How do catenanes form when DNA replicates? So I am taking a course in DNA replication and repair. And we are talking about catenanes forming when DNA replicates (two circles of dsDNA interlinked) How is this possible?

The first DNA circle is double-stranded. If you could melt the double-helix completely you would not be able to pull the two stands apart without breaking the sugar-phosphate backbone of at least one of the two strands. This is a topological problem, the two strands are linked to each other.

Now consider DNA replication. In the simplest example there is a single origin of replication and there will be two replication forks proceeding around the circular genome in opposite directions. This is exactly what happens during DNA replication in the bacterium E. coli.  The DNA double helix of the parental molecule "melts", the RNA primers are synthesized by primase, and the DNA polymerase complexes initiate synthesis. Behind each replication fork there are now two hybrid DNA strands, each with a parental strand, and a new daughter strand.

Thus far no sugar-phosphate bonds have been cleaved. When replication is done each daughter ds DNA helix will have a single-stranded nick at the origin, and another one at the site where replication terminated, but those will be quickly repaired by DNA polymerase I and DNA ligase. Even if those two repair enzymes were inhibited, and you could somehow melt the DNA strands of both the daughter chromosomes, you would only be able to pull out the new DNA molecules (with the nicks), the two original parental strands are still topologically linked.

To resolve two concatenated DNA circles you need to make a double-stranded break in at least one of the ds circles. This  enzymatic activity is provided by a class of enzymes named Type II DNA topoisomerases.


What difference does it make in the organism's physiology/metabolism whether oxygen binds reversibly or not? A follow-up to How does hemoglobin-free blood transport oxygen?

I'm unsure about the use of physiology/metabolism in the title there. The question in mind is whether this reversible binding makes an organism slower, or faster; perhaps more capable of surviving in rarefied atmosphere.

EDIT:
I apologize that my comment made it appear this question is only about the Icefish; it is not. There are still other species (for instance, molluscs, and arachnids) which acquire oxygen by means other than haemoglobin.

I think I see where you are coming from.  There is a misunderstanding here.

Ice-fish have relatively lost their hemoglobin gene over time because they have adapted such a slow metabolism in the cold water where the oxygen is richer (oxygen content in cold water is higher).  The don't need any binding of oxygen to a carrier protein like hemoglobin because enough oxygen diffuses in from the water for the needs of their tissue.

There is no binding - reversible or irreversible in their blood - that would imply that the oxygen is binding to a protein like hemoglobin or hemocyanin, which the fish does not have.   The oxygen is just diffusing into the fish from the water around it.  The circulatory system is helping by flushing the system out and keeping everything fresh as well.


Why are people tired after surgery? I had surgery when woke up I felt like I only had 20% energy & felt extremely tired. Is this a common sensation? Why do people feel so tired after surgery?

Answers in comments are correct. The tail effect of hypnotic drugs combined to opiates given for pain relief will make you feel really tired just after surgery.

But if you are referring to a more long-term effect, such as feeling tired for several days after surgery, then several factors combine:

psychological stress
physical deconditioning: inpatients usually do not move much. And even a few days of immobility will have a huge impact on your physical abilities. That is why in modern medicine, every effort is made to make the patient move as quickly as possible. Intensive physical therapy, readaptation therapy, and fast-track pathways are a result of this effort.
physical stress: undergoing surgery is a physical effort. Your body needs to accommodate for large shifts in volemia, positive pressure ventilation, reaction to pain (which still takes place during anesthesia), etc. The physical abilities of the patient are evaluated by the anesthesiologist for that reason, using MET effort units (often measured in number of flights of stairs you can climb without stopping). People with angina pectoris or diagnosed atherosclerosis can also be submitted to an ergometric test (cycling) or stress echocardiography/scintigraphy to evaluate if their heart can tolerate the physical stress of surgery.


Which Hawaii bird makes this call at night? I'm on Big Island right now and keep hearing this bird starting at 6-7PM every night: https://voca.ro/18XEepbDmpCy. Which bird could it be?

Thanks to the magic of Reddit I was able to figure out that this is the Coqui frog rather than a bird. Apparently its an invasive species on Big Island and attempts are underway to eradicate them.


Self-replication in the genome in the seed Is the genome in the seeds of the plant turned off?  That is, does the DNA in the seed not self-replicate?
My second question is, what are the cells feeding on inside the seed before it is planted?

DNA in cells in general replicates when cell division occurs (unless it is a cell that contains many nuclei or multiple copies of its own genome, in which case DNA would replicate as copies are made. Multinucleate cells include things like the mycelium of fungi, and here is an example of a bacterium with thousands of copies of its own genome).
As long as a plant embryo is developing, then the cells are dividing and the DNA is replicated. You might be thinking of the stage of seed dormancy; insofar as during this stage the embryo is no longer growing, cells aren't dividing and therefore DNA is indeed not replicated. I don't know whether we could say the genome is "turned off" however, DNA's role isn't just being replicated, more importantly its role is to be transcribed into RNA which leads to the proteins the cell needs to function being created. I couldn't find whether DNA transcription happens during cell dormancy but it's plausible enough that it is at least slowed down as well. The cells presumably don't have much to do during this period and you wouldn't want them to do much, to conserve energy.
Seeds contain nutrients that can feed the embryo until it can feed itself (for plants that is the moment when they germinate enough to photosynthesize). That is where flour comes from!


Is metastatic cancer always lethal if uncured? Can matastases spread in different parts of the body of an animal suffering from cancer grow in a limited way, such as not to cause much more harm that a benignant tumor in those parts of the body would, or are metastases guaranteed to eventually cause death, if left uncured?

What you're asking is essentially to prove a negative ("Are there no ways an unchecked cancer can be non-lethal?"), which is unfortunately more of an exercise in imagination than anything else. The best way I can answer is by highlighting what about cancer actually kills, from which you can personally evaluate if a particular type of cancer fits and would be lethal.

You need to remember that it is not the metastization per se that kills something, it is the growth interfering with critical systems that causes death. Many systems in a body will prove lethal if sufficiently compromised. The brain is an obviously vulnerable point (a sample of one of its mechanisms can be found here), but even something like the lymphatic system, which is notably able to maintain its duties with some components compromised or removed, are ultimately necessary (a compromised lymphatic system will, among other things, leave one vulnerable to otherwise harmless infections). The primary checks to take away from this are "Can a body survive with this system compromised, or to what degree?".

Even in the case of a hypothetical cancer that is not particularly metastatic, but simply growing in a particular area (we'll even be generous and say the particular area is not vital to survival), tumors take resources to maintain, both chemically and mechanically (pulmonary issues are known to occur with this sort of unguided growth). Many of these effects can be highlighted in overgrowth diseases such as in Proteus syndrome (Note - My apologies, this is behind an academic paywall). Considerations for this part are "How many resources can a body afford to lose?" and "Can the heart support this extra mass?".

As an additional factor, tumors that don't allow infiltration by cells from the immune system can be prone to infections, both internally and externally. This is circumstantial, though, and not a core component of a cancer's lethality (mostly).

The mere presence of a tumor is not guarenteed to be lethal, but I would say, ultimately, any continuously-growing tumor will lead to death, simply by subverting the proper mechanisms of the body to a sufficient level.

References:

Papadopoulous et al., Neuroscience (2004);129,1009–1018
Cohen, AJMG (2005);137C,38–52


brain and fingers movement theorie I heard somewhere that when we want to do a repetitive movement of one finger (ex the index) . Our brain (in a very crude way) sends a first message to move all the fingers, and then a second message to hold the fingers that we don't want to move.

The person who said it, was explaining about brain evolution and the fact that the old reptilian part of our brain is the one that send the first message and the higher brain sends the second message.

So is that true ?
If so, do other parts of our brain work like that too? For example more complex behaviors, like sexual mate choice?

The body indeed uses lateral inhibition / surround inhibition. When using a muscle, neighbouring muscles are sometimes activated to. So active muscles are excited while nearby muscles are (partially) inhibited (Beck and Hallet 2011)

This surround inhibition is true for fingers (Sohn and Hallet 2004).


How to understand certain protein names I am looking for a reference to help me understand what is meant by acronyms such as : H3K9me1, H3K9me2, and H3K9Ac.

I know that these are all histone proteins, but is there a general nomenclature algorithm for all cellular proteins? Are H3K9me1 and H3K9me2 just different proteins that methylate the same region? What is meant by H3K? Etc.

Thanks!

For H3K9me1:

H3: name of the histone
K9: amino acid and position (K = lysine, position 9) of modification
me1: modification (me = methylation, ac = Acetylation), and number of modifications

So H3K9me1 means that the 9th residue (lysine) of histone H3 was monomethylated. Similarly H3K9Ac means that same residue was acetylated.

Wikipedia gives a decent explanation of the nomenclature of histone modifications, and there is also a more detailed table in Nature Structural & Molecular Biology.


What does (-;-) after a gene mean? I'm using Promethease to examine genome data originally downloaded from 23andMe. Some genes I notice do not show allele information (eg. (G;G), (C;G)) and instead seem to be blank (-;-) like in the screenshot I provided. Can someone please tell me what this means? Thanks in advance.

I suggest you to take the tutorial you can found from here
Before the $(-;-)$ there is the specific location of the gene in the DNA. Between the brackets you have your specific genotypes at the location marked before. So, whatever is inside the brackets is referred to a single nucleotide polymorphism (SNP) found in your gene. If there is nothing, as the case of the screenshot that you provided, is possible that they are not able to determine the SNP (so the SNP is not found and this information is missing).


Manual Primer Design for a gene on the reverse strand My question might sound very naive and stupid but I am hopeless now. I read so many websites and pages but could not figure out this PCR primer design thing completely.

Some genes are on the reverse strand of the DNA as we can see on the certain databases. Like this:

Source: http://www.wormbase.org/species/c_elegans/gene/WBGene00019616#0de1-9g4356caf-3

So when I click and get the sequence data of that gene, it also says it's on (-) strand. My most potentially silly question is: Do I just copy paste that sequence and try to find my primers manually or do I need to get a reverse complement of that sequence to make it (+) strand so I can design my primers? This minus, plus stand and reverse complement thing confuses me a lot! And I also do not get why do we get the reverse complement of the reverse primer sequence once we design it.

