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A study has found that cell phones cause infertility, is this something to worry about or is the study flawed?
Is this a worrying study, or is it flawed?
A study has found that cell phones are detrimental to male sperm quality (Lower sperm motility and sperm concentration). It’s original goal was to determine if image content has a effect on sperm quality, but accidentally discovered that men who said they kept their phone in their pocket had worse sperm quality than those who didn’t have a phone in their pocket. As far as I can tell, from my limited knowledge, the study isn’t very flawed. What I do know is that they used 52 men, which doesn’t seem like a lot.
Another possible flaw is in regard to how they took sperm samples. Sperm parameters can vary amongst healthy individuals, the WHO recommends taking at least 2 samples to determine fertility. This study took one sample from all 52 men, then asked them if they wanted to participate the second time around and only 25 men agreed. So, they did take more than one sample but only for 25 men. I’m not sure, but this doesn’t seem like very good methodology as only 25 of the samples are representative.
Another issue is that the study had a variable that it changed from person to person. As stated, it’s original goal was to find out if image content affected sperm quality, and they concluded that it can. They gave different images to each mam, meaning that some of the images would have had a detrimental affect to the sperm quality. So, they could have gave a healthy cell phone user a type of image that causes poor sperm quality. However, it would be coincidental that cell phone use was still correlated with poor sperm, even if the study randomly gave out out different images to different people that could cause poor sperm in the analysis the ones with poor sperm.
I was wondering if certain lifestyle factors that tend to be associated with phone use where causing the infertility, not the phones themselves, but the study had a very extensive questionnaire and adjusted for many different factors from bathing habits to diet, so I don’t think that the study can be flawed in this are. What do you guys think? Is this something that we should be worried about and change our habits over, or is it scientifically limited and no cause for alarm until bigger and better studies conform their findings?

The effect was 49.3% plus-or-minus 8.3%. Not a worry. I couldn’t get the data on how many carried their phones in pocket.

In addition to the dubious quality of the study, why would one necessarily worry about infertility?  After all, quite a bit of effort has been devoted to the development of male contraceptives, so far unsuccessfully AFAIK.  If a simple and fairly inexpensive electronic device could do the job, and also let you make phone calls & check your email, we should be celebrating, not worrying :-)

@PolypipeWrangler what do you mean by ‘The effect was 49.3% plus-or-minus 8.3%’?

@jamesqf firstly, few men using contraceptives choose pernanent snd irreversible contraception; secondly, here they don't even make a choice - they might be rendered infertile without wishing it.

@Vadim: Does the study claim that the supposed infertility is irreversable, or just a temporary effect?  As for the choice, any and every action will have unforeseen consequences.

The study is basically worthless.
First, the study was not constructed to test this hypothesis, so it's just something interesting that may point to future studies. It does not provide sufficient evidence.
But the biggest problem is that the study was of 52 individuals with only one or two samples, which makes it statistically useless.
Any uncontrolled variable could account for all the difference detected. If one person had low sperm count because they wore tight underwear it would completely account for the difference.
This would barely qualify as an exploratory study, much less anything conclusive. This study would need to be reconstructed with a minimum of thousands of people, or control the participants' behavior (preferably both), to produce useful conclusions.
Any study with a really small N that deals with human behavior is basically worthless as far as any certainty goes.
The questionnaire is not any better — cellphone position is just binary: 1 belt and/or pocket, 2 anything else. Since most of the people are going to fall in the first category, there are very few degrees of freedom to work with. They just ran all the numbers hoping to get something. This is barn door statistics at its worst.

Thank you! The study did have a relatively good questionnaire which account for thing like diet, tight underwear, etc. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1617155/bin/rsbl20050324s01.pdf) But I take your point over the small sample size. Do you think that the fact that the study was done in 2004, a time when phone where very different to what they are today, makes it hard to apply their results to the modern day world?

the sample size makes the outcome useless any variation could be entirely do to outside events. the issue with questionnaires is people get answers wrong. "my underwear's not tight this is how you wear them" large number help wash out these errors. also check out the survey, the options for phone are 1 "in pocket or on belt" 2"everything else" which is bad construction. all those questions on the survey actually make it worse, with the tiny N it becomes impossible to check for confounding between variables. there literally is not enough degrees of freedom to account for all variables.

thank you so much! So you think that nothing should be concluded because of this study? Or, at least nobody should avoid using a phone because of it?

Yes nothing can be taken from this study, its not even worth giving consideration too.

Thank you so much! This has been really worrying me for a year now and I’ve been avoiding using a phone around people out of fear it would make them infertility. May I ask how you know so much about this area of science?

Its just basic statistics and experimental design. which is why I argue the basics should be taught in primary school. recognizing bad statistics in not too hard but it is not taught. I minored in statistics but you really don't need to know any the the math involved to stop such problems.

@John — Your post came up in the edit queue. I improved on the suggested edits by adding a link to what I infer you mean by "barn door statistics", but I'm letting you know in case I guessed wrong!

@tyersome that is it exactly.  thank you;.

You're welcome! An added bonus is this means I've leaned a new term today.


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How do viroids and virusoids cause infection to a specific host ? How could they indentify the host without protein?
We know, the capsule provides specific  pathogenecity for the virus right ? Then ,  how do viroids and virusoids cause infection to a specific host ? How could they indentify the host without protein ? Seems like they could infect any possible living being ? Please make it clear

Welcome to Biology.SE! Thank you for taking the [tour], but please also go through the [help] pages starting with [Ask] questions effectively on this site and [edit] your question accordingly. In particular, I suggest adding more information about viroids and virusoids (including references and links). It would be especially helpful if you were to discuss what you have learned about their host specificity. This will both help you get better answers and demonstrate that you have done the expect prior research. Also note that your first sentence is not relevant to enveloped viruses! Thanks!

Wikipedia says that virusoids have a protein coating, which presumably is involved in infectivity.

source: Stack Exchange

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Could two different pairs of humans generate the same child
What I mean is this. Take male A, female A, male B, female B. Is it possible for the pair of male A x female A generate a child that is genetically identical to a child from the possible children from the pair male B x female B? Assuming neither of the four are related in any way. In simple terms, take me, for example: could my genetic code be generated from a different mother and a different father that my mother and father? Would the answer change if one of the parents is the same (say, male A x female A versus male A x female B)?

What do you mean by 'genetically identical'?

Well, say, two people with the same genetic code. Like twins, for example. Except not from the same parents.

