. These cells are quiescent. What though, if a strawberry is crushed to smithereens or a disease infects all of the cells? In this case the "death" of the cell has ceased function as in apoptosis, but this is externally mediated. This type of non-programmed cell dysfunction is called necrosis.

So, in direct answer to your question, you must taken into account the mechanism (internal or external) for cessation of function and the permanency. Internal and permanent = apoptosis. Internal and temporary = quiescent. External and permanent = necrosis. External and temporary = ...maybe injury?

To be clear, I've used a multicellular plant as an example (because it is easier to relate to than yeast), but the principles are the same for unicellular organisms.

@Flo made the good suggestion to add references for those interested:

Buttner et al. (2006) Why yeast cells can undergo apoptosis: death in times of peace, love, and war. Journal of Cell Biology

Gordeeva et al. (2004) Apoptpsis in unicellular organisms: mechanisms and evolution. Biochemistry


Why is a urea solution hypotonic relative to RBC? If I place a RBC in 0.5M urea we see haemolysis.

My textbook says that "the solution is hypotonic. Urea enters the RBC down it's concentration gradient. Water follows the movement of urea by osmosis. This influx of water causes lysis".

I am very confused by this, for a number of reasons.

I thought tonicity only applies to non-penetrating solutes (i.e. a solution is hypertonic relative to a cell if the solution has a greater concentration of non-penetrating solutes then the intracellular fluid). If urea can penetrate the membrane, then why is the solution hypotonic? As a penetrating solute isn't it not factored into tonicity.
If urea is a penetrating solute, then won't it just come to an equilibrium across the cell membrane, and hence there will be no net osmosis since the concentration inside the cell will the same as that outside the cell.

I feel like I have a conceptual failing here, but the more I google the more confused I get.

I think you have the conceptual understanding down, but my guess is that the textbook is not representing the situation quite correctly.  Based on the phrasing of the statement, I can imagine they are describing one of two situations:

Imagine a dropping a cell in to a solution of 0.5 M urea with no other solutes.  Urea will diffuse across RBC membranes due to facilitated diffusion.  It won't really factor in to this situation much.  So, the RBC contains proteins and other solutes that cause water to flow in to the cell and the cell lyses.  I don't think this is what the textbook means.
Now, imagine a situation in which you precisely calculated the water potential of a RBC.  You mixed up an isotonic solution of urea and some non-penetrating solutes.  This solution is perfectly isotonic at first, but as the urea diffuses in to the cell, it alters the water potential of the cell and the outer solution leading to osmosis.  I think this is the situation the textbook is trying to describe.

Imagine a third situation now in which a RBC is at equilibrium with a solution.  If you just added urea to the solution, it would not affect osmolarity in the long term for the reason you describe.


Highest bite force of a wolf? Some sites say wolves can bite around 400 psi. But this site claims that when facing a peril they can deliver upto 1200 ?https://plexidors.com/myths-around-dog-bite-force/(skip to the 'How does that measure compared to cousins in the wild?' portion to save time)
  -That's a huge range, and could in theory put them on par with big cats.Is what the site says true?
-I looked online extensively in the internet but I only came across a reddit post where they discuss this and it wasn't conclusive.Why is there a maximum bite force of other animals like crocodiles,gorillas,hyenas etc but not for wolves?

The range from mean to maximum of wolve's bite force is huge.

Is it really? According to this Wikipedia page, (Scully, C. (2003). Oxford Handbook of Applied Dental Sciences. p. 151) claims that human masticatory forces range from 70 N to 700 N. Also, (Kim et al., 2018) claims that domestic dogs have a bite force of (147-3417) N, so I don't think it's too implausible for wolves to have the value of (774-2255) N of wolves that @Olga_Swider claims. We see also, on Table 4 on p. 550 of (Eng et al., 2013), the estimated maximum bite force (MBF) spread over the $M^2$ area of the jaw. Eng claims that Gorillas and Chimpanzees have MBFs of 3200 N and 1800 N respectively. I think there's quite a large degree of control of masticatory muscles, which wouldn't make it too surprising that you can have a large range of forces.