Thanks for the help in advance!

Not a stupid question at all. I was just as confused by this as a beginner in molecular biology. You get the hang of it after a while. :)

I find it much more difficult to design primers from just one strand, especially the minus strand, so I always try to get both to work with. If you don't feel like doing that, just one strand is sufficient (plus or minus), but I would recommend at least getting the reverse complement in your case because plus strands are much easier to work with.

For a quick example, let's say I have a ten bp sequence I want to design primers for and this is my plus sequence:

5' ATAACTTCGT 3'

Now let's say I want a three bp primer. So the forward primer would simply be 5' ATA 3', that's easy. The reverse primer, if I just take it from there without flipping it, would be 5' CGT 3'. But if I put that into my PCR reaction, it will not do anything because DNA binds to it's complement strand, meaning that primer would only bind to 3' ACG 5', or 5' GCA 3'. So instead, I'm going to want 3' ACG 5' because it will bind to its compliment, the 5' CGT 3' part of my sequence. (Technical issue here, suppliers usually only give the option to write in 5' to 3', which makes sense, but you must remember to flip your reverse primer before giving it to them because it will be in 3' to 5' originally. In this case, I would ask for 5' GCA 3'.)

This is easier to visualize if I have both the plus and minus strand though, which would look like this:

5' ATAACTTCGT 3'
3' TATTGAAGCA 5'

If you have both strands like the example above, you can find both the forward and reverse primer without much difficulty.

I could give a more comprehensive answer of how this all works out during DNA replication that would involve illustrations, allegories, and maybe a few mildly humorous jokes, but I would hate to bore you unnecessarily, so let me know if you understand now or if you need more. ;)

Edit: Exactly (to your third comment I mean)! Remember, DNA is always read and replicated 5' to 3', so the forward primer will bind to the minus strand and be replicated 5' to 3', so will extend the sequence to the right. The reverse primer is the opposite, 3' to 5', so it will extend the plus strand to the left. After both of those happen, you will end up with two full strands. As promised, here is an illustration:

Now, to your question about Primer-BLAST. You do not have to enter a plus strand, but the tool is assuming that you are entering the plus strand, so you will get the right primers, it will just call them the wrong names (i.e. with the example above, it would give you 5' GCA 3' as your forward primer and 5' ATA 3' as your reverse). The forward and reverse primers are treated exactly the same, so this wouldn't throw off your PCR, but it would be incorrect nonetheless. To avoid confusion, I suggest utilizing a tool to reverse-compliment your minus sequence into plus before running it. It's rather easy to get the reverse compliment of any sequence; here is a good tool for that.

I hope this helps. :)


What exactly is the neural receptive field? Neural receptive fields map the spatial or temporal distribution of the data to individual neuron excitation, if I understand correctly, but I do not understand if receptive fields (especially in the higher cognitive areas such as the various layers of the visual cortex, etc.) are:

Actual structural distributions of neurons that help map specific spatial or temporal properties of stimuli (such as concentric arrangement for contrast detection, rectangular arrangement for orientation detection, or movement detection, etc.), or,
Merely a mapping of the structure of the stimuli that can excite specific neurons.

If it's the latter, isn't it basically as simple as a pattern/feature/vector that individual neurons are sensitive to?

I think is closer to 2. It is the subset of sensory space that elicits a reaction in a given neural population.

So you should:

Pick your neural population. Usually it is a single neuron (but can be easily extrapolated to bigger populations). It may be a sensory neuron, or a neuron in a higher processing region.
Determine your sensory space. That is, you should decide the kind of stimuli you'll be dealing with. For example, not only "visual stimuli", but you should identify the parameters, or independent variables, you will vary in your experiment.
Define a criterion to discriminate between reaction and non-reaction. This implies to choose what is the dependent variable in your study (for example neuron firing rate). Then you could define what features in the relation $\frac{dependent\:variables}{independent\:variables}$ you will search for. That is the tuning curve (which well may be a high dimensional curve).
Perform your experiment and analyze your curve. The region of parameters (independent variables) whose reaction goes above threshold according to your criterion is the receptive field. Sometimes is not trivial to define such a criterion (see: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.0040092)

A good general reference is the article in Scholarpedia: http://www.scholarpedia.org/article/Receptive_field

This type of analysis is very useful for position coding, that is, when you expect that the activation of a specific region in the brain correlates to stimuli in a region of sensory space. But sometimes things are more complicated (e.g Olfactory coding http://www.jneurosci.org/content/30/27/9017.full).


How do DNA-binding proteins recognize the correct DNA base pairs? My professor posed this question to the class today - "How do DNA binding proteins specifically bind to base pairs?"

He alluded to the different arrangements of hydrogen-bond donor and acceptors in A-T, T-A, C-G, and G-C base pairs. However, they are not always significantly different in some pairs (i.e. the minor groove of the C-G and G-C base pairs have the same acceptor - donor - acceptor pattern).

So how would a binding protein know the difference between C-G and G-C on the minor groove of a DNA base pair? How does a DNA binding protein know it's reached the right base pair, more generally?

Thank you!

There are different kinds of DNA binding domains; the ones involved in base identification in the major groove can differentiate between different base pairs of the same nucleotides i.e. AT vs TA because they bind to functional groups on a nucleotide and not the base-pair per se. The stereochemistry i.e. which nucleotide is in the major groove, is important. The location of the nucleotides in the major groove also is a factor (Figure 1).

  Figure 1: DNA sequence identification by Helix-Turn-Helix transcription factor. This is the example case of the Engrailed protein in Drosophila. Reproduced from Paro and Sauer (1992) [1].

You can see that Adenine is recognised differently than Thymine. In many cases such as that of zinc finger proteins (ZF), sequence identification usually happens for dinucleotide pairs such that each finger (a modular unit) can identify a di/tri-nucleotide (Figure 2,3). An array of fingers in case of ZF and helices in case of Helix-Turn-Helix motifs can recognize a unique stretch of DNA sequence (which is certainly more unique than individual base pairs). Usually the binding of the fingers are co-operative which leads to increased affinity and specificity of the protein-DNA binding [2,3]. Analogous mechanism may exist for other kinds of DBD too (I haven't specifically looked for that). Moreover, many DNA motif binding proteins oligomerize, which is again co-operative. This increases the specificity and the overall binding kinetics becomes sigmoidal and thresholded (see Hill kinetics).

Binding mechanisms are best understood for ZF proteins that led to the development of zinc finger nucleases which was one of the first modern methods of targeted genome editing [4] (though they have now been obsoleted by CRISPR-Cas system).

  Figure 2: DNA sequence identification by zinc finger proteins. This example considers the Zif268 protein. Reproduced from Paro and Sauer (1992) [1].

  Figure 3: A more detailed depiction of Zif268-DNA interaction. Reproduced from Durai et al. (2005) [4].

References:

Pabo, Carl O., and Robert T. Sauer. "Transcription factors: structural families and principles of DNA recognition." Annual review of biochemistry 61.1 (1992): 1053-1095.
Krishna, S. Sri, Indraneel Majumdar, and Nick V. Grishin. "Structural classification of zinc fingers SURVEY AND SUMMARY." Nucleic acids research 31.2 (2003): 532-550.
Lee, Juyong, Jin-Soo Kim, and Chaok Seok. "Cooperativity and Specificity of Cys2His2 Zinc Finger Protein− DNA Interactions: A Molecular Dynamics Simulation Study." The Journal of Physical Chemistry B 114.22 (2010): 7662-7671.
Durai, Sundar, et al. "Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells." Nucleic acids research 33.18 (2005): 5978-5990.


Does natural selection still increase biological complexity? I recently read The Selfish Gene by Richard Dawkins, which I found very interesting. In one of the last chapters, he gives multiple possible explanations to the question "Why did natural selection give rise to complicated lifeforms?".

Since complex (say: multi celled) life exists, that means natural selection at some point did increase complexity, as we went from the primal soup to multi celled organisms (with many steps in between). My question is whether this trend of increasing complexity is still going on? Is natural selection a never-ending arms race, tending towards increasingly complicated genomes? Or did natural selection reach some plateau, local optimum, of biological complexity, after which the only evolution taking place is "on the same level".

I have thought a bit about a metric for complexity, but since I have no background in biology I am not at all certain. At first thought, the length of the genome sounds like a promising candidate, but the phenomenon of freeloading, not-functioning DNA (conveniently described in The Selfish Gene too) undermines this. I hope it is clear what I mean by "complexity".

Thanks for answers in advance, it has been fun speculating.

There are multiple definitions of complexity, ranging from algorithmic complexity to computational complexity.  In biology, I'd say that algorithmic complexity (Kolmogorov complexity) is most relevant.  Unfortunately, we don't yet know enough about genetic circuits and all the other things that go on at the subcellular level even to make plausible estimates of an organism's complexity.

If the complexity of a human being were analyzed all the way from physiology down to the subcellular & molecular level, I think it would be apparent that most of the complexity is present at the subcellular & molecular level.  In fact, essentially all of the complexity of a multicellular organism is encoded at the subcellular level, so it's appropriate to say that's where the complexity resides.
It is not entirely clear that a human being, whose genome contains ~3 billion base pairs, is more complex than a protozoan Amoeba Proteus whose genome is ~34-43 billion base pairs.

All of the processes that have been active in evolution since the beginning are still active, and changes in complexity - regardless of the definition of complexity - are still going on.

The closest things there is to a "plateau" is a relatively static distribution of genotypes that can last only as long as the adaptive landscape is unchanged.  However, the adaptive landscape is always changing because of climate changes, plate tectonics, invasive species, disease, intra-species iteractions, and even because of chance fluctuations in the distribution of genotypes.


Which nucleotide as start point for maximum parsimony? Background
Maximum parsimony is used to build an evolutionary tree by choosing the "simplest" one. I see a lot of examples about how this should be done. For example:

Question
However it's not clear for me WHICH nucleotide should be used as starting point?
Let's consider the first tree(from the figure above):

Nucleotide G was chosen as starting point resulting in one mutation, however if we choose T we would have two mutations and if we choose A we would have three. So what determines the nucleotide which should be used to start with?

