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What is the minimum sample size to get reliable results in haplotype and nucleotide estimations?
Different software have different methods for estimating diversity and each method will have assumptions about the quantity of
data required to produce a reliable result. I am estimating the haplotype and nucleotide diversity by DnaSP6 program of Sanger sequences. I would like what is the minimum sample size requires to get reliable results.
Thanks in advance.

Can you provide a little more information regarding what methods you are trying to use? Can you indicate the specific feature of DnaSP6 you are trying to use? This program implements many different analyses, each of which likely has different requirements. What are your input data? Are they just reads or have you done any postprocessing? How many loci? How many individuals, 10, 100, 1000?

I am trying to estimate haplotype and nucleotide diversity using gene flow . My input data are fasta files from sanger sequences, they code an unique protein. I have in some cases for some groups 2 or 3 individuals and I though that It could not be enought

"in some cases for some groups" what cases, what groups? are these population groups, groups that are the same protein, regions of the gene?

I have 13 groups defined of the total dataset, all of them of the same protein. 2 of these 13 groups have a sample size of 3 individuals each of them

I'm still a little unclear on what the analysis looks like, but I'm going to assume for the sake of this answer that it's a single locus sequenced across multiple populations, with some number of individuals per population, and that the concern is that some of these populations are represented by only a few individuals. I'm also going to assume that the individuals are diploid, so you in fact have a little more data than it appears.
All the same, this paper indicates that n<5 individuals in a population leads to quite noisy estimates of $\pi$ and $h$ (section "The effect of sample size on haplotype and nucleotide diversities"). This is of course specific to a certain ~500bp region that they collected sequences for. That doesn't mean that you can't compute these metrics, only that they may not be very reliable.
For reference, the early Neanderthal genome papers compute some measures based on only the two copies present in their diploid genomes- of course, they are assisted by a large amount of modern human data for making comparisons. If you have supporting data from other populations, you may still be able to say something about the populations with few individuals. But you will likely have to use measures other than $\pi$ and $h$ to do so.
Some other tools that you might use to "borrow" information from other individuals outside those groups are ordination analyses such as PCA, or clustering tools like STRUCTURE. One way of thinking about how this works is that you can "embed" your populations with few individuals in the population structure of your overall dataset. This allows you to still learn from those populations even if the number of individuals is small. The Neanderthal papers implement versions of this, but with much more elaborate statistical frameworks, for a whole genome rather than just a single gene.
I'm not sure if DnaSP can carry out these analyses, but there are a lot of tools that do similar things, one tutorial here. Of course looking at the DnaSP manual is probably a good idea to see what you can do with your current tool.
Depending on your goals it may also be interesting to compute F-statistics across your populations, this is done by most population genetics tool suites. I used GenePop many years ago to do this, it appears to still work, though I am sure there are better alternatives now.
An important note is that most of these measures are purely descriptive, not inferential. Low sample size makes descriptive statistics noisy, but doesn't invalidate them. Inferential statistics are a bit more dangerous.

Thanks you Maximilian, my sequences are haploid and the other assumtions are correct.  I checked one article that use a sample size with n<3 for π and h (Host abundance and identity determine the epidemiology and evolution of a generalist plant virus in a wild ecosystem). However I would like to know what other measures than π and h  you mean to do. Thanks in advance

see edit with more info.

Thanks a lot Maiximilian for your properly answer. I will take consideration of your suggestions. Thanks


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Could an exposure to a small amount of viruses result in an easier course of the disease?
According to Gunther Hartmann (Professor of Clinical Chemistry and Pharmacology at the University of Bonn) cited in this article (Süddeutsche Zeitung, in German)

Die Zahl der Erreger hat bei Erstinfektionen Einfluss auf den Schweregrad der Erkrankung.

My translation:

The number of pathogens during the initial infection affects the severity of the disease.

Leaving ethics aside I was wondering about the following:

Might it be an option to get infected by only a tiny amount, suffer only light symptoms and reach immunity (similar to a vaccination but probably more risky)?
Does the transmission path also affect the severity of the disease(inhaled vs. infected vs...)?

Edit: As Chris pointed out in his comment there is not enough research for Covid-19 yet so I would be also interested in findings from other viral infections.

Simple answer: We don't know yet as this disease is too new and we haven't done enough research on it.

@Chris Thanks for the comment, I edited the question.

SE Biology is a question and answer site — not a discussion site — about the mechanisms of biological processes. Questions are generally answered by people with biological rather than those with medical or epidemiological expertise, who are more likely to be on SE Medical Sciences. Your question asks for subjective views on factors affecting the disease. Such questions are off-topic here. I draw your attention to a list of reputable sources for information about the pandemic on Meta.

@Chris In mice the severity is always dose-dependent (for short acting viruses), thus... Also I would mention Rotaredom answer is about the viral load found 1 week after the infection, it is related but not directly. And the viral load in the lungs is of course correlated with the (lack of) pneumonia and its severity https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30113-4/fulltext#fig1 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30232-2/fulltext https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30196-1/fulltext#figures

I think the answer to your question is actually found in the paragraph surrounding the quoted statement:

Auch Gunther Hartmann, Professor für Klinische Chemie und Pharmakologie an der Universität Bonn, berichtete, nach ersten vorsichtigen Einschätzungen sei davon auszugehen, dass der Schweregrad der Erkrankung über Hygienemaßnahmen reduziert werden könnte. "Die Zahl der Erreger hat bei Erstinfektionen Einfluss auf den Schweregrad der Erkrankung."

Approximate translation:

Gunther Hartmann, Professor of Clinical Chemistry and Pharmacology at the University of Bonn, also reported that, after initial careful assessments, it could be assumed that the severity of the disease could be reduced via hygiene measures. "The number of pathogens influences the severity of the disease in initial infections."

Notice that the language is not absolute but rather asumptive: "initial careful assessments," "It could be assumed," "could be reduced."  It's tentative language and suggests that research is ongoing.  Furthermore, if you search for that quote, you'll find that this is not published in peer-reviewed journals; it's simply a preliminary observation to encourage the public to limit intake of pathogens.
We already know that in some other cases the viral load affects the severity of symptoms. But we don't actually know that that's the case with COVID-19.  In fact, initial reports from Italy suggest that there is no statistical difference between viral loads between symptomatic and assymptomatic cases of COVID-19. So Chris's short answer is absolutely right; we don't know.  For all practical purposes, it's just as well to assume that it's the case, as it will lead to more hygeinic practices, but further research will be required to demonstrate that it is actually the case.

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How can viruses have an incubation period of only 3 days?
Cold viruses seem to typically have incubation periods of 3 days, but from a mechanical point of view, I wonder how this is possible?
For example, if we read this viral assay protocol document: https://www.virapur.com/protocols/Virus%20Plaque%20Assay%20Protocol.pdf we can see that when a viral plaque is grown, then the plaque becomes visible in "5-7 days". So, since viruses have reproductive cycle of 6 hours, then that would be about 24 generations. Presumably each generation can only infect cells immediately adjacent to the infected cells since viruses cannot move on their own. So, the virus spreads in rings emanating outwards from the initial innoculation site.
If the visible plaque is 4mm in diameter, then we presume each generation is growing by 4mm/24 = 0.17mm which in itself is kind of suprising because a cell is only about 0.005mm in diameter, so the virions would seem to be simultaneously spreading by 0.17/0.005 = 34 layers of cells per generation. It is hard to see how they could do that without moving in some way. Maybe diffusion of some kind is occurring?
In any case, from geometrical standpoint I don't understand how a viral plaque in the wild could spread fast enough in only 3 days given what we see in the lab.

Viruses could easily be carried by the circulatory system, even if they actively infect only certain kinds of cells.

A viral plaque assay is an artificial system which limits the physical dispersion of newly released virions. It is designed to count the number of infectious virions (plaque forming units) in a given sample, not to measure the rate of reproduction or spread. Since each plaque begins with a single infected cell, the number of new cells infected with each cell burst is going to be limited by the physical proximity of cells to the infected cell, not by the number of infectious virions released.
In a living system, a single cell burst from a viral infection can release anywhere from a few hundred to up to several tens of thousands of new virions which will then be carried in all manner of different bodily fluids to infect new cells, dramatically increasing the potential number of new cells infected after each replication cycle, compared to a plaque assay.
Another consideration is that some of the symptoms of the common cold are generally similar to those common in the prodrome phase of most viral infections, so it is probably difficult to distinguish its true incubation period from the onset of any acute viral infection.

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Why the length constant of passive current flow isn't depend on the membrane capacitance?
I read that the equation for the length constant for passive conductance along a neuron depend on the resistance of the plasma membrane, the intracellular axoplasm and the extracellular medium. My question is why it's not dependent also on the membrane capacitance, since it can also affect how far the current can propagate (if for example the capacitance of the membrane is large, more negative charge will be on it's intracellular side, and will cause to the positive current to attract to the sides of the membrane).
Thanks!

Length constants are defined in the 'steady state' regime of constant voltage; capacitance is important for time-dependent electrical functions but disappears in the steady state.
In a real neuron, where you have other time-dependent (dynamic) features like ion channel opening, time constants and length constants interact to determine how current flows in a length of neurite, as you intuit, but these passive properties by themselves are insufficient to describe that behavior: you need to also consider ion channel gating and conductances.
See also https://en.wikipedia.org/wiki/Cable_theory - note how the capacitance is always multiplied by a changing voltage dV/dt in the differential equations.


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What does it mean for a species to be ancient?
When we say that a species like cockroaches is ancient, what does it mean exactly?
Does that mean that cockroaches haven't evolved for a long time? But isn't evolution always occurring? So is that because they haven't evolved as much and are very similar to their ancestors, ie they had a "very slow rate of evolution"?

It depends on the context.
first "cockroaches are ancient" is different than a species being ancient, cockroaches are not a species but a group of species with a similar morphology and ancestry (similar to a clade).