  This range of wolves' bite forces could put them on par with big cats.

According to p. 621 of (Wroe et al., 2005), lions have a bite force of around 1768 N, while tigers have a bite force of 1525 N. So, it seems that wolves have a significantly smaller mean bite force than big cats. But bear in mind that while dogs and wolves might have a fairly similar jaw size, lions jaws are much larger so their bite force is spread over a much greater area. So exercise caution when comparing them. Similarly, note that PSI is a unit of pressure (force over area), while newtons are a unit of force.

  Why isn't there a maximum bite force for wolves?

Says who? Of course there's a maximum. Wolves can't make arbitrarily large forces with their mouths, that's physically impossible.


Does the false positive covid-19 PCR % referred to by Surkova & Nikolayevskyy in The Lancet mean % of all tests, or % of positive tests? In False-positive COVID-19 results: hidden problems and costs it is said:

The current rate of operational false-positive swab tests in the UK is
unknown; preliminary estimates show it could be somewhere between 0·8%
and 4·0%

My questions:

Are there any more accurate estimates or research done on the real false positive rate than what Surkova & Nikolayevskyy are referring to?
Is Surkova & Nikolayevskyy referring to a percentage of total tests done, or a percentage of positive tests?

To clarify. Let us, for the sake of example, say that the false positive rate they are talking about is 1%, and one day we test 100.000 people, and that we get 5000 positive results. Will that mean that:
A: 1% of the 100.000 are false positives, therefore there are 1000 false positives?
or that
B: 1% of the 5000 that tested positive are false positives. Therefore, 50 are false positives?

Actually, neither A nor B in the example are a correct interpretation of a false positive rate, because there isn't enough information provided to determine a false positive rate. In the terminology of clinical diagnostic testing evaluation, testing outcomes can be classified into one of four fundamental categories: True positive, false positive, true negative, or false negative.
While there are four possible outcomes, any given patient only has two possible test results, positive or negative. And the assessment of that result depends on whether they have the disease or not. So patients with the disease can only have a true positive or a false negative, and patients without the disease can only have a false positive or a true negative.
Since it's not possible for a patient with the disease to have a false positive, we get to ignore them in calculating a false positive rate. So a false positive rate would be the number of false positives out of the total number of possible false positives (or the percentage of patients without the disease who test positive). With an ideal data set in which you knew both the test result and true infection status of each patient, you could calculate it like this:
$$ FPR = \frac {False\ Positives}{False\ Positives + True\ Negatives}$$
The thing is, we don't usually use this in evaluating clinical diagnostics, but rather it's complementary value, which is called "specificity" (for some reason), and is essentially true negative rate.
$$ Specificity = \frac {True\ Negatives}{False\ Positives + True\ Negatives}$$
But note that neither of these values can give you the number of false positives in your example without more information. If you assumed that all 100,000 people tested did not have the disease, then you'd expect 1000 false positives (given your 1% false positive rate). But it gets more complicated when you have a non-zero rate of infection in the tested population. The greater the underlying infection rate, the fewer false positives you expect to see (and vice versa, with a lower infection rate, you expect a greater proportion of positives to be false, which I think is pointed out in the article you linked). Basically, it's really hard to determine something like a false positive rate on the fly and even harder to estimate it's impact in the real word, especially when the test you're trying to evaluate is also the best means you have for determining true infection.
Another consideration is that, for a well designed PCR diagnostic test (most COVID tests are), the majority of false positive results will come from technical errors (i.e. cross contamination, mislabeled specimens, etc.), rather than randomly from the test itself. And the rates of those kinds of errors can vary with the underlying rate of infection, the number of tests being processed by a given lab, the level of training those lab workers have, the number of hours they're putting in (tired people make more mistakes), and probably other factors I'm not considering.