'Genetic code' isn't really a term that means anything. It sounds like I am being pedantic, but it terminology is very important for understanding. 'Genetic code' could mean either the same sequence of base pairs or the same sequence of codons. Which do you mean? And is there a specific reason why you are asking this question? Knowing this might help give a better answer, since sometimes the questions are based on a false understanding of the science.

Welcome to Biology.SE! Please take the [tour] and then go through the [help] pages starting with [Ask] questions effectively on this site and [edit] or delete your question accordingly. In particular, we expect you to do some research on your own and then, informed by what you have learned, ask any questions you still have (ideally with references to reliable sources). See also this sites criteria for "homework", which can apply to questions even if they are not assigned as homework. Thanks!

I have found that when learning about a new area starting with a relatively accessible and reliable source like Khan Academy is very helpful. Wikipedia is also generally a good starting point and you can then check their references. Online platforms called MOOCs offer free (or very low cost) courses on a wide variety of subjects — two I am familiar with are Coursera and edX. Finally, textbooks with a good level of detail are also freely available online e.g. from NCBI.

Forensic DNA analysis is essentially based on the fact that such coincidence cannot happen.
More precisely, the comparison between the DNA is done on multiple genetic locations, and the probabilities are evaluated that such a coincidence happen by chance. The standart use includes 13 locations, which is sufficient to confirm the identity beyond reasonable doubt:
Upon collection, the cells' DNA is extracted,
 and 13 genomic locations that vary among
 individuals are assessed to confirm suspects or exonerate those that are
 innocent.

This is to say that there is always a non-zero probability that the DNA of two different persons (even coming from the same pair of parents) are identical on all the 13 loci, but it is unreasonable to consider that such an event happens, given the human population size.

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Help with understanding XKCD's “How Vaccine Failure due to Viral Vector Immunity Works” Why is this response a failure exactly?
Full disclosure; no biology since 9th grade, so please go easy on me!
XKCD's 2406 shows a literal wooden Trojan Horse outside a castle, but instead of bringing it inside the castle walls, the soldiers recognize the shape as horse-like:

Look! It's a statue of that horrible animal that trampled Steve!

and the soldiers decide to destroy and dispose of it rather than to let it in.
The title of this XKCD is

Viral Vector Immunity

with the subtitle

How Vaccine Failure Due to Viral Vector Immunity Works

Wikipedia's Viral_vector; Vaccines explains the basic idea, which is (I think) that the viral vector's genome is modified so that it includes a new protein on its surface that serves as an antigen, and the host builds and learns an immune response to this antigen that will then immunize the host against an infection by another organism that also presents this antigen.
Question: The XKCD shows recognition and an analogy of an immune response, so why does the subtitle call this a "Vaccine Failure"?

XKCD image License

Yes, the cartoon is a description of immune action.
Traditionally shown is first exposure being a vaccine, and the second exposure being the bad virus being destroyed.
However, this cartoon is describing viral vector immunity.
The first exposure is a viral vaccine. This alerts and educates the immune system about not just the intended antigen, but also the (harmless) carrier virus which is represented by a horse.
The second exposure is a different viral vaccine.
The immune system immediately mounts a successful response against the vaccine because is recognises the carrier virus.
So the immune system doesn't get the chance to learn about the antigen associated with the second virus.
A example of viral vaccine failure would be useful - I will see if I can find one if no-one else does.

Viral vector only serves to deliver to cells the proteins/mRNAs necessary for triggering the immune response. In this sense it is like a Trojan horse - it is not supposed to cause suspicion, since otherwise it fails.
In this case the immune system recognizes the vector as a dangerous virus, destroing it before it delivers its load.
I find this xkcd rather convoluted...

This cartoon imagines that, rather than sacking Troy, the Greek soldiers inside were planning to help the Trojans recognize dangerous aliens who were preparing to attack. The horse represents the viral vector that carries the genetic material for producing the antigens that the immune system needs to learn to detect. The vaccine fails because the Trojans recognize the horse as an invader and destroy it, killing the soldiers who they didn't realize wanted to help them.


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Is there a term for the opposite of intergenic?
I am looking for a term that describes DNA regions that overlap genes, i.e., non-intergenic DNA regions.
For example, say I am writing a paper about DNA-binding sites (i.e., DNA sequences that proteins bind to), but my paper focuses exclusively on DNA-binding sites that happen to overlap genes. What would my title be? "Non-intergenic DNA-binding sites are [...]" is one option, but I wonder whether a more appropriate term exists.
If I understand correctly, "Gene-overlapping" seems to be used for referring to genes that overlap other genes (https://en.wikipedia.org/wiki/Overlapping_gene).
Also, Google says that "genic" means "relating to genes".
Is any of my ideas appropriate? Or maybe another term?

To clarify what I mean by intergenic and non-intergenic, here is the figure from https://en.wikipedia.org/wiki/Intergenic_region. I added an example for a non-intergenic DNA region.

Explicitly, an intergenic DNA region is a DNA region that doesn't share any base with any gene. A non-intergenic DNA region is a DNA region that shares at least one base with a gene.

What do you mean by "regions that overlap genes" and how is that different from genes themselves?

inter means between, intra means within, think inter-state highway.

@BagiM and John, I tried to clarify. Please point out if it still isn't clear.

Your "non-intergenic DNA region" overlaps the purple gene and possibly some of the red, too, so I don't understand what's non-intergenic about it.

@MattDMo If I understand correctly, "intergenic" means between genes, i.e., doesn't overlap genes. Thus, "non-intergenic" means not between genes, i.e., does overlap genes. If this is not accurate, please let me know

@MattDMo I apologize. I made a horrible mistake in the definition I gave at the end. I fixed it now.

I wouldn't use non-intergenic to refer to sequences that contain at least one base of a gene, because, at least according to your graphic, a large portion of it still could be intergenic material. Maybe just call them gene-overlapping regions? I'm really not sure.

@BagiM There are sequences/regions in a genome that are not genes, e.g.: https://en.wikipedia.org/wiki/DNA_binding_site, https://en.wikipedia.org/wiki/Enhancer_(genetics)

I understand the terms genic and intergenic to be dichotomous, so non-intergenic to me just means genic and I doubt you will find a term of art applicable to your scenario. Some kind of descriptive phrase may be more useful: ”DNA binding sites at the boundaries between genic and intergenic regions are…” or perhaps ”DNA binding sites at intergenic boundaries are…”

It seems to me that "genic" is a perfectly good word.
This paper uses "genic" directly as a contrast to "intergenic", so that seems like a reasonable precedent:

‘Noncoding DNA’ can be found both surrounding genes, and within genes (see schematic Figure 1). We will call the first type ‘intergenic’, and the second type ‘genic’, a ‘gene’ referring here to a transcribed DNA sequence.