It can mean they are mrophologically similar to their ancestors. Which is very different than saying they have not evolved. It means the pressures on the linage have not favored much in the way of morphological change. Some shapes just work well,(or reach equilibrium) and once you reach it the morphology don't change much even when other things are changing.
It often means that the split between the lineage in question and other groups is old. example, you could say mammals are ancient for instance because the mammal lineage split off the rest of the amniotes 275 millions years ago. They have changed a great deal since then but the groups as a whole goes back a long time. the issue here is these splits are minor when they occurred, like any other specialization event, but look big due to human constructed categories.
But it can also mean that the lineage has not undergone a specification event for a long time, It has changed but has not left behind any offshoots, this is the rarest case but can happen.

Note however this is a phrase the media like to throw around when it doesn't have a solid scientific definition, it is a qualitative contextual statement. They often have little understanding of its meanings. They also often fail to clarify which they mean, and often fail to properly define the "thing" being ancient.


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Can Covid-19 (similarly to HIV) infect T-Cells?
I'm interested in better understanding this Nature publication, discussing the potential for Covid to infect t-cells.
After describing the results they conclude:
"Based on the results of pseudovirus and live virus infection, here we proved that (1) SARS-CoV-2 could infect T cells, (2) SARS-CoV-2 infected T cells through receptor-dependent, S protein-mediated membrane fusion, and (3) infection could be inhibited by EK1 peptide."
Is this big news? I am not an expert but I believe that HIV's special trait is it's ability to infect CD4+ T cells. If this virus has this ability, does it mean it will have long-term effects like lymphocytopenia, which occurs in HIV?

Cell-cell fusion means it can probably infect and even replicate inside any kind of cell? But this is probably a minor target compared to type II cells. In the paper they obtained significant virus entry and cell-cell fusion but not significant replication inside their T-cell line. It might explain partially some of the pathogenic effect in particular if the virus induces apoptosis or just cytokine release in immunity cells.

As referenced the publication you shared, other human corona viruses also infect, but do not replicate in T cells, so it's not "Big News" in the sense of being a novel or unexpected finding. This also differs from HIV, which actively replicates in CD4+ T Cells. However, it does seem like CoV-2 patients have reduced T-cells after recovery, and that reduced lymphocyte levels during infection are associated with greater risk of mortality from COVID-19.
It doesn't seem like there's any evidence in the literature for long-term lymphocytopenia in recovered SARS and MERS patients, but it's still too early make any strong conclusions about long-term effects from the current outbreak.

So, the T-Cell is susceptible, but not permissive?

Now 20 months later are there any newer results?


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Why doesn't the spinal cord get thicker the further up we go?
The cervical and lumbar enlargements exist on the spinal cord as a result of the increased nerve input/output required for the arms and legs respectively.
However, I don't understand how the enlargements could exist by themselves without the rest of the spinal cord getting thicker.
The following is an exaggerated view of what I think a spinal cord should look like. The cervical region needs to be thicker as it has to accommodate the original nerves from the legs (blue) AND the new nerves from the arm (red). There are now ~2x as many nerves needed to go to the brain - thus the spinal cord above the cervical area should be twice as big. It is not - it just enlarges around the cervical area and returns to normal.
Why does the spinal cord not get thicker the further up we go? Doesn't it need to accommodate more nerve fibers and thus be thicker?

Try this on a piece of paper: sketch out an outline of a human body, with head, arms, and legs. Start drawing fibers that travel from the brain to each of those areas. What does your "spine" that you draw end up looking like?

@BryanKrause I understand that there  will be branching out from the central cord - is that what you're getting at? I'm asking why won't the central cord itself get thicker

Do you see how your drawn spinal cord (not the outline, the bundle of "wires") got thicker where your red lines come in? That's the cervical enlargement.

Also yes some nerves do go to the spine then turn around and go right back, look up something called a "reflex arc".

@JohnHon I think this is a good question for someone just starting out learning about this system such as yourself (+1), but in fact, many nerves play a role in reflexes (especially for our sensitive and highly mobile limbs! ) without traveling to the brain. As John says above, read more into reflex arcs

@BryanKrause Yes I do see how it got thicker, but my question is that in diagrams it looks like a bump not a sustained increased in thickness. Given that there are now more nerves that must run to the brain after the cervical area, I don't see how the thickness of the spinal cord does not increase all the way to the brain (not just locally in the cervical area)

You might consider that the primary function of the spine is structural.  That it also contains nerve bundles is secondary.  In humans, it needs to support the weight of what's above it (for a standing human), but it evolved from mostly quadrupedal ancestors.

Posting as an comment because I lack sources: from what I understand the spinal column does not just relay data like wires.  It does processing.  So its diameter need only grow enough to support the "bandwidth" needed to talk to the brain.,


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How do I interpret SNP nomenclature?
I am combing through my 23 & me raw data and I am a little confused on SNP terminology. I am using NCBI's genome browser and SNP database. As an example we can all follow here is a link to a CYP1A1 SNP https://www.ncbi.nlm.nih.gov/snp/rs28399430. When you open this link you will see alleles listed as G>C. Which one of these is the reference genome and which is the pathogenic allele? Is the relationship always constant (like in x>y, x is always the reference and y is the substitution). If you scroll down to the genome browser view, there also doesn't appear to be any way to tell + vs - sense strand (ie making it difficult to tell G for C mutations or vice versa). I would just assume its the top strand? The ultimate goal here is for me to look through 23&me and compare my SNP genotype to the reference genome and see if my genotype exhibits pathogenic SNPs in certain genes.

"Which one of these is the reference genome and which is the pathogenic
allele?" How have you concluded that the less common, non-reference allele is pathogenic? I don't see any clinical data for that

For specific examples I’m looking at it’s the case. Not globally- should have made my self clear sorry

Quick answer is yeah, the G is the "reference allele" as you put it.  The greater than symbol is acting as an arrow, ie, G goes to C, that is, G is replaced with C.
Actually you get a pretty clear indication of that if you look down a line it two where it mentions the frequency:

C=0.000419 (104/247982, GnomAD_exome)
  C=0.000494 (62/125568, TOPMED)
  C=0.000538 (62/115296, ExAC)

The C frequency is way too low to be the "normal" allele.  It's rather the substitution which results in a missense variant. You can see more specific stats by clicking on the frequency button.  In this case they basically just say that in all studied populations the G variant is by far the most common.


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Has there ever been a published experiment to take a viral "census" of a human subject's blood?
Has there ever been a published experiment to take a viral "census" of a human subject's blood?
By a "census", I mean to identify every active virus in the subject's blood with some probability.
So, for example, we can imagine taking different samples of blood, diluting them, then taking the dilution and using it to innoculate a lawn of hemocytes. Presumably, different viruses would make different plaques, so they could be separated, isolated and identified. By doing different combinations of dilutions, one could I suppose make a table or curve that would show the probability of detection of a given virus based on its concentration in the blood. Thus, at the end of the experiment the researcher could state, "I have isolated all the viruses in the subject's blood having a concentration above X with a probability of Y." Obviously, this would require hundreds of samples and thousands of innoculations to achieve an accurate census.
Has anyone published a study like this?

Here's a deep sequencing paper characterizing the DNA virome of human blood. I'm not sure if anyone has attempted viral "Culturomics" work for viruses. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006292

You wouldn’t try to isolate viruses, this being the 21st century.  You’d perform metagenomics analysis, which is much more sensitive.
That’s been done several times.  Two examples:

Anellovirus and pegivirus C (GBV‐C) were detected among these donors. None of them were found solely in donors with abnormal liver enzyme. Anellovirus was highly prevalent (93.3%) and the co‐infection with multiple genera (alpha, beta, and gammatorquevirus) were more common in the donors with normal ALT values in comparison to those with elevated ALT ...

—-Full annotation of serum virome in Chinese blood donors with elevated alanine aminotransferase levels

Anelloviruses were detected in each of the 10 plasma pools. Human pegivirus A (HPgV; GB virus type C) sequences were identified in eight of the 10 pools, more than 90% of which belong to Genotype 2. The recently described human HPgV2 in Flaviviridae was not detected. A small number of sequence reads of human papillomavirus were also detected in three pools. In one pool, two different gemycircularvirus genomes were identified and fully sequenced.

—-Viral nucleic acids in human plasma pools

I don't see what this has to do with a viral census. In my copy of Fields Virology (6th Edition) there is no mention of "metagenomic analysis" so I don't know what that is.

Metagenomics


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Proteoglycans vs Glycoproteins

On the left, is my histology book, on the right there's qoura (the internet).
My histology textbook says that "unlike glycoproteins, proteoglycans have attached GAGs which often comprise a greater mass than the polypeptide core"
What I found on qoura is "The carbohydrate content of proteoglycans (10-15%) is far less than glycoproteins is (50-60%)"
I tried googling the question but couldn't find the answer so which of these is correct ?

Campbell Biology (11th edition) states that proteoglycans are up to 95% carbohydrate.

More context would be helpful, but it's possible the data from the Quora post was incorrectly transcribed from a table on this biotech site, which states that the carbohydrate content of proteoglycans is 50-60%, compared to 10-15% for glycoproteins.

However, the first comment on that page suggests that the table was initially incorrect:

Hi Anne,
This is a great post, but the numbers for the carbohydrate content are reversed. It’s 50-60% for the proteoglycans and 10-15% for most common glycoproteins (and things like uromodulin and most mucins would be 30+% sugars).
Best,
Jared Gerlach

So that may be the source of confusion, here.  It seems the commenter is an expert in the field of glycan research, so the table is likely correct.

Was the table edited afterwards ? Because the table shows 50-60% carbs in proteoglycans and 10-15% in glycoproteins which the writer and the commenter agree on

Yes, it seems that is the case.  I've edited my answer to reflect that, thanks.