The "starting point", or ancestral state, is chosen so as to obtain the most parsimonious tree.

Parsimony is used both for choosing the topology and for choosing the ancestral states for a given topology:

1) The parsimony score for a given topology is computed for the set of ancestral states minimizing the number of transformations.

2) Then, the topology minimizing this minimized number of transformations is chosen as the most parsimonious tree.


Time required for RNA precipitation in ethanol I precipitated bacterial RNA during 1 hour at -80ºC after depleting rRNA with Ribo-Zero kit.

Does more time lead to better results?

As far as I know this has never been thoroughly analyzed for RNA, but there is an excellent paper on the precipitation of DNA and the usual conditions in BRL Focus by Zeugin (see below for the paper). Since DNA and RNA are pretty much the same (except for one OH-Group) and the conditions used for precipitation are also similar, I think we can use this for a very close estimate.

Interestingly neither the time nor the temperature of a precipitation have a great influence on the outcome - they change the yield only by a few percent. If you look on figure 2 from the paper mentioned, you see the following:

This subfigure shows that the recovery is almost not influenced by the temperature, but only by the conconcentration of the DNA (or RNA). Depending on how much RNA you expect (how much cells did you use for the isolation) I would add a co-precipitation agent when you have only very small amounts on RNA. Glycogen works very well here. Otherwise I wouldn't worry.

This figure shows that the incubation time has only an influence on the percentage of the recovery when then time is too short. If you incubate for an hour, you are on the safe side.

Reference:

Ethanol Precipitation of DNA.


Why do vaccines cause your arm to hurt? When you get a shot for a vaccine (for example, the annual flu vaccine), the nurse frequently indicates that your arm will ache for a day or two, maybe more. This ache is typically not just a pain from having your skin punctured, but is actually an ache of the entire arm.

What mechanism causes the entire arm to ache from a vaccine? Why doesn't that ache extend to other parts of the body, like the hands or the shoulders? Why do non-vaccine arm punctures (such as drawing blood, injecting drugs) not cause the ache?

The goal of the vaccine is to provoke an immune response, therefore some degree of inflammation is expected in order for the vaccine to work. As swbarnes2 says, vaccines contain adjuvants, pro-inflammatory molecules that produces local inflammation and recruits immune cells to the site of the inoculation.

Since you get the shot intramuscularily, intradermally or subcutaneously, it is local, and the inflammation does not spread. The reason why your whole arm seems to hurt (rather than the place where the vaccine was deposited) is, I think, that where you got your shot, you have not many pain receptors, and your brain is not able to determine the pain source very exactly.


Determining a patients biological age? I am looking for an algorithm that shows the exact coefficients some variables that have on a hospital patient's chronological age versus their biological age.

I understand a lot of the variables that go into determining ones biological age (i.e. Blood pressure, diet, family history of disease, obesity etc.) but not the amount of impact that it has on the actual scoring of their age.

I have found many sites that will calculate it, however I need the actual variable coefficients and influence in order to produce a proper score for thousands of patient records.

Thanks in advance for your input!

As the definition of biological age is very ambiguous, I propose that to generate an algorithm, you first need to create a quantifiable definition. I submit:

  Biological age is a measure indicating what portion of one's calculated life expectancy is already expended, adjusted proportionately for the average life expectancy of their major demographic.

Wow, that's a mouthful! So, let's break it down.

Life expectancy is calculated :

Ascertain a person's major demographic (Geographic residence, Race, Gender and Generation).
Find the average life span of that demographic.

This is negligibly speculative as a living person's Generation has not yet fully perished
Statistical outliers, such as infant mortality, are generally excluded from this calculation

Adjust for known major factors that have accepted statistical impact.eg:

Lifestyle
Current medical conditions
medical history

Average Life expectancy of subject's demographic was calculated in #2 above.

So, now let's throw in some sample numbers.

Statistical Facts: (totally made up)

Caucasian males living in the France, born in the 1970s have an average life span of 72 years.
Exercising 30 minutes or more daily increases life expectancy 6 years
Smoking decreases life expectancy 7 years
Not smoking increases life expectancy 2 yearsHold on a second?! Wouldn't not smoking already be accounted for in the "Smoking..." section? Well, no, because our demographic sample are all "unknown" so having specific knowledge would statistically change the results in either direction
Heart Disease decreases life expectancy 8 years
Devout religious affiliation increases life expectancy 6 years.
Family history of diabetes decreases life expectancy 2 years.

Two subjects both Caucasian, french males born in 1974 (40 years old chronologically):Their mom's actually shared a labor and delivery room!

Beavis - known: Smoker with heart disease.
Butthead - known: Devout Buddhist, very athletic, non smoker with a family history of diabetes

Beavis' life expectancy is 57 (72-7-8)Butthead's life expectancy is 84 (72+6+2+6-2)

Beavis has expended 70.2% (40/57) of his life expectancyButthead has expended 47.6% (40/84) of his life expectancy

Despite sharing a birthday:Bevis' biological age is 50.5 years (.702*72)Butthead's biological age is 34.3 years (.476*72)

Note: It's almost 6 hours past my bedtime, so please excuse any stupid mistakes or miscalculations.  The general concepts are what is important


What do animal cells store pigment in? So I know plants store pigment in chloroplasts, chromoplasts, etc., but what do animal cells store pigment in? For example, is there like a chromoplast for melanin in the human body?

I tried Googling my question and didn't find anything, but maybe I was looking at the wrong sources.

Melanine is produced and stored in melanocytes. They contain melanosomes that are organelles that store melanine.


Where are doxycycline's anti-inflammatory properties derived from? I have been looking at this antibiotic called doxycycline which is used mainly as an antibiotic. It has however some interesting anti-inflammatory properties. Does anyone know where these anti-inflammatory properties come from, chemically?

Doxycyline inhibits iNOS and TNF-alpha expression.   It also influences secretion of IL-1beta, IL-8, and TNF-alpha, as well as other inflammatory cytokines.

[These are results collected from multiple systems.]

For appropriate references, see: Leite et al (2011). Anti-inflammatory properties of Doxycycline and Minocycline in experimental models: an in vivo and in vitro comparative study. Inflammopharmocology.

As for the chemistry of how doxycycline accomplishes these things, I'm afraid I don't know the answer, but hopefully, this gives you a place to start.


How does the ideal free distribution work? I have recently completed a study on Brent Goose. I found that Brent Geese occupy high quality habitat first then once this is full of geese, they fill up low quality habitat. However, there were always fewer geese in the low quality habitat.

This pattern therefore seems like a good match for the ideal free distribution…but is it?

Under the ideal free distribution, do birds fill up high quality first, then low quality habitat second?

Or do birds fill up both high and low quality habitats simultaneously, but fill up high quality at a faster rate?

Or does the ideal free distribution not make explicit the order/rate at which birds fill up high and low quality habitats?

The order of settling depends on the resource availability in different patches (in your case the difference between high and low quality habitat), but generally speaking, the pattern you observe conforms to the ideal free distribution.

The key factor in the ideal free distribution is that habitat patches are filled according to the current resource availablity (~per capita resource access), given the current density of individuals in the patch (so the marginal resource availability). If the high quality patch has much higher resource levels than the low quality patch, this means that many individuals can settle in the high quality patch before the marginal resource availability becomes equal to the resource availability in the low quality patch, at which point individuals will start settling in both patches. Therefore, the two observations you make; 1) lower overall density in low quality habitat and 2) the high quality patch being settled first, both agree with the ideal free distribution.

This graph (from wikipedia.org) illustrates this pattern nicely, for the standard version of the ideal free distribution:

Here, the marginal, apparent value of a patch is shown on the y-axis and the number of individuals in the patch on the x-axis, and the numbers refer to the order that individuals will settle in the two patches (so the first 6 settle in the high-quality Patch B, ind. 7-9 in Patch A, ind. 10 in Patch B etc).

However, I encourage you to read about other theories on habitat choice, and the pattern you describe can probably be explained by other processes as well. The ideal free distribution also has some rather restrictive assumptions (e.g. equal quality of individuals and no dominance/territorial/interference behaviours among individuals), which you have have to consider.


Do brain cells regenerate in the adult brain? I know that most cells in the body regenerate, dying and being replaced with new cells. For example, in bone special enzymes move radially outward from the marrow in a narrow tunnel, destroying the old bone as they go and replacing it with new bone cells. In this way, our bones are slowly regrowing and being replaced constantly.

Is a similar process at work in the adult brain? Do neurons in the adult brain die and become replaced with new neurons? If so, how are the connections re-established? Each neuron is connected to other neurons by a complex network. If cells are regenerated, how do they re-connect to existing cells?

Short answer
Neural regeneration in the adult brain is confined to two localized hot spots, namely the hippocampus and the anterior lateral ventricular wall. Establishing connectivity between new cells and existing neurons is mediated, at least in part, by the growth cones present on axonal tips of newly formed cells. The growth cone responds to various stimuli and guides the axon towards it new target.

Background
As to your first question: Also adults can regenerate brain cells, albeit in a few restricted, specific regions of the brain. A continuous level of neural regeneration occurs throughout adult life in at least two locations. The first is the subgranular zone of the dentate gyrus of the hippocampus, the region of the brain involved in learning and memory. The other is located in and near the anterior lateral ventricular wall of the cerebral cortex. While neurogenesis in the adult hippocampus is relatively limited, the subventricular zone is thought to continuously replace interneurons in the olfactory bulb (Clarke, 2003).

Studies have shown that neurogenesis folloing neuronal cell loss due to injuries occurs only within the germinal structures mentined above, and not in cortical or striatal structures. Even when neurogenesis in the striatum (but not cortex) has been reported following ischemic injury, the resulting neurons survive only a short time. Hence, under normal circumstances structural or functional recovery in non-neurogenic brain regions is limited (Hallbergson, 2003).

