Is scalable growth the main reason why Darwinian systems select Fibonacci sequences? The other day I was thinking about evolution of multi-cellular organisms, and why from the earliest onset of the development of communal cellular structure building, life may have selected a simplest possible strategy for building scale-able structures.

We humans employ relatively complex mathematics and measuring tapes to engineer structures, and we build them to full size, or modular so they assemble. We like proportionality, and there are strength and weight considerations associated with it, but we are not entirely ruled by these considerations. But it maybe that life is far more dependent on proportionality considerations. Life grows sequentially from a single cell, and each cell possesses both the building machinery, and what must be a relatively simple genetic program to govern growth. Because the generic programming operates on the basis of individual cells, there is conceivably a limit to the complexity of program you can expect life to be employing. And even if genetic coding is capable of tremendous complexity, life’s still going to select the simplest most effective approach. So how does lifes growth system achieve such consistently proportional results?

The answer may reveal itself, when you try to conceive of a building method that achieves the same outcome life does. That is to say, building a small scale structure, that will later scale up to full size through a growth cycle, and maintain a proportionality. If for example you build a small scale brick building, whereby the bricks can replicate and divide like living cells. Then so long as each brick does so at an overall synchronous rate, starts with select proportions and follows a very simple program governing growth that abides a proportionality which stays constant at all scales. Like the Fibonacci series rectangle does. Then the building can be scaled up through a smooth growth cycle while remaining structurally proportional. What you start with will determine your end result. And most importantly, having used a minimalistic coding system.

So what’s interesting, is that this is potentially a sound reasoning for why Fibonacci series emerges from such a fundamental level within Darwinian life. Life in the oceans subsisted as single celled organisms, but as soon as it started experimenting with multi-cellular structures, it needed to solve these issues of scale-able growth.

If this is correct, then it opens a fascinating window on a process of early life. Who knows what types of biological evolutionary insights might be derived from it.

Does this scenario sound plausible to more people than just me?

I really wanted to put my thoughts into words as to why biological systems conform to Fibonacci's series.

What you say is entirely plausible and it does make sense. But what I wanted to address was why do these systems conform to it.

It is because of the interactions with the environment

Explaining this concept on multicellular organism first requires answering the same question in bacteria. Towards this end, I would like to point you towards this wiki page

It comes down to parameters such as medium concentration and hardness, parameters which we can influence. If we can extrapolate from this that cells, any cells will always follow a chemokine/nutrition gradient then we can start to understand why the system conforms to a fibonacci sequence.

Next, check out this video on a wound healing assay, what i would like to bring to your notice is that you'll find the cells replicate and move at the same rate.

If you follow a chemokine gradient, and move at approximately the same rate as your 2 billionth cousin, wouldn't you end up inevitably creating a symmetric structure?

Finally, I would, point you towards this article, where they explain a phenomenon called cell migration. This is particularly responsible for creating the symmetry which you see. And this is a similar article as the top one but it should be open access. Both support an idea which has been observed, I tried searching for the video but couldn't find it. The idea being that cells migrate collective, but there are some cells which are leaders and some followers. The leaders lead the collective migration (creating some sort of chemokine gradient) while the followers follow this gradient.

I attended a seminar last year by D Gilmour from EMBL. He showed us this particular video on collective cell migration and deposition of small clusters of cells which go on to establish the lateral line in zebrafish. You will find that a periodicity exists in this migration pattern. He relates it to a ligand activation. The related article to the video should be this one (I thought so after reading the abstract)


Staining cells for FACS at 4 degrees or ambient temperature I'm sorting a 293 derived line. One thing that is worrisome for me is cell viability after the sort. Usually I have been staining and washing at room temperature (on the benchtop) on a nutator. I have been reading that most sorting procedures indicate that you should be doing this at four degrees in the dark. It is my understanding that this helps with clumping, but is this at the expense of viability? Does the cold cause these cells to apoptose?

Currently my procedure is the following -

Using HBSS + 1 mM EDTA + 1% BSA (sort buffer) I suspend approx 10-15 million cells per/mL.

Stain with primary
Spin at 300 x g for 5 minutes
Add 15mL of sort buffer, spin again
Stain with secondary in 1 mL of sort buffer
Wash x2 with 15mL
Strain
Sort

One thing I can do to minimize cell death is do a live/dead stain (we just added that capability). The other thing I read was to use 50% FBS in your collection tube.

The other thing that might be of concern is that if we are doing many sorts, then some of the tubes may be sitting in sorting buffer for a long time in the queue. How long is too long?

Lastly, we use puromycin and blasticidin as selection markers for our libraries and we usually add these right to the sort after we replate. Should we wait a while?

Thanks for the advice

You have several questions, please try to limit your posts to one question each. That being said, I'll try to address each of your concerns.

  Does the cold cause these cells to apoptose?

No. The purpose of staining at 4°C and washing with cold buffer is twofold - to maintain viability (all cellular processes slow down at lower temps) and to prevent receptor internalization. This second point is especially critical as you're using a primary and conjugated secondary, which I really wouldn't recommend for sorting unless absolutely necessary, for example if the antibody you're using isn't available in a directly-conjugated format.

  One thing I can do to minimize cell death is do a live/dead stain (we just added that capability).

Live/dead stains are generally a good idea, but make sure the stain you're using isn't cytotoxic. L/D should always be the last staining step before running your samples. A better way (if your sorter supports it) is to use forward scatter (FSC) and side scatter (SSC) height and area measurements to discriminate single, appropriately-sized cells, then gate on them first before gating on your antibody stain (FITC or PE or whatever your secondary is).

  The other thing I read was to use 50% FBS in your collection tube.

I'm not sure how much that will help, especially 293s, which are pretty tough. Just make sure you're diluting the collected cells enough in medium to bring the serum percentage back down to 10%.

  if we are doing many sorts, then some of the tubes may be sitting in sorting buffer for a long time in the queue. How long is too long?

As long as your samples are kept in the dark on ice or at 4°C, they should be fine for several hours at least (I wouldn't go overnight, though). Also, make sure your collection medium is chilled, as it can shock the cells to go from 4° to 37° too rapidly. Collect your sample, plate it, then put it at room temp or in the incubator (depending on your workflow) and let it warm up that way.

  Lastly, we use puromycin and blasticidin as selection markers for our libraries and we usually add these right to the sort after we replate. Should we wait a while?

Nah, don't worry about it. You can wait if you want, or add it right away - I would lean towards adding it more quickly than not, so you don't give unwanted cells any chance of growing out.


How did aquatic dinosaurs go extinct? Dominant theory is that 'normal' dinosaurs went extinct from ether super volcano or meteor impact or combination of both. However there were aquatic dinosaurs that are not present at this day. Was it one of the events above that caused them to go extinct, or was it something else?

How did aquatic dinosaurs go extinct?

Spinosaurs (like Spinosaurus) are currently only known from 112-97 million years ago, although isolated teeth push the origin possibly back to ~150 Mya. At least now, there isn't any definite spinosaur material younger than 97 Mya.

So spinosaurs were already extinct when the rest of the non-bird dinosaurs went extinct at the end of the Cretaceous, whether by meteor impact, volcanism, a combination, or something else completely.


What is most ancestral: isogamy or anisogamy? Sexual reproduction can be feasible with anisogamy (gametes of different sizes i.e. genders) or isogamy (gametes of same size i.e. mating types) or with undifferentiated gametes (i.e. true random mating; although I have to confess that I am not aware of such example).

De novo evolution of sexual reproduction happened several times independently. What seem to be the most ancestral states of gamete differentiation (isogamy or anisogamy)?. Does it differ between lineages?

As stated here the first sexual reproduction seems to be isogamy, which's purpose was likely to repair the DNA, as a damaged cell could repair its' (DNA) strands via recombination with a "healthy" one.

As for lineages, the only thing I could find was also in this book at the very beginning, but there doesn't seem to be a difference as for which is the most ancestral.


What is the mass of a human retina? I'm struggling to find a reference for the mass or density of a human (monkey or rabbit would also work) retina.

I'd appreciate any help!

I did some research and I found this site : https://www.covance.com/content/dam/covance/assetLibrary/posters/StrubleEVER14.pdf

It has the weight for ocular tissues for different kinds of animals ( rabbit , human  etc. ).

I also found that the area of a retina is 1094 mm² and the thickness is 0,12 mm , so if you can find the density you can find the mass.

(found on this site https://faculty.washington.edu/chudler/facts.html#sensory )


Significance of Nissl bodies What is the significance of Nissl bodies? How are Nissl bodies different from any other RER seen in any other cell of the body?

I am going to try answer this question.

The origine of this name came from article writen by Franz Niessl (18660-1919) and published in 1894. HE found this substance after he visualized it by nissl stainning method invented by him.

This basophilic substance was just only find in dendrites of neurons, not axones. It is composed by RNA polyribosomes.

Basicly i am tring to tell you that Niessle body is just older name from old ages of histology.

Niessel body is not diffrent with others rought endoplasmatic reticulum(RER). It same pourpose as normal RER.


Do repeated freeze-thaw strip nutrition from vegetables/food? Some of my family and friends seem to believe that vegetables/food should be subjected to as few freeze/thaw cycles as possible. The rationale put forward is that each such cycle reduces nutrition (sp. nutritive?) value, and accelerates rot.

I'm skeptical; Do repeated (sp. repetitive?) freeze/thaw cycles strip nutrition from vegetables/food?

Repeated freeze-thaw has virtually no effect on macronutrients, such as proteins, lipids, and sugars, because these are broken down to their basic building blocks (such as amino acids and simple sugars) upon food digestion anyway.

According to this paper freeze-thaw has no effect on micronutrients, such as vitamins, as well.

What affects nutritious quality is the length of time the food remains frozen. Most household freezers maintain a temperature of -20°C. At this temperature, the food doesn't get spoiled by bacteria, but degradation of vitamins still occurs, albeit at a slower rate. This is critical for some unstable vitamins, such as vitamin A and C. But elements such as iron, calcium, zinc, and phosphorus are not affected at all.

If you want to prevent vitamin degradation for a very long time, you need a freezer that maintains food at -80°C. This is only if you want to keep the food frozen for many months though.