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What determines if a small protein / large peptide is immunogenic?
I'm wondering if there is some threshold in size or a specific structural property that determines if a small protein or large peptide would cause an immune reaction.
Context: there are a number of drugs being developed based on antibody mimetics (small protein scaffolds with stable folding).  These tend to have a size around 50-60 aminoacids (6-7 kD).  These tend to be much easier to design than human / humanized antibodies.  However, it is not uncommon for these to cause anaphylaxis, especially if administered repeatedly.  It may be good to somehow design a version of a small antibody mimetic which itself does not cause an immune reaction.
Are peptides around 10-20 aminoacids typically immunogenic?  What about slightly larger ones up to 30 aminoacids?  Does it matter if they have a stable secondary or tertiary structure?

Do you mean "antigen mimetics" instead of "antibody mimetics"?

I mean proteins like affibodies or minobodies  - see https://en.m.wikipedia.org/wiki/Antibody_mimetic

Here is a useful article on this, https://www.prosci-inc.com/resources/antibody-development-guide/what-is-an-immunogen/

Fundamentals and Methods for T- and B-Cell Epitope Prediction

Edited to delete off-topic section:
Most (all?) proteins are ultimately immunogenic. You can't really design your way around immunogenicity, which is a good thing, because otherwise we'd all be dead from viruses.
Obviously not all proteins are equally immunogenic, but basically all protein therapeutics are immunogenic at some rate. One thing that seems positively associated with immunogenicity in that review is quaternary structure, but it's quantitative not qualitative.
Some of the commonly used synthetic antigens used in biochemistry such as HA C-terminus (24 residue) or FLAG (8 residue) are quite small.
More generally, this study finds that even 3-5 residue peptides can be sufficient to raise immune responses. So likely any polypeptide is potentially immunogenic.
Such small peptides are unlikely to have meaningful secondary/tertiary structure. My guess is that that you would have to have a pretty structurally strange protein to avoid any potential immune response. However if you had an insoluble or somehow sequestered protein you might be able to avoid it, but I'm not an expert so I can't say how.

Thank you, fascinating info.  I'm looking in the opposite direction, for ways to have peptides not be immunogenic / less immunogenic - so the exact opposite of adding a carrier protein.  Basically the idea is to have engineered small protein as a drug; if the drug itself causes an immune response that's a problem.  For example Ecallantide is a ~6kDa protein drug based on Kunitz domain scaffold; it causes anaphylaxis in about 4% of people who take it.

yeah, i realized that halfway through writing it and had to go back and rewrite it with the knowledge that that was your motivation. basically, as i said above, it's hard to make proteins not immunogenic.

see also wikipedia on immunogenicity: https://en.wikipedia.org/wiki/Immunogenicity. basically, (nearly) all peptides are immunogenic.

@AlexI deleted irrelevant hapten section and added some more refs.

"Such small peptides are unlikely to have meaningful secondary/tertiary structure" - That should be mentioned in any basic textbook (hapten chapter)!


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How Do Pressure and Temperature affect arthritis?
Here, in Houston Texas we were hit by a cold front tonight and I remembered the old saying that I'm sure you've all heard "My joints hurt, must be a storm (or change in weather) coming in". It piqued my curiosity as I wasn't sure if it was due to the temperature itself or the atmospheric pressure difference causing the flare up of pain. I looked into it and, as far as I can tell from what I've read, scientists are unable to agree on what exactly causes the flareup of pain as the evidence from the myriad of studies done on the subject are inconclusive and different in each situation. The evidence being that both temperature and atmospheric pressure changes have shown to affect flare ups in joint pain due to arthritis as well as the opposite. It almost seems like all of it can affect arthritis pain, as well as none of it. However, I began to think "What if it has nothing to do with how much the atmospheric pressure or temperature changed, or in which direction they changed? What if it's simply due to change itself?"
My source: https://www.amjmed.com/article/S0002-9343%2806%2901026-6/pdf
The article expresses that temperature drops cause pain. However, it also states that the reasons for why this occurs is unknown. I also believe temperature raises may cause this as well as I myself, along with others I've talked to with arthritis, have felt that arthritic ache in both increases and decreases of temperature. I am posting this question because I have learned that temperature is unrelated to atmospheric pressurization as both high and low temperature air may have either high or low pressures.
I'm no expert in any of the scientific fields that are involved in this question. So, what do you as the community of StackExchange Biology think?
Bonus source from SE Physics for those of you unfamiliar with temperature and atmospheric pressure: https://physics.stackexchange.com/questions/326315/does-hot-air-have-high-pressure-and-does-compreesed-air-have-high-pressure/471775?newreg=ef5c317e3a114a3d8e4bb5fb680c477e

The first two sentences are completely unrelated to my question and only act as an, hopefully interesting, introduction into how I began to ponder my question. However, this was closed as it was deemed a personal medical question when it isn't. I am in no way asking for advice or help in my situation and just want to know how pressure and temperature affect arthritis in general. I believe my question to have been unfairly closed, or even not read fully before being closed.

I edited the question further. I would advise you to add your prior research and additional sources of the connection between arthritis  pain and weather conditions. As a sufferer from it myself, I've noticed cold has a pronounced effect, and my martial ars teacher, quite proficient in the physique of man, affirmed that notion. However, I have no knowledge about the topic whatsoever. Please add sources  and background info and perhaps the question can be re-opened.  I really like this topic btw.

Lastly, feel free to roll back my edits; but I'd advise to not put the personal background information back in, as it may trigger people thinking it's self-help. The Medical Sciences SE site may be helpful as well. We can migrate it for you (please don't cross-post).

I rolled back, but edited the post to be more-so in accordance to your advice on how to pose a question. I returned my internal ponderings as they are the questions of the post and I believe they are integral to the topic itself. Thank you for your time and help.

If you believe that the SE site is a better location for this post, then by all means move it. I'm am a new user (this being my first question) so I was unsure where exactly to post it.

Meant The Medical Scientists SE. Also, I included my source and what I was able to conclude from said source.


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Question about the Derivation of the cable equation for neurites
I read in Wikipedia how the cable equation was derived (here) and had a specific problem regarding one of its equation:
At the start of the derivation it states that we first need to pretend that the membrane is perfectly sealed (Rm=∞) and that the capacitance of the membrane equal zero. Then we can say that the change in voltage over distance depends only on the resistance of the axoplasm, by the equation:
 and from that, the current equal:
But later when they derive the last equation, , they set  as in the equation above, which seems to me incorrect, since the resistance of the membrane also affect  . What did I get wrong?
Thanks!

The part you are quoting is about helping you conceptualize the cable equation by starting from some approximations that let you remove most of the terms. See the sentence beginning (emphasis mine):

To better understand how the cable equation is derived, first simplify the theoretical neuron even further and pretend...

They then walk you through how, because these approximations are just pretend, one needs to include terms to account for the actual permeability and capacitance of the membrane. This means that you do not have a constant internal current with distance as you travel along; instead, the current decays with distance because of leak through the membrane and membrane capacitance.
This is what the last equation you quote from says: the change in internal current over distance x (written as dil/dx) is equal to the current lost to the membrane, which includes two parts: leak through the membrane (V/rm) and charging the membrane capacitor (cm*dV/dt).

Another correction that might be tripping you up: you write

change in voltage over time

in your question, but that is not what the equations are representing, they are representing change in voltage over distance x.

Thanks for the answer. I also corrected another mistake I wrote (I mean I(i) instead of I(m) at the end).
But I didn't understand yet how they can set I(i) (as was derive at the beginning) to the I(i) at the last equation, because when they set I(i) in that equation (the second-order partial differential equation) its the equation which don't take into account the R(m).

@Idop11 Did you miss equations (7) and (8) from the Wiki page? Note that the definitions are changing throughout, this is not a derivation per se, where you can connect different steps algebraically.  Don't confuse symbols that are based on certain assumptions with the same symbols once those assumptions are changed.


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Why doesn't infection with Clostridium Tetani immunize you?
What Immunity to COVID-19 Really Means - Scientific American

It is less clear what those antibody tests mean for real life, however, because immunity functions on a continuum. With some pathogens, such as the varicella-zoster virus (which causes chicken pox), infection confers near-universal, long-lasting resistance. Natural infection with Clostridium tetani, the bacterium that causes tetanus, on the other hand, offers no protection—and even people getting vaccinated for it require regular booster shots. On the extreme end of this spectrum, individuals infected with HIV often have large amounts of antibodies that do nothing to prevent or clear the disease.

Clostridium Tetani - StatPearls - NCBI Bookshelf

It should be noted that infection with C. tetani does not provide immunity, and thus, all patients with the diagnosis of tetanus should receive immunization immediately with three doses of tetanus and diphtheria toxoid.

What research have you done to try to answer this question yourself? The top hit when I searched with "Clostridium-tetani immunity" was this book chapter ...

@tyersome That abstract doesn't answer my question? That book chapter is pay-walled.

Interestingly if I do the search I suggested and click on the link to that article I can see a preview of the first two pages, but if I go directly following the link I can't see it either ...

There is a big difference with tetanus compared with other infections. The amount of toxin that produces tetany is extremely tiny. Even a small infection that the immune system has yet to react to can be lethal.
To produce a long-lasting response against the bacterium would require a lethal number of bacteria.
Vaccination with the toxoid results in antibodies against the toxin, not the bacteria.