Re-establishing connectivity between new cells and the existing tangle of neurons in the neurogenic regions of the brain is complicated. An important structure in this regard is the growth cone (Fig. 1); it is present in developing axons that are not yet synaptically connected. They are motile structures present on the tip of the growing axon and guide axons to their synaptic targets. They control the cytoskeleton and determine the course and rate of axonal outgrowth. Neurons and growth cones can detect a variety of external signals to establish neuronal migration and neurite outgrowth. A key in this process is chemotaxis. Several classes of molecules, e.g., secreted factors, adhesion molecules and cues from the surrounding extracellular matrix and adjacent cells are involved in the process of neuronal pathfinding and growth. To advance over larger distances however, gradients are insufficient and neurons use mechanical cues (durotaxis). For instance, neurite outgrowth has been shown to be affected by the mechanical stiffness of the substrate. Glial cells have been shown to be softer than their environemnt and neurons preferentially seem seek out glia to grow to (Lu et al (2006); Park (2002); Pawlizak (2009)).

Fig. 1. Fluorescently labeled growth cone on the tip of an axon. source: wikipedia

References
- Clarke, Bone Marrow Transplantation (2003); 32: S13–S17
- Halbergson, J Clin Invest. 2003 Oct 15; 112(8): 1128–1133
- Lu et  al., PNAS (2006); 103(47): 17759-64
- Park, et al., Bioessays (2002); 24(9): 821-7
- Pawlizak, Thesis, University of Leipzig (2009)


If what you want is to find a consensus structure for a group of alignments in stockholm format then you might try with
RNAalifold
 and for single sequence folding check RNAfold. Both have online servers and can also be run offline.

After you get the consensus structure update the stockholm file by adding  a structure consensus line as: #=GC SS_cons followed by the dot bracket notation.

A nice RNA structure editor that will make your life easier is EMACS when complemented with RALEE. It allows you to view and manipulate RNA structures, predict structure folding and color the alignments based on basepairs relationships. It will be worth it to invest time into mastering RALEE.


How can RNAse degrade any RNA? Every RNA has an unique sequence. Since RNAse is an enzyme and substrates react to its active site in a lock-key mechanism, how is RNAse able to degrade any kind of RNA?

Enzymes vary in substrate specificity

This is covered in most textbooks of biochemistry, but you can find explanations on the web, e.g. here. As far as ribonucleases are concerned, there can be high specificity (e.g. recognition of a RNA with a specific base sequence), lower specificity (3′- or 5′-exonucleases — act from these respective ends) or specificity limited to the particular bond to be broken (e.g. pancreatic ribonuclease digests any RNA phosphodiester bond — but not DNA). (There is also specificity of strandedness—  between double- and single-stranded RNA.)

What determines this varying specificity?

Evidently, the substrate specificity is determined by the extent of the structure of the substrate that the enzyme has to recognize — i.e. bind to like a ‘lock and key’, refered to in the question. This requires familiarity with the chemistry of the substrate, in this case RNA:

In the diagram above (modified from Berg et al.) the phosphodiester bond which must be cleaved is highlighted. We can deduce from this diagram that in order to be specific for RNA — but no more — a ribonuclease needs to be able to recognize the ribose 2′OH (i.e. distinguish it from 2′-deoxyribose) as well as recognizing the phosphodiester bond. There is no need to recognize the bases.

The mechanism of action of bovine pancreatic ribonuclease

The mechanism of pancreatic RNase was established in the 1960s, long before any RNase that recognized particular sequences, although it has been refined subsequently. A diagram from the paper by Roberts et al. (1969) is shown below.

The diagram does show a ‘pocket’ for one of the bases adjacent to the phosphodiester bond, but this need only be generally hydrophobic, able to accomodate any of the four bases.

To study the interaction of the bases with RNAase one has to obtain crystal structures of RNAase complexed to pseudo-substrates or inhibitors (the true substrate hydrolyses, of course). The literature here is complex, and I am unable to provide a convenient review of the topic. It does appear that the binding of RNA is stabilized by the interaction of particular bases with the protein, but the key point is that any such interactions are not a requisite for the binding of the substrate. As a starting point to the literature I suggest the Protopedia page on RNase A, and a paper by Birdsall and McPherson.


MRI maximum field strength More tesla = more resolution, is there limit of human body of how much strong magnetic fields it can handle safely which means there is limit to how strong MRI magnets we can use?

Engineering problems aside, could we scan live humans if we had 20 or 40 tesla MRI machine?

Technically, higher main magnetic field strength doesn't mean more resolution.  There are three parts to the scanner: 1) main magnetic field, 2) gradient coils and 3) RF coils.

The main magnetic field strength (1.5T, 3T, 7T, 9T, the last two typically more for research) determine more of the signal to noise (in a very simple sense).  This is static - it doesn't ever change.

The gradient coils are what determines the resolution and the rate of switching is the biggest determining factor. There are limits on what they can switch at when used on humans as they can cause peripheral nerve stimulation, vertigo, nausea, metallic tastes etc.

I don't believe static field of 20T etc would be a problem, though there is not much research to prove or disprove that.  The problem would be moving into that field as that will cause the same types of effects as the gradient coils switching.  Even for 7T, one must not run into the scan room as it can cause peripheral nerve stimulation (and some other effects). Currently, I believe the strongest full body human MRI scanner is 10.5T. Another article talks about 11.7T human scanners (one of them is a "head only" scanner. It also has some nice pictures).


About the definition of ketogenic amino acid I am studying biochemistry and have been looking at metabolic network diagrams showing the different intermediates of glycolysis and the citric acid cycle that amino acids can be converted to.
I have gone over a list of which amino acids are considered ketogenic and which are considered glucogenic. I was surprised that Serine, Glycine, Cysteine, and Alanine are not considered ketogenic as they can be converted to pyruvate and pyruvate can be turned to acetyl-CoA, so that these 4 amino acids seem like they can then be used for ketogenesis.
I then looked at the definition of ketogenic amino acids on Wikipedia and it says "A ketogenic amino acid is an amino acid that can be degraded directly into acetyl-CoA".

The question is if there's some reason this is the definition of ketogenic amino acids; it seems to make more sense to me to classify Serine, Glycine, Cysteine, and Alanine as ketogenic due to what I said.

Thank you.

The fundamental 'problem' with acetyl-CoA is that it cannot be converted to glucose via the tricarboxylic acid (TCA) cycle: a two-carbon compound (acetyl-CoA) enters the TCA cycle, but two carbons are lost as CO$_2$ during each round of the cycle (in the two decarboxylation steps, ie in the reactions catalyzed by isocitrate dehydrogenase and by the alpha-ketoglutarate dehydrogenase complex).

There is no 'net gain' of carbon when acetyl-CoA is 'burned' in the TCA cycle.

This is why animals cannot convert even-number fatty acids (even-chain fatty acids) to glucose, and a basic principle of animal nutrition is that triglycerides, with the exception of the glycerol backbone, cannot be converted to glucose.

This, is seems to me, is also the key to understanding the difference between 'ketogenic' and 'glucogenic' amino acids.

Amino acids that directly give rise to acetyl-CoA (or acetoacetyl-CoA) cannot be converted to glucose but that can be converted to ketone bodies (such as D-3-hydroxybutyrate)  are referred to as ketogenic amino acids.

Pyruvate can be converted to glucose (via glucneogenesis), and amino acids that may be converted to pyruvate are considered glucogenic. A very good example is alanine which may be converted to pyruvate simply by transamination (alanine aminotransferase).

Alanine is a key protein-derived glucose precursor, especially in times of starvation (Felig, 1975). A commentary on the discovery of this key finding is given in this citation classic

In addition, amino acids that may be converted to TCA intermediates that in turn may be converted to phosphoenolpyruvate (and are thus precursors of glucose) are considered glucogenic (Lehninger, Biochemistry, 2nd Ed, 1975, p629).

We need to be aware that propionate (a three-carbon compound) is glucogenic (and this is particularly important in ruminants): it is even-chain fatty acids (and their CoA derivatives) that are non-glucogenic.

Furthermore, an amino acid may be both ketogenic and glucogenic.

Only leucine and lysine (LK) are exclusively ketogenic
Tryptophan, Isoleucine, Phenylalanine, and Tyrosine (WIFY) are both glucogenic and ketogenic
The other 14 'protein' amino acids are glucogenic

See  D'Mello (2003) for a great ref (it must be good, he's from Scotland).

The catabolism of the branched-chain amino acids (Ile, Leu, Val) provide an example of each type (Harper et al., 1984):

The catabolism of isoleucine gives rise propionyl-CoA and acetyl-CoA and is both glucogenic and ketogenic.
Leucine catabolism yields acetoacetate and acetyl-CoA (ketogenic)
Valine catabolism yields succinyl-CoA (glucogenic)

A quote from Metzler (2001) may help to clarify the origin of the terms.

  According to a long-used classification amino acids are ketogenic if (like leucine) they are converted to acetyl-CoA (or acetyl-CoA and acetoacetate).

  When fed to a starved animal, ketogenic amino acids cause an increased concentration of acetoacetate and other ketone bodies in the blood and urine.

  On the other hand, glucogenic amino acids such as valine, when fed to a starved animal, promote the synthesis of glycogen

  ... isoleucine is both ketogenic and glucogenic, a fact that was known long before the pathway of metabolism was worked out.

Thus, in feeding experiments, a glucogenic amino acid gives rise
to the synthesis of glycogen, whereas a ketogenic amino acid does not
(but does give rise to an increase in the concentration of ketone bodies)`

We may note that plants can circumvent 'the acetyl-CoA problem' as they have the enzymes of the glyoxylate cycle, where the two decarboxylation steps of the TCA cycle are 'bypassed' (the key enzymes are malate synthase and isocitrate lyase) [and plants can convert acetyl-CoA to glucose].