Is there any evolutionary advantage of selection of L-amino acid over D-amino acid? After listening to a scientific talk, I had this question that why in the natural selection process, are the L-amino acids selected over the D- form. However, we still we produce D-amino acids; specifically in the brain there is a higher concentration of D- amino acids. One possible reason is that they act as neurotransmitters.

The current thinking amongst biophysicists is that if we all woke up tomorrow to find that someone had edited the book of life so as to exchange all of the L-'s and D-'s (and made similar mirroring changes to all of the molecules that any protein interacts with), everything would be exactly the same.

Milton, et al. (Science, 1992) lent supporting empirical evidence to this view by carrying out the total chemical synthesis of a D-enzyme, D-HIV-1 protease. They showed that the L- and D- versions of the enzyme had identical and reciprocal activity, meaning that L-enzyme cut the L-substrate well and the D-substrate poorly, and vice-versa for the D-enzyme:

They also showed that the structures the L-enzyme and D-enzyme were mirror images of one another:

The preference for L- forms over D- emerged sometime early in evolutionary history, and there's a lot of speculation as to how the preference arose (it could have been cosmic rays!), but the evidence is thin.


What determines whether a reaction using ATP produces ADP or AMP? Most reactions using ATP seem to involve:
ATP → ADP + Pi
but in some the reaction is
ATP → AMP + PPi
followed by hydrolysis of the pyrophosphate:
PPi → 2Pi
Is there any principle that determines which ATP-requiring reactions generate ADP and which generate AMP? And is there any reason why the generation of inorganic phosphate does not proceed as follows?
ATP → ADP + Pi
ADP → AMP + Pi

Summary
It is the nature of the biochemical reaction that determines whether a reaction of ATP involves hydrolysis of the β- or γ- phosphoanhydride bond. If a part of the ATP molecule is incorporated into one of the products, the choice of bond to be cleaved emerges from the chemistry of the reaction. If the hydrolysis (with a negative free energy change, ΔG) is being coupled to a reaction with a positive ΔG, hydrolysis of single (γ-) phosphoanhydride bond usually suffices, with the production of ADP and Pi. If the free-energy of hydrolysis of the phosphoanhydride bond is being ‘transferred’ to another molecule in order to ‘activate’ it for a specialized group-transfer role (often in the synthesis of macromolecules) two bonds are often broken: the first (β-) transfers the free energy with the production of pyrophosphate, whereas the second (now in the pyrophosphate) is hydrolysed non-productively (free energy lost as heat) to ensure that the overall reaction is irreversible.
Energy considerations in reactions involving ATP
I have discussed some of this at greater length in an answer to another question, however it is important to clarify this at the outset. In considering biological reactions, it is usual to adopt a thermodynamic approach in which the thermodynamical (Gibbs) Free Energy change (ΔG) of the reaction is considered. This is because, to quote from Berg et al.:

A reaction can occur spontaneously only if ΔG is negative.
A system is at equilibrium and no net change can take place if ΔG is zero.
A reaction cannot occur spontaneously if ΔG is positive. An input of
free energy is required to drive such a reaction.

The literature provides values of the standard free energy changes, ΔGo, for reactions, i.e. the values obtained under conditions in which the concentration of all reactants and products are set at the same concentration. The actual free energy change, ΔG, depends on the concentration of reactants and products (mass action effects).
The hydrolysis of the β- and γ- phosphoanhydride bonds of ATP both have a high negative values of ΔGo of ca. –45 and –30 kJ per mol, respectively†.
Use of ATP to drive unfavourable reactions
In many cases the hydrolysis of ATP is coupled to an energetically unfavourable reaction (one with a +ve ΔGo) so that the coupled reaction has overall negative free energy change and hence the energetically favourable reaction can take place:
A → B                    ΔG =  20 kJ/mol (unfavourable)
ATP → ADP + Pi           ΔG = –30 kJ/mol (favourable)
A + ATP → B + ADP + Pi   ΔG = –10 kJ/mol (favourable)