Do ants or other insects sleep, and if so why? I was thinking yesterday about insects (as there was a spider in the house, and I couldn't help but think of anything else, even though they aren't insects), and I started to wonder if ants sleep?

After thinking about it for a while I decided that they might sleep, but then what would be the purpose of sleeping for them? My limited understanding of the need of sleep is that it is used for the brain to compartmentalise the events of the day and allow memories to be formed. But ants don't really have to think about much during the day, given that they act more as a collective than an individual. Or in the case of other insects, they have simpler more instinctive brains which rely on taxis, reflexes and kineses.

So, do ants and other insects sleep (or do they have a different type of sleep to us) and what would the purpose of it be for them?

A quick search on Web of Science yields "Polyphasic Wake/Sleep Episodes in the Fire Ant, Solenopsis Invicta" (Cassill et al., 2009, @Mike Taylor found an accessable copy here) as one of the first hits.

The main points from the abstract:

Yes, ants sleep.
indicators of deep sleep:

ants are non-responsive to contact by other ants and antennae are folded
rapid antennal movement (RAM sleep)

Queens have about 92 sleep episodes per day, each 6 minutes long.
Queens synchronize their wake/sleep cycles.
Workers have about 253 sleep episodes per day, each 1.1 minutes long.
"Activity episodes were unaffected by light/dark periods."

If you study the paper you might find more information in its introduction or in the references regarding why ants sleep, although there doesn't seem to be scientific consens. The abstract only says that the shorter total sleeping time of the workers is likely related to them being disposable.


Does mechanical shock kill animals? I heard that loss of blood kills shot animals, a lot. But a few times, I heard that mechanical shock kills animals. For example in this video (starts to play at the right spot; relevant from 14:35 to 15:03).

That loss of blood kills an animal seems pretty obvious as the brain can't function without being supplied oxygen and it can't be supplied oxygen if there is no blood to carry the oxygen.

If the mechanical shock is applied to the head, it also seems somewhat reasonable. I guess it could be that the shock destroys vessels in the brain. But other than for a headshot: Is there a biological reason why an animal couldn't continue to live after experiencing mechanical shock due to being hit by a small projectile (being hit by a truck which is able to accelerate the entire animal doesn't count)?

With a small projectile you will always get some sort of shearing forces: the tissues directly impacted will accelerate faster than adjacent tissues, and so on. This can cause tearing of many tissues, including blood vessels, but other tissues as well.

In the context of the brain, the effects of traumatic brain injury are a constant area of research, for example see here.


What is the probability of an offspring sharing identical HLA typing as one of their parents? DISCLAIMER: I have yet to thoroughly study HLA 100% to the bone, and hence I won't know everything about it at the back of the hand.

Recently I came across this information on a San Francisco hospital website claiming the chance of a full HLA match between 2 randomly selected people is 1/1,000,000 and the chance of a full HLA match between a child and one of their parents is 1/200.$^{[1]}$

What struck me as odd is the 1/200 chance of a parent matching their offspring's HLA, which seemed too high of an estimate. The immediate intuition is for a child to have identical HLA typing as one of their parents, their parents need to share some HLA haplotypes, which on its own should be a rare occurrence. Hence I decided to attempt verification of this number to confirm if it was within the realm of possibility

According to Stanford$^{[2]}$, the HLA cell surface receptors that mix during inheritance are HLA-A, HLA-B in MHC I, and HLA-DR in MHC II. A set of these 3 forms a haplotype. [HLA-C and HLA-DQ are probably involved too, but we'll omit them for simplicity's sake.]

For our estimation, we use data from the same Stanford source$^{[2]}$ and find there are 59 HLA-A serotypes, 118 HLA-B serotypes, and 124 HLA-DR serotypes. This gives us $59\times118\times124=863288$ different possible haplotypes.

To get the probability of 2 parents sharing at least 1 common haplotype, we do some math: $\frac{1}{863288} \times \frac{863287}{863288} + \frac{1}{863288} \times \frac{863287}{863288} + 2 \times \frac{1}{863288} \times \frac{1}{863288} = 1/431644$

The above is assuming the parents have met randomly in the world and no inbreeding has taken place. Inbreeding will pretty much ensure 2 parents share common HLA haplotypes.

This means the chance of an offspring to even possibly have the same HLA typing as one of their parents is 1 in 431,644, which is already way lower than the 1 in 200 chance stated on the hospital's website.

Just for calculation sake, the precise chance of an offspring sharing the same HLA typing with either one of their parents after accounting for different possible haplotype combinations produced by the parents would be: $100\% \times \frac{1}{863288}^2 \times 2 + 25\% \times \frac{1}{863288} \times \frac{863286}{863288} \times 2 + 50\% \times 2 \times \frac{1}{863288}^2 = 5.792 \times 10^{-7}$

An exceedingly small chance.

Issues with my estimation:

There were 2 assumptions made during this estimatey computation. I didn't take into account the weighted and uneven distribution of the haplotypes, and just assumed they are all statistically evenly distributed. Some haplotypes are more common than others, and this factor was not considered during the estimation. If existing data on haplotype occurrence is used, it will likely affect the estimation quite a bit, however, this is highly difficult as the data varies by region and ancestry.

I also did not take Genetic matchmaking into account, which is a factor that will lower the chance of 2 parents sharing common HLA haplotypes.

If exact computation for the probability proves to be difficult, what would be a reasonable estimation on the order of magnitude of said probability? Is 1/200 within the realm of possibility once you take into account the uneven distribution of haplotypes caused by certain more common ones?

Sources:

$^{[1]}$https://www.ucsfbenioffchildrens.org/education/types_of_bmt_donors/#2

$^{[2]}$http://web.stanford.edu/dept/HPST/transplant/html/hla.html

If you follow your math, you will definitely not find a 1/1,000,000 chance of two random people being an HLA match, so it seems clear that the independence and equal weighting of types is not a great assumption.

We can make a different set of back-of-envelope assumptions, and just say that the 1/1000000 number comes from having 6 combined matches. In that case, you would interpret 1/1000000 as due to 6 independent matchings of probability 1/10. In that case, with a parent you only have to randomly match the other three. 1/10^3 = 1/1000, much closer to the 1/200. Further non-independence, unequal frequencies, and homozygosity makes 1/200 seem reasonable in a whole population (though individuals with more rare HLA would be less likely to match a parent or a random individual), and I presume the 1/200 number comes from actual observed frequencies rather than theoretical calculations.

Perhaps someone with more HLA expertise (I have basically none) will provide a better answer based on more specifics, but I just meant this as a quick napkin calculation for whether the numbers given are plausible, and I think that they are.


Help with jellyfish species identification Our research group (Evolutionary Genetics Group, University of Zurich) has received a letter from a special needs child who has kindly asked us to identify three jellyfish species.

Unfortunately, the letter does not include anything else except three rather low quality cutouts from what I assume is a childrens book. Nobody in our lab has any knowledge about jellyfish taxonomy so any help is greatly appreciated.

Be warned that these are just best guesses - as you said yourself, these aren't great images for identification as they appear to be simple drawings:

1) this looks a lot like Aurelia aurita - though the lack of any internal patterning in the drawing makes me think perhaps otherwise.

image source: https://www.leisurepro.com/blog/wp-content/uploads/2017/05/shutterstock_272438348.jpg, https://holidays-majorca.co.uk/wp-content/uploads/2017/01/Aurelia-Aurita-S-300x225.jpg

2) possibly a Turritopsis dohrnii or nutricala - if so then this is the 'immortal' jellyfish. shape of bell is correct and the lappets seem reasonably close, it's just the internal structures that I'm not sure about.

image source: https://www.cairnsholidayspecialists.com.au/shared_resources/media/irukandji-jellyfish-in-far-north-18836_400x322.jpg

3) Very unsure about this one, but potentially a Atolla wyvillei? definitely has some visual features in common and I can't find anything else that's similar. I can also see how an artist would derive that image from this species.

Image source: https://www.mindenpictures.com/cache/pcache2/90194947.jpg, https://c8.alamy.com/comp/E45A4H/deepsea-medusa-jellyfish-atolla-manubrium-gulf-of-maine-atlantic-E45A4H.jpg

I hope these at least give a starting point and are of some help, I think the nature of those images will make it hard to get many better answers. Good luck!!


Does male or female DNA contain more information? I wonder if the male or the female DNA contains more or less information than the other?

Define "information" — females have more base pairs and more individual genes because X's are larger than Y's, but males have a large number of unique loci and thus unique genes, because they have an X and Y chromosome.


How to calculate the percent of mitochondrial heteroplasmy How do people calculate the percent of mtDNA heteroplasmy?

Does 7% heteroplasmy out of 10 cells, represent a mutation found in the same position on the genome among 700 mtDNA genomes out of 10,000 mtDNA genomes assuming there are 1,000 genomes per cell?

Thanks for helping me understand this concept a little better.

I emailed the authors of the paper "Age-Related Accumulation of Somatic Mitochondrial DNA Mutations in Adult-Derived Human iPSCs" and they confirmed that they calculated the % of mtDNA heteroplasmy by the following:
Aligned all mtDNA genomes against the reference sequence. Any deviance at a specific position from the reference was a "mutation". The % heteroplasmy was calculated by dividing the total number of mutations at a certain nucleotide position by the total number of genomes represented at the position multiplied 100.
So in other words, to go back to my original question- if there were 10,000 genomes aligned and there were 700 mutations at the same position, that mutation would have 7% heteroplasmy.


Are there any anatomy books focusing on etymology? I noticed that I can remember names for a very long time if I now their etymological background, the reason is easy I love etymology, especially when it is connected to mythology. However when I learn anatomy searching for the etymological background consumes too much time.

Are there any books or even preferably searchable online materials focusing of the etymology of anatomical nomenclature?

Though a little bit outdated looking this from the university of Sydney is pretty good and searchable.
I find it pretty useful for aiding memorisation or just a quick entertaining read.

Arnold's Glossary of Anatomy - The University of Sydney


Why do teeth ache after fillings? I had a filling which involved drilling the tooth, but the drilling did not touch the nerve. According to the x-ray taken at the same time, the nerve is in fact some distance from where the filling was taking place (lower right molar).