The problem is different: Tetanus toxin is so supertoxic that the amount needed to poison you is so small that this is not enough to trigger an immune response.


text:
How do we formulate the mutational load for "junk DNA"?
Question(s)
Based on Joe Felsenstein's textbook, I was trying to formulate the mutational load for the majority of eukaryotic genomes that are junk DNA ($L_{most\_of\_genome}$). (See background section for more details and relevant quotes.)
Extrapolating from what Joe writes about non-junk loci and removing one simplifying assumption (Muller-Haldane), I believe that this should be equal to the allele frequency of each locus (simplifying here to the average across these loci, $q_e$) multiplied by whatever infinitesimal selection coefficient each locus has ($s$, on average), summed across all loci ($N_{positions}$):
$L_{most\_of\_genome} = N_{positions}q_{e}s$
(Ideally we would sum this across individual estimates of $q_e$ and $s$ for each locus, but that's obviously impractical here so we use the mean across loci.)
here are some closely related questions:
1) Is the above a reasonable formulation for $L_{most\_of\_genome}$? If not, what would be? (I can readily imagine that a lot of assumptions start breaking with hundreds of millions of positions etc.)
2) If it is a reasonable formulation, what are "reasonable" parameter ranges for $s$ and $q_{e}$ of "deleterious" nearly-neutral mutants for this majority of the genome? (For example, we might say that $s$ can take values less than the inverse of the population size.)
Note that I'm talking about junk DNA, not non-coding DNA. We know a fair amount about mutational load of (non-junk) non-coding DNA.
Possible problems with this
Let's plug in some values here, let's say across a billion loci with very small selection coefficients of $10^{-10}$ and $q_e$ equal to the mutation rate $u$ of $10^{-8}$ (e.g. all deleterious variants are new mutations), I can write:
$L_{most\_of\_genome} = N_{positions}q_{e}s = (10^9)(10^{-8})(10^{-10}) = 10^{-9}$
This is a subset of the overall mutational load. For these parameter values that seems plausible, but if we take seriously Joe's argument (see below) that many of these loci will fix deleterious variants, e.g. $q_e \approxeq 1.0$, then this value could get quite high.
For example, here's a different calculation assuming that $q_e \approxeq 0.1$:
$L_{most\_of\_genome} = N_{positions}q_{e}s = (10^9)(10^{-1})(10^{-10}) = 0.01$
That's a non-trivial load!
In fact, asymptotically we expect that every locus will fix slightly deleterious variants. In this case of universally fixed slightly deleterious variants, this load is closer to $10^{-1}$ for the above example. For conifers and axolotls with >10Gbp genomes, we would then expect the load just from junk DNA to be greater than 1 for these parameter values, e.g. dead. Joe has a section "Why aren't we all dead?" but it doesn't directly address this, and it uses principally verbal arguments.
Background
I am refreshing my knowledge of the mutational load by reading the section of Joe Felsenstein's book on the subject (pp. 152-158), and I am now remembering something I struggled with while taking the class he taught on the subject.
Joe writes in the section "Weak selection and mutational load":

As the mutational load is said to be a function of the mutation rate, but not the selection coefficient, it is natural to wonder how a very weak selection could impose a load. Surely the Haldane-Muller principle cannot hold all the way to $s = 0$. Of course, it does not. In the haploid case, the mutational equilibrium gene frequency $q_{e} = \frac{u}{s}$ is only correct if $u < s$, otherwise the only equilibrium of the system (III-21) is $q_{e} = 1$. If $u \geq s$, so that $q_{e} = 1$, the load is $L = q_{e}s = s$, so that as we consider cases with progressively smaller values of $s$, the load will remain $u$ until $s = u$, then below that point the load will smoothly decline to zero as s declines.

(Where $s$ is the selection coefficient for a mutant allele, $q_{e}$ is the mutant allele frequency, and $u$ is the mutation rate at that locus.)
Joe then talks about some other stuff and concludes:

The load will be a simple function of $u$ unless $s$ is so small that it is not substantially greater than $u$. Below that point the load will decline to zero as $s$ does.

This last sentence (my emphasis) is not obvious to me based on what I've read.
I am having trouble following this logic. Here is what I understand of it:
1) Muller-Haldane asserts that $s$ has very little impact on $L$, such that to a close approximation $L \approxeq u$ (for a haploid; shown on p.153 and elsewhere), in other words the load is mostly unrelated to $s$ because $s$ only has an effect if $q_{e}$ is not close to zero, which is rarely true for new mutants.
2) At very low $s$ there is a higher chance that the mutant will go to fixation (e.g. reach the $q_{e} = 1$ equilibrium) due to the lesser action of selection.
3) From (2), I think that this means that $s$ is then part of the load formulation again at low $s$.
4) So as $s$ goes to zero the contribution of such variants still goes to zero.
5) Joe also uses the C value paradox/junk DNA/onion principle to argue that the mutational load isn't affected by most of the genome for large genomes e.g. human. But that argument seems to say that we just shouldn't worry about these regions of the genome because their selection coefficients are in the region of negligibility close to zero.
But these are not formally worked out here in the book. Can anyone formulate an expression or approximation for exactly how we can treat the load associated with very small selection coefficients that are found in most of a large eukaryotic genome?

I ended up writing directly to Joe after not getting an outside answer here. I won't directly quote him without his permission, but to sum up, he wrote the following:

This paper (among others) gives an numerical treatment of different selection coefficients in small populations, which effectively means loci that are not under selection but still have coefficients (which I am defining as junk DNA in my question). It shows a smooth decline (Figure 1) with decreasing $s$ and population size, indicating that my instinct was correct that there exists a load for such "junk" DNA.

Figure 1 from Kimura, Maruyama, and Crow 1963

Joe was rather skeptical that such loads were actually significant for evolution, except in the case of very small populations. I think that this also agrees with my intuition, but as an important practical note it's important to not get too excited about junk DNA from a biological standpoint (see e.g. Graur et al. 2013).


text:
What does sympathetic and parasympathetic 'tone' mean?
My professor's lecture notes say that " The basal rate of firing is called “sympathetic tone” and 'parasympathetic tone"  , but a table I found on the internet  says that the parasympthetic system has no tonic activity.
Does saying the ANS has tonic activity mean that it sends impulses continuously and at a low rate to effectors? How is the ANS considered rapid then?
On Euroform Healthcare
It is written that without the sympathetic and parasympathetic tones, we would not be able to regulate the activity of organs or bring it up and down, I don't understand why that's the case ?
I'm very new to this whole topic (ANS) so please go lightly on me.

Thanks for the edit!  We do still need more context... are we talking about tonic activity in cardiac muscle?  Peripheral blood vessels?  Urethral sphincters?  Without seeing more context my guess is that your professor and the articles / pictures you're running across are talking about totally different physiological systems which accounts for the difference.

The thing is, I am so naive when it comes to this topic so I can't be sure but, my professor's notes seem to give a general idea on the topic but the topic's name in the book is " The Autonomic Nervous System and the Adrenal Medulla" If that helps. Regarding the table and the website, no specifications are made ,  I just want understand the general concept

Short answer
Parasympathetic tone is not necessarily mediated by tonic firing.
Background
Nice question! I think part of the confusion stems from terminology. Let's start with some definitions first.

'Tone' in sympathetic tone can be translated as mean activity level (Hayano & Yuda, 2019).
'Tonic' firing by neurons may be translated as a sustained response, which activates during the course of the stimulus (Wang et al., 2014), although some neurons have intrinsic tonic activity as well, like thalamocortical neurons. This opposes to phasic firing neurons.
'Phasic firing' refers to a transient response with one or few action potentials at the onset of stimulus followed by accommodation (Wang et al., 2014).

In your post you seem to assume that parasympathetic tone equals tonic firing activity. I'm not so sure about this. For example, I found a catching paper on the parasympathetic regulation of lung function in guinea pigs (which lacks sympathetic innervation altogether). The paper nicely illustrates (Fig. 1) that parasympathetic regulation of the bronchi in guinea pigs is mediated by both tonic and phasic (burst) stimulation (Myers, 2000):

[P]hasic neurons in guinea pig bronchial parasympathetic ganglia
  respond to a prolonged suprathreshold stimulation with a
  high‐frequency burst of action potentials ..., whereas tonic neurons are nonaccommodating and will respond with relatively lower
  frequency action potentials...

Fig. 1. Phasic and tonic neurons in guinea pig bronchial parasympathetic ganglia. source: (Myers, 2000)
References
- Hayano & Yuda, J Physiol Anthropol (2019); 38(3) (2019)
- Myers, JCN (2000); 419(417): 439-50
- Wang et al., Channels (2014); 8(4): 298–307

Missed this Q&A when it was posted. I'm not as familiar with peripheral nervous system stuff so I'm not sure what to answer for OP but definitely agree that "tonic" has separate meanings. The tonic/phasic firing mode of certain CNS neurons is pretty specialized and completely unrelated to, for example, muscle tone. I would assume (para)sympathetic tone is referring to something more akin to muscle tone which I wouldn't necessarily characterize as "mean activity level" but rather "activity level when we (experimenters) don't perturb it".

@BryanKrause Agreed! That's a nice way of putting it. Did you downvote btw? Should I adjust my text anywhere? I though this was a quite OK answer imho.

Nope I added an upvote around the time I commented (and just double checked I didn't misclick :-D ). Not sure where the downvote came from, alas, it seems misplaced.

@BryanKrause - thanks for explaining. That helps!


text:
How far can locust swarms expand and beplague?
March 2020 is the the latest map that I see. I'm asking about all relevant species of locusts. What's the maximum effective range for these locusts swarms? Southern Europe? China? Japan?
I read Michel Locoq's answer on Dec 9 2013 but it doesn't answer for swarms.

In 1988, locusts swarms travelled some 5000 km non-stop from West Africa to the Americas. Several waves of locusts arrived between 7 October and 4 November 1988. This was not at all a single event. There is other examples: migration of swarms from Africa to British Isles in 1954, migration half-way across the Atlantic in 1865 and 1916, etc.
Desert locust can resist to starvation and cold temperatures. Just a few days without food is not too much for an insect living normally in desertic areas, migrating during months for food and humidity for its eggs. And they can survive quite well at low temperatures. I have seen swarms crossing the Atlas mountains in Morocco, they can settle in the snow and start again when the sun appears. No need for human help (and what kind of help for large swarms of bilion of insects ?) to cross the ocean. it's just a good flying insect. Its flying capacity is so developed that there is no genetic differences between mauritanian populations and populations from Pakistan.


text:
Bit by unidentifiable spider
Live in South Florida and was outside cleaning and believe I got bit by this spider.
It is painful and need help identifying.