In this hypothetical example, 20 kJ/mol of the free energy of hydrolysis of ATP is used to convert A to B, the other 10 kJ/mol is lost as heat, but makes the reaction essentially irreversible. The energy of hydrolysis of only a single phosphoanhydride bond is sufficient for this, and is achieved by the hydrolysis of the γ bond with the production of ADP. (Hydrolysis of the β bond would ‘loose’ the second bond in pyrophosphate, where its hydrolysis cannot be used productively.) An example is the conversion of pyruvate to oxaloacetate in gluconeogenesis, in which energy is required to form a carbon–carbon bond:
CH3COCOO– + HCO3– + ATP → COO–CH2COCOO– + ADP + Pi
Incorporation of ATP into products
In some cases there is not only hydrolysis of a phosphoanhydride bond, but a chemical component of ATP is incorporated into one of the products. In this case the actual chemical reaction determines which bond is hydrolysed.
In the first type of reaction a phosphate group is incorporated into the product, in which case this will obviously be the γ-phosphate and ADP will be generated. A simple example of this is the hexokinase reaction:
Glucose + ATP  → Glucose 6-P + ADP
The reaction is essentially irreversible as the energy of the hexose phosphate bond is much less than that of the phosphoanhydride bond.
In the second type of reaction the AMP component of ATP (or similar molecules) is incorporated into one of the products, so that the other product must be pyrophosphate. The obvious example is the RNA polymerase reaction, which for our purposes can be represented as:
------ribose-3′OH + ATP → ------ribose--3′O-PO2-O-5′-Adenosine + PPi
ATP and ‘activation’ reactions: rationale for pyrophosphate
In certain reactions of ATP the energy of a  phosphoanhydride bond is being used to created a bond of similar free energy of hydrolysis, which can itself be used subsequently to activate other reactions. In this case the reaction may involve little of no free energy change, so that it would appear to be easily reversible. In many such cases the β phosphoanhydride bond is cleaved, generating pyrophosphate. The rationale for this is that the pyrophosphate is then converted to phosphate in a reaction catalysed by pyrophosphatases, which has a high negative DG and is hence essentially irreversible because the free energy of hydrolysis of the phosphoanhydride bond in pyrophosphate is lost as heat.
A + ATP → B + AMP + PPi     ΔG = 0 kJ/mol (reversible)
PPi → 2 Pi                  ΔG = –33 kJ/mol (irreversible)

The examples often given to explain this are the nucleic acid polymerase reactions, but, although this applies also to them, the nature of their reaction necessitates the generation of pyrophosphate. To some extent this is the case with most other activation reactions, but it may be clearer to consider one in which the component of ATP is incorporated as a temporary intermediate, rather than as a component of the end product. Such a reaction is amino acid activation for protein synthesis:
amino acid + ATP → aminoacyl-AMP + PPi
aminoacyl-AMP + tRNA → aminoacyl-tRNA + AMP
The ‘activation’ is the formation of bond with a high free energy of hydrolysis in the aminoacyl-AMP from the β phosphoanhydride bond. This is then used to drive the reaction forming a bond between the amino acid and the tRNA. The generation of pyrophosphate ensures the effective irreversibility of this key step in protein biosynthesis.
†Possible role of differences of free energy of hydrolysis
The fact that the standard free energy of hydrolysis of the β phosphoanhydride bond is greater than that of the γ phosphoanhydride bond may also be relevant in some cases, as @user1136 has argued in his answer to this question.


Genetic Drift: Models, assumptions and empirical observations There two main mathematical models to describe the process of genetic drift are Moran model and Wright-Fisher model.

My questions concern the assumptions of these models, the existence of other models of genetic drift, explanation of the advantage/disadvantage of these models and the empirical results supporting one or another model.