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Standard notation for crossings (female, male)
Is there any standard for the notation of a crossing (hybrid) which tells me which part is the mother and which is the father?
Example
StrainA: egg cell
StrainB: sperm cell
Which notation is correct?
StrainA x StrainB or
StrainB x StrainA
or isn't there a rule for this?

For plants, seed (egg cell) parent is shown first and pollen (sperm) parent second.
The rule is mentioned in wikipedia,
http://en.wikipedia.org/wiki/Hybrid_(biology)
section : in plants.
Another mention of plant example:
https://www.rhododendron.org/v50n1p36.htm

Thanks. Do you have a scientific reference for this?


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What obstacle(s) would be most prevalent in an attempt to use virotherapy to inject Cas into cells to target a cancerous mutation?
Let's say a human cell mutates cancerously, we identify the mutated gene sequence and use CRISPR to mutate the patient's cells to include some variation of the cas genes and spacer sequences matching the mutated cancerous sequence.
Then design a virus to "infect" cells (cancerous and healthy) with this cas gene sequence and spacer sequences.
The infected cells would then produce a specific cas9-like protein targeting the mutated cancerous gene sequence in the patient. As the modified protein producing cells multiplied to replace the old ones, the custom cas9-like protein would detect and remove the targeted cancerous sequence.
More elaborately the approach could be used to inject a large library of known cancerous sequences as cas spacers in reproductive cells to start developing a species-wide defense against a significant range of cancerous mutations.
What primary obstacles would be in the way? I suspect research has been done on this.
My knowledge so far:

Basic understanding of virotherapy - I'd like to clarify my question is asking about something beyond research I've seen on anti-cancer oncolytic viruses which target cancer cells. My question is about repairing the cells rather than killing them.
A big picture of how CRISPR functions and how it can be modified to achieve specific gene editing functions. Spacer DNA sequences matching targeted gene sequences (usually threats such as bacteriophages) are used by the cas genes to produce proteins called cas9 (or some variation) which couple with crRNA and tracrRNA to match and slice targeted DNA sequences.
a closer look at the specifics of cas9 and its behavior.

Potential problems I considered but couldn't find specific studies on:

Whether the viral delivery of the modified dna would be prevented by the immune system before all the cancer cells could be "infected".

Whether human DNA's size (roughly 1000x the size of some bacteria DNA) might be too "large of a search space" for the cas9 or cas9-like proteins to "find" the targeted sequence.

Whether customization of cas9 into some more specialized / effective variant would overcome any obstacles to this approach.

I don't have time for a real answer with citations, but briefly - by the time a cell becomes cancerous, it has already suffered at least two major mutations, and in reality tumors have many more. Genome instability is a hallmark of cancer. So, your targeted CRISPR/cas9 may have some effect in, say, repairing a major tumor driver, just like an antibody therapy, eventually the tumor is going to mutate around it and keep growing through some other mechanism.


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What type of insect is it?
I've found this insect in my apartment and I don't know it could be bed bug or not. Could it be hazardous and what are the ways for getting rid of it?

@PolypipeWrangler Answers should be in answers, not in comments.

Approximately where in the world are you? if you can, a close up photo would be useful.


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gene mutation occurs on two strands of DNA or just one strand?
Suppose we have one strand with 3'-AAA-5' and the other strand is 5'-TTT-3'.
So when point mutation occurs, does it happen to two strands at the same time? e.g. 3'-AAA-5' becomes 3'-AGA-5' and 5'-TTT-3' becomes 5'-TCT-3'?
Or the mutation can occur with only one strand? e.g. only 3'-AAA-5' becomes 3'-AGA-5'? but in this case, A would pair up with G.
When transcription starts, the 3'-5' strand is transcribed, if the mutation does no occur in this strand, does it mean this mutation wouldn't affect any downstream products?
Is it same for indel?

A "mutation" is a permanent alteration of the genetic composition of an individual. To obey this definition, a base change in one strand must be accompanied by a corresponding change in the opposite strand. Only in this way a mutation can be transmitted to the offspring.
The situation where only one of the strands has undergone a base change constitutes a pre-mutational DNA damage, as the double strand will show a deformation at that site. The enzymes of DNA repair mechanisms recognize and correct many such "deformations", but sometimes they do not know which was the original base, and introduce a change that become fixed in the DNA sequence.


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Meaning of the word "targeted" in a description of chromatin immunoprecipitation
From a research paper:

The ChIP assay demonstrated that CIC physically binds to the promoter region of FOLR1, PCFT and RFC1.
Compared with IgG control antibody, CIC antibody enriched 4.1-fold more targeted FOLR1 promoter DNA, 13.8-fold more targeted PCFT promoter DNA and 4.2-fold more targeted RFC1 promoter DNA (figure 3B).

As far as I understand, the authors used chromatin immunoprecipitation to look whether and to what extent the CIC gene influences the promoters of folate-related genes (FOLR1, PCFT, and RFC1). And well enough, they discovered that the antibody to CIC precipitates more "promoter sequences" compared with the control antibody (IgG).
What does the word "targeted" mean here? If I remove this word, the meaning seems unaffected to me. In my Russian translation, I just omitted this word, because it does not seem to bear any additional meaning, but I'm not sure.
Can one simply omit "targeted" or does it have a meaning?

Looking at the article, I think they could leave out the word "targeted".
I think they used it because what is being enriched is not a promoter DNA, but the section of promoter DNA bound to the protein and antibody.
I suppose they could use  "...enriched 4.1-fold more FOLR1 Promoter DNA-CIC protein complex,..."
It is a little awkward or clumsy because the protein targets the DNA, and the antibody targets the protein.
So it is not always very obvious what the word "targeted" is referring to.
But without "targeted" I think the meaning is still clear enough.

I think you're right. By definition, any sequence amplified in ChIP is "targeted" by the antibody, because that's the assay. Seems strange they put it in there...