Now the local anesthetic has worn off, my tooth is aching. The gums do not hurt (so it is not caused by the dentist applying pressure to the area) and as far as I am aware there are no other nerves within the enamel of the tooth.

So, why does my tooth ache? Is it something to do with the nerve 'waking up' after being anesthetized?

Just to be clear it is not a severe ache or of any concern, only in the background, and I am curious as to the cause. The dentist did say it would ache, so it's obviously a normal thing, but I didn't think to ask why!

See, since it was a simple drilling followed by restoration or filling, that means the infection was superficial, not involving the pulp where the nerves and blood vessels are situated.
Ok, so now to remove the superficial infection the dentist might have used an airotor. It's an instrument which rotates at high speed, has a hole for water spray to cool the fictional heat generated while it removes the caries or the infection from the tooth.High speed handpieces
Now as you may be knowing the crown portion of tooth has three layers- enamel, dentin and pulp. Only the pulp portion is innervated.
Now when the instrument is drilled into the tooth the infected enamel and superficial infected dentin must have been removed.
The dentin has numerous tubules known as dentinal tubules. These contain a fluid called dentinal fluid. Whenever there is any stimulus which has not yet reached the pulp, but may have reached the dentin, eg of stimulus in the form of pressure, temperature change, sweet food, sour food etc, cause the fluid to move or get displaced. The displacement of dentinal fluid stimulates nerve endings in the pulp and hence generates a pain/ sensitivity response to your brain.Hydrodynamic theory
Now the drilling causes heat generation, even though little, due to the coolant, plus pressure and hence causes the fluid to displace and hence pain. This pain usually ends after the treatment.
However the restoration placed, you should have specified which restoration- silver coloured (amalgam) or the tooth coloured. These again have chemicals. These chemicals can penetrate through the tubules to the pulp to elicit a painful response even after the treatment. To prevent this, a liquid known as varnish is applied which acts as an insulator. Also if the infection is deeper, a base or other material depending on the type of restoration is also applied to prevent other stimuli. Varnish and bases
So either there may be a failure in these insulating materials or your pulp may require some time to heal from the procedure. It may have got healed by third or fourth day, if it was due to procedural trauma. In either case you should contact your dentist.
Hope I have solved your question :)
References have been given in the parentheses


Why there are no plants that offer salt fruits as opposed to sweet fruits? Why there are no plants that produce salt fruits?

Is it because other animals do not like salt to the same degree of humans?

Soil salinity and sodicity cause severe problems in agriculture worldwide, and salt tolerance in crops is an extremely important trait and a major focus of research. Detrimental effects of high salinity on crops are multifaceted and affect plants in several ways: drought stress, ion toxicity, nutritional disorders, oxidative stress, alteration of metabolic processes, membrane disorganization and reduction of cell division and expansion (Hasegawa et al. 2000; Munns 2002; Muscolo et al. 2007, 2013; Zhu 2007; Sidari et al. 2008). As a result, plant growth, development and survival are reduced (Muscolo et al. 2011; Schleiff and Muscolo 2011). Two major stresses affecting plants under salinity are osmotic and ionic stresses. Osmotic stress, occurring immediately in the root medium on exposure to salts, can result in inhibition of water uptake, cell expansion and lateral bud development (Munns and Tester 2008). Ionic stress develops when toxic ions (e.g. Na+) accumulate in cells causing increase in leaf mortality, chlorosis, necrosis and decrease in the activity of cellular metabolism including photosynthesis (Yeo and Flowers 1986; Glenn and Brown 1999). In fact, excess Na+ and Cl− have the potential to affect plant enzymes, resulting in reduced energy production and other physiological processes (Larcher 1980; Morais et al. 2012a,b). Ionic stress results in premature senescence of older leaves and in toxicity symptoms (chlorosis, necrosis) in mature leaves due to high Na+ and Cl− which affect plants by disrupting protein synthesis and by interfering with enzyme activity (Munns and Termaat 1986; Hasegawa et al. 2000; Munns 2002).

Source: Effect of saline water on seed germination and early seedling growth of the halophyte quinoa

Salt is really good at inhibiting enzymes and biochemistry, which translates into not being great for seeds. So to have a fruit that has a high concentration of salt is really risky and not likely to be successful. Sugars on the other hand attract a multitude of other organism that would help move seeds around or create an ideal growth environment. To have crops that are resilient to salt would be useful but would require a lot of wasted energy to maintain osmoregulation. So it's not so much that animals wouldn't eat a salty fruit but more that it would be harmful to the seeds.


By what mechanism does coeliac disease cause excess fat in the feces? Wikipedia states that “Severe coeliac disease leads to the characteristic symptoms of pale, loose and greasy stool (steatorrhoea)”. However thumbing through the causes and the pathophysiology it did not become clear to me what leads to this key symptom.

By what mechanism does coeliac disease cause excess fat in the feces?

Coeliac disease is an immune disorder resulting from a reaction to ingested gluten (a protein found in wheat, barley and rye). It is associated with inflammation of the small intestine resulting in a generalised reduction in the capacity for digestion and absorption. According to this paper:

  Celiac disease is associated with pancreatico-biliary disease. Postulated mechanisms include reduced gallbladder emptying due to impaired cholecystokinin release and pancreatitis due to malnutrition.

Cholecystokinin is a peptide hormone that is produced by specialised cells in the small intestine and which stimulates the production and release of pancreatic enzymes and bile. Digestion of fat is critically dependent upon the emulsifying properties of bile salts in bile, together with pancreatic lipase. Any breakdown in this stimulatory pathway would result in reduced capacity for digestion of dietary fat.

Failure to digest fat results in fatty stools (steatorrhoea) which is one of the classic symptoms of the disorder.


Genetic mutations and new alleles Amongst silent, nonsense and missense genetic mutations, is the latter the only one that leads to the creation of new alleles?

If we define alleles as a specific form of a gene, and a gene as a heritable factor consisting of a length of DNA that influences a certain characteristic, since the missense mutation is the only one that leads to the physical creation of a new protein, is it not the only one that would lead to the creation of new alleles?

Or would nonsense also lead to new alleles as the lack of the protein may lead to the expression of a different characteristic?

So the term allele is a broad one, and simply refers to the different versions of any piece of DNA in circulation in the gene pool - it doesn't need to refer to a gene. I can talk about the alleles at a random place in the genome.

But if we proceed with your question and ask - 'do nonsense mutations within coding genes also lead to the creation of different proteins' - the answer is 'sometimes'. A nonsense mutation is just one that introduces a stop codon. The result is an mRNA that codes for a shortened protein. Sometimes, the mRNA will be recognized as faulty and degraded, and so little to no protein gets made. Sometimes, if made, that protein will be unstable, or the result will be as if no protein had been made. Sometimes though, the protein will be stable, and could hang around uselessly, or even do damage.


What are negative and positive after potentials? After depolarization: is the slow repolarization phase which follows a rapid fall in spike potential and extends up to attainment of the RMP level. It is called phase of negative after potential and lasts for about 4 ms.
After reaching the resting level (–70 mV) the potential further falls and becomes more negative (–72 mV).This phase is called after hyperpolarization or phase of positive after potential.

What is the reason for naming them as negative and positive after potentials?
My attempt: I think we are naming them based on the direction
of current, i.e. during after depolarisation membrane potential is going further negative , so the name negative after potential, and during after hyper polarisation, membrane potential is going from hyper polarised state to resting state, so its named as positive after potential.
Am I correct?

Source:Textbook of physiology

Yes, you are correct. The negative current is hyperpolarising the axon and the positive current is returning it to baseline from a hyperpolarised state.

They are often referred to as inward/outward (negative/positive respectively) currents as well, due to the direction of the flow of ions. Which is further compounded when you start looking positive/negative ions.

Inward currents are inflow of +ve charge, or outflow of -ve charge.
Outward currents are vice-versa.


Can monoclonal antibodies be used to transport insulin Quick question
Monoclonal treatments in cancer require the drug attached to the antibody which then attaches itself to the neoantigen on a cancerous cell, would it be possible to
transport insulin in the same way?

Technically you can link two proteins together, but why would you want to do this?
Antibody drug-conjugates are used to specifically target cells which can be differentiated from the healthy cells by their cancer neoantigens. This provides a high specificity of the drug delivery and also limits side effects on healthy cells.

For insulin on the other hand this is not necessary, since insulin receptors are ubiquitous thoughout cell surfaces in the body, hence supplementing insulin is enough.


How does evolution get around the combinatorial problem? Imagine a combinatorial tree showing all the possible arrangements of nucleotides. Some arrangements are functional, meaning they can be plugged into a cell and create a living organism capable of reproducing. Some arrangements are nonfunctional, meaning they can't sustain any living system at all.

In evolution, new information is created as the result of what are essentially an accumulation of copying errors. My question is, would the ratio of functional to nonfunctional arrangements have to be relatively large  so that enough genetic information can arise in response to natural selection? If so, what scientific studies have led biologists to conclude that this combinatorial space is rich with functional arrangements. If it isn't necessary please explain why.

No, with some caveats. First, about the actual value of the ratio: it's probably tiny, with almost all possible genetic sequences failing to lead to living organisms.

Why does this not make evolution impossible? Each sequence can have billions* of neighbors in sequence space. If even a very small number of those are functional, evolution can proceed. More importantly, the functional sequences are clustered in sequence space. If you pick 3 billion nucleotides randomly, you'll get nonsense, but if you mutate a single nucleotide in a human you'll most likely get a perfectly good human.

There are interesting open questions here, though, especially regarding the origin of life, and whether natural selection tends to drive populations to regions of sequence space that are especially dense with functional sequences.

*Just looking at point mutations. Including the full mutational spectrum gives many more.


Could we eradicate mosquitoes? Researchers have proposed the application of CRISPR/Cas9 and gene drive to genetically alter wild mosquito populations such that they don't transmit malaria. The government of New Zealand has announced a program to eliminate several invasive mammals from that island, also using gene drive (among other things).

Could we use this technology to completely eradicate from the world all species of mosquito that prey on humans? Also, could we accurately predict the extent of the resulting ecological disruption so we could decide if it was worth it?

Could we use this technology to completely eradicate from the world
  all species of mosquito that prey on humans?