What are the assumptions of each of these models?

stable population size?
iteroparous/semelparous
what about the probability density function of the fitness?
…?

What advantage/disadvantage do these models have? Or I should say, to which population do these various model applies?
What kind of biological population has been empirically shown to fit better one model rather than another one? What are the key experiments to test the validity of these models?

Please do not hesitate to post even if you answer only partially to the questions! Thank you!

This question has been around for a while, so I'll try to start with a partial answer.

The basic assumptions of the standard Wright-Fisher-Model are:

Constant population size $N$.
Discrete, non-overlapping generations.
Neutrality (e.g. all individuals are equally likely to reproduce)

I prefer looking at the model for haploid/chromosomes. If you bundle up chromosomes to polyploids, then you get the additional assumption of random mating, e.g. all pairs of individuals are equally likely to reproduce.

I might have missed something, but these assumptions should be sufficient to generate the Wright-Fisher-Dynamics: When we build a new generation, we have to fill $N$ spots again (follows from the first two assumptions). As each old individual is equally likely to reproduce (third assumption), e.g. to become parent of a new individual, we get the multinomial offspring distribution.

The main difference in the Moran model is that it assumes overlapping generations. Main assumptions here are:

Again constant population size.
Individuals reproduce at a constant rate.
Neutrality (however the Moran model can relatively easily be adapted to incorporate positive selection).

Every time an individual reproduces, another one instantly dies to maintain the constant population size.

Interestingly, the models have the same diffusion limit, e.g. they behave similarly for large populations (and identically for an 'infinitely large population'). If you trace the ancestry of a sample back in a large population, you will get close to Kingman's Coalescent under both models.

I think the two models exist more because of their distinct mathematical properties, than because one fits better to certain natural populations than the other. I'm not aware of any experiments that have shown how well they fit, maybe someone else can jump in here.


How do we predict the lifespan of dinosaurs? Of course, they are fossils now. I found a link here which states that herbivors lived far longer than carnivores. The example being a T-Rex being "old" at 29, and a herbivorous Bothriospondylus having not reached half it's adult size at 43 years old.

But, is there any evidence that can indicate their life spans, or life spans of at least one kind of the dinosaurs?

An additional brief question is are their lifespans comparable with modern day descendants?

Your first question appears to be answered (tentatively, at least) in the article you linked to...

  "Traditional" estimates based on slow, reptilian growth rates,
  combined with the enormous size of dinosaurs, led scientists to
  conclude it could be up to several hundred years. However,
  palaeontologists today believe that dinosaurs grew much more quickly,
  rather like birds and mammals.

Then...

  Dinosaur bones grew like those of other vertebrates, by adding new
  bone matter to the outside of the bone. Because of annual variation in
  temperature or the availability of food, periodically bone growth
  would slow down, and a thin layer of a vascular bone would form a ring
  or "growth line" in much the same way that tree trunks do. By taking
  thin slices of bones, these rings can be viewed under a polarised
  light source. Counting the rings can give an idea of the dinosaur's
  age at death.

Theoretical ages of some specific species are given in various articles, including Wikipedia and LiveScience.

The infamous T. rex theoretically reached adulthood at the age of twenty (similar to humans) and reached an age of at least twenty-eight years. I think most contemporary animal species mature much more quickly than that...but few approach T. rex in size. The hypothetical ages given for some of the smaller dinosaurs appear to be more in line with modern living species.


Why is compensatory negative supercoiling generated in a positively supercoiling ccDNA? I was reading DNA replication in E.coli in Lehninger Principles of Biochemistry 6th Ed. and stumbled upon the following --

  The tight right handed wrapping of DNA around DnaA oligomeric complex induces an effective positive supercoil. The associated strain in the nearby DNA leads to denaturation of AT rich DUE region.