You need to provide a photo and an approximate size

The only North American spider species of concern are the black widow (Latrodectus mactans) and brown recluse (Loxosceles reclusa). Unfortunately, these both occur in south Florida - but so do many other spiders.
I'm guessing the spider that bit you wasn't one of these two, for the following reasons:

Black widows are widely identifiable by the general public, and you'd likely have recognized that by the highly characteristic red hourglass on black.
Black widow bites hurt a lot. It takes an hour or so for the pain to really set in, but you'd know it was a serious problem.
Brown recluse bites are rare, despite their wide range, and tend to happen indoors.

If you were bitten by anything else, the odds are incredibly high that the worst you'll deal with is a little red bump of irritation that goes away shortly.


text:
Non-radioactive nucleotide labeling compatible with reverse transcriptase?
Are there any methods for nucleotide labeling which are compatible with use for reverse-transcription, besides radiolabeling, and for which the regulatory framework in the EU / USA are permissive ? Regulatory obligations around radionucleides being too strict.

Biotin-labeled nucleotides can be incorporated into cDNA by reverse transcriptase.  Jena Bioscience, a provider of biotin-labeled nucleotides, has a table showing which nucleotide chemistries have been successfully used with reverse transcriptase, though you'll have to delve into the data sheets of specific products to get the references.
One reference provided on the product page for biotin-11-dCTP:
APOBEC3G Inhibits Elongation of HIV-1 Reverse Transcripts
This study looks at natural endogenous reverse transcription (nERT) in HIV.  From the methods:

For this assay, a nERT reaction was performed essentially as above, with the exception of the dNTP addition: pelletted virions were resuspended in PBS, 2.5 mM MgCl2, 15 µg/ml melittin and 0.5mM biotin-11-dCTP (Jena Bioscience), and incubated at 37°C.

Yes, Biotin is non radioactive option used for labeling of nucleotides. Various enzymes used for incorporating this biotin labelled nucleotide are:  Taq Polymerase for Ploymerase Chain Reaction, DNA Polymerase for Nick Translation, Moloney Murine Leukemia Virus Reverse Transcriptase for Reverse Transcription, Klenow Exonuclease for Primer Extension and Terminal deoxynucleotidyl Transferase for 3'-end labeling.
The detection of these Biotin labeled probes is done using streptavidin conjugated with a horseradish peroxidase, alkaline phosphatase,  or agarose/magnetic beads.
(Via: https://www.jenabioscience.com/probes-epigenetics/dna-cdna-labeling/hapten-labeling-of-dna-cdna/biotinylated-nucleotides
https://www.promocell.com/f/product-information/manual/PK-CA-BIO-DUTP-1000P.pdf)


text:
Is the SHC014 chimeric coronavirus "eerily similar" to Covid-19 in anything but a journalistic sense?
Gulf News writes:

In the virology community, their project is known as "chimeric coronavirus", eerily similar to COVID-19. This chimera is created in a petridish, reportedly with the "surface spike protein (S protein) of a coronavirus found in horseshoe bats, called SHC014, and the backbone of a SARS virus that could be grown in mice".
Here's the scary bit: In the lab (we don't know which one), this new coronavirus was found so potent it could infect and replicate in human airway cells naturally. It also infected mice lung cells. It's one of the experiments which prompted Prof Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris, to warn that such research is "misleading" and "irrational", stating thus: “The consequence of any accident would be anywhere from a handful of infections to a catastrophic pandemic.”

Is this SHC014 chimeric coronavirus "eerily similar to COVID-19" in a scientific (not just journalistic) sense? Have any scientific publications drawn a parallel between the two viruses?
(I know that SARS-CoV-2 is most closely similar to RaTG13 at whole genome level and at RBD level [most likely] to Pangolin-CoV. I'm asking what if any scientific relevance does SHC014 have to Covid-19.)

And I think this worth answering because people keep bringing up this SHC014 on skeptics, unfortunately just in the form of "nudge nudge wink wink" https://skeptics.stackexchange.com/questions/47429/were-zhengli-li-shis-and-ralph-s-barics-research-groups-the-only-groups-in-th ; https://skeptics.stackexchange.com/a/47378/29579 rather than any claims that could be directly answered. Likewise journalists like to bring it up as per above, but it's a again a wink-like statement. So, I can't use/challenge it as such on skeptics.

The lab is Baric lab at Chapel hill, North Carolina.

The "similarity" of this specific chimera was addressed in a recent paper concerning the lack of evidence that SARS-CoV-2 is lab-grown:

Another claim in Chinese social media points to a Nature Medicine paper published in 2015 [7], which reports the construction of a chimeric CoV with a bat CoV S gene (SHC014) in the backbone of a SARS CoV that has adapted to infect mice (MA15) and is capable of infecting human cells [8]. However, this claim lacks any scientific basis and must be discounted because of significant divergence in the genetic sequence of this construct with the new SARS-CoV-2 (>5,000 nucleotides).

Liu, S. L., Saif, L. J., Weiss, S. R., & Su, L. (2020). No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2. Emerging Microbes & Infections, 9(1), 505-507.
The "eerily similar" nature seems at most to be something well recognized by virologists, particularly in the wake of SARS: coronaviruses circulating in bats could become dangerous to humans if mutations occur in key parts of their genome or recombinations occur with other coronaviruses in bats or intermediate hosts. That's more or less what happened with the first SARS and more or less what happened with SARS-CoV-2, as best as can be told right now.
I'd also take a bit of umbrage at the language used in that article:

this new coronavirus was found so potent it could infect and replicate in human airway cells naturally

seems like a bit of fear-mongering. Any virus that affects humans can "naturally replicate" in human cells: the author could have merely written that instead of calling it "so potent".

Coronavirus main lineages

alphacoronavirus : bats and many mammals including 229E and NL63 (ACE2), Feline-CoV, TGEV
betacoronavirus : bats and many mammals, 15% similarity to the previous, need to look at the RNA polymerase and the general structure to establish a phylogenetic relation

Mers (Camel) plus a bat lineage
MHV, OC43, HKU1, plus a rat and a bat lineage. Humanity probably had a great influence on this lineage
Sarbecovirus

SARS-CoV (ACE2) and SHC014 (ACE2, 93% similarity) and many non-(ACE2) bat viruses (90% similarity)
SARS-CoV-2 (ACE2) 80% similarity to the previous and 96% to RaTG13 (ACE2) and 92% to Pangolin (ACE2)

gammacovonavirus (avian, beluga)
deltacovonavirus (avian and swine)

As you see SARS-CoV-2 is very very close to the virus you are mentioning, even if there are enough difference (and bat and Pangolin viruses) to be 100% sure its emergence is totally unrelated to the SARS-CoV and SHC014 experiments. Until this year everybody would have considered SARS-CoV-2 as too distant to SARS to be a danger.
Wuhan's lab is specialized in ACE2 Sarbecoviruses. But the chimeric CoV and the controversy and condamnation of gain-of-function researches was about Baric lab in Chapel Hill, North Carolina, to which Wuhan participated by providing SHC014, the bat virus using ACE2 they found 2 years before. Note everything was published in Nature, there was nothing hidden. Also the chimeric study proved that SHC014 wasn't able to infect human cells, not because of its spike but its backbone, which was reassuring for a possible reemergence of SARS. On the Neertheland, USA and Japan side there was a similar story about H5N1 mutants and chimera.

Interestingly that last story mentions a funding pause for GOF research between 2014 and 2017. The Shi-Baric paper on SHC014 was published in 2015, but I guess the work was done in 2014 before the "freeze". Also Baric has published such papers before e.g. in 2008 without Shi being a co-author, which lends credence that (most of the) work was done at the NC lab.

Actually the 2015 paper even says "These studies were initiated before the US Government Deliberative Process Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS and SARS Viruses (http://www.phe.gov/s3/dualuse/Documents/gain-of-function.pdf). This paper has been reviewed by the funding agency, the NIH. Continuation of these studies was requested, and this has been approved by the NIH."


text:
What could independent investigators learn from the first (known) copies of the virus from Wuhan, if they had (physical?) access to these samples?
RFI reports:

"You have to remember -- these labs are still open inside of China these labs that contain complex pathogens that were being studied. It's not just the Wuhan Institute of Virology," Pompeo told reporters.
"It's important that those materials are being handled in a safe and secure way such that there isn't accidental release," Pompeo told reporters.
Pompeo cited the example of nuclear facilities, pointing to the rigorous global inspections to ensure safety.
He renewed concerns that China has not shared a sample of the initially detected virus, known scientifically as SARS-CoV-2.
"We still do not have a sample of the virus, nor has the world had access to the facilities or other locations where this virus may have originally originated inside of Wuhan," Pompeo said.

(China has now rejected this US call as being "politically motivated" but they weren't terribly specific beyond that.)
Would China [physically] sharing "a sample of the initially detected virus" (which of course begets the question which sample is that precisely--but let's assume they share all 40 or so initial samples they reported/discovered back in Jan) have any scientific value? E.g. is [physically] sharing those samples (more broadly) likely to shed any additional light on the virus' origins? (In that regard, have Western scientists asked for those [physical] samples, or said they are important for China to [physically] share them, independently/before the US political leadership's involvement in the matter?)
For more context, a Yale med page from January says:

Two weeks ago, we didn't even know what the nCOV2019 virus was. Today, thanks to China’s quick public release of the initial nCOV2019 virus genome [...] To go from unknown pathogen to diagnostic tests so quickly is incredible! The scientists at the Fudan University, China CDC, Chinese Academy of Medical Sciences, Chinese Academy of Sciences, Zhejiang Provincial CDC, and the Thai National Institute of Health should be highly praised for making their data rapidly available to the public.

A bit later, Chinese researchers published a paper on 10 genomes from the initial outbreak in Wuhan. The (FASTA) data for those seems publicly available, although behind a registration page.
So, per comments below, if Pompeo means something else by "sample of the virus" (not physical sample[s]), what is that?

You interpolate [physical(ly)] throughout - does that mean that you are asking about physical sharing only, as opposed (e.g.) to sharing complete genome sequences of all the samples?

@BenBolker: I'm willing to be corrected that Pompeo meant something else, as you suggest. (E.g. if non-Chinese experts said that such extra sequences would help.) I know China shared some genome sequences, do you think if they shared more that would elucidate the kind questions that Pompeo is interested in, like the origin of the virus?