Yes, implemented correctly, a gene drive has this capability.

  Also, could we accurately predict the extent of the resulting
  ecological disruption so we could decide if it was worth it?

The current scientific and political consensus is that, no, we can't predict the potential consequences with high enough confidence to move forward with such a large-scale manuever.

One of the leading scientists studying and improving gene drives, Kevin Esvelt at the MIT Media Lab, instead supports a "daisy chain gene drive" which is pre-programmed to weaken with each successive generation, allowing humans to effectively control the spread of gene drives to a specific geographic area and time frame.


Why do sperm have centrioles and do female eggs cells even have centrioles? I was just wondering why it is that sperm have centrioles underneath the acrosome, but that also prompted a thought as to whether eggs have them too?

Oocytes do not have centrioles. During fertilization, the centrioles of the sperm become the centrioles of the zygote. Only one pair is needed, as there is only one cell (i.e. zygote) right after fertilization.


Chromosome picture, how to interpret? In this guide i was reading for annotations, there is a diagram of chromosomes of D.mel, I am confused as to why the chromosomes are all attached to one another, is this picture taken in a certain stage of mitosis in which they are all condensed?

Original source
 (page 2).

You need to look up polytene (giant) chromosomes.

  Polytene chromosomes are over-sized chromosomes which have developed from standard chromosomes and are commonly found in the salivary glands of Drosophila melanogaster. Specialized cells undergo repeated rounds of DNA replication without cell division (endomitosis), to increase cell volume, forming a giant polytene chromosome. Polytene chromosomes form when multiple rounds of replication produce many sister chromatids that remain synapsed together.

You can read more about it at wikipedia (http://en.wikipedia.org/wiki/Polytene_chromosome)


Is brachydactyly due to mutation? I have this so called "clubbed thumbs"also known as brachydactyly.

It is of D-type.

I searched for it on internet and found that it is a dominant inherited disease.

But to my surprise,none of my family members have such thumbs.Not even  my great grandfather/mother had this type of thumbs.

If it is a dominant trait then why didn't it show in any other family person. Is it that I have had any mutation in my genes?

You are correct that brachydactyly is a dominantly inherited disorder and is usually caused by mutations in the BMPR1B gene.

However, not everyone who has the mutation, will have clubbed thumbs (the phenotype). This is due to a phenomenon known as penetrance and expressivity.

Penetrance essentially is an all-or-none phenomenon whereby certain individuals who have a mutation express the phenotype (in this case, clubbed thumbs) and some do not express it at all.

Expressivity is when individuals who have the mutation, will express the phenotype to varying extents. For example, only one thumb may be clubbed.

I hope this helped.


num_tol_term in PeptideProphet result What is the meaning of the num_tol_term attribute in a PeptideProphet (pep.xml) search_hit?

<search_hit hit_rank="1" peptide="DATDDFEDVGHSTTAR" peptide_prev_aa="K" peptide_next_aa="A" protein="Traes_5AL_64120ED6B.1"
    num_tot_proteins="4" num_matched_ions="9" tot_num_ions="30" calc_neutral_pep_mass="1735.7364" massdiff="-0.0269"
    num_tol_term="2" num_missed_cleavages="0" is_rejected="0" protein_descr="| AT2G32720.1 | member of Cytochromes b5">

Found the answer in the PeptideProphet paper: number of tryptic
termini (NTT)

  This number, which can be 0, 1, or 2, measures how
  many of the peptide termini, on the basis of amino acid sequence,
  are consistent with cleavage by trypsin.


What is working definition for female infertility? I've studied infertility and found that its quite complex to define. However, I came to know about a useful working definition of infertility; which was " Failure to achieve pregnancy".
Few days later I've hit upon a idea that proves that definition wrong. As I studied the turner syndrome, in which condition was XO but individual was infertile female. Further I studied that if they are subsequently treated with Gonadotrophin hormones, they have menstrual periods as well. There I found that if a fertilized egg is implanted in their uterus, pregnancy would be achieved. Now how would we call that female infertile?

Infertility is defined as the inability to conceive after one year or longer of intercourse without the use of contraception or therapeutic donor artificial insemination.

That definition does not include a state of permanence.  That is, with treatment, fertility can indeed be achieved in many cases.

  You may want to consider the term sterility as a definition, which has a permanence to it. But even then, if you consider tubal ligation (female sterilization) or a vasectomy (male sterilization), then you'll quickly conclude that sterilization can be reversed.  At that rate, you may want to state "irreversible sterility" where a genetic basis cannot be overcome with treatment/intervention.  Even then definitions may vary.

As you've discovered, even some genetic-based infertility can be overcome with IVF.  In terms of your genetic interests, the condition of XX male syndrome, resulting from loss of the SRY gene during crossover, causes the inability to produce any sperm (azoospermia).  There is no existing treatment for that or even a reasonable theoretical one.

This could get more complicated/interesting as new medical therapies mature.  If one were to clone a human for example, is that a type of reproduction? Likewise, there is gene therapy, which could overcome some types of genetic-based sterility.

Sources:

http://medical-dictionary.thefreedictionary.com/Infertility
http://medical-dictionary.thefreedictionary.com/sterility
http://www.acog.org/~/media/For%20Patients/faq011.pdf


How does adjuvant enhance the immunogenicity of antigen? My question is, How does adjuvant enhance immunogenicity of antigen?

I just want to know deeply about it , Any suggestions will be helpful!

This is a quick answer to a very broad question since the mechanisms of adjuvants are very different. I'll try to summarize just a few. For a deeper understanding please start reading this paper and its references.

1) Aluminum salts (aluminum phosphate or hydroxide)

  Studies suggest alum salts work by causing the formation of an antigen
  depot at the inoculation site from where the antigen is released slowly.
  The trapping of soluble antigen in the alum gel may also increase the
  duration of antigen interaction with the immune system. Other
  mechanisms of action involve complement, eosinophil, and macrophage,
  activation and increased efficiency of antigen uptake by antigen
  presenting cells seen with particulate matter with a size under 10
  micron.

2) Calcium salts

They work pretty much like aluminum salts but they are much better tolerated by the organism.

3) Bacteria-derived (peptidoglycan or lipopolysaccharide)

They are naturally recognized by the immune system and for this reason, they are used to simply boost the immune response.

4) Emulsions

They form a depot at the injection site, enabling the slow release of antigen. The immune system has more time to recognize the antigen and react.

5) Liposomes

They help to extend the half-life of antigens in the blood leading to a higher antigen exposure to antigen presenting cells after vaccination. A Very similar effect is achieved using microbeads made of artificial polymers.


oversecretion of the thyroid gland What are the reasons for the oversecretion  of thyroxin in the thyroid glands?
Its name was mentioned in my book but there was no explanation.

What are its symptoms,can it be fatal?

Elevated levels of thyroid hormone in the blood is called thyrotoxicosis. If this is due to a hyperfunction of the thyroid gland, it is known as hyperthyroidism. In common parlance, these terms are often interchanged.

Although a simple google search would tell you more, I add some detail here.

Hyperthyroid can have various causes. There can be a functional cancerous/ non-cancerous mass in the thyroid gland producing the hormone. Or as in graves disease which is an autoimmune condition where antibodies mimic to stimulate the thyroid gland to hyperfunction.

Non hyperthyroid causes of thyrotoxicosis include inflammation of thyroid or thyroiditis, where preformed hormone is released. It can also occur sometimes in a condition called struma ovarii where the tumor in the ovary turns into a thyroid like mass producing the hormone. Another possible case is an iatrogenic one where the the problem is due to the patient taking exogenous thyroid hormone.

Thyrotoxicosis is not fatal and can be controlled by drugs. Symptoms include cardiac problems, high BMR, ocular changes (bulging eyes), diarrhea and many more.
A special case of Graves disease called thyroid storm is a medical emergency and can be fatal.

Heres the medscape link for further reference. http://emedicine.medscape.com/article/121865-overview


Besides hemoglobin, what proteins are present in red blood cells? I knew that mature red blood cells (RBCs) lacked nuclei, but I wasn't aware until just now that they also lacked ribosomes and mitochondria. Most cells in the human body all contain a common laundry list of housekeeping proteins and RNAs (including mitochondrial proteins and ribosomal RNAs), but I guess RBCs lack a number of them. Do they still have all of the other organelles? Obviously hemoglobin (and to a lesser extent carbonic anhydrase) makes up a large portion of the dry weight of RBCs, but are other proteins still present? If so, what are their relative abundances?

For example, do red blood cells have any of the normal metabolic (i.e. ATP producing) proteins? Obviously they don't have any of the TCA cycle proteins, but do they still have the glycolysis ones?

Reticulocyte stage is when the ribosomes are still present and after that no new protein synthesis occurs. However RBCs have a lot of proteins and major proteins other than haemoglobin are cytoskeletal proteins and ion channels/pumps (In fact, cytoskeletal proteins are more abundant than haemoglobin). It is the Na+-K+-ATPase that consumes most ATP. As you correctly identified the RBCs produce ATP via glycolysis and glycolytic enzymes are also present. Note that deficiency of pyruvate kinase leads to haemolytic anaemia.

For a detail on the proteins present in human RBSs, see this paper. They have studied the RBC proteome by ion-trap MS. The top 5 proteins (from Table-1) are:

No.    Protein description              Molecular mass (Da)    Gi Number    Sequence     No. of identified
                                                                           coverage(%)      peptides
1      Spectrin α chain, erythrocyte         279,916.5          1174412       48.0           77*
2      Spectrin β chain, erythrocyte         246,468.1          17476989      48.0           76*
3      Ankyrin 1, splice form 2              206,067.9          105337        45.0           55
4      Ankyrin 1, isoform 4, erythrocytic    203,416.6          10947036      45.0           50
5      Ankyrin 1, isoform 2, erythrocytic    189,011.2          10947042      46.0           48

Although in this table you cannot find glycolytic enzymes other than GAPDH and Aldolase, but other enzymes are also present. They are perhaps not detected in this experiment because of overwhelming levels of structural proteins. You can check this old paper that shows a study of different glycolytic enzymes from erythrocytes. It is also to be noted that the glycolytic pathway flux is not as smooth as in other cells. So some accumulated metabolites are probably exported out of the cells to keep the flux smooth[ref Full text not found].