It is also of interest, maybe, that both arginine and taurine (not one of the 20, of course) are essential in cats (see D'Mello, 2003). Arginine is required because of an inability to synthesis ornithine and a single Arg-free meal may cause a cat to become comatose due to the build-up of NH$_3$ (see D'Mello, 2003; Bequette, 2003) , and taurine is required to prevent retinal degeneration (see D'Mello, 2003; Bequette,2003). In addition, cats need high levels of Phe/Tyr for melanin biosynthesis, otherwise hair color may change from black to red-brown (see Bequette, 2003)

Reference

Some key references given above are from the following book:

Amino Acids in Animal Nutrition (2003) Edited by J.P.F. Mello, CABI Publishing, 2nd Edition

D'Mello, J.P.F (2003) Amino Acids as Multifunctional Molecules by J.P.F. D'Mello (Chapter 1)
List Bequette, B.J. (2003) Amino Acid Metabolism in Animals:an Overview (Chapter 4)

In Addition (Taurine in Cats)

Carnivores Herbivores and Omnivores in Blondes in Venetian Paintings, the Nine-Banded Armadillo, and Other Essays in Biochemistry by Konrad Bloch


Are there COVID-19 citizen science projects to compare habits and outcomes? I've seen some "citizen science" projects for coronavirus that are not really collaborations, but simply requests for processing time.  Are there any "real" projects where people who have gotten their diagnoses could go, chat with one another, volunteer to publicly disclose their virus status, test results such as O2 perfusion, and daily self-rating of symptoms, and agree on group surveys to profile what they eat and other activities they do?

I would like to see ordinary people work together toward answers to basic questions.  For example:
a) does salt intake affect symptoms?  [re: blood pressure]
b) does drinking coffee affect symptoms? [re: type II diabetes risk]
c) does exercise affect symptoms? [re: HIFs]
d) do dietary supplements such as flax, curry, and elderberry affect symptoms?
e) does the overall intake of calories, or ratio of carbohydrates/protein/fat, affect symptoms?

Of course, trying to correlate actions by a patient with immediate self-reported changes in symptoms is fraught, as is a comparison of subsequent hospitalization or death between groups of online survey respondents.  Yet such disorder on an informal basis is where ideas often come from, and citizen science might mark out candidate factors for formal validation by professionals.  Is there anything like this going on?

I think you are looking for a very specific design of 'citizen' projects. But, if we relax a bit your criteria, there are some examples. Here, and here, for instance. One worth discussing, I think, is what Google has done for mobility tracking. Yes, the users did not 'opt-in' the study, but in essence, they provided the data!


What is the mechanism by which passive immunity works? My idea is that passive immunity can be used to cure an individual who is infected with a certain disease. For example, for someone infected by clostridium tetani, you would inject them with an antiserum. The antibodies give protection against bacteria, until the active immune response takes action. In this link (http://pmt.physicsandmathstutor.com/download/Biology/A-level/Notes/Edexcel-IAL/Unit-4/6-Infection-Immunity-and-Forensics/Set-A/Vaccines.pdf), page 3, the graph shows that the level of antibodies in the blood actually rises after injection! To me, this naturally begs the question, what is the mechanism by which passive immunity operates (because I want to know why the level of antibodies rise in order to understand the situation dynamically)?

[Note: would I be correct in saying that a short answer would be that the level of antibodies rises because the active immune system is stimulated due to the enhancement of phagocytosis by macrophages when the antibodies attach to the antigens? My book states that release of antibodies (by B-cells) that bind to the antigen is required to allow the macrophages to engulf the pathogen with the specific surface antigen.]

I commented on this question, but the OP's response prompted me to think again. Here is the graph from the document that the OP linked to:

Clearly what is confusing is that the parameter referred to as 'antibody level' rises quickly, but not as a step. In terms of the x-axis, vaguely labelled as weeks, it looks as if the level of antibody continues to rise over several days at least. The OP attempts to read into this an effect whereby the injected antibodies somehow stimulate the immune response in the recipient.

My knowledge of immunology isn't extensive enough to rule that out completely, but I don't think that is what this sketch graph is illustrating since the levels of these antibodies is shown as falling to zero due to destruction and excretion. This indicates that what is being graphed is just the injected antibodies.

In the absence of some real data for the time-course, my explanation for the rising phase illustrated is that this is showing levels of antibodies in the blood. However the prophylactic use of injected antibodies will often involve an intramuscular injection near the site of an injury. Here for example is a quotation from a recent review on the use of recombinant immunoglobulins (RIG) against rabies:

  Because vaccination needs time to induce a humoral response, application of RIG immediately after exposure is important to inhibit viral spread, even when accelerated vaccination schedules are applied. As much of the RIG dose as anatomically feasible should be injected into the area around the wound, and the remaining volume then given intramuscularly at a site distant from rabies vaccine inoculation. Isotope-labelled HRIG, injected around simulated bite wounds, diffused readily into surrounding tissue and about 25% was still detectable around the injection site 24 h later.

Thus the level of antibodies in the blood will continue to rise as they slowly enter the circulation from the site of injection.


The role of atomic theory in biology Feynman writes, in his Lectures on Physics Vol. 1, Chapter 1:

  The most important hypothesis in all of biology, for example, is that everything that animals do, atoms do. In other words, * there is nothing that living things do that cannot be understood from the point of view that they are made of atoms acting according to the laws of physics.* This was not known from the beginning, it took some theorizing to suggest this hypothesis, but now it is accepted and it is the most useful theory for producing new ideas in the field of biology.

He would have written this around 1961-1963. Was he right then and/or is he right now? Is what he says applicable for the entirety of biology (say evolutionary theories) or only for a subset of biology?

Would Feynman have been referring to a few specific advances or to the general state of biology at the time?

Please note that this question comes from an (interested) amateur to both physics and biology, I hope the question is appropriate for this site.

Edit: Perhaps this will clarify the intentions behind my question:

I would be interested to know how much atomic theory actually helps biological research. For instance, it often happens that the specific low level details are not necessarily important for explaining the high level theory. A nice example is abstract algorithms vs implementation in programming languages vs hardware implementation. Is this the case with biology or do the details of atomic theory matter? For instance, have advances in physics led directly to new biological discoveries?

Yes it is still true for all of biology, of course physics has expanded a bit, and likewise we have discovered cases of biology exploiting these new parts, for instance photosynthesis might involve quantum tunneling.

Feynman's quote basically restating that there is no magic or supernatural aspect to biology, no vital essence or spirit required to explain how it works or seperate living matter from non-living, it is all just chemistry and physics. The most complex chemical process ever discovered but still just chemistry and physics. Of course he does not mention chemistry becasue of course chemistry is just physics as well, the laws of physics control both, so saying it is a result of atoms obeying the laws of physics expresses both.

He is saying biology is still obeys the laws of physics and are made of atoms, this is true for all of biology, but as Feynman points out took some time to be accepted, keep in mind this is the time of the Miller–Urey experiment which showed organic molecules could form through entirely non-biotic means, which was not as widely accepted at the time as many think, especially to a general audience. Many similar discoveries a t the time were showing the same thing, there was nothing special about biological molecules or their interaction. things like evolution is the inevitable result of the interaction of basic properties (reproduction and heredity)just as a salt crystal is the inevitable result of the interaction of charge of sodium and chlorine. Vitalism still hung around in the popular mind and a few corners of academia at the time Feynman was growing up so taking a few moments to help dispel this notion in his lectures makes a lot of sense, especially given how much advancement was done by abandoning it.


"Other" classification for epitopes in the Immune Epitope Database (IEDB) I used the immune epitope database (IEDB) to search for epitopes. I found some epitopes derived from antigens called " other" by IEDB.  When I asked about it,  the answer was "We use the "other" category to group epitopes from the same species that only BLAST match to GenBank entries that are nonhomologous to the reference proteome".

Could someone explain this?

I presume that these epitopes represent peptides that have been eluted from MHC molecules and then sequenced by mass spec.  You can then compare these peptide sequences to a reference genome (more specifically to the proteins predicted to arise from the reference genome).  If the peptide matches perfectly to a predicted protein, then you assign it that identify.

But many peptides will not align to the predicted proteins, and so they can't be unambiguously assigned a gene of origin.

There are many reasons why MHC-derived peptides may not match the proteome.  Most obviously, the reference genomes are typically from a single individual, so if the sequenced peptide has a SNP, or other allelic variation, it won't line up.  As well, a significant number of peptides undergo some form of modification during antigen processing, such as deglycosylation changing Asn to Asp, proteasome-mediated cleavage and re-annealing, and so on.  These modified peptides also won't line up to the predicted proteome.


What are the effect of microtubule or microfilament inhibition on yeast expression profile? I was wondering whether anyone has looked at what are the expression changes in yeast when the microtubule or the microfilament polymerization is inhibited? Have there been whole-genome studies?

Browsing around GEO, I see 13 experiments focusing on microtubule disruption in yeast.

This CHIP-CHP experiment actually uses nocodazole.

This is a microarray experiment with benomyl treatment.

The rest focus on specific mutants that try to perturb the microtubules in specific ways.

What's more if you broaden the search there is an extensive body of work including human cell lines work as well...


Why proximal muscle weakness is seen earlier than distal muscle weakness in Dermatomyositis? It is said that in dermatomyositis(DM) , proximal muscle weakness is seen earlier than distal muscle weakness. It is also said that , DM is due to damage to small blood vessels contributing to muscle injury.( from Robbin's textbook of pathology pg.no: 1238-1239, 10e)

Shouldn't the distal group of muscles being smaller show weakness earlier? Why inclusion body myositis does not follow the pattern as in DM?

Usefull links:
https://www.mda.org/disease/dermatomyositis/causes-inheritance
https://emedicine.medscape.com/article/332783-overview#a1

My hypothesis are

1) Since skin, is commonly involved in sunexposed areas, may be enviornmental factors do play a major role. So, Proximal Muscles are more used in day to day work, so are more favourable site for drugs, autoantibodies to act upon.

2)May be, in case of due to drugs or vaccines, proximal muscles may be are preferrential site of action of these, making these group of muscle more suceptible.

By the way correct answer would be: Its under research.