Edit:

Yet again I have come across the following in  in Indian Molecular Biology books which certainly contradict Lehninger.

Binding of DnaA protein to oriC initiates unwinding of the DUE by introduction of negative superhelical turns.

I've done a little more research and found this paper, which clarifies the problem I previously had:

  As a right-handed ATP-DnaA spiral would be expected to
  wrap DNA into a positive supercoil, adjacent DNA regions would be
  subjected to compensatory negative writhe (Fig. 6d, left). Although
  any superhelical strain generated by DnaA-mediated wrapping would
  be expected to spread throughout the topological domain that con-
  tains the origin, it may preferentially affect the nearby DUE, which is
  unstable and prone to spontaneous unwinding (Fig. 6d, top arrow).

Changed question: Why is this negative supercoiling generated in a positively supercoiling ccDNA?

For a piece of topologically constrained DNA, Lk is constant. Since Lk = Wr + Tw, if you increase Wr in one area, it can be compensated by decreased Wr or Tw in an adjacent area. You may ask why the unwinding is concentrated in the adjacent region and not spread throughout. This is explained in the paper you link to:

  Although any superhelical strain generated by DnaA-mediated wrapping would be expected to spread throughout the topological domain that contains the origin, it may preferentially affect the nearby DUE, which is unstable and prone to spontaneous unwinding.

The DNA unwinding element (DUE) is unstable because it is AT rich:

  …the opening of individual AT/TA base pairs in the three DUEs investigated differs from that of GC/CG base pairs in at least two respects. First, the opening of AT/TA base pairs is significantly more favorable, kinetically and energetically, than that of GC/CG base pairs. Second, the opening of AT/TA base pairs is affected by long range effects of the DNA base sequences, whereas the opening of GC/CG is insensitive to the base sequence beyond that of nearest neighbors. The first difference confirms the earlier proposal that the high content of AT and TA base pairs is necessary to lower the stability and enhance the dynamics of the three DUE sites. The second difference suggests that the sequences of these AT and TA base pairs have been selected by evolution as a means to modulate the energetic stability of the three DUE sites according to their location and function in the origin of DNA replication.


Is sexual reproduction outside the same biological family possible? Has it ever occured successfully? Are there any examples of two species taxonomically classified in different biological families that have successfully hybridized and produced viable offspring? If not, is there an example of where reproduction occured with non-viable offspring?

To be clear, I mean regular sexual reproduction that could occur in the natural world outside a lab. Even so, I'd be curious to know if it could even occur in a lab without direct genetic manipulation.

For example, grolar bears which are ursid hybrids between different species in the Ursus genus are known to exist. Also ursid hybrids between bear species in different genuses have been produced in captivity (sloth bear Melursus ursinus x Malayan sun bear Ursus malayanus and sloth bear x Asiatic black bear Ursus thibetanus). Would an extra-familial hybridisation be possible? Would this be more likely in the plant kingdom?

This question is inspired by a separate question on the Gardening SE which hints at a general lack of understanding of the genetic similarity required for cross-pollination in plants. It made me wonder whether there are any exceptions to the general assumption that extra-familial hybridisation is impossible.

Interfamilial hybrids have never, to my knowledge, been recorded occurring naturally (without human intervention).

In plants, somatic inter-familial hybrids have been produced for a wide variety of species pairs in the lab (e.g. between carrot and barley; Kisaka et al. 1997).

In animals, there are some historical reports of hybrids between chickens (Mathis & MacDougald 1987) or peafowl (Serebrovsky 1929), both in Phasianidae, and guineafowl (in Numididae). The animal example meets your condition of being outside the lab, although they were produced by breeders.