Interleukin 6 class cytokines Wikipedia says:

  Leukemia inhibitory factor, or LIF, is an interleukin 6 class cytokine that affects cell growth by inhibiting differentiation.

So does this means that il6=LIF ? or does it implies that both il6 and LIF belong to some common class of cytokines?  If latter is true then what is the name of that class?

From the interleukin wikipedia page for IL6 :

  number of other cytokines may be grouped with IL6 on the basis of sequence    similarity.[21][22][23] These include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF)

from the Leukemia inhibitory factor wikipedia page:

  LIF derives its name from its ability to induce the terminal
  differentiation of myeloid leukemic cells, thus preventing their
  continued growth.

From this we can suggest that LIF is grouped with the IL6 because of its action on myeloid leukemic cells and specifically on their growth (MGF).


Interdependency between organsims on our planet and its relation to ecosystem? I am not a biologist but I just wonder if all species are interdependent. I mean if the tiger becomes extinct does it affect the ecosystem? If the mosquito or mouse become extinct does it affect the environment and us?

I am asking because this question was raised by one of my friends when I was in favor of protecting tigers, lions but I had no answer to "tiger extinction will not affect humans".

So, is it true that the extinction of any species will affect all other species?

The problem is not really that we don't understand some stuff (lthough this is certainly true) but that an ecosystem, or the biosphere is a highly complex network of interactions. This network is continuously displaying some chaotic (determinist but not foreseeable) behavior. In such a system it becomes very hard or practically impossible to predict what the impact of a change (even a minor one) might be. To illustrate, one could say that killing half of the world's lions might cause the population of rabbits in Norway (!) to increase but killing two thirds might cause the same population of rabbits to decrease. Note: Stuart Kauffman wrote some articles where he argues that life is a system which is always balancing between chaotic dynamic and non-chaotic dynamic. Today, many conservation biologists use the tools of graph theory (network analysis) in order to get a better understanding of how things are influenced by a minor change.

But defending an endangered species like the pandas or elephants is certainly much more a matter of ethics than of human security faced with environmental shifts. I would guess (a reference on how the world's money is spent on conservation action would be interesting) that an important part of the money  spent on programs for the defense of endangered species are for ethical reasons, just because these species are big, clever, sing well or display nice colors.

There are many false reasons in ecology (in the political sense of the word) where people act for their ethics rather than to defend humans from environmental change. (I don't mean that ethics is stupid, or that only defending the environment for the benefit of the human species should be considered). You may already have heard "the amazonian forest is the lung of our planet" suggesting that this forest produces lots of $O_2$. This is completely wrong! Cutting down this forest would not change much in terms of either $O_2$ or $CO_2$ levels (except if the wood is burned!).

So to summarize I would say:

We spend quite a lot of money defending species for ethical reasons rather than to protect humans from environmental shifts.
Changing a little thing might affect the world-wide biosphere in a way that is practically impossible to predict.


Reward pathway sequence of events So I've been reading a lot of papers on the reward pathway. But since I'm not schooled in any relevant knowledge I'm having trouble grasping the chain of events. Most papers detail just bits and pieces, but not the full sequence of events.

I'm trying to grasp how the error prediction signal works.

This is my guess so far:

Players:

  Photosensitice cell A
  Light processing neuron B
  Dopamine neuron C
  Motorneuron D

Event:

  Light strikes A
  A triggers B
  B spikes after N triggers.
  B triggers C
  C spikes after N triggers.
  C keeps repeadetly spiking for as long as its internally coded reward size/duration expectation.
  D receives predecition triggers spikes causing action.
  Reward comes, neural connections are strengthened.
  If reward doesnt come in predicted time connection degrades.

Am I correct in this deduction or way off?

How does the actual reward get communicated? By dopamine release in blood?
By the same neurons that coded the reward prediction? If so, how do those exact neurons get triggered to release reward?

Essentially that's what I remember, but there can be a lot more steps between A and C, i.e. more pathways interacting in different systems to produce an associative memory. Pavlov's dogs is the classic example:

1: Pavlov rings bell, dogs hear bell

2: Pavlov feeds dogs, (dogs rewarded)

3: Repeat 1 and 2 for a few days.

4: Ring bell, dogs will salivate and expect food, even if no food is on the way.

So, in the skull, the dogs are making a link between hearing a bell and a reward.

Dopamine is released at dopaminergic synapses, the limbic system is probably the best understood part of the memory/reward system, particularly the mesolimbic pathway for reward.

Neurons get triggered by presynaptic neurotransmitters, some require convergence of signals to reach threshold and trigger an action potential. Connections are strengthened by long-term potentiation, which has been argued to be the basis for memories, but that's a massive topic I'm not qualified to discuss.

I haven't heard of the "error prediction signal" before, might be a new discovery/thinking that I'm a bit behind on.


Neuroscience: zapping an axon connected to thermoreceptor Let’s say an experimenter has an electrode that can give a shock to a single axon. She takes that electrode and zaps an axon connected to thermoreceptors in the hand of her subject.

I) What would the subject’s perception of the stimulus be?

II) Why?

III) If she zaps that axon AND ONLY THAT AXON so hard that it destroys the axon, would the subject feel pain?

I and II depend on the type of electrical signal applied to the axon. for III, most receptors can perceive other sense as well, so for example striking a vision receptor may produce the perception of light (even in complete darkness) - my guess is the you would feel pain, even if you could isolate the destructive signal away from nearby pain receptors.

search "action potential" in duckduckgo.com, it will get you going.


How does the ebola virus attack? How does the ebola virus attack and how do some people get away with it? Normally any virus would attack a cell with some kind of receptors and some kind of lock and key mechanism entering the cell and then multiplying.

What happens to the virus if a person manages to live through it, does the virus die and is thrown out or still remains inside the host?

I am not sure about a normal virus attack i tried to explain please correct on that also.

It is known that Ebola uses at least one cholesterol transporter called "Niemann-Pick C1" (NPC1) to enter its host cells. Cells with a mutated form of this transporter were not infected by the virus (this extends to other viruses from the Filovirus group as well), which seems like a proof that this can make people "immune" to the virus. However, these are only experiments in cell culture. Other experiments show that a small molecule inhibitor that mimics the transporter can inhibit Ebola from entering cells and infecting them.

There are two papers on this topic:

Ebola virus entry requires the cholesterol transporter Niemann-Pick
C1
Small molecule inhibitors reveal Niemann-Pick C1 is essential for
Ebola virus infection

If a person manages to survive an Ebola infection the immune system fights the virus by making highly specific antibodies against it. These antibodies bind to the viruses and mark them for the immune system (mainly through mast cells) for take-up and degradation while inhibiting them from infecting other cells. Serum from Ebola survivors has been used as experimental treatment for infected people (here mainly the antibodies can be helpful). People who survive the infection are immune against another infection of the same virus strain.


Can anyone give me the common name of this flower/vine? Photo taken in NYC in April 2017

I think this is Rosa foetida, the yellow rose. Unfortunately the leafs are not visible very well but the flower, together with the growth, is pretty characteristic. See this image (from here) for comparision:

The German Wikipedia also has a drawing of the plant (from here):


Organisms as potential Bio-Weapons? Question:

Given that with genetic engineering we can customize organisms as bio-weapons. Which species have the most worrying potential to be weaponized for mass destruction?

Background:

  Biological warfare — is the use of biological toxins or infectious agents such as bacteria, viruses, and
  fungi with intent to kill or incapacitate humans, animals or plants as
  an act of war.

Examples:

  E.G. bio-weapon species: Anthrax fungus -  was first tested as a biological warfare agent by Unit 731 of
  the Japanese Kwantung Army in Manchuria during the 1930s; some of this
  testing involved intentional infection of prisoners of war, thousands
  of whom died. Anthrax, designated at the time as Agent N, was also
  investigated by the Allies in the 1940s.

  E.G. bio-weapon vector: Anopheles labranchiae (malarial mosquito) - According to Prof Frank Snowden, a history professor at Yale
  University whose book The Conquest of Malaria in Italy draws on
  American archives and the diaries of Italian soldiers, the scheme was
  orchestrated in the autumn of 1943 by Erich Martini, a medical
  entomologist, Nazi Party member and friend of the SS commander
  Heinrich Himmler.

There is both a set "list" of agents, but more importantly, a set of properties that an organism needs to be in order to be truly worrisome.

First, the list:

The CDC classifies agents into one of three categories, Class A, B, or C.

Class A: These are organisms that are hard to control, highly transmissible, and lethal:

Anthrax (Bacillus anthracis)
Botulism (Clostridium botulinum toxin)
Plague (Yersinia pestis)
Smallpox (variola major)
Tularemia (Francisella tularensis)
Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo])

Class B: These are organisms that are fairly easy to disseminate, make people sick but don't necessarily have high mortality rates, and may be difficult to detect.

Brucellosis (Brucella species)
Epsilon toxin of Clostridium perfringens
Food safety threats (e.g., Salmonella species, Escherichia coli O157:H7, Shigella)
Glanders (Burkholderia mallei)
Melioidosis (Burkholderia pseudomallei)
Psittacosis (Chlamydia psittaci)
Q fever (Coxiella burnetii)
Ricin toxin from Ricinus communis (castor beans)
Staphylococcal enterotoxin B
Typhus fever (Rickettsia prowazekii)
Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis])
Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum)

And finally, Class C, which are emerging threats that may be dangerous if engineered largely due to their novelty and their potential lethality/transmissability. The CDC uses examples like Nipah virus and hantavirus.

So that's the list of what the CDC thinks is a big deal. You'll note influenza isn't even on there. I'd argue that any given novel influenza strain belongs in Class C, and likely not Class A because, while potentially both transmissible and virulent, a known vaccine exists and simply needs to be formulated.