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Why do some enzymes have giant structures around the active site?
As a part of my inorganic chem. course (it's a required course at my college), we have a module called Introduction to Bioinorganic Chemistry. There, the prof. showed examples of enzymes like Cytochrome P450 and the drug erythromycin, and circled the active portions.
From what I can see, the active portions are a tiny portion of the actual drug/enzyme, so my question is: why do enzymes (and drugs, for that matter) have huge structures surrounding them?
I tried Googling my question but couldn't find anything relevant to what I was looking for. I suspect that I wasn't using the correct terminology, so the search engine had no idea what I wanted to know.
Simple explanations are preferred, preferably from the high-school level biochemistry side. I've never taken a biology course in school or college. I am a math major and this inorganic chemistry course is a required one. However, I still want to know why the amino acid chains are required, as they don't seem to be doing anything (that's what the active site is for.)
Picture for reference:


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Garden Hose Analogy for Blood Vessel Resistance
I've been trying to reconcile the resistance component of Poisseuille's law with a mental analogy of a garden hose; specifically, I had assumed that the effects of reducing the radius of a blood vessel (of an arteriole in vasoconstriction for instance) would be the same as when you put your thumb over the opening of a hose, causing water to leave at an increased velocity. However, the law instead predicts that a decrease in radius like this would increase resistance, actually decreasing flow by a proportional amount equal to r^4. Why doesn't arteriolar flow actually end up increasing because of the pressure from the arteries, much like its "hose equivalent"? Does the hose analogy even work in this scenario? What am I missing that separates the two scenarios?

It comes down to the distinction between velocity and flow rate.
While you are right that the water would leave a an increased velocity if you put your thumb over the end of the hose, this is deceptive, because the water is exiting the closed system, so it can go absolutely anywhere.  So the fact that the velocity is increased could give one the impression that the flow rate is increased, but in fact it is the inverse.
Imagine that instead of putting your thumb on the end of the hose, you pinched the hose in the middle instead. This would result in the water flowing out of the end of the hose at a reduced flow rate (lower volume of water coming out per minute) and velocity (lower speed of the individual water particles).  Why?
It might help to take a snapshot of the place where you are pinching the hose.  the pressure behind the pinch zone goes up, causing the water to pass through the pinch zone at a faster velocity. However, because the hole is smaller, less water is able to pass through.  When it reaches the other side of the pinch zone, it slows down again because it has a very low pressure, and the smaller volume of water must fill the entire tube. However, because the flow rate was lowered because of the pinch zone, the amount of water at the end of the pinch zone is lower.  Consequently, the water flows slower and the flow rate is reduced simultaneously.
Another analogy that might help would be the comparison between a garden hose and a fire hose.  Let's say they have the same flow rate (same volume coming out of the hose per unit time).  You can immediately realise that for the garden hose to put out the same amount of water that the fire hose is putting out in a minute, the water would have to be flowing many times faster in terms of velocity.

Furthur reading

Grunwald JE, Petrig BL Riva CE, Sinclair SH. Blood velocity and volumetric flow rate in human retinal vessels. Invest. Ophthalmol. Vis. Sci. 1985;26(8):1124-1132. Available online: https://iovs.arvojournals.org/article.aspx?articleid=2159754
Baker M, Wayland H. On-line volume flow rate and velocity profile measurement for blood in microvessels. Microvasc. Res. 1974;7(1):131-143. Available online: https://doi.org/10.1016/0026-2862(74)90043-0

At a constant volumetric flow-rate, the product of velocity and vesicle cross-section area is constant.
In a real-life scenario, the volumetric flow-rate decreases when you hold your finger over the opening. So while water exits 'faster', at higher velocity, you would fill less bottles of water per minute.


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Does N1-methyl-pseudouridine occur naturally in any RNA?
Pseudouridine occurs naturally in some RNAs. But what about the methylated variant of it, N1-methyl-pseudouridine? The latter is a key ingredient in both the Pfizer and Moderna Covid-19 vaccines, probably due to its relative "potency" in evading immunogenicity to exogenous mRNA itself and its ability to apparently put ribosomes in a sort of "overdrive". (It's use in mRNA therapeutics has been patented by Moderna in 2012 or so.)
Does N1-methyl-pseudouridine occur naturally, in particular, does it occur in RNA?

N1-methyl-pseudouridine occurs naturally in the tRNAs of most archaea. It replaces the ribothymidine found in the TΨC-loop of eubacterial and eukaryotic tRNAs.

Although the enzyme responsible for the conversion of uridine to pseudouridine has been known for some time, it is only relatively recently (2012) that the gene for the methylation of the pseudouridine was reported in a paper, the introduction to which provides a useful background to the topic.
Original References
Pang, H. et al. (1962) J.Biol.Chem. 257 3589-3593
Gupta, R. (1964) J.Biol.Chem. 259 9461-9471

These articles claim it occurs naturally:
Pederson, A layperson encounter, on the “modified” RNA world:

Ironically as to my friend’s concern, N1-methylpseudouridine also occurs naturally (11), a final element in my “case” to him.

N1-Methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells:

Lastly, as a naturally existing modified base in both prokaryotic (37) and eukaryotic cells (38), our findings imply that m1Ψ might play unique roles in cells.

Both are referencing this paper:

R. C. Brand, J. Klootwijk, R. J. Planta, B. E. H. Maden, Biosynthesis of a hypermodified nucleotide in Saccharomyces carlsbergensis 17S and HeLa-cell 18S ribosomal ribonucleic acid. Biochem. J. 169, 71–77 (1978).

which finds 1-methylpseudouridine in the ribosomal RNA of yeast and human-descended HeLa cells.  (However, if I understand correctly, this is only a precursor molecule that exists temporarily and is then modified further?)
This one is a little more detailed:
Morais The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines

One N1-modified Ψ-derivative is N1-methyl-Ψ, a naturally occurring modification found in 18S rRNA (Brand et al., 1978) and tRNA in many organisms (Boccaletto et al., 2018). This N1-methylation is catalyzed by N1-specific Ψ methyltransferase Nep1 found in archaea and eukaryotes (Wurm et al., 2010) (Figure 1). Potentially N1-methyl-Ψ could be more widespread than reported in human RNA, given that the current standard Ψ-detection (-seq) methods, which rely on the use of CMC-modification followed by primer extension (Morais et al., 2021), may not be able to distinguish N1-methyl-Ψ from Ψ (Svitkin et al., 2017). Possibly, therefore, some Ψs thus identified so far (Schwartz et al., 2014) could actually be N1-methylated Ψs.