@BenBolker: https://www.thelancet.com/article/S0140-6736(20)30251-8/abstract "We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. [...] The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. "

@BenBolker: "These data have been deposited in the China National Microbiological Data Center (accession number NMDC10013002 and genome accession numbers NMDC60013002-01 to NMDC60013002-10) and the data from BGI have been deposited in the China National GeneBank (accession numbers CNA0007332–35). " And the data seems available on http://nmdc.cn/nCov/en although it seems to require a login to download the actual fasta files. (They have a registration page, alas the latter seems to only be in Chinese, and I haven't tried to use it.)

The premise of this question presupposes the veracity of a Trump agent, whose behavior is political, in the least.

@AlexReynolds: it doesn't presuppose it, I'm asking if there's some science base base/logic behind that demand. That last sub-q was because of Ben's (initial) comments which suggested that Pompeo wasn't asking for physical sample, although later in his answer Ben seems to have changed his mind about that.

Per related q here I see that asking for login in order to download full sequences is not uncommon even in some Western countries. And from the MIT article linked by iayork, it seems there are bioterrorism reasons to ask for logins.

I'll take a shot at this. It's my impression that most of this is political rather than scientifically grounded.  There are reasons to want physical samples of viruses (rather than just genomic sequences), e.g. if you want to do experimental (in vitro or in vivo) studies on a particular virus strain. (It might be theoretically possible to edit the genome or reconstruct the genome of an earlier strain, but it's much easier if you have the desired viral strain in hand.)
Based on this Financial Times article (which may or may not be accessible without a subscription/accepting cookies)

Mr Pompeo added the Chinese Communist party had still not shared virus samples with anyone outside China, impeding efforts to understand how it emerged.
A researcher at Wuhan Institute of Virology, who declined to be named, told the Financial Times earlier this month that China had not shared samples of the live virus with the WHO as the country “had already published plenty of information” such as the genetic code of coronavirus.

It does seem that almost all of the research on the origins of SARS-COV-2 is based on genome sequences rather than on phenotypic studies (i.e., in vitro and in vivo studies of actual viruses).
I don't think viral samples would actually be very useful (that's why I said at the beginning that I think most of this argument is political rather than scientific). In principle I guess you could use the viral samples from an early stage  do experimental infections in different animal species, but I don't know that any researchers actually want to do that, and I don't think there's been enough phenotypic evolution in the last few months that the early-epidemic viral samples would behave that differently from current samples ... it's also likely that researchers could study the effects of particular mutations (observed in genomic sequence) by modifying viral samples they had in hand.
To take an example from an earlier pandemic, researchers have done experimental studies in mice to show how particular mutations influenced the virulence of earlier flu strains. This is an example where it's useful to have an actual virus rather than just the genome - but in this case the virus was actually reconstructed from knowledge of the genome ("two isogenic recombinant chimeric viruses were created with an influenza A/WSN/33 virus background containing the PB1 segment from the HK/156/97").

Thanks for that clarification. So. as I suspected, the Chinese rejected the US request interpreted as a request for live virus samples because they though/said the genetic info they have published suffices. But besides validating my q to some extent, this isn't really answering it. Why are domestic live samples not enough? Why are live samples from China in particular necessary in the US?

More precisely, in re your last para, when have "phenotypic studies" elucidated the origin of an outbreak? Are there [past] examples?

Thanks for the update. (+1)

Ralph Baric already cloned the virus from Chinese sequence data. This is just politics.

@layork feel free to post your own answer, or edit my question (if I don't do it first)


text:
Is this trial that reversed aging in humans worth taking seriously?
In September 2019 Fahy et al. published results from the TRIIM (Thymus Regeneration, Immunorestoration, and Insulin Mitigation) trial. Their stated goals were to investigate whether they could restore the immune systems in eight healthy older men (ages 51 - 65) using a combination of recombinant human growth hormone, dehydroepiandrosterone and metformin. While they achieved impressive on-paper results partially restoring the thymus, the most impressive result came from their epigenetic measurement of aging of subjects in the trial.
Fahy et al. had successfully reversed aging in their subjects according to four epigenetic measures of aging. The effect size was large: each measure indicated an average gain of over 2 years after 1 year of treatment.
In other words, if hypothetically a subject was 60 years old at the beginning of the trial, both chronologically and epigenetically, then by the end of the year they would be 61 years old chronologically but less than 59 years old epigenetically.
Of the epigenetic measures of aging, GrimAge is thought to be the best available predictor of lifespan. From the paper introducing GrimAge,

Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death, time-to-coronary heart disease, time-to-cancer, its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause.

Fahy et al. demonstrated a mean age reversal of 2.16 years after 1 year of treatment according to the GrimAge measurement (see Table 1 in the paper).
Fahy is reportedly spearheading a new trial, called TRIIM-X (see this part of his recent TEDx talk). He hopes to investigate the effects of a modified version of the same treatment with the benefits of a larger trial and a more diverse set of participants.
The skeptical side of me has a question:

Is a reversal of the epigenetic clock good evidence that aging was reversed, or is there a good theoretical reason to think that you can reverse the epigenetic clock without reversing “true” aging and thus increasing lifespan?

SE questions need to be targeted and should be a single question rather than a collection of questions. I've edited out your second question to help you adhere to this rule, and also because I think that second question is going to be a pretty broad/chatty/opinion-based one.

I'm skeptical that the "biological age" can be estimated with 4% accuracy.

Also would like to see the results of a longer study checking for increased cancer and autoimmune disease rates. Testing the blood for increased autoimmune activity would be nice too.


text:
Are there any drugs that target the lipid envelope of viruses?
Many drugs go after the unique viral enzymes but do any target their lipids? Viral membranes are of course similar to the host membrane but might have a different composition and do have a different curvature and protein composition. Is anybody aware of research or even existing drugs that attempt to hit the lipid envelope of viruses to limit them?
There are evolved molecules that target the lipid membrane, for example. A subgroup of those pore-forming toxins are cholesterol-dependent, so they might target a membrane high in cholesterol over one low in it. I'm trying to think out of the box here whether properties of the viral lipid membrane could be exploited in a similar way.

For sarscov2 it would be more about S than E and M proteins. Otherwise there are molecular patterns in the lipid membranes that can serve to distinguish between self and invaders (this is more about bacteria than viruses for which double stranded RNA is a more common recognition target) but the exact recognition process is not understood enough to produce some drugs.

Soapification is the process by which detergents break down the lipid envelope. Are you asking about soapification specific to viruses, or are you thinking more along small molecule targetting of lipis?

Thanks, James. Most detergents would dissolve the virus and host cell membrane equally, don't they. If only we could make them more specific to the virus to also use inside the body?

The lipids in the viral envelope come from chunks of the host cell membrane. Therefore, something targeting those lipids is unlikely to be virus-specific, and not suitable for use in a living animal.
Out in the environment where the virus is found in surfaces and such, sure, one can target the lipid envelope using soaps/detergents and such, but you wouldn't want to take those internally.

Thanks Bryan for weighing in. You think there's no way to make those prefer the viral membrane over host membrane using the lipid composition if different, the higher curvature or the unique membrane protein mix?

@SeanJ It's not really a different lipid composition, it's ripped right from the host - even if there were measurable differences it's not really plausible biologically to sit and count them to start getting suspicious from a slightly different ratio. If you're targeting membrane proteins you're not after the lipids anymore :) - MaxB's answer covers this but you said in a comment there you were thinking of the lipids themselves, so I added this answer.

@BryanKrause "it's ripped right from the host" - that may not be exactly true.  1. It comes from viral factories, which are a kind of modified part of ERGIC; the composition is not the same as that of exterior cell membranes, and 2. leaflet asymmetry!  I haven't seen any references about asymmetry of viral membranes, but given the equilibration times, it is hard to see how there wouldn't be (eg) phosphatidylethanolamine on the outside (which mostly doesn't occur in living cells)

If you are talking about the proteins in the envelope, then yes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259279/
But if you are talking about the actual lipids, I don't think it's feasible: First, a drug molecule has to bind a lipid while not binding the host's lipids (seems unlikely, since they don't have well-defined pockets) Second, even if you could find a drug molecule that binds a lipid molecule strongly, there are just way more lipid molecules than protein molecules, so you'd need a lot more drug molecules than usual (protein-targeting drugs)

I was thinking about the lipids themselves. Proteins are of course the usual target. It just struck me that I hadn't thought about whether targeting the lipid membrane is a possibility.

If there was a molecule that could selectively bind the virus lipid membrane and punch a hole in it like in human complement defense or like the bacteriocin nisin, you would need only one of those.

Short answer: no in vivo drugs; yes for disinfectants.  Most detergents and solvents would deactivate the virus at least partly by means of breaking up (emulsifying) the lipid membrane (as well as possibly by denaturing proteins).
Targetting the membrane is hard in vivo since it comes from the host cells; most possible drugs (eg snake venom phospholipases) would affect both equally.  However, the host cell membrane has a strongly assymetric composition ("leaflet asymmetry") due to the action of enzymes that maintain it (flippases), otherwise the inside vs outside lipids would tend to equilibrate over time.  This is used a recognition signal, and there may be some natural compounds that recognize specifically inside-out membranes eg lysenin.  It is likely that the viral membrane is equilibrated, and so may be targetted by compounds like lysenin (although I haven't been able to find any experiments or published results along those lines).
I haven't been able to find much detailed info on the virus lipid membrane, so I asked a somewhat related question here before I found yours:
What is the lipid membrane of SARS-CoV-2 made of?


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How does the surface of the eye remain moist during sleep?
When we are awake, blinking helps distribute the tears so the cornea and the entire conjunctiva are wet and moist. But how is this maintained during the night, when we are sleep and there is no blinking.
Doesn't the tear just pool down? Or is there some sort of tone in the palpebral muscle of the eyelids.