Refs

Kisaka, H., Kisaka, M., Kanno, A. & Kameya, T. (1997) Production and analysis of plants that are somatic hybrids of barley (Hordeum vulgare L.) and carrot (Daucus carota L.). TAG Theoretical and Applied Genetics. 94 (2), 221–226.
Mathis, G.F. & McDougald, L.R. (1987) Evaluation of interspecific hybrids of the chicken, guinea fowl, and Japanese quail for innate resistance to coccidia. Avian Diseases. 31 (4), 740–745.
Serebrovsky, A. (1929) Observations on interspecific hybrids of the fowl. Journal of Genetics. 21 (3), 327–340.


Stay young by reinserting own DNA from years ago? As far as I know, the DNA sequence becomes shorter every time a cell divides.
A shorter sequence results in information loss and aging characteristics.

As a countermeasure, shouldn't one stay young and healthy at least longer, if the DNA in a cell is changed with a "better" DNA (from years ago... let's say your DNA was extracted with the age of 20 and you reinsert it every 10 years or so)?

If this is true, then (as for today's technology)
- is it already possible to perfectly reproduce the DNA? (I only found articles about XNA)
- is it possible to easily replace the DNA in all human cells? (I found articles about bacteria inserting pieces of DNA into human cells)

Lots of questions here. I recommend taking college level courses in Biochemistry, Molecular Biology, and Medical Physiology, and Geriatrics.

There are other issues than just DNA. Systemic failure is system-wide, and probably most of the issues are still yet undiscovered. Good news I guess if you want to be a researcher in this exciting field! As for DNA-ends, read up on Telomerase. As for DNA copying learn about PCR and sequencing methods. Generally speaking, reverse transcription can be dangerous. Please see many of diseases we are having a hard-time solving, which often use these pathways. Seriously avoid that one. Not everything in DNA is used by the organism at any given time, and some information is elsewhere. Moreover, what if we use DNA as DATA storage besides blueprint information? Hint: while the jury may be still out on Neurons, environmental factors may be passed as epigenetic traits by not just primary shape such as DNA methylation but by obstructing access via conformation and histone wrapping. Not even mentioning mitochondrial dna or prenatal development factors.

Instead: A good diet and exercise.


Kinetics and de novo protein prediction De novo conformation predictors usually function by producing candidate conformations (decoys) and then choosing amongst them based on their thermodynamic stability and energy state. Most successful predictors will have the following three factors in common:

  1) An accurate energy function that corresponds the most thermodynamically stable state to the native structure of a protein

This is an excerpt from Wikipedia. I have a very, very limited understanding about de novo protein prediction so here goes.

I asked the post-doc I'm working with about whether there are kinetic barriers to protein folding. Yes, everything wants to be at an energy minimum, but sometimes that just can't happen due to kinetic barriers (the reason your diamond ring doesn't turn into graphite/pencil "lead"). So, why does protein prediction software look for energy minimums? Do they also consider activation energy barriers? Do they take into account the presence of chaperonins? Are there examples where the thermodynamically most stable protein conformation is not the biologically active protein? The post-doc told me that perhaps most proteins do reach their thermodynamically most stable state. True?

Generally speaking, structure prediction programs look only at the thermodynamic minimum, without consideration of the kinetic trajectory of folding.

The main reason for this is mostly time considerations. It's very difficult to accurately model the true folding pathway of even a moderately sized protein. With special tricks and a bunch of computing power, we're barely able to simulate a folding trajectory of small, simple proteins. We aren't (yet) able to do so with anything of reasonable size.

Instead, what protein structure prediction programs do is take a shortcut, skip the physically-realistic folding simulation, and instead look for low energy models, with the assumption that these low energy states will look like the natively folded proteins.

(One such program I'm familiar with - Rosetta - effectively takes small backbone structures already seen in crystallized proteins, stitches them together and asks if that looks like a reasonable structure for the sequence. If not, it tweaks which backbone fragments it uses, repeating until it gets something it thinks looks good.)