The Boccaletto reference is presumably this database entry:
which says

Found in phylogeny    Archaea, Eukaryota
Found naturally in RNA types  rRNA, tRNA

and Naturally occurring modified ribonucleosides shows Euler diagrams of m1Ψ occurring in

Archaea tRNA
Eukarya rRNA
but not in mRNA or ncRNA


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Why is the 3'UTR AES of the Pfizer/BioNTech vaccine preceded by a CUC GAG?
According to the WHO submission and one of the preprints from BioNTech/Pfizer, the 3'UTR of their Covid-19 vaccine's mRNA is the combo of the AES and mtRNR1 sequences, which (in the preprint) BioNTech cites to a paper on library screening of 3'UTRs that achieve high mRNA stability etc.
But as far as as I can tell, BioNTech added a "CUC GAG" between the (doubled) stop codon and the beginning of the AES as it's given in Supplementary Table 3 of the library paper cited, i.e. the actual AES starts with CUG GUA CUG, or more precisely using the global Ψ substitution as given in the WHO submission, the sequence starting with the stop codon(s) is:

ΨGA ΨGA CΨC GAG CΨG GΨA CΨG CAΨ GCA

So, what's the point of the bolded "glue" CUC GAG?

There is also this part at the end ACCCTGGAGCTAGCAAAAAAAAA...

@reuns: FWTW, they did not add any glue in between the AES and mtRNR1 sequences (which form the "double UTR" as they call it)  GACACCΨCC CAAGCACGC.

The final part of mtRNR1 has something appended though compared to the library paper (it ends with AGCCACACC in supp. table 3), but in the WHO doc it has AGC CAC ACC CΨG GAG CΨA GCA AAAAA

Looking at the library paper more closely they, speak of a "motive core area" and "flanking areas" so these might be the latter, and were perhaps not interesting enough to publish at the time.

I think your linked article explains perfectly how they came with the 3'UTR. I am not too worried that there is a 15+6 nucleotide difference with the vaccine as they didn't show exactly how they are mixing two 3'UTR. If you really really want to know you can try asking directly to Kariko on twitter.


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Questions on mid-2019 Covid-19 Spread in Spain
I recently read in the news from Reuters that Covid-19 was already present in the Europe in March 2019 as reported by the study by Chavarria-Miró et al (2020). According to  Chavarria-Miró et al they found traces of SARS-CoV-2 in March 12, 2019 sewage samples from Barcelona.
I am interested in this news because I do research on effects of covid-19 pandemic and government responses to covid-19 on macreconomic indicators. In macroeconomcis we are unable to run randomized control trials but sometimes nature can create natural experiments or situations that allow for use of quasi-experimental statistical techniques, and I think I can use the situation above in such way.
Consequently, I have the following questions:

How conclusive is that  Chavarria-Miró et al study? Are there any red flags that would indicate the conclusion drawn from the study should not be taken at face value? Essentially, I am interested in knowing if the study is reliable or if there are possibly other corroborating studies.

Is the SARS-CoV-2 found in march 12 the same SARS-CoV-2 that was circulating in 2020? Or we can't tell? Or to what degree it is similar if it is possible to know (in terms of infectiveness and mortality/morbidity)? If it is not possible to answer this empirically, is it at least possible to answer it theoretically based on how similar viruses mutate? (Here I would also appreciate some references to literature/data if possible).

The reason why I ask this second question is that given how dangerous and infectious is Covid-19 considered, I am surprised that there weren't spikes in deaths in Spain. In fact, according to statistics provided by Statista the number of deaths in 2019 was highest in January and even declined after March. When the number of death is totaled across whole year 2019, and compared to years prior years in data from Statista here, again the number of deaths was comparable to 2018. I realize that just looking at a crude naïve statistics like this is not rigorous but I would expect at least some visible effect if Covid-19 was already spreading in March 2019.

Do you maybe have your years mixed up? 2019 vs 2020? It's 2021 now, last year was 2020.

@BryanKrause no actually no, as the Reuters reports "Spanish virologists have found traces of the novel coronavirus in a sample of Barcelona waste water collected in March 2019". Although I was surprised as well and thought it was mistake initially but apparently it is so

Ah; that's definitely a false-positive then. This is probably a better question for Skeptics.SE, there isn't much if any actual biology in your question.

@BryanKrause but the paper is from actual biologists - and I am interested in reliability of the paper. As far as I understand skeptics site is more for credibility of general claims not research papers. Also why about my second question? Isn’t that biology question?

@BryanKrause just to clarify because maybe this was not clear - I learned about the information in Reuters but then I actually went and searched up the study on Google scholar and the chavarria-miro et al study also states it was March 12, 19. I mean of course it could be false positive but is there anything in the study that would indicate that their method is not rigorous (in the study they mention multiple samples in March 12) and I am not familiar with what’s the proper procedure but I would assume the such tests are on samples multiple times to reduce chance it’s false positives

Especially before publishing research. But that publication might of course also be of low quality- it is hard for me to judge without formal training in biology. I don’t think it belongs to skeptics since their site is according to their help center for “for challenging unreferenced notable claims” and this claim has whole study behind it - it is just difficult for me to judge the results of the study.

It's a preprint, not a publication. Regardless of the publication quality, it makes zero sense. We have seen what happens clinically with COVID-19: respiratory distress in a sizeable fraction of infections, a pandemic lasting several months. It isn't feasible that the virus was somehow present in one place in Spain and yet resulted in no broader spread and no clinical notice.

@BryanKrause sorry you are correct about it but still most scientists don’t put up preprints if they are not confident in their paper (at least in my field that is usually the last step to gather some extra comments before sending it out to journals - not sure if biology works differently in this regard)

@BryanKrause well if it is impossible or very improbable given the general consensus of epidemiologists that actually answers my question as well, so if you would consider expanding that into an answer that would support that with some references I would be willing to accept it after letting the question to sit for while to potentially collect more answers. The paper itself tries to claim that early 2019 cases were probably misdiagnosed as influenza - maybe that is just handwaving claim - this is why I came here to see what experts have to say about such claims

This seems unlikely given most phylogenetic studies estimate the emergence of SARS-CoV-2 in China somewhere between October and November 2019, e.g. this study.

@user438383 fair enough but then there are also reports of covid spreading in Italy in September 2019 in a study that was looking at covid antibodies which is still month before October  see here - this one is not even preprint but published in journal, I mean  perhaps its another false positive and publication bias, could you maybe consider expanding your comment into an answer providing more complete explanation?

@1muflon1 Consider that it is much more likely that a PCR artefact (like Chris described in his answer) can give a one-off false positive results, such as the Italian or Spanish study, than 1000s of SARS-CoV-2 genomes all happen to coalesce to the wrong date, which also happens to be just before the first recorded case occured. The two studies aren't an equal weight of evidence.

Related q on Skeptics: https://skeptics.stackexchange.com/questions/47583/did-europe-have-a-covid-19-case-in-december-2019 Note that someone tried to give that Bacelona study as answer but it ended up negatively scored... On the other hand (and this is why I'm linking) you can see there what water analysis looks like in other less controversial instances (Italy, later in 2019); there's a continuous series of positive results... By the way, China could have published such studies too, but they seem very skittish to do so...