What is the surface area to volume (SA:V) ratio of a red blood cell? According to this author, red blood cells (RBCs) are biconcave to allow easier bending. The standard explanation in biology for higher surface area to volume ratios is that it improves reaction rates. When a RBC squeezes through narrow veins I imagine that it gets deformed. Considering that a RBC's function is to exchange oxygen in narrow capillaries, I was wondering whether it is appropriate to reason that the biconcave shape promotes gas exchange. So what is the SA:V of a biconcave RBC and by how much does the SA:V change depending on where in the body the RBC is traveling?

I googled "surface area of a red blood cell" and this paper was the first result.  It should answer your first question. Though it was unclear to me what the surface area unit of measure was, which may require a bit further reading.  There's also this article, which goes a lot more into the math of calculating these two things.

As for your second question about how much it changes, intuitively I would guess very little and it probably does not significantly change exchange rates.  I couldn't find any research on the topic.  The hard part is defining all the shapes they may get squeezed into, then either calculating or measuring SA:V. Possible?  Surely, a well written computer model could do it at some point.  But worth the time/money?  Probably not.


RT-PCR: Not seeing how it can measure mRNA expression levels From my understanding, in RT-PCR we start off with an mRNA molecule, use the enzyme reverse transcriptase to create a cDNA copy (hence creating a double-stranded mRNA / cDNA hybrid), degrade the mRNA, and finally create a complementary strand to the cDNA with a DNA polymerase. If we're ultimately creating DNA and it's being duplicated at each cycle, how are we able to deduce the original quantity of mRNA in our sample? It seems like we would need to combine it with some other method, but a lot of sources I'm seeing seem to imply that RT-PCR alone is enough to "quantify" the amount of mRNA in a sample. Any thoughts on this are welcome

There might be a confusion of terminology. There is real-time quantitative PCR, which can sometimes be called RT-PCR. There is also reverse-transcriptase PCR, which is also confusingly called RT-PCR. To try to reduce confusion, real-time quantitative PCR is also called RT-qPCR or qPCR.
What you describe in your question is the reverse-transcriptase type of PCR. This is used for amplification, not quantification, of starting material.
QPCR or quantitative PCR, on the other hand, uses fluorescent dyes to measure the amount of amplified gene product. Standards provide a baseline measure of how much genetic material you should expect to see over time, at each PCR cycle, for a given amount of measured fluorescence. Measuring fluorescence of your own sample over time, and comparing it against the standard, gives you an estimate of what you started with, initially.


RNA or ribosome, which one moves during translation? During translation ribosomes decode the genetic information present in the mRNA and protein synthesis takes place.  During this process which of those two does move, the ribosome or the mRNA?

Here's an example in which the ribosome is fixed:

During co-translational translocation, the ribosome is essentially anchored onto the ER membrane through the Sec61 complex. It certainly cannot move along the mRNA. The mRNA is fed through the ribosome and the nascent peptide traverses into the ER lumen.


How is the exogenous DNA protected from degradation during bacterial transformation? During transformation, a bacterium can take up DNA from its environment. A small fraction of bacterial species are known to be naturally competent, meaning that they can engage in this sort of horizontal gene transfer in their natural environments.

As I understand it, naturally competent bacteria carry genes that encode the machinery necessary to facilitate the transport of this DNA across the membrane and into the cell. The exogenous DNA binds to a receptor located on the surface of competent cells, gets fragmented into small pieces, and then one strand is degraded while the other strand is transported across the membrane into the cytoplasm with the aid of a DNA translocase enzyme. Ultimately, assuming a sufficient degree of homology, it incorporates into the host genome via recombination.

During this process, however, the DNA has to be protected from degradative nucleases. I remember reading something about a transformation-specific DNA binding protein that coats the entire length of the DNA strand and prevents degradation. Is it the same translocase enzyme that facilitates movement across the membrane that is responsible for this? Or is there another protein involved?

And then, regardless of which protein is responsible in the case of natural competence, how does that protein get expressed and activated in the case of artificial competence? When we induce competence in the laboratory through one of various methods (e.g., electroporation), the DNA is essentially forced into the cell through openings in the membrane, so no transferase protein is needed. What signals the bacterium, then, to express the protective binding protein? What keeps the exogenous DNA from being readily degraded by endogenous nucleases? Whatever signals induced the expression of this protein in the case of natural competence would seem to be absent when competence is induced artificially, and it doesn't make any sense that the bacterium would constitutively express such a protein.

Different bacteria have different modes of transformation and as I understand it is Haemophilus influenzae that takes up the single strand whereas ?Streptococcus [i am not sure which bacteria it is] takes up dsDNA.

I intuitively think that DNAses are not that common like RNAses. Moreover, natural competence is associated with stress and is even triggered by DNA damage. Therefore we can speculate that DNA repair proteins will be prevalent and DNAses will be low in the cell, under these conditions. The chance of foreign DNA being damaged goes down.

In the case of artificial transformation, I guess the entire concept of heat shock is a way of providing stress. Moreover, the lab strains such as DH5alpha have certain mutations which disable them from recognizing a plasmid as "foreign".


What fruit did I just accidentally buy? I live in Oxford, in the United Kingdom, in a part of the city with a vibrant multicultural community. My local corner shop has an excellent selection of spices, pulses, and obscure and vegetables fruit that mostly tends to be from the region of Pakistan and India, and only labelled (illegibly) in a language that I do not speak.

I've just bought a fruit I thought at first inspection was an unripe mango -- previously they have had excellent, cheap, small alphonso mangos for sale that I'm rather partial to. I'm completely wrong, however, for I've bought something about the size of my fist with striking white seeds that taste very peppery, a green coat, and somewhat sour flesh. It floats in water, and the skin exuded a slightly sticky, partially white gummy substance when I removed it from the bag. It's not particularly soft to touch. The seeds look a bit wrinkly, and are not hard at all to touch. The flesh has a consistency of an apple.

I can't for the life of me identify it! I'd love to know any suggestions! Thank you!

Looks like a papaya that isn't ripe yet. Being said, if you already cut it in half it probably isn't going to ripen any further. A ripe papaya has pink/orange flesh and the seeds turn black.


What does enzymatic equilibrium in % represent? I am studying an enzyme which can catalyse a chemical reaction in both directions. The paper I am looking at is mentioning a thermodynamic equilibrium of 1% in the synthase direction.

What does that mean more intuitively? I am mostly confused by the percent unit as I expected a constant rate without unit...

My guess would be that under these specific concentrations of substrates/products, the enzyme is catalising 1 synthase reaction and 99 inverse reactions for each 100 reactions it is catalising. In other words, the equilibrium constant K of the synthase reaction under these conditions would be 0.01.

Is that correct?

You are correct in stating the relative rates of the two reactions.  What may have you confused is the percent sign in the statement.  The percent sign is not a unit in the sense that you are taking it.

What you have in a simple reaction like you are examining are two opposing rates of reaction.  The rate of a catalytic reaction, like others, usually depends on the concentrations of at least some of the reactants in the direction under consideration.

At equilibrium, by definition, the concentration of every material involved in the reaction is unvarying.  Otherwise, the reaction would not have reached equilibrium yet.  What that also means is that the rates of the forward & inverse reactions are equal at equilibrium.  So what does the statement signify?   It means that thermodynamically, the synthase reaction is the more unfavorable direction.  That is, at equilibrium, the product concentration of the synthase direction will be in the minority.

The statement involving the percent sign is just giving the ratio between the [arbitrary] forward direction, here stated as the synthase direction, and the inverse reaction.  The percent sign is just a mathematically short way of stating that the number stated is parts per hundred.

The equilibrium constant K is exactly the same ratio, stated as a decimal value rather than a integer per hundred.


What is the function of dreaming? Does a particular hormone secretion interfere with dreaming? Why do some people dream more? I'm really interested to know when we are sleeping how a series of stories come to our mind that we called this process dreaming. If you know a useful article on this topic, please tell me thanks.

Dreams are hallucinations that occur during certain stages of sleep. They’re strongest during REM sleep, or the rapid eye movement stage, when you may be less likely to recall your dream.
Research is yet to reveal the true reason of dreams. But we know for sure it is not one reason.

Speculated Reasons:

1. Dreams as fight-or-flight training

One of the areas of the brain that’s most active during dreaming is the amygdala. The amygdala is the part of the brain associated with the survival instinct and the fight-or-flight response.

One theory suggests that because the amygdala is more active during sleep than in your waking life, it may be the brain’s way of getting you ready to deal with a threat.

2. Dreams as memory aides

One widely held theory about the purpose of dreams is that they help you store important memories and things you’ve learned, get rid of unimportant memories, and sort through complicated thoughts and feelings.

Research shows that sleep helps store memories. If you learn new information and sleep on it, you’ll be able to recall it better than if asked to remember that information without the benefit of sleep.

How dreams affect memory storage and recall isn’t clearly understood yet.

3. Creative times!

One theory for why we dream is that it helps facilitate our creative tendencies. Artists of all kinds credit dreams with inspiring some of their most creative work. You may have awakened at times in your life with a great idea for a movie or a song, too.
Without the logical part of the brain working, emotional and illogical thoughts take over your mind!

Eectroencephalography (EEG), electro-oculography (EOG), and
electromyography (EMG) are used to monitor neurological data from the brain to reveal information about neurological activities in the sleeping brain.

Here is a scientific literature (pdf) you can go through for in-depth study ( this link leads to ResearchGate page, you can read it there or download the pdf) :
https://www.researchgate.net/publication/281071308_The_Role_of_Dreams_in_the_Evolution_of_the_Human_Mind


How much does capillary action contribute to blood flow to the human brain? The BBC News Universal Wonders short video Why water is one of the weirdest things in the universe says after 01:50:

Water molecules can float upwards against the force of gravity. That’s because they love to stick to each other. They’re so good at it that they can actually pull each other up through tiny channels, such as the tiny blood vessels in your body. That’s how oxygen and nutrients reach the edges of your brain.
The same process, called capillary action, allows plants to move water from deep below the ground to nourish the leaves and branches that grow in the sunshine.

We learn about the importance of capillary action in water transport in plants, but I'd never heard that it was important for blood transport in Humans.
Question: How much does capillary action contribute to maintaining blood flow to the human brain? Is it a small effect compared to the difference between arterial and venous blood pressures, is it a substantial contributor?