With the eyelid closed, what would cause the eye surface to dry out?

tears would be sucked by gravity into the nasolacrimal duct. So the tears aren't distributed throughout the eye surface, that's what I am saying.

Welcome to SE.Biology! You might find it helpful to look at this guide for asking a question that's more likely to get a good answer: https://biology.stackexchange.com/help/how-to-ask. Can you identify a specific source or a quote on eye wetting that is leading you to confusion? You might also consider posting this question on SE Medical Sciences where people are more familiar with human physiology.

The tear system supplies your eye with moisture and lubrication while you sleep:

Also, your eyes move when you sleep, so that probably helps redistribute the moisture.

What about Bell's Phenomenon? If the eye does move at night, how many times does it do this? Is it enough for even distribution of the tear throughout the outer surface?

Tear production is decreased at night.

@Mhkhm one stage of sleep is even named Rapid Eye Movement.

@Mhkhm you probably don't need as much tears, since your eyes are closed, and there is less evaporation.


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Can fats clog veins or capillaries?
I know that so much fats running in the bloodstream could deposit in arteries, harden forming a plaque and cause atherosclerosis. But what about veins (which are formed from same types of layers as arteries) and capillaries?
I googled a bit but everything was regarding arteries.
Is it because veins have a much wider diameter than arteries that even if some fats deposit they won't clog it?
And for capillaries, they are much smaller so shouldn't they be more vulnerable to this?
In addition, I guess since one of the lymphatic vessels functions are to transport fats from  capillaries in villi to bloodstream, how are they adapted to prevent deposit of fats as they carry out the transportation?
N:B I'm just an OL biology student, and also horrible at chemistry

I know that so much fats running in the bloodstream could deposit in arteries, harden forming a plaque and cause atherosclerosis. But what about veins (which are formed from same types of layers as arteries) and capillaries?

Wikipedia says this:

Veins do not develop atheromata, because they are not subjected to the same haemodynamic pressure that arteries are,[8] unless surgically moved to function as an artery, as in bypass surgery.

The cited study isn't freely available, but seems to have tested in rabbits by surgically modifying their blood flow and giving them a high fat diet.
As for capillaries, they are continuously remodeled, so while they do become clogged for a variety of reasons, once flow stops they're disassembled and new capillaries formed if the tissue becomes hypoxic.


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Self-study genetics
I'm new at the field of genomics. I'm a theoretical physicist by training and now we would like to translate some of the ideas to the DNA, possibly in real genomic instances. The concrete example would be the line contained for example in this book, charge migration in DNA.
Before jumping to this specific line of research, I would like to understand more fully the general theory on DNA and genomics. I have read that Lewis, Genes is kind of standard, but I'm too far from this text at this time. What books would you recommend to self study from scratch?
Extra points will go to someone who can give also references for a basic course in molecular biology; it has been a while since I took chemistry, so I have been rusty at this topic also.

What does "I'm too far from this text at this time" mean?

I used "Essential cell biology" by Albert et al,
and then "Molecular biology of the cell" for  more detail. Also by them.
Experts originally from other fields contribute greatly to biology, so dont be discouraged. For self education (which I did before formal study) I recommend incremental learning based on learning everything about a drug, disease, molecule etc of interest and work out from there.
In "Biochemistry" by Lehninger, browse and look at the side panels and pictures and work through the interesting ones.
Good luck


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

This seems really ill-defined.  Do you mean some/most individuals of every mammalian species, or every individual mother?  For the latter, H. sapiens provides an obvious counterexample.

I edited my question.

Propagating their species to the future is an important & continuous function of plants,birds,mammals & many other living organisms. Parental care is part of the evolution. If
all the mammal mothers start to abandon or cannibalize their own babies then all the mammal species will become extinct. As propagation is an important function,these extinctions are not at all supposed to happen. As mammal species are surviving & propagating to the future, it's clear that almost all mammal mother
species protect their helpless babies from predators.

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

It's a hard question to answer definitively, because it's almost a black-swan problem. By definition, all mammal species secrete some form of milk to nourish their offspring (to my knowledge there are no known exceptions to this) [See "Mammalogy: Adaptation, Diversity, Ecology" by Feldhammer et al.]. It could be argued that the mere proximity of smaller young to their larger mothesr would deter some predators who might otherwise prey on those young. So, from a behavioral perspective, it's difficult to completely separate parental feeding from other protective parenting behaviors.
If you are only interested in more specific exceptions, it's not uncommon for some mammals to reject and abandon their offspring, or even cannibalize their young. But these behaviors are generally based on situational or environmental cues, like whether the mother has enough nutrients available to raise the young.
If you think about the evolutionary implications, it seems fairly straight forward why this is the case. Most mammals give live birth. For all parenting bahavior to completly vanish from a given population, there would have to be a greater fitness advantage for offpring of mothers who completly abandon their young at birth compared to those who provide nourishment and therfore (arguably) protection from predators.

Likewise, from the opposite side of the evolutionary perspective, mothers who would always fight to the death to protect young would be at an evolutionary disadvantage (since they could have no future young) to those who would expend only "reasonable" efforts in protection.


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Flies without wings
some time ago I spotted a wingless fly in my small garden. I thought to myself that it's rather weird and most likely just a random thing. But after some time I spotted more wingless flies and just a minute ago I took a photo of one specimen:
You can see that it also lacks a leg. The sightings were separated with at least few days each (I wasn't paying too much attention at first), so I think it's very unlikely it's a same fly, because spiders and ants would probably hunt it down long time ago. Unfortunately it's the only documentation I currently have although I'll try to get more. Does anyone know what could be the cause?

I just saw two today! It's strange honestly, I just thought it was some weird wingless flies. First time I saw them and I laughed  I think they're called Wingless Solider Flies.

louse flies are known to drop their wings after they find an animal to lay their eggs on,i am not saying that it is a louse flie as they have a very flat body.

Please [edit] your post to include as much of the following essential information as possible to improve your chances of getting a good answer: 1) one or more clear closeup photos of the organism (photos from multiple angles if possible)); 2) the location (e.g. country and region — the more specific the better) where you observed this organism; 3) habitat information; and 4) an estimate of the size of the organism. ——— Please also take the [tour] and then go through the [help] pages starting with [Ask] questions effectively on this site.

It would help a lot if we knew where you are, many islands have wingless flies for instance.


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Do lack of sleep affects the process of digestion?
Many times due to lack of sleep I felt discomfort in digestive tract.Why did it happen?Do lack of sleep affects the process of digestion?


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How a person can transmit COVID-19 while his COVID-19 is still in incubation state?
A person with SARS 2003 cannot transmit that disease while his SARS is in incubation state but how a person with COVID-19 is transmitting COVID-19 even though his COVID-19 is in incubation period?

The incubation period is the time it takes from the infection of a patient with a disease until he develops symptoms. How fast this happens depends on the disease.
According to the references the main difference is that SARS 2003 replicates in the lung/lower airways, while SARS-CoV-2 also replicates in the upper airways and sheds high viral loads there early in the course of the disease.
Since both diseases are transmitted by droplets, it is much easier to have a sufficient viral load in infected cells from the upper airways compared to the lower ones.
References:

Severe Acute Respiratory Syndrome Coronavirus Infection of Human
Ciliated Airway Epithelia: Role of Ciliated Cells in Viral Spread in
the Conducting Airways of the Lungs
Virological assessment of hospitalized patients with COVID-2019


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Why would Aspergillus Oryzae produce lactase when no lactose is present?
Studies [1] have shown that lactase is produced by A. oryzae when grown on wheat bran and spent beer grains.

Why would A. oryzae produce lactase when these substrates have no lactose?
In [1], it's shown that A. oryzae produces more lactase when grown on wheat bran vs when grown on whey, which has lactose in it - what might explain that?
Since lactose is found in mammals and is not common elsewhere, how/why could A. oryzae have evolved the ability to produce lactase in the first place?

[1] Bailey, M. J., & Linko, M. (1990). Production of β-galactosidase by Aspergillus oryzae in submerged bioreactor cultivation. Journal of Biotechnology, 16(1-2), 57–66. doi:10.1016/0168-1656(90)90065-j

"Although beta-galactosidase is mainly produced for utilization in the hydrolysis of lactose in milk or whey, in natural systems this enzyme is also involved in the breakdown of galactan-based hemicelluloses. Wheat bran contains almost 30% hemicellulose, including considerable amounts of galactose residues (Salo and Kotilainen, 1970). Similar residues are presumably also present in spent grain (wheat). "

From the paper linked in the question.


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Basic Molecule Editor for use in journals / theses?
My background is Geosciences and Physics and I am going to study water and biomolecules in the Autumn.  I was reading a PhD thesis about peptides and peptoids by someone in my research group and I had a really basic question abouting the drawing program that they would have used to create molecular diagrams.  I found this link https://en.wikipedia.org/wiki/Molecule_editor and it looks like a good starting place but could someone recommend a default app for creating drawings like the ones below?

Thank you!

Might be better to ask on the Chemistry site.  Or the LaTeX site: I know there are some extensive LaTeX chemistry packages, though I've never used them.

With the exception of the protein, which may have been generated with Pymol or something similar, the illustration looks like an artist or designer job for a book or review.  Professionals would not be using diagrams in the style of the rest for presenting either chemistry or protein chemistry. If you search past questions on this list you will find some on protein graphics.

Thanks for the comments.  The references for the figures don't credit anyone so I assumed they had created them themselves.


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Can you help identify this bird in Louisville Kentucky?
This bird shows up in my back yard every night.  It is calling and sometimes I hear a bird in the distance calling back.  I think its an owl but I haven't seen it yet.  Any ideas what it is?

To me that sounds like the distinctive "who cooks for you" call of the Barred owl.
Compare with the recordings available from the Audubon Society, Cornell's All About Birds, and many others such as this YouTube video from a Cornell Lab Bird Cam of a Barred owl calling from its nest.

That it!  Thanks.  Now got to find a way to get a camera on this bird...

My Gravitar is from one we observed that was hunting around mid-day so this is definitely possible. Looking for owl pellets around largish trees in your neighborhood may help you identify where it roosts or nests.