To judge about this assay, it is important to see how they worked. They used different sets of primers to analyze for SARS-CoV-2. Namely targets IP2 und IP4 from Institute Pasteur in Paris (see reference 1) and to validate results also primers targeting the "E" sequence (reference 2) and two against the nucleoproteins N1 and N2 (reference 3).
Then they tested frozen samples taken between January 2018 and December 19. Of those, only the sample from March 2019 come back positive for 2 out of 5 primer pairs, none of the samples before and after tested positive, despite mentioning that samples where already positive as early as January 2020 again.
If you look at the published amplification curve you see a very late Ct value for the sample (I would eyeball it somewhere between 39 and 40), which is basically in the area of non-specific amplification. Running the PCR another 10 cycles until 50 is highly unusual in my experience.

Conclusion: I see this result as a PCR artefact and I doubt, this will be published (at least I hope it will not). The reasons for it are:

only two of five sets of primers is positive. Since these are highly specific, I would expect all five of them positive.
the Ct value is very high, around the usual endpoint of qPCR. If you let PCR run long enough, it will eventually amplify something. The also show no melting curve to prove the have a good PCR product.
it is highly unlikely that the virus appears in March 2018 in the wastewater of Barcelona and then disappears again without leaving any trace. This is clearly not the experience we have been making throughout 2020.

References:

Protocol:Real-time RT-PCRassays forthe detection
ofSARS-CoV-2InstitutPasteur, Paris
Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR
CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic
Panel

Unfortunately the study has already been cited rather uncritically in the news section of Nature https://www.nature.com/articles/d41586-020-03165-9


text:
Are humans more adapted to "light mode" or "dark mode"?
I was discussing with a colleague about using dark-mode vs. light mode and remembered an article arguing that humans vision is more adapted to light-mode rather than dark-mode:

I know that the trend “du jour” is to have a dark mode for pretty much
everything, but look around the world is not dark with a bit of light,
it’s actually the contrary. And as the human has evolved its vision to
adapt to this reality, it’s asking extra efforts on many people.

Unfortunately, no reference is provided to support this claim, so I am wondering if this is just an opinion or there are some studies to support this.
Wikipedia seems to confirm this somewhat since we are adapting much faster to "light mode" transition than to dark mode one:

This adaptation period is different between rod and cone cells and
results from the regeneration of photopigments to increase retinal
sensitivity. Light adaptation, in contrast, works very quickly, within
seconds.

Also, some studies confirm that working using light mode is on average more efficient than using dark mode:

light mode won across all dimensions: irrespective of age, the
positive contrast polarity was better for both visual-acuity tasks and
for proofreading tasks.

I am looking for arguments coming from evolutionary biology to confirm (or not) the assumption that human evolution favors light mode.

Meh, this evo thing is probably the wrong angle here. If you're looking at something dark in an otherwise fairly bright (room) environment, it is actually tiresome.

As an aside, you're less sensitive to flicker in a dark environment. https://www.sciencedirect.com/science/article/pii/B9780123742032002359 (see full text) So if that bothers or tires you (which is plausible with screens), then dark mode in a dark environment does help in that regard.

@Fizz: Yes, the world does not have a raster scan running through it :-(  Not so bad with LCD/LED displays as it was with CRTs (which would give me splitting headaches if I worked for a prolonged period in "light mode".  But the evolutionary biology arguments are beside the point: it is observed fact that many people do prefer dark mode.

Challenge: "Adapted to" is insufficiently specified. Visual resolution will be higher with a brighter display due to pupil constriction, but night vision will be impaired.

The "some studies" are wrong. Astronomical citings routinely have greater precision than the lens rules calculated in bright environments say they should have. Optical resolution simply is better with withe on black.

dark mode looks better to me at night, and light mode during the day, so...

Even if the article’s conjectures were to hold, they would do so for quite other reasons than that “the world is not dark with a bit of light”. Yes; and the world is also experienced predominantly as indirect reflected light rather than direct projected light. Conditions rightly described as “optimal” in one environment (the great outdoors) may legitimatey differ in another (my home study). Even if my study is objectively sub-optimal, it may be beyond my means/power to make it so; thus, in the dark vs. light debate, one does not take all — providing both is important for accessibilty.

Most of us programmers who practically spend our life behind monitors, we prefer dark mode right from the start. It's better for the eyes, it doesn't take a lot of research, a white background is simply annoying. You can't focus, you turn on every light source in the room to help your eyes but still, white screen is disturbing and your eyes get tired a lot sooner. Dark mode is there for a reason. We've been using it since the age of Unix and MS-DOS, it's nothing new, it's only reinvented, as in, finally everyone else realized it too. It was a long lasting fight to convince people that no matte

"we are adapting much faster to "light mode" transition than to dark mode one" Of course: It's better to not see anything for 10 seconds than to have pain in the eyes for 10 seconds.

We should not forget that not all humas are equal. People from the autism spectrum (about 1% of all humans) tend to have a sensory processing disorder which can mean that bright light appears unpleasant. So even if light mode would be the better choice for most, it is not necessarily the best choice for all.

Found myself revisiting this in the wake of 2 developments: 1. I learned those w/ astigmatism can find dark-modes unusable due to the ‘starburst effect’, which light-modes don’t provoke as much due to diffs in pupil dilation. 2. My own eyes now hate light-colored backgrounds (especially on IPS displays). Bloodshot within minutes. No idea why; it’s never been an issue before! Since I’m now experiencing physical discomfort w/ lighter colors, I’m using dark-modes for respite… I stand by my earlier claim: it’s an accessibility issue, not mere style preference. One size does not fit all.

A question that requires quite a lot of guts to ask on this site :) Nonetheless, and risking sparking a debate, there are a few arguments that spring to (my!) mind that can support the notion that we thrive better in 'day mode' (i.e., photopic conditions).