In terms of properties for an organism, I'd suggest the following, in no particular order (it likely depends on what said organism is meant to do):

Highly virulent: The disease needs to be able to cause human disease, with high rates of both morbidity and mortality.
Highly transmissible: Unless the goal is to cause a "one off" incident, the disease needs to be able to establish a productive chain of human-to-human infections. Humans can't be a dead-end host. Ideally, this needs to be direct human to human transmission, rather than a vector born disease like West Nile.
Stable and amenable to engineering. It needs to be something that's easy to culture and grow in large numbers. This one often gets overlooked somewhat, but despite the fact that its now somewhat commonplace, bioengineering isn't exactly easy.
Not amenable to treatment. The organism needs to not be easily treatable - broad spectrum antibiotics, existing vaccine stock, etc. mean that the normal public health infrastructure can address, or at least mitigate, an attack. For an attack to be truly effective, it needs to swamp existing infrastructure, and one way to do that is to necessitate intensive, unusual care in hospitals and out of the ordinary action on the part of public health officials.


Do proteins generally contain phosphorus and sulfur? I've heard that proteins generally contain six main elements - carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur.

I know that proteins are made from amino acids. Amino acids are composed of an amino group, a carboxyl group, a lone hydrogen atom, and a side chain that varies between amino acids. Of the 20 major amino acids, none of them have a side chain that contains phosphorus. Only cysteine and methionine contain sulfur.

So, are sulfur and phosphorus atoms really characteristic in the structure of a protein?

Of the 22 known proteinogenic amino acids, all contain hydrogen, carbon, nitrogen and oxygen. Some (methionine and cysteine) contain sulfur while one (selenocysteine) contains selenium. None contain phosphorus, but this element can be incorporated by:

Post translational phosphorylation of various residues. This often allows/prevents binding of other proteins and/or triggers a conformational change in the target protein. It is also necessary for proper folding of some proteins (example). Sulfur can also be incorporated in a similar manner (sulfation).

Incorporation of phosphorus containing prosthetic groups. This can occur covalently and is necessary for the function of some proteins. Sulfur can also be incorporated as part of prosthetic groups.

You may also consider the other elements necessary for the structure/function of many proteins: iodine in thyroglobulin, iron in hemoglobin, etc...


How does Artificial Selection work? As far as I know for evolution to work mutations  are necessary. Mutations are the raw material on which natural selection works.

But mutations are always completely random and human beings have no control over it.Then my question is how artificial selection works? Would it have been possible to domesticate dogs from wolves, if there would have been no mutations in wolves to begin with?

Both natural selection and artificial selection require genetic variation in the underlying population to work.  The exact source of this genetic variation is not particularly important theoretically.  In reality this genetic variation originally comes from mutations of various sorts (not just point mutations, but also duplications, recombinations, etc.).  If you had no genetic variation then artificial selection would not be effective.

You might be interested in Stephen Jay Gould's essay "A Dog's Life in Galton's Polyhedron" (found in the collection "Eight Little Piggies"), where he explains that domestic dogs have very little variation in skull length (relative to body size), but large variation in skull width.  It seems that it is very difficult to artificially select for dogs whose skull and body don't have the correct ratio, even though you can wildly change the sizes of dogs, the width of their skulls, the length of their legs, etc.


Gene vs. Protein Expression Assays Are the terms gene expression assays and protein expression assays used interchangeably in molecular biology? Or is it expected of you to differentiate between the two terms.

For example, if I replace the DNA sequence of a gene of interest with the GFP DNA; and then subsequently quantify the fluorescence levels, am I measuring the gene expression of the gene of interest OR the protein expression?

Gene expression is the production of a functional gene product from a gene. So protein expression is a functional read-out of gene expression for gene loci that encode proteins.

However, gene expression is frequently, and erroneously, used to refer to measures of mRNA levels. The production of mRNA is a prerequisite step for the production of protein from a gene and it provides information about the transcriptional activity of a gene loci.

Translation of mRNA is a highly regulated process and
global assays highlight that mRNA transcript levels explain less than half of the variation in protein concentrations.

  For example, if I replace the DNA sequence of a gene of interest with the GFP DNA; and then subsequently quantify the fluorescence levels, am I measuring the gene expression of the gene of interest OR the protein expression?

You are measuring both gene expression and protein expression from the promoter + GFP gene loci. If you are interested in transcription from the promoter then measuring transcript would provide a more direct measure.


How do insects know what is edible? What is the current scientific consensus on how insects innately know what is food and not food? If they are introduced to new food sources do they experiment with eating the new food? Could you teach a preying mantis to eat beef?

Insect feeding behaviour is generally triggered by one or more conditions which may include colour, shape, chemical traces or temperature.
Insects generally locate food based on some combination of olfactory, thermal and visual queues (colour and shape). If their minimum criteria are met to specified tolerance, they will attempt to feed on whatever is nearby using their usual feeding method.

When these conditions appear on the 'wrong' target, it attracts insects and triggers feeding attempts. Insects can be triggered to feed on atypical food sources if the relevant aspects of their environment match those of their normal feeding environments. For example, here is a report from a professor of entomology recollecting his observations of being bitten by pea aphids while handling plants, which he assumes is because of the scent on his hands.

We can exploit this in various ways for research. One is for artificial blood-feeding of insects: most systems, like the Hemotek membrane feeding system, warm blood to the body temperature of the host. They do not normally resemble a target host in any other way. Some blood-feeding insects have very specific requirements for temperature (for example they will only feed on blood if it is heated to the body temperature of birds; the same blood heated to mammalian body temperature will be ignored) but we do not need to make the target look or smell like the natural host. Other species may need olfactory cues, which can be provided by researchers rubbing the membranes on their forearms before placing them on the feeding system, or by breathing on cages as you add the food.

A second way we exploit this is for insect traps. Although not all traps work this way, some work by mimicking the host and attracting insects that are looking for a meal. This can be via olfactory/chemical mimicry (for example carbon dioxide baited traps - try Googling "CO2-baited traps") or visual. Different degrees of visual 'deception' may be needed; for instance to attract tsetse flies, colour is important but shape is not:

  [tsetse traps] often use electric blue cloth, since this color attracts the
  flies. Early traps mimicked the form of cattle but this seems
  unnecessary

(https://en.wikipedia.org/wiki/Tsetse_fly#Trapping)

The exact reason why blue is so attractive to tsetse is unclear:

  But, why are tsetse flies attracted to blue and black colors? What is
  the evolutionary advantage for them? It has been hypothesized that
  certain areas on humans, where tsetse like to bite, are a darker
  shade. Or, that the dark color simply identifies the object as not
  plants.

(https://www.acsh.org/news/2016/11/28/do-dark-colors-really-attract-tsetse-flies-10471)

If such behaviour increases the fitness of the insects, there is a selective pressure to change the cues used to identify situations where feeding behaviour is appropriate, which may result in consistent feeding shifts. We can infer by comparing insect taxonomy and feeding modes when shifts in diet have occurred. For instance, the moth family Calpinae has evolved piercing mouthparts to feed on fruit, but species in the genus Calyptra ('vampire moths') have adapted to feed on blood (which generally moths cannot access because their mouthparts cannot pierce the skin).


Does gene editing have any technical cross-species limits? How far could you go in cross-species gene editing?

Is it possible for example to introduce plant genes into human DNA and vice versa?

Question: How is gene editing limited by the "donor" and "target" species?

So, I'll assume that you are talking about gene editing in a laboratory (e.g. using a technique like CRISPR).

Theoretically, there are almost no limits to what you can do - or at least try. Fundamentally DNA is the same in all living (and non-living) things on earth, so you can absolutely take a gene from a plant and "paste" it into a human cell/genome (with some additional work needed to make the pasting work). You probably even go further and try to isolate whole chromosomes from one organism and (literally) inject them into cells of another one.

The problem with this radical approach to gene editing is, that it probably won't do much (good). A human cell likely doesn't recognise a plant gene as a gene and so just ignores it (it might still cause indirect problems for the cell though) and if you start making very drastic changes like adding chromosomes the chances that your cells will just die are super high.

This means that in practice you either need to (heavily) modify a gene you want to insert to match the structure and 'expectations' of the target organism - you basically have to make a humanised version of a given plant gene - or you can only use genes from similar enough organisms: as a general rule genes from the same kingdom (bacteria, archaea, plants, fungi, animals) are likely to retain some degree of function in another species (but how much exactly or even a general effect is almost impossible to predict).


What is the evolutionary rationale for palm sweating? Sweaty palms seems to be a reaction to stress, anxiety, etc. For our forest-inhabiting primate ancestors sweaty palms could cause unwanted side-effects such as slipping off tree branches under stressful conditions, like when being chased by a predator.

Why did palm sweating became a reaction to fear, worry, anxiety etc in the course of human evolution? What is the benefit of sweaty palms?

As @Ben states, every theory of 'why' we evolve a trait is just a guess and never more than part of the story.   But there are theories.
The palms of our hands are a major source of heat transfer out of our body.  For bears it is the nose and pads of their feet, for dogs it is their toungue, for us a major portal for heat out of our body is the palms of the hands.

Black bears are extremely well-insulated animals, equipped with a heavy coat of fur and a thick layer of subcutaneous fat that help them maintain their body temperature as they hibernate through winter. But once spring arrives and temperatures rise, these same bears face a greater risk of overheating than of hypothermia. How do they dump heat without changing insulation layers?
Heller and Grahn discovered that bears and, in fact, nearly all mammals have built-in radiators: hairless areas of the body that feature extensive networks of veins very close to the surface of the skin.
Rabbits have them in their ears, rats have them in their tails, dogs have them in their tongues. Heat transfer with the environment overwhelmingly occurs on these relatively small patches of skin. When you look at a thermal scan of a bear, the animal is mostly indistinguishable from the background. But the pads of the bear's feet and the tip of the nose look like they're on fire.
These networks of veins, known as AVAs (arteriovenous anastomoses) seem exclusively devoted to rapid temperature management. They don't supply nutrition to the skin, and they have highly variable blood flow, ranging from negligible in cold weather to as much as 60 percent of total cardiac output during hot weather or exercise.

Given this, one could see how the palms of our hands are more likely to react to emotional situations where the heart rate elevates and sometimes we get hot under the collar.  The AVAs will
I am not physiologist, but the quote above comes from an article I stumbled upon a few months ago.  They use the AVAs to reduce the swelling associated with exercise and got some amazing results.  I guess that's another story though.


Is using Hidden Markov Models to find homologues sensible in abstract, short sequences? HMM alignment tools like hhpred excel at finding subtle homologues of folded proteins that simpler scoring techniques (such those used in BLAST algorithms) would miss.