None. I have no idea what that video is talking about.

Capillary action of water happens when you have a thin tube and water likes to stick to the "edges." Blood vessels are already full of water, there is nothing for them to capillary up against: there is already water there, so there is no surface tension (there is no surface at all). Blood flow through capillaries is caused by the heart which creates a pressure gradient between the arterial and venous circulation, in the brain and everywhere else.

Cipolla MJ. The Cerebral Circulation. San Rafael (CA): Morgan & Claypool Life Sciences; 2009. Chapter 2, Anatomy and Ultrastructure. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53086/


Why apes started to contemplate and become altruistic? I was asking this first on philosophy forums, but it is suggested, that answer could be found from evolutionary view of point, so here we go:

Again my question raised when thinking of myths, their origins, mysticism and religious institutions. It is said that prieshood came to existence, when ape first landed from trees to earth collecting and gathering fruits, hunting and then started to plant and farm. Whole agriculture was build organizating leadership of the society among whom were the priests and shamans who tried to understand natural forces with limited knowledge and superstition. Accelerating need for planning future, not only own family's, but whole society's future forced thinking process of humanized apes to become more involved with contemplating. Did some of the deep thinkers find that there was a dimension on meditation which is next to impression of using herbs and drugs to bring mental experiences, were they hallucinations, visions, calmness or anything similar alive? Thus they became ascetics and adept on focusing mind toward itself while other part of high class of the society became adept on aiming mental activity outward, improving skills to master matter and physical nature. On ancient times both still shared same concept of need of supernatural forces to be placated or otherwise controlled to get or avoid certain every day results.

This also brings up a huge evolutionary problem so to say. While apes, if they were just lead by rather unconscious instincts, they would have reproduced and build on the principle of the strongest is the leader. But when reasoning, ability to think "cunning plans" as stated by Baldric on Blackadder came to existence, then the most clever often won the game. But what is clever on the other extreme of the religious practice, self sacrificing and altruistic ethics? It feels almost unnatural, that religions evolved to direction, where ethic and moral rules fights against physical existence or surveillance of the individual. There is a strong hope of afterlife compensation, which explains some of it, but I'm still a bit struggled, why (and when) apes started to retire to the forests to meditate and rather practice altruistic ethics, loving enemies for example instead of getting justice and their own benefit fulfilled in first hand, instead of reproducing and fighting for their lives and space?

To bring whole question to modern life, I think zen buddhism is a good example of such practices brought to other level. While on the most plain form they don't expect belief on the existence of the self nor karmic relations of the acts, they still rather follow high ethics of the teachings of Buddha and live simple middle way life just being aware and mindfull of the things happening at the moment, which is the ultimate goal of the practice and life.

I think this is a difficult question all around, which is why its a little uncomfortable for some to be entertaining questions which are often seemingly metaphysical in nature.

I think also that it is true that biology and neuroscience will have a big impact on the question, its also fair to say that the jury is still out on this question.

The genetic anthropologist Svante Paabo is one of the most engaging researchers in this question.  He started out studying the difference between the human gene sequences and the chimpanzee to try to suss out the specific genes which might be be responsible for out social selves.  So from this point of view, it might be that intelligence started at most about the time of human chimp divergence, 8-25 million years ago.

Finding the specific genetic structures that convey our unique cognitive or social abilities would certainly pinpoint that time much more accurately.  There is just 1-4% difference between the chimp and human genome sequences (depending on how you calculate it), but even 1% of a 5 Gb genome is a lot of differences and no intelligent mutant chimp has been found (that they've told us about!) .

Since then, a lot of interest has focused on assembling a complete Neanderthal genome sequence.  Since Neanderthals diverged from humans about 500k years ago, and there's plenty of evidence that they were intelligent, comparing the three genomes (human chimp and neanderthal) would help pinpoint the specific genetic elements which are distinctly human.

If it is a mutation or set of mutations as the current thinking implies, there is a good chance that it is a combination of strong selection and accident.  Its true that cooperation is often enjoys a strong selective advantage, but it doesn't make you smart or hospitable.  When we talk in biology we don't say altruism, we say cooperation.  If such cooperation happened only because of selection, we would see such behavior in other primates.  So if we see this, I would lay odds to look for a rather complicated story...

Another interesting person to read is anthropologist Terrence Deacon, who is trying to understanding the terms with which we define intelligence.  About ten years ago there were actually experiments that showed that chimpanzee some strong candidate intelligence genes related to cognition could be put into people (who needed gene therapy because they had lost cognitive function) and restore that function.  Apologies, this is anecdotal - i saw him give a great talk, but he's moved on a bit and can't find the references.

This is important I think because the fundamental definitions of human intelligence have failed over the years, from the old chestnut of using tools, to a recognition of mortality, to awareness, animals have surprised us, particularly primates.   I wonder whether we will be able to confirm these vital factors until we get a monkey asking for the keys to the car so that they can go get some pizza.


What evolutionary pressures pushed Galápagos tortoises to mature so slowly and live so long? I read that they take up to 40 years (in the wild) to reach the age of reproduction and are thought to live over 100 years, with one in captivity reaching over 170 years.

Can someone explain in layman's terms how taking longer (especially spending years as a small tortoise) to reproduce was a winning trait, and how their biology delays the processes of senescence to the extent that it does compared to most other species?

This isn't so precisely focused on tortoises, but a general theory in evolutionary biology for why some animals live longer is K vs r selection theory.

The idea here is that animals will make a sort of evolutionary 'choice' and configure themselves to breed as numerously and quickly as they can.  This is called 'r' selection, named after the constant that is proportional to the rate or speed of breeding.  r selected animals adapt quickly to a rapidly changing environment and their lives are pretty cheap.  Many insects that lay hundreds or thousands of eggs every few weeks are examples of r selection. They do not care for their offspring (and may even eat them!).

K selected animals breed to be highly competitive in the environment.  They tend to be highly optimized for success and this often means they are larger, they live longer and require more investment as newborns.

By this theory the galapagos tortioises live longer because their environment changes very slowly and the tortoises are so optimized for that particular way of life that they have no predation or any competition at all.  Islands like the Galapagos are studied in fact because they are so isolated by the water that new species rarely ever arrive.  Such new arrivals may cause drastic changes in their ecosystems because islands are stable environments because migration happens so rarely.

There are other theories that emphasize other factors in the evolution of larger, longer lived animals, but I think r/K selection may describe the environmental pressure on the Galapagos tortoise.


Where to start understanding chemical principles of human body? I have no background in chemistry.

What is a good way to start understanding principles of human body - how it works, determine which meals are good or bad for health. Maybe it is not just chemistry, but some other fields, too. I just want to know how human body works, lets say - improve health - but on my own. Knowing just that this is not good for health is not enough for me. I want to build deep knowledge.

I want to know how it is functioning at the lower level (based on chemistry).

Where to start?

(sorry for my incompetence)

If you want to start from the chemistry upwards I'd recommend you to either look into a biochemistry textbook (buy or borrow one/get a used one, since they are quite expensive) or look for some (online) courses in that field.

The textbooks I know from university studies are:

Biochemistry (Stryer, Berg, Tymoczko) [possibly downlaodable from here]

Biochemistry (Voet & Voet)
Lehninger Principles of Biochemistry (Cox, Nelson)

The MIT offers quite a few (free!) online courses and there seem to be quite a number of biochemistry ones (I haven't looked into any of them, but I reckon the MIT courses aren't too bad).


Why is it thought that silicon based lifeforms never flourished on Earth? Reading the recent ScienceAlert article "For the first time, living cells have formed carbon-silicon bonds", it is stated that despite the relative abundance of silicon in the surface of the Earth, there are no silicon based lifeforms.

Specifically, the article asserts:

  Why silicon has never be incorporated into any kind of biochemistry on Earth has been a long-standing puzzle for scientists, because, in theory, it would have been just as easy for silicon-based lifeforms to have evolved on our planet as the carbon-based ones we know and love.

I have read the question and answers "Why are we carbon-based?", which looks at the importance of carbon, what I am seeking information of is why carbon and why not silicon in the first place. So, therefore my question:

Why is it thought that silicon based lifeforms never flourished on Earth?

At temperatures above -195C, "C" wins the day. "Si" based chemistry may be more versatile than carbon in some environments, for example in a frozen nitrogen atmosphere.
Silicon accounts for 43% of rocks, Carbon is less than 0.1 percent, except that carbon is similar to water for reactivity and dissolving stuff, and organic "C" compounds are a molecular sludge like flowing-dissolved-stone, room-temperature-lava: tar/margarine/oil/diesel/glucose/alcohols/acetone are sludgy, liquid, the molecules can rotate, flow, coalesce... Carbon molecules are fluid, sludgy, rotating, pivoting, kind of lego material, whereas silicone chemistry doesn't flow, it vaporises and precipitates out of any flowing state.
Carbon reacts with both the molecules of water, O and H, and almost everything else, to make millions and millions of compounds. Silicon can't bond H. It's like the difference in between lego technic and lego. Try making a robot from lego!
That gives life millions of times more chemistry building blocks compared to silicone, and permits life to interact with water. Silicon life can't really interact with water.

10/1 cosmic abundance of carbon vs silicon

A carbonaceous contrite meteorite can contain 70 extraterrestrial amino acids and other compounds including carboxylic acids, hydroxy carboxylic acids, sulphonic and phosphonic acids, aliphatic, aromatic and polar hydrocarbons, fullerenes, heterocycles, carbonyl compounds, alcohols, amines and amides.

If you put silicon in a flask with, metals, sulphur, nitrogen, water, etc, and do the same with graphite, and you mix and heat them all up, the carbon will tend to make a vast population of larger sludge molecules, tars, formadehyde, amino acids, and the silicon will tend to form rocky crystals, as found in geology.

SiO2 is sand, quartz, very unreactive, takes a lot of energy to make it, whereas CO2 is a relatively reactive solube compound.