To start with a controversial assumption, humans are diurnal animals, meaning we are probably, but arguably, best adapted to photopic (a lot of light) conditions.
A safer and less philosophical way to approach your question is by looking at the physiology and anatomy of the photosensitive organ of humans, i.e., the retina. The photosensitive cells in the retina are the rods and cones. Photopic conditions favor cone receptors that mediate the perception of color. Scotopic (little light) conditions favor rod activity, which are much more sensitive to photons, but operate on a gray scale only. The highest density of photoreceptors is found in the macular region, which is stacked with cones and confers high-acuity color vision. The periphery of the retina contains mostly rods, which mediate low-visual acuity only. Since highest densities of photoreceptors are situated at the most important spot located at approximately 0 degrees, i.e., our point of focus, and since these are mainly cones, we apparently are best adapted to photopic conditions Kolb, 2012).
An evolutionary approach would be to start with the fact that (most) humans are trichromats (barred folks with some sort of color blindness), meaning we synthesize our color palette using 3 cone receptors sensitive to red (long wavelength), green (intermediate) and blue (short). Humans are thought to have evolved from apes. Those apes are thought to have been dichromats, which have only a long/intermediate cone and a blue cone.  It has been put forward that the splitting of the short/intermediate cone in our ape ancestors to a separate red/green cone was favorable because we could better distinguish ripe from unripe fruits. Since cones operate in the light, we apparently were selected for cone activity and thus photopic conditions (Bompas et al, 2013).

Literature
- Bompas et al., Iperception (2013); 4(2): 84–94
- Kolb, Webvision - The Organization of the Retina and Visual System (2012), Moran Eye Center
Further reading
- Why does a light object appear lighter in your peripheral vision when it's dark?

The di/trichromat approach really isn't all that relevant to computer displays, unless you're really into syntax colorization.  (Something I detest, but tastes differ.)  What matters is contrast between light and dark, and you could probably have readable displays at intensity levels where only the rods are activated.  The example I like to use is stars on a dark sky. Tt's easy to see individual stars, or lighted pixels, on a black background, not so easy to pick out a few dark pixels on a white display.

This answer gives some interesting thought directions, but they don't really have anything to do with dark mode vs light mode. Dark mode isn't dark in the sense that the range of brightness is lower, but in that the bright features are smaller. In practice, it is perfectly possible to use dark mode in photopic vision. Vice versa it is even possible to use light mode in scotopic vision, though that requires turning the total luminosity way down (which I'm pretty sure is worse for the eyes than scotopic dark mode).

@jamesqf, I agree, but the fact we can operate well in the dark  doesn't take away the fact we do better in daylight overall. In the end, evolution will not have favored spotting stars in the sky, or pixels on a dark screen. I chose to approach the question from a scientifically more likely angle.

@leftaroundabout I personally want my screen to be generally similar to ambient brightness, easier to ignore surroundings (= light mode during day and dark mode during night with lights off). From this answer we should preferably be in a well-lit environment. Then the question becomes - should the features be even brighter, or darker? Tech to make them darker is trivial (just not turn those pixels on) while not many screens let you make them even brighter - though it would be interesting to see what is better in that case.

@jamesqf the brightest stars are seen with cones. This is easy to understand if you remember that you can see e.g. Sirius looking at it directly, with your fovea. OTOH, it takes significantly more effort to view very dim stars (that can stimulate only rods): one needs to use the averted vision technique, which not only gives smaller resolution, but also is a bit uncomfortable: one has to train to avoid the temptation to look at the object directly, since in that case it will become invisible.

@AliceD I'm sure spotting night predators in the dark would have been quite important to early apes and humans. Cats and wolves are very easy to spot for humans in the dark. It's also handy for things like finding water, and in general, specular reflections are a typical example of light-on-dark objects of interest. And of course, there's considerable variation in what different people find comfortable or efficient; I feel people overly focus on finding the "one best thing". If dark-on-light works for you, great; if it doesn't, also great. It's not as if there isn't choice.

@AliceD: As usual, the problem with saying "we do better" is that we differ.  The demonstrated fact that a significant fraction of computer users prefer dark mode demonstrates that, I think.  And I would bet that a good many of those who say they prefer light mode have never given dark mode a real chance :-)

@jamesqf I personally highly prefer dark mode as it is more relaxing to the eyes and mind. But the visual system hasn't evolved for 10-hours-per-day-screenwork. I guess that's the point of my post. I've never attempted to defend 'use light mode when behind the screen'. I've just attempted to write an answer that highlights the evolutionary backgrounds of the visual system, without stepping into an opinion that cannot be backed up by literature.

Humans are thought to have evolved from apes... replace this with Humans share a common ancestor with apes, and.... Our evolutionary history is more fleshed out than just a "thought"

@jamesqf I don't think it's clear-cut. I've always found that light-on-dark themes cause me more eyestrain when dealing with text.

@ssokolow: As I said, people differ, and one size, or one color scheme, obviously doesn't fit everyone.

@Isaac and more recently, "Apes" is used as a monophyletic group, including humans and other hominids. So Humans are apes.

Scotopic periphery vs. photopic fovea seems like it may correspond to my preference for "dark lite" themes, where only the UI elements are dark, while content areas remain light.

From experiments it seems you should better use dark mode if you want to prevent myopia:

Using optical coherence tomography (OCT) in young human subjects, we
found that the choroid, the heavily perfused layer behind the retina
in the eye, becomes about 16 µm thinner in only one hour when subjects
read black text on white background but about 10 µm thicker when they
read white text from black background. ... Therefore, reading white
text from a black screen or tablet may be a way to inhibit myopia,
while conventional black text on white background may stimulate
myopia.

https://www.nature.com/articles/s41598-018-28904-x

So although humans are commonly awake during the day and sleep at night it seems that this fact is actually irrelevant when it comes to the effects of dark/light mode for the health of your eyes.

This makes sense. I've been using white text on dark backgroun since the early nineties - not because it was something the cool kids did (none of them did it back then :) ) but because when most pixels on your screen are at RGB 255,255,255 - i.e. full intensity white - it's like staring into a floodlight all day - something I didn't think was a healthy option. A few people asked why my screen looks weird and I explained my eyes never get tired this way and some switched to dark backgrounds on their PCs and were amazed at the difference to their eye fatigue.

Both.
More specifically, we're a kitbashed light-mode version of a primarily dark-mode group of animals. Mammals famously have terrible color vision, most mammals are dichromats (red color-blind) whereas most other animals like fishes, amphibians, reptiles, and birds are trichromats or even tetrachromats (seeing into the ultraviolet spectrum). In their evolution mammals got rid of a lot of their cones and replaced them with rods, giving them much better dark vision at the expense of not being able to see good colors. But this was back in the Mesozoic, when most mammals were nocturnal, crespuscular, or burrowing, and color vision wasn't a huge deal.
Primates then re-evolved color vision by duplicating and repurposing a cone for green some time in the Eocene. It is thought that they did this because it helps in identifying ripe fruits, which are often some shade of red, orange, or yellow, from green unripe fruit. We also lost our tapetum lucidum, which is the reflective layer of the eye that you see when shining a light in most animal's eyes that greatly enhances night-time vision. No one knows why, it may be genetic drift. Unfortunately our color vision isn't great, so we're kind of stuck in this awkward intermediate between other mammals, which can see great in the dark but have no color vision, and birds and reptiles, which have amazing color vision but are borderline blind in the dark (owls being the obvious exception).


text:
Why do animals yawn? What is the biology behind it?
We yawn whenever we are tired and body needs rest. Why does the mouth open wide and a large volume of oxygen is inhaled?