@tyersome I agree that this is definitively a barred owl. Very distinct call. As my wife always says when I imitate the call: "you do!!" :p


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What vitamins exist for other animals but not humans?
As you probably know, humans are among the minority of animals that require Vitamin C and don't produce it ourselves. For whatever reason (multiple theories exist), we lost the ability. Meanwhile, the vast majority of animals out there that require Vitamin C simply produce it internally, so they have no need for food choices that contain it. Had it not been for the discovery of scurvy as Vitamin C deficiency, we likely wouldn't have ever known that Vitamin C exists at all as a requirement for human health.
Are there known to be cases in other animals of dependence on food containing vitamins that we humans produce ourselves?

what a cool question!

The best example I can think of is taurine, which is a non-proteinogenic amino acid.
Taurine is "conditionally essential" for humans1, but essential for cats2,3.
References:
1: Stapleton, P. P., Charles, R. P., Redmond, H. P., & Bouchier-Hayes, D. J. (1997). Taurine and human nutrition. Clinical nutrition, 16(3), 103-108.
2: Knopf, K., Sturman, J. A., Armstrong, M., & Hayes, K. C. (1978). Taurine: an essential nutrient for the cat. The Journal of nutrition, 108(5), 773-778.
3: Markwell, P. J., & Earle, K. E. (1995). Taurine: an essential nutrient for the cat. A brief review of the biochemistry of its requirement and the clinical consequences of deficiency. Nutrition research, 15(1), 53-58.

@user1136 — Yes and No. Depends on there being a formal accepted definition of vitamin that would exclude taurine. Can you supply one?

@user1136 —  No. There is an obvious difference between "essential amino acids", which are needed in stoichiometric amounts as components of proteins, and taurine, which although chemically an amino acid is not a constituent of proteins. I don't actually know what taurine is needed for in the body, and a quick glance at the summaries of the papers cited doesn't make this clear, but it does not appear to be an energy factor in nutrition. A key criterion would be the quantities needed in the diet. My impression is that the definition of vitamin is something of a post hoc fudge.

Could you flesh out your answer a little to address the points made by @user1136. I imagine you have a strong case, but it would be good to have it in the open.

Historically, the vitamin concept arose out of nutritional studies that demonstrated the dietary requirements of additional factors not supplied by a diet of protein, carbohydrate and fats. These substances are 'specific in function' and are required by the body in very small amounts, and were termed vitamins by Casimir Funk (see Hopkins' Nobel Lecture).
One substance that comes very close to being a vitamin for another organism but not for humans is biopterin, although I suspect that the term  'essential growth factor' is more appropriate than 'vitamin', given the current state of biochemical knowledge.
The organism is the protozoan Crithidia fasciculata, which requires the unconjugated pteridine biopterin as growth factor (Patterson et al).
Despite this requirement, and despite the fact that this metabolic need is the basis of an assay for unconjugated pteridines (Dewer and Kidder), no one knows the molecular basis (although there are some suggestions that is it required in pyrimidine biosynthesis) (see Kaufman)
Dewer and Kidder go further and state that "the only organisms at present known to have a dietary requirement for an unconjugated pteridine are members of the flagellate order Kinetoplastida (trypanosomids)" although personally I have never been able to confirm this except for Crithidia. Trypanosomes (the causative agent of sleeping sickness), for example, have never been shown, as far as I am aware, to require an unconjugated pteridine.
Humans, of course, do require an unconjugated pteridine (in the form of tetrahydrobiopterin, or BH4): it is the cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, trytophan hydroxylase, for an enzyme involved in the oxidation of glyceryl ethers, and for nitric oxide synthase (among other roles).
However, it is not a vitamin! We can synthesis it (from GTP, as it so happens). This aspect is discussed in detail by Kaufman, as is the essential role of BH4 in neurotransmitter biosynthesis.
None of the above enzymic systems are known to occur in Crithidia  (Kaufman). This organism, for example, cannot convert Phe to Tyr: the only enzymic system, or enzymic systems, capable of converting Phe to Tyr require an unconjugated pteridine (no cytochrome P450 system, for example, is capable of this transformation).
Both plants and E.coli are also of interest.
The evidence for any BH4-requireing enzyme in plants is scant. Plants can synthesise Phe and Tyr (they have the enzymes of the shikimate pathway) but they cannot convert Phe to Tyr. Phenylalanine hydroxylase, for example, has never been isolated from a plant source.
The same applies to E.coli.  This organism has no requirement for an unconjugated pteridine and cannot convert Phe to Tyr (see Miller and Simmonds and Kaufman).
But this is not the case for all bacteria. Those, such as Chromobacterium species (ref), that are capable of using Phe as a carbon source have phenylalanine hydroxylase, which requires BH4 (or a closely related pteridine) as cofactor.  In these cases, too, the pteridine (BH4?) is not a vitamin but is synthesized de novo from GTP.
Thus, to summarize.  The only organism known to require an unconjugated pteridine as a dietary growth factor is Crithidia fasciculata but no one knows why. You and I (as humans) require BH4 as cofactor for key hydroxylation reactions, including the conversion of Phe to Tyr, but it is not a vitamin: we synthesis it.  Plants and E.coli have no known requirement for biopterin (or any unconjugated pteridine) and cannot convert Phe to Tyr. Some bacteria, however, do require BH4 (or a closely related pteridine) as cofactor for hydroxylation reactions but these organisms also synthesis it.

Could you clarify? Is your answer “none”, or just “not pteridine”?

OK. That is interesting. I have no specialist knowledge in this area, only a wish to clarify and improve answers to help raise the standard of this site. I feel that we should give a fair consideration to the answer given by @tyresome. It may need expanding, but I don’t think it should be dismissed in a perfunctory manner.

This is exactly the type of thing I was looking for! How fascinating that a single species requires a "vitamin" (essential growth factor? tomato, potato) which is either synthesized or unnecessary in every other known organism. Good argument as well


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How can DNA replication result in hair pin structures?
My professor said that one of the reasons SSB proteins are so important was to prevent the formation of hair pin structures, I can't see how or why DNA would form hairpin structures and there's not much about it on the internet so can anybody explain this hair pin thing and how SSB proteins prevent it from happening ?

DNA Hairpins are formed when two regions in same single stranded DNA are complementary in nucleotide sequence but in the opposite directions (as represented in image below). These two sets of nucleotide sequences base-pair with each other by forming hydrogen bonds between adenine-thymine and guanine-cytosine respectively to form hairpin loop. Same structures can be seen in case of RNA.

(Figure via: https://brilliant.org/problems/dna-zipper/)
Single stranded binding (SSB) proteins bind to single DNA nucleotide sequences and prevent the breakdown of newly synthesized DNA because of nucleases and it also removes the secondary structure of the DNA  strands like hairpin loops so that other enzymes can bind to DNA strand and operate properly. As represented in figure below SSB bind to ssDNA through electrostatic interactions and prevent the bond formation within the nucleotides of single DNA strand, thus preventing formation of hairpin loops in DNA.

(Figure via: http://helicase.pbworks.com/w/page/17605582/Amanda-Kinney)
(via: https://proteopedia.org/wiki/index.php/Single_stranded_binding_protein)

If you have a stretch of single-stranded DNA that is palindromic, that palindromic region can form hydrogen bonds to itself, forming a hairpin. SSB proteins bound to and travelling along ssDNA physically get in the way of and undo hairpin folding.


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Peptide oxidation bias during sample preparation for LC-MS/MS
Problem description
In bottom-up proteomics, a commonly observed amino acid modification is the oxidation of methionine (Met-O). I wonder if the observed Met-O reflect natural protein oxidation or if they rather stem from oxidation during sample preparation.
Observations
During sample preparation, several factors could influence the Met-O:

Typical sample preparation protocols include reduction of the sample by either DTT or TCEP. This step serves to reduce disulfide bridges. I wonder if this step would also lead to reduction of oxidized methionines. Still, this reduction step seems to be used even in studies that analyse natural protein oxidation (e.g. Walker et al., PNAS, 2019, Methods)
Sample preparation takes several hours at least, typically the digestion is even prolongued over night. Several modifications typically happen during sample preparation or during the measurement, e.g. deamidations. I did not find studies about the extend of Met-O happening during sample preparation. Klont et al. report differences between Met-O in four different sample preparation methods, but it is not clear where the differences stem from. They could either happen during sample preparation or the four methods have different capacities of detecting natural oxidations.

My questions

Does the use of reducing agents modify oxidized methionines?
Do methionine oxidations occur during LC-MS/MS sample preparation and measurement? How strong is this effect?
Does anyone know a technique that discriminates native protein oxidations from those occuring during sample preparation? I found this publication, using 18O, but I cannot access it and thus cannot estimate if the protocol would be useful.

I know this was posted a long time ago and I'm not sure if you have found your answer but I am an author on two of the publications you  andcite can offer some insight.
1.) Methionine oxidation, unlike cysteine oxidation, is irreversible without the action of a dedicated enzyme or catalyst. Neither TCEP nor DTT is able to reduce methionine sulfoxide. The only reducing agent that I know of that is strong enough to reduce methionine sulfoxide is MMA.
2.) The in-vitro oxidation of methionines during sample preparation is a well documented issue in LC-MS/MS analysis and it is known that the majority of in-vitro oxidation occurs during peptide digest as well as during electrospray ionization. The strength of the effect is highly variable and dependent on how long you digest proteins. For a typical overnight digest we observe effects that range from 0%-400%, depending on the peptide.
3.) The use of 18O labelled blocking reagents is the only currently available method that can prevent the accumulation of in-vitro oxidation. I'm the first author on the publication you cite and would be happy to send you a copy if you email me (jbetting@ur.rochester.edu) I have also been working on improved methods using the same general strategy and would be happy to share those with you after publication

Hi John. Thanks for your reply. In the meantime, I found your paper on PMC. I will look into this.

could you please comment whether there was a study that directly showed that TCEP cannot reduce Met?