Silane SiH4 is the equivalent of Methane CH4, but SiH4 oxidizes instantly in contact with water and oxygen and air and is totally unstable, not naturally occuring, and it's difficult to make it, it combusts and becomes elemental silicon and water.

A silicate rich meteorite will only contail a wide array of silicate minerals, which are simpler, mineralogical, unreactive substances compared to organic chemistry that can exist in a meteorite.

Carbon forms double electron bonds a lot easier than silicon because it is smaller and lighter with a small atomic radius.

Silicone carbide SiC is a very rare mineral which illistrates Silicon's fussiness in making bonds.

Silicon-hydrogen molecules react spontaneously with water and they exist more easily in suphuric acid, which kindof limits silicone to a square root of the combination possibilities available to carbon. The H reactions give it that extra connection ability, any time a carbonate molecule becomes unstable, it absorbs an H and it's stable. Silicone can't do that.

Silicon doesn’t want to let go of Oxygen, but it doesn’t want to attach to hydrogen. try burning or dissolving quartz and silicates, compared to carbonates and "C-H" compounds = organic compounds.

An AI life-form could make good use of silicon: it's unreactivity with water means that a silicon transistor brain can exist anywhere in frozen space, using metals and electricity for the animal's functions, and avoiding water. A robotic species of life would more probably be made of silicone, so if some alien life forms land on earth, they will probably be transistor and metal electric beings rather than carbon based ones.

Wikipedia page.


Insect identification (SP/Brazil) Found this insect in São Paulo/Brazil. Its length is ~2cm

Any help to identify this insect would be appreciated.

Also see my video

Well, it's a type of firefly, belongs to the order of 'Coleoptera' (beetles), suborder of 'Polyphaga', family of 'Lampyridae' (firefly beetles). It's quite similar to the 'Photinus obscurellus' species (and probably the same species too), however it doesn't always have a black head like yours, however, articles have suggested that  firefly species in Brazil (Sao Paulo State) have 'adapted to mesophyl tropical forests, secondary growths, marshy areas, and open fields' (source = https://www.researchgate.net/publication/233574632_Fireflies_Coleoptera_Lampyridae_from_Southeastern_Brazil_Habitats_Life_History_and_Bioluminescence).

This adaption may have led to species having black heads as oppose the more colourful head of the Photinus obscurellus. However the bodies and the dimensions match yours very closely.

This image is from Google Images (more specifically : http://bugguide.net/node/view/194980/bgimage)


Real time PCR normalization algorithm When performing normalization of real time PCR results, I found two ways of doing it:

In my lab they follow the next layout: $\text{Efficiency}^{-(CT\ _{\large\text{interest gene}} - CT _{\large\text{ housekeeping}})}$ each time controls with controls and treatments with treatments. Then they divide the all values (treated and controls) each with controls.
On the other hand I found another way to normalize that follows this steps: $\text{Efficiency}^{(CT_{\large\text{control}} - CT_{\large\text{treated}})}$. Then you make the same for the normalizing gene and divide the first by the last.

The values obtained are similar but not exact. Also I noticed that first algorithm gives rather different values for most diluted when performing a standard curve.
Which is correct?

First step is the calculation of efficiency, denoted by lets say $E_{gene}$. See this post for calculation of primer efficiency.

So the fold change for that gene will be calculated by $E_{gene}^{-\Delta Ct_{gene}}$

Where:

$\Delta Ct  = Ct^{treated} -Ct^{control}$

But these Ct values are not normalized. For normalization, you take some reference gene which need not be a housekeeping gene. Reference gene should chosen such that it is not affected by the treatment. In some cases usual housekeeping genes can also get affected for e.g. in treatments affecting cell cycle or differentiation. In such cases you should use a spike-in (an artificial RNA bearing low resemblance with any known gene).

You can either normalize the fold change (Case A) or find fold change of the normalized expression (Case B).

Means the same mathematically.

Case A:

$E_{gene}^{-\Delta Ct_{gene}} / E_{ref}^{-\Delta Ct_{ref}}$

Case B:

$\large\frac{[E_{gene}^{-Ct^{treated}_{gene}}]/[E_{ref}^{-Ct^{treated}_{ref}}]} {[E_{gene}^{-Ct^{control}_{gene}}]/[E_{ref}^{-Ct^{control}_{ref}}]}$

You can rearrange the numerator and denominator to get Case A from Case B. I'm not sure how you are ending up getting different values. Recheck once. It may be because of numerical approximation errors.

Case A looks much neater; so it is best to calculate that way :)


Reason behind formation of different shapes of cell I have always wondered how cells are modified to give them a specific shape. On what specific part of a cell does gene regulation act  for giving the shape ?

Cell shape is dictated by the cytoskeletal arrangement. There are both intrinsic and extrinsic factors that control cell shape.

Extrinsic factors consist of environmental factors such as extracellular matrix. Rho-GTPases relay the environmental signal to the cells to cause cytoskeletal rearrangement.

Intrinsic factors are basically the stable transcriptomic identity (a gene regulatory programme) which determine a cell shape. I personally don't have an idea about what genes give an intrinsic cell shape. For e.g. why does hela cell look different from HEK cell in the same type of cell culture plate under same conditions (even at low densities where there is no neighbor effect).


Why is Benzylpenicillin better in Bacterial Meningitis than Amoxicillin? Both are beta lactams.
However, benzylpenicillin, which is also called penicillin G i.e. narrow group antibiotic.
I have now in both the following as a mechanism of action

  Binds to PBP in bacterial cell wall, causing deficit in the cell wall and causing cell death.

where I would like to differentiate clearly benzylpenicillin from amocillin.

How is benzylpenicillin better in bacterial meningitis than amoxicillin?

Amoxicillin is just penicillin with a hydroxyl group off the ring and an extra amine group..

Their mechanisms of action are the same. Their ability to cross the blood-brain barrier are the same. They can both cause seizures.

Both are used to treat to meningitis. The selection of one over the other would be based on the sensitivity of the infecting organism, and the ability to cross the blood-brain barrier in inflamed meninges.

There are better drugs to treat meningitis.

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections


Mutated cell proliferation Reading Jennifer Doudna's fascinating book on CRISPR. So she describes rare cases where a mutation in a single cell removes the gene responsible for a genetic disease. The cell proliferates and the disease is cured. What I don't understand is--aren't all the aberrant cells also still dividing and passing on the harmful mutation to their progeny? How does the single healthy cell edge out all the other cells to "cure" the patient.

There are some diseases in which a minority population of normal cells can rescue the organism, even in the presence of a majority of mutant cells.  Sort of like a group vacation to Kazakhstan with one friend who can speak Kazakh.  Very different experience from a vacation where none of you speak Kazakh.

Take for example hemophilia A.  Cells have a mutant gene for factor 8.  Without factor 8 blood does not clot properly and people have bleeding trouble.  You do not need much factor 8.  Just a little bit can prevent spontaneous bleeds.  People who are heterozygotes for hemophilia A (carriers) are fine at 50% normal.  So if you edited mutant liver cells such that they could produce factor 8, even if they were only 10% of the total cell population of the liver, having some factor 8 would sidestep the full hemophilia phenotype.

Likewise metabolic mutants - some children are born unable to handle certain substances.  Phenylketonuria is the one you read about every time you drink a diet coke.  If a minority population of cells could be produced that were able to handle phenylalanine, those would rescue these kids even if most of the cells still could not.


Transcription when Chromosomes are Condensed Are genes transcribed just as well when chromosomes are condensed?

I want to design a screen that depends on genes not transcribed when chromosomes are condensed (to identify cells that can't condense).

The compaction of DNA into chromatin is a very complex process that involves not only DNA, but on the histone code. Some may say that the histone code plays more of a role in chromatin state To develop a screen you would have understand the act of methylation, acetylation, ubiquitination, and phosphorylation of all modifiable histone residues. The modification of histone residues determine if the chromatin is in a heterochromatin or euchromatin state and even in which sections of DNA are accessible and transcriptionally active.

It is also important to note that the same modification of any of the 8 histone proteins in any nucleosome (the fundamental unit of chromatin) may not produce the same result.

For example: The methylation of H2 histone in the first nucleosome of a chromatin "string" may cause silencing while the methylation of H2 histone further down the chromatin "string" may cause activation.

It's alot of information but maybe one day you will be the one who solves the pattern! It sure is fascinating.


What is the difference between infected and infectious in epidemiology? I am studying the SIR model and in the infected class I, both infectious and infected individuals are included, as stated here

I know that the model uses the assumption that the disease has an insignificant incubation period so infected individuals are capable of transmitting the disease as soon as they become infected. But what is the specific difference between these two terms? Does infective mean anything different?

(The document you link to says "see Chap. 1 for distinction between infected and infectious individuals", but I'll assume you don't have access to that - I certainly don't.)

Infected individuals have been infected by a pathogen.
Infectious individuals have the potential to transmit a pathogen to
others.

Note that the definition given for "infected" in the source you link to is actually wrong: hosts may have a subclinical infection, in which case they are not "now sick with it".


What keeps mitochondria from multiplying out of control? What keeps mitochondria from multiplying out of control and killing the cell?
According to endosymbiotic theory, mitochondria were once free-living bacteria that got ingested but not metabolized by the host cell. What prevents mitochondria from replicating out of control and overpowering the host cell? The question was inspired by this brainstorming session about engineered endosymbiosis.

I'm guessing at the motivation for your question -- In the evolutionary history of eukaryotic cells, mitochondria were once free-living bacteria.  What prevents them from acting as intracellular pathogens and replicating out-of-control?
Yes, by endosymbiotic theory 1, mitochondria were once free-living prokaryotic organisms.  This is evident because they have their own DNA, undergo replication by fission, and have characteristics similar to proteobacteria.
However, some of the genes required for mitochondrial replication have been moved to the nuclear genome.  This means that, while mitochondrial replication is not necessarily tied to cell replication, factors encoded in the nucleus are necessary for mitochondrial replication.2

https://en.wikipedia.org/wiki/Symbiogenesis
Ali, et al. Nuclear genetic regulation of the human mitochondrial transcriptome. eLife 2019;8:e41927.