I am only looking at a small (20AA) sequence and it is helical throughout.

Is hhpred still likely to pick up on subtle similarities in the basic secondary structure as it would in a folded protein sequence, or would simpler alignment be just as appropriate?

TMHMM is a very good standard on predicting the TMHs in the first place, so it stands to reason that predicting homologues using this approach is completely viable.


What causes REM atonia to be lost in sleepwalking? I understand that in normal REM sleep the voluntary muscles are in effect paralysed in order to prevent an individual acting out their dreams.  This paper indicates that there are likley to be multiple causes of this atonia. I am interested to know what are some of these methods by which natural atonia is achieved by the body in periods of sleep?

Furthermore, what causes these mechanisms to fail in individuals who suffer from sleep-walking?

There's an excellent, comprehensive review article on the entire process of REM sleep:

  Vetrivelan,R, Chang, C, Lu,J (2011). Muscle tone regulation during REM sleep:
  neural circuitry and clinical significance. Archives Italiennes de Biologie, 149 [DOI] [Free PDF]

Projections from the sublaterodorsal nucleus (SLD) of the Pons in the brainstem are responsible for the suppression of the spinal motor output/movement (for an anatomical schematic, see the article).

  Descending SLD glutamatergic projections activating the premotor neurons
  in the ventromedial medulla and spinal cord interneurons bring about muscle atonia and suppress phasic muscle twitches in spinal musculature.

Lesions in this area in rats have resulted in REM sleep without atonia.

  Many studies have
  suggested that the ventromedial medulla (VMM),
  which receives glutamatergic inputs from the SLD,
  may be the relay site for the pontine inhibitory area
  on spinal motor neurons

The SLD axons relay through the VMM, but also directly projects onto interneurons within the spinal cord, directly inhibiting their activation.

Most of the knowledge we have about this subject comes from animal studies, so it will take some time to verify whether these same mechanism and relays are the same in humans.

The area that is lending the most credence to these issues of REM atonia is not sleepwalking as much as REM sleep behavioral disorder (RBD).  In this condition, sufferers act out their dreams and generally lose atonia during REM sleep.

Evidence points to the fact that such behavior is often seen decades before such conditions as Parkinson's and Lewy Body dementia.

  Ferini-Strambi,L (2011) Does idiopathic REM sleep behavior disorder (iRBD) really exist?
  What are the potential markers of neurodegeneration in iRBD? Sleep Medicine 12, S43–S49 [DOI]

They summarized two studies which explored these anatomical changes:

  [Diffusion tensor imaging, a type of MRI scan] changes have been reported in the
  brainstem (pons, substantia nigra) as well as the fornix, the right
  visual stream, and the left superior temporal lobe suggestive of
  brain tissue disintegrity[1]

  significant decreases of [fractional aniosotropy] in the tegmentum
  of the midbrain and rostral pons and increases of [mean diffusivity]
  within the pontine reticular formation overlapping with a cluster
  of decreased [fractional anisotropy] in the midbrain [2]

So, the answer is, we don't know for sure, but we have some clues from the animal models as to what stages of the signals to suppress movement are interrupted.

[1]Unger MM, Belke M, Menzler K, et al.(2010). Diffusion tensor imaging in idiopathic
REM sleep behavior disorder reveals microstructural changes in the brainstem,
substantia nigra, olfactory region, and other brain regions. Sleep,
33(6),767–73.[FREE PDF]

[2]Scherfler C, Frauscher B, Schocke M, et al. (2011) White and gray matter abnormalities
in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor
imaging and voxel-based morphometry study. Ann Neurol,69(2),400–7. [DOI]


Topology of closed circular DNA Why are covalently closed circular plasmid DNAs naturally found in an underwound state ?

Is it because this makes it easier for the DNA replication machinery to access and unwind DNA ? Or is it because underwound state is energetically more favourable than an overwound state ?

DNA is not always negatively supercoiled naturally. It is important to keep in mind that different regions of topologically constrained DNA can have different supercoiling values. For example, the action of unwinding DNA for transcription or replication introduces positive supercoils ahead of the polymerase and negative supercoils behind it.

Additionally, supercoiling is present in DNA normally. Supercoiling is the result of more or less twist in a DNA helix, which is most stable when it has ~10.5 bp/turn (for B-DNA). Supercoiling allows under- or overwound DNA to return to its most stable twist. Negative supercoiling is the result of underwound DNA. Underwound DNA is not thremodynamically favourable and will actually lower the melting point of DNA (the point where strand separation occurs). This can be compensated by introducing supercoils but it is also important for processes such transcription, which require ssDNA. Negative supercoils and ssDNA can be thought of as interchangeable. Negative supercoils are also used to package DNA around histones in eukaryotes and archaea. On the other hand, positive supercoiling is the result of overwound DNA (also not thermodynamically favourable) and will increase the melting point of DNA. Positive supercoiling is often found in thermophiles which live at higher temperatures and need to prevent their DNA from melting excessively. It has also been suggested that positive supercoiling can play a role in regulation of gene expression (by inhibiting promoter melting). Organisms like to keep an approximately constant amount of supercoiling in their DNA for the above reasons; this is called the superhelical density and is characteristic of different classes of organisms.


How is human biological clock modelled in modern science? Im an engineer by education and i program a lot, so the question sounds weird to people from other disciplines.

Im trying to better understand the human biological clock. Yet i do not really know what it is. I read about clock genes, endogenous cycles, and other observed phenomena that is time sensitive or cyclical in nature. But is there a centralized model of what the circadian rhythm is or how itis exhibited within the human body?

For example an electrical clock can be modelled with feedback loops or electrical flip flops that control the timing. Ive seen the heart modelled as Van Der Pol oscillator.

Does modern science have some notion of how the "master" clock within the human body work? Is there a feedback or an oscillator model of the master clock?

Thank you for any articles or keywords that ican use to research this question!

The situation is quite complex, and there are certain things that we do not fully understand, but I will try to give you an explanation.

First of all, at the cellular level, you have the genetic components of the circadian clock, the clock genes and their protein products.

You can divide clock proteins into positive and negative regulators: the positive regulators modulate transcription of clock-controlled genes and are inhibited by the negative regulators in a loop that lasts approximately 24 hours (in Latin: circa = around and dies = day).

For instance the Clock and Bmal1 nuclear proteins, when present in sufficiently large amount, will dimerize and act as transcription factors on a series of genes that contain a region in their promoter element called E-box. Amongst these are the Period (Per) genes.
Per is then synthesised, and exported to the cytoplasm. Here, if in a sufficiently large amount, it can heterodimerize with the Cryptocrome (Cry) proteins: the dimer will then enter the nucleus and inhibit the transcription actions of the Clock/Bmal couple. This will in turn, block the transcription of Per, that will therefore not be able to dimerize with Cry and stop the inhibition of Clock/Bmal and so on. All of this takes approximately 24 hours.

This basic loop (and some more) is nicely schematised in this review by Reppert and Weaver

Coordination of circadian timing in mammals. - Reppert and Weaver, Nature. 2002 Aug 29;418(6901):935-41.

I report here the legend of the figure:

  The clock mechanism comprises interactive positive (green) and negative (red) feedback loops. CLOCK (C, oval) and BMAL1 (B, oval) form heterodimers and activate transcription of the Per, Cry and Rev-Erbalpha genes through E-box enhancers. As the levels of PER proteins increase (P, blue circle), they complex with CRY proteins (C, diamond) and CKIε/CKIδ (ε/δ, circle), and are phosphorylated (p). In the nucleus, the CRY–PER–CKIε/CKIδ complexes associate with CLOCK–BMAL1 heterodimers to shut down transcription while the heterodimer remains bound to DNA, forming the negative feedback loop. For the positive feedback loop, increasing REV-ERBα levels (R, circle) act through Rev-Erb/ROR response elements in the Bmal1 promoter to repress (-) Bmal1 transcription. CRY-mediated inhibition of CLOCK–BMAL1-mediated transcription de-represses (activates) Bmal1 transcription, because REV-ERBα-mediated repression is inhibited. An activator (A, circle) may positively regulate Bmal1 transcription (?) alone or by interacting with mPER2. There are probably kinases (?) other than CKIε and CKIδ that participate in phosphorylation of clock proteins.

The clock machinery, however, is even more complex than this and different tissues need to integrate different signals (e.g. light, hormonal concentrations and so on).

However, as nice as this may be, our bodies are not constituted by one single cell... if we "zoom out" a little bit and we go to the tissue or the whole body level, we see that circadian rhytms are present in all sorts of tissues and involve all sorts of different physiological processes. A very interesting question is then: how do cells from different organs coordinate each other so that the interrelation of different circadian processes is always the same? For instance, the release of cortisol peaks in the morning, our body temperature has a peak in the late afternoon and a trough in the early hours of the morning, and our heart rate is higher during the daytime.

In 1972, an article by Moore and Eichler was published, showing that lesioning the suprachiasmatic nucleus (SCN) of the hypothalamus (a region at the base of the brain) resulted in the "breakage" of the circadian rhythm of corticosterone (the stress hormone).

Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. - Moore and Eichler, Brain Res. 1972 Jul 13;42(1):201-6

The fact that lesioning a bit of the brain resulted in loss of circadian rhythm in the adrenal gland was obviously a very big deal: the central circadian clock of the organism had been discovered.

I will not going too much into that but, since 1972 many advances have been made and nowadays we know that, although the role of the SCN is very important, it is not the only clock in the body. Several peripheral clock exist, in organs such as the pituitary gland, the liver or the pancreas. How all these clocks communicate between each other and what is their contribution to the generation of non-circadian rhythms (ultradian and infradian) are questions that still have to be solved.

A few interesting papers on the matter:

A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus. - Guilding et al., Mol Brain. 2009 Aug 27;2:28.

A clockwork web: circadian timing in brain and periphery, in health and disease. - Hastings et al., Nat Rev Neurosci. 2003 Aug;4(8):649-61.

Peripheral circadian oscillators in mammals: time and food. - Schibler et al., J Biol Rhythms. 2003 Jun;18(3):250-60.