This assumption - that the native structure of the protein is the global energy minimum - is called Anfinsen's hypothesis. One rationale is related to Levinthal's paradox: unlike simple chemical reactions, a protein folding trajectory has too many degrees of freedom for even nature to exhaustively sample all conformations. This implies that stably folded proteins evolved with well defined "energy funnels" - that is, the energy landscape of well-folded proteins is such that the folded form is "downhill" from a large number of potential states. Since a large number of potential states need to point toward the folded form, this implies that the local minimum of energy which is the folded form is also likely the global minimum of folding.

The energy differences in protein folding also tend to be small - it's relatively easy for proteins to climb back up of local minimums and go elsewhere. Without the strong, global energy funnel to direct them toward a stable state, it's difficult to keep proteins from unfolding and refolding. This is why kinetic considerations like controlling the trajectory of folding from a ribosome, or having special chaperonins don't really work. Because chaperonins are catalysists, they change the rate of the reaction they're involved in, but not the equilibrium. Microscopic reversibility means that any protein which randomly collect enough energy can use the chaperonin to escape the dead end it was put in: it's not a one-way gate.

Now having the kinetic minimum be the thermodynamic minimum doesn't have to be the case - it's just the case for the vast majority of proteins we've seen. There are certain systems where we're pretty sure the normal folded form is in a local kinetic trap, and with time it can escape into a more stably folded version. Amyloid fibrils and prion proteins are thought to be one such instance. The normally produced version is in a low-energy kinetic minimum, but over time or through various interactions with amyloid or other prion proteins those proteins can relax into an alternative, lower energy conformation.

The keyword here for future literature searches is "kinetic trap". Some kinetic traps are very short lived (microseconds), but other may be longer.

Finally, I'll point you to the paper "The Protein Folding Problem" by Dill et al., which is a good review on the topic of protein folding.


Is there a simple way to generate sets of sequences that re-capitulate the topology of pre-defined phylogenetic tree I would like to generate ensembles of N sequences in such a way that the phylogenetic trees obtained from my ensembles (e.g., by neighbor joining) have the same (or nearly the same) topology as a specified "real" tree obtained from an alignment of N proteins.

My starting point would be an empirically determined amino acid substitution matrix. The matrix would be used to generate a "random" sequence representing the root of my simulated tree. The root sequence would then be evolved, "split", and its products evolved, iteratively until N sequences are generated. Somehow, the topology of the "real" tree would be used to guide the branching process.

This problem arises in determining the significance of correlations between mutations at different sites in a protein (specifically, the "mutual information" measure). One would like to determine the contribution of "pure phylogenetic" correlations to the mutual information for a given alignment of proteins.

The answer to my question seems connected to the "parametric bootstrap procedure" commonly used in phylogeny reconstruction. In fact, the reference below seems to use this procedure to generate the ensembles I describe above. However, their procedure is not explained in detail. This makes me think that there may be a simple answer to my question.

reference :

"Separation of phylogenetic and functional associations in biological sequences by using the parametric bootstrap"
K. R. Wollenberg and W. R. Atchley (2000) PNAS 97, 3288–3291

Yes, what you are looking for seems to be an alignment simulator, which is quite commonly used in phylogenetics. Given a phylogenetic tree and a substitution model, you can use for instance INDELible or DAWG to simulate the extant sequences (N sequences at the tips). These programs can also simulate the indel process (gaps), which means your final sequences won't have, by default, the same length -- but you can change the settings to exclude insertions/deletions.

There is no absolute guarantee that the tree estimated from the simulated sequences will follow the "true" one (used to simulate the sequences), but they should be close enough if:

you don't simulate gaps
the branch lengths are not too short
the sequences are large enough


Why DMSO is used as a control? Coming from a non-biology background, I've realised many academic papers on experiments use DMSO as like a control. This is an example:

  KN-93, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation in vitro

What make DMSO so special that so many scientists use it for their experiment and report their results? Why do we need it in the first place?

DMSO can be used as a solvent for a range of experiments. In these cases it makes sense to use the solvent as the control.