How does paracetamol interfere with immune system? Paracetamol is used to reduce body temperature when it is to high. The high body temperature (fever) is known to be an indication that immune system fights against an infection.

In this context I have two related questions:

Is high body temperature one of the mechanisms of immune system to suppress an infection or it is just a side effect?
If it is just a side effect, does paracetamol remove it by decreasing the intensity with which immune system fights with an infection or not?

First question: Yes. The immune system releases pyrogenic cytokines such as IL-1. Bacteria aren't typically used to 37C, they prefer working at under that temperature to function in the environment. Our body however can take a few degrees here or there however this severely compromises the bacterial enzyme activity. The same is true for other pathogen enzymes. The body also increases copper concentrations in the blood for similar reasons. Problem is of course if the body goes into overdrive and raises our temperature too much, this compromises our own ability to fight the infection so in that case antipyretics like paracetamol can reduce fever.

Second question. It isn't a side effect, however paracetamol works by blocking things like IL-1 that raise temperature. How IL-1 raises your temperature is quite interesting, it tells the hypothalamus (our thermostat) that it should be set higher. So we feel cold (so we try to keep ourselves warm) and the body thinks it's cold (so it increases the temperature by burning glucose mainly)


Why are red blood cells considered to be cells? Wikipedia states that a cell is

  the basic structural, functional and biological unit of all known living organisms. Cells are the smallest unit of life that can replicate independently.

It then goes on to state that

  All cells (except red blood cells which lack a cell nucleus and most organelles to accommodate maximum space for hemoglobin) possess DNA.

Then why are red blood cells still considered cells, while they can't replicate? Is the definition on Wikipedia just a bad definition? Or are red blood cells wrongly considered cells, but remain so for historical reasons? Or are they considered cells for some other reason, such as this answer which states that red blood cells do contain a nucleus at some point?

A very good question, and it is most likely because of the last option.  It had a nucleus for part of its life. After the RBC jettisons its nucleus, it still remains very metabolically active for approximately 3 months.  It maintains its cell membrane integrity, it metabolizes glucose, it interacts constantly with its environment, numerous cellular functions and structure remain intact...  It is extremely specialized for a primary purpose, and no longer requires the nucleus to provide more proteins.  It has limited capacity to heal from injury, so it has a limited life span.

Speculation:  I wonder if it might lose the nucleus early on so that when it is destroyed in the spleen at the end of its life as RBCs are, the spleen macrophages are not overwhelmed with additional processing of nucleic acids?  Macrophage type cells are already working hard in there to clear infectious agents and some immune cells from the blood.


Hardy Weinberg problem help! The three common genotypes at the hemoglobin locus have very different phenotypes: SS individuals suffer from severe anemia, AS individuals have a relatively mild form of anemia but are resistant to malaria, and AA individuals have no anemia but are susceptible to malaria. The frequency of the S allele among the gametes produced by the first generation of a central African population is 0.2.

(a) Assuming that mating occurs at random, what are the frequencies of the three genotypes among zygotes produced by this population?

I know that this is 0.2 for the S allele (q in the hardy weinberg equation)
and 0.8 for the A allele (p in the hardy weinberg equation).

So for the frequencies I got
AA = 0.64
AS = 0.32
SS = 0.04

(b) In this area, no SS individuals survive to adulthood, 70% of the AA individuals survive, and all of the AS individuals survive. What is the frequency of each of the three genotypes among the second generation of adults?

I don't know how to do this! I don't understand what to do! I tried multiplying

0.64 by 0.7 (because only 70% survive), but I know that is wrong answer. I know you have to divide 0.64 x 0.7 by the total that survived, but I don't understand why you have to do that. You didn't have to divide for part a, why do you have to divide for part b?

Also for some reason the frequency of the AS is not 0.32 for the answer. I don't understand why! Please Please help me.

(c) What is the frequency of the S allele among gametes produced by these adults?
I dont know this either!

PLEASE EXPLAIN ALL OF THIS TO ME IN CLEAR STEPS! THANK YOU SO MUCH.

Your answer to a) is correct (standard Hardy-Weinberg equation).

For b) you have to consider that you are calculating proportions of the population, which should sum to 1. Since 30% of the AA individuals and all SS individuals die, this is not the case after selection, which is why you should divide the frequencies by the total proportion that survive (also for the AS genotype), such as:

$$
\begin{array}{c|cccc}
\text{genotype} & \text{freq before} & w_{survival} & \text{freq after selection} & \text{corrected freq}\\
&\text{selection}&&&\text{after selection}\\
\hline
AA & 0.64 & 0.7 & f(AA)\cdot w_{AA}=0.45 & 0.58\\
AS & 0.32 & 1 & f(AS)\cdot w_{AS}=0.32 & 0.42 \\
SS & 0.04 & 0 & f(SS)\cdot w_{SS}=0.0 & 0.0\\
\text{sum} & 1 & & 0.768 & 1
\end{array}
$$

here $w$ is the fitness of genotypes. And for your comment on why you didn't have to divide by the sum of freqencies in a): you could do this, but since the sum of genotype frequencies is 1 it doesn't make a difference.

For c) you use the standard formula for calculating allele frequencies from genotypes, so that $f(A)=f(AA)+f(AS)/2= 0.79$ and $f(S)=f(SS)+f(AS)/2= 0.21$.


How does Sodium Valproate cause neural plasticity I have been reading a fascinating paper: Valproate reopens critical-period learning of absolute pitch

18 individuals were given Sodium Valproate (VPA) for a fortnight during which they trained on a pitch-training game. Results suggest that VPA reopens the plasticity window that normally closes by adolescence.

However, the paper seems to suggest that the exact mechanism of action is unknown.

  Valproic acid is believed to have multiple pharmacological actions,
  including acute blockade of GABA transaminase to enhance inhibitory
  function in epileptic seizures and enduring effects on gene
  transcription as an histone deacetlyase (HDAC) inhibitor (Monti et
  al., 2009). Of relevance here is the epigenetic actions of this drug,
  as enhancing inhibition does not reactivate brain plasticity in
  adulthood (Fagiolini and Hensch, 2000), but reopening chromatin
  structure does (Putignano et al., 2007). While systemic drug
  application is a rather coarse treatment, the effects may differ
  dramatically by individual cell type (TK Hensch and P Carninci,
  unpublished observations). VPA treatment mimics Nogo receptor deletion
  to reopen plasticity for acoustic preference in mice (Yang et al.,
  2012), suggesting a common pathway through the regulation of
  myelin-related signaling which normally closes critical period
  plasticity (McGee et al., 2005). Future work will address the cellular
  actions of VPA treatment in the process of reactivating critical
  periods. Future MRI studies will also be needed to establish whether
  HDAC inhibition by VPA induces hyperconnectivity of myelinated,
  long-range connections concurrent with renewed AP ability (Loui et
  al., 2011).

So it is saying that the standard use of VPA is to increase GABA levels (which keeps firing rate down -- it is used as an antiepileptic), however it also acts as an HDAC inhibitor, which means it causes unwrapping of chromatin and consequently increased mRNA transcription, maybe even transcription of genes that would normally be entirely deactivated in an adult.

So my guess is that some protein is getting produced that messages neurons to generate new axon/dendrite growth and/or new synaptic connections.

Can anyone clarify how VPA might accomplish plasticity?

EDIT (one month later): I have more detail, but I still can't quite make the connection. Here goes:

Neurites get wrapped by myelin/oligodendrocyte, which produces and exudes some of the chemical messagers {Nogo, OMgp, MAG}. The membrane surface of the neurite contains nogo 66 receptors (NgR-s) that get triggered by these messagers and inform the neuron to inhibit axon-growth. Somehow the 'HDAC inhibition' property of VPA is unwinding DNA enough to alter transcription rates of certain proteins, and one of these must be disabling the NgR.

But how is this happening?

As far as I can see this paper is being a little misleading, by saying "VPA mimics Nogo-66 receptor deletion".

The action of VPA doesn't seem to be related to this receptor.

It seems that blocking this receptor and applying VPA both increase plasticity, but it is like taking a car or taking a train -- entirely different modes of transport that achieve the same effect.

VPA seems to facilitate LTP through increased availability of relevant proteins.

That is unconnected with growing new neural structure.

The principal problem with growing new structure is, as hinted at the end of the question, that the adolescent/adult brain secretes a chemical that gets picked up by Nogo 66 receptor, which signals to collapse the axon growth cone.

It's why adult humans can't recover from spinal injuries. The axons won't reconnect.

It so happens that a small molecule Nogo Antagonist has recently been developed by Professor Strittmatter.  He was kind to reply to my query, and I learned that this molecule is currently in the early stages of FDA approval. It's a very exciting discovery!

I would caution anyone against taking VPA -- I have been encountering chest pains since experimenting with it (even though I dropped the experiment after a week due to pain). It looks as though this pain is inflammation of the stomach lining and a common reaction to VPA (VPA is an acid!).

If someone is determined to take VPA, they should at least investigate taking it together with Omeprazole, which discourages the stomach from producing excess acid.

I am disappointed that I now need to take omeprazole quazi-regularly, it appears that my brief VPA experiment has caused some long-term upset in my chemical balance.

Also of note is that (again discovered by Strittmatter) Ibuprofen has been found to also interrupt the signalling pathway that leads to axon growth collapse. But it requires a high dosage, and ibuprofen also causes a similar imbalance.


Xylem in the centre of the root I want to ask a question about xylem in the centre of the root.

I am reading a book about transport in plants, and it reads this regarding the root structure:

  Roots are subjected to vertical stresses - they have to be able to resist being pulled out of the soil.  A central core of strong xylem tissue gives ideal resistance to being uprooted and at the same time gives economy of space.

I'm confused about this passage.
How does the centre of the root being xylem tissue exactly prevent the resistance to pulling forces upwards out of the soil?

The is something called the Pressure Stiffening Effect (turn on a coiled garden hose and watch it try and uncoil for instance), pressure in the fluid filled xylem stiffens the root, making it harder to pull out, Roots are rarely completely vertical or straight to pulling them from the soil generally involves them flexing, which the stiffening pressure resists. its the same reason an Inverted Y of steel can anchor in soil but an inverted Y of rope will not, the steel resists bending thus you have to displace all the soil above it to remove it.