Does this answer your question? Why do we yawn?

To some extent. Thank you for the link.


text:
What does "culture" mean here?

India becomes first country to culture U.K. variant strain.

Source
What does "culture" mean here?

Are you asking about the exact culture conditions? (The general meaning of "culture" was given in the source: "Culture is the process by which cells are grown under controlled conditions, generally outside their natural environment.")

Since viruses cannot reproduce outside of a cellular environment, they are cultured by infecting a living culture of host cells. In this case, it means human cells are cultured in a sterile dish and infected with a specimen of SARS-COV-2 virus, most likely collected from a patient during the early stages of infection. After infection of the cultured cells is confirmed, the new virus particles are collected from the culture media and put into storage.

Why does this need citations? This is just knowledge picked up from working in a virology/cell biology lab.


text:
Cystic Fibrosis Genetic Risk Determination
Let's say Jane has Cystic Fibrosis and we know her brother doesn't. What are the chances of her brother's future child having CF? (The chances of Cystic Fibrosis in the general population can be taken as 1 in 25)
My apologies for the very incomplete question, this was all I could remember of the actual question.
And the solution went like something along the lines of:
Possibility of Jane's brother's partner having CF: 1 in 25
Possibility of Jane's brother being a carrier: 2 in 3
And this is the part that I am not getting. For me, Jane's brother could only have a 1 in 2 chance of being a carrier (Cc or CC). But the solution went CC, Cc or cC-- this last one, cC, how is that possible? If it's a recessive trait, do we not write the dominant one first? Then how could there be cC and Cc as two separate possibilities?

Welcome to Biology.SE! Please take the [tour] and then go through the [help] pages starting with [Ask] questions effectively on this site. In general, we expect you to do some research on your own and then, informed by what you have learned, ask any questions you still have (ideally with references to reliable sources). In particular, this "addresses a basic biology concept that may seem trivial to biology professionals" and thus fits this sites criteria for "homework". (Note this can apply to questions not assigned as homework.) Thanks!

I have found that when learning about a new area starting with a relatively accessible and reliable source like Khan Academy is very helpful. Wikipedia is also generally a good starting point and you can then check their references. Online platforms called MOOCs offer free (or very low cost) courses on a wide variety of subjects — two I am familiar with are Coursera and edX. Finally, textbooks with a good level of detail are also freely available online e.g. from NCBI.

And this is the part that I am not getting. For me, Jane's brother
could only have a 1 in 2 chance of being a carrier (Cc or CC).

Wrong, because those are not equally likely.
There are 4 equally likely possibilities for any of Jane's siblings:
inherit good allele from Mom, good from Dad,
inherit bad allele from Mom, good from Dad,
inherit good allele from Mom, bad from Dad,
inherit bad allele from Mom, bad from Dad.
We know that the last is not the case for the brother.  The first 3 are still equally likely.  And in 2/3, brother is a carrier.

Let me elaborate on swbarnes2’s answer.
The “Possibility of Jane's brother being a carrier” is indeed the trickiest part of the overall question. I have seen that even some teachers of genetics were puzzled when seeing the correct answer (2/3).
It is true that before the brother is born the probability of he being Cc is given by the standard Mendelian rule, which states, for a Cc x Cc mating, ¼ of the offspring will be CC, ¼ cc, and ½ Cc.
But that answer ignores the fact that the brother is already born and (presumably) has an age by which all cc homozygotes have been recognized. Then, we know that he is not cc and can only be CC or Cc, whose probabilities sum up to ¾. It follows that he is Cc with probability ½ / ¾ = 2/3.
This kind of problems are generally tackled by using the Bayes theorem, which is a way to transform a prior probability into a posterior probability. In this case, we know that the prior probability, Pr(Cc), of the brother being a carrier is 50%, and want to calculate the posterior probability, Pr(Cc | not-cc), which is the probability that he is a carrier given that he is not affected. The Bayesian rule has the general form
Pr(A|B) = Pr (B|A) x Pr(A)/P(B),
which in our case reads
Pr(Cc|not-cc) = Pr(not-cc|Cc) x Pr(Cc)/Pr(not-cc).
As the first factor in this equation equals 1 (it is certain that a subject is not cc if he is Cc), it easy to see that the solution corresponds to the above, perhaps more intuitive, calculation. In more complex situations (consider for example if Jane's brother is young, and a certain proportion of cc subjects are diagnosed only late in life) the Bayes rule is useful, as it help decomposing the problem.


text:
DNA extraction from parasitic worm
I have a part of a parasitic worm frozen at -20°C. Do you think that DNA extraction using DNeasy kit without any pre-treatment is sufficient for DNA extraction?
Or would you recommend bead beating / nitrogen?
I do not need high quality DNA. It is just for the identification via shotgun metagenomics (shotgun metagenomics because 1) the parasite identification failed so far via PCR/immunostaining and 2) there is some human traces as well).
I refer to " DNeasy Blood & Tissue". It comes with protocols for eucaryotic tissue. The sample is extracted from ejaculate. I also do not need a whole lot of DNA, about 100ng should be enough.


text:
What is the mechanism through which fractals arise in plants and animals?
Many biological organisms -- such as trees, broccoli, and the blood vessels in animals -- can be approximately described using fractals.
What is the reason behind such fractals? Specifically, do we know of the way certain cells split that lead to fractals? Do we know if there are specific genes that tend to generate fractals?

because fractals are emergent structures created by simple rules, as are many biological structures. The same kind of simple recursive signals that lead to fractals are simple enough to be stumbled on by biological evolution and are effective ways to deal with the scaling problems created by the square cube law.
https://www.complexityexplorer.org/system/explore/model_series/pdf_files/000/000/008/original/Biological_Scaling_Series_.pdf?1554498961
https://www.jstor.org/stable/2898653?seq=1

Essentially, eukariote cells use internal and external signalling hormones, so the cells can have a front/back/top/bottom end and can orient themselves at specific angles using signalling hormones, which also travel outwards through chains of cells and form signalling hormone concentration gradients. Eventually, when the gradient reaches a certain level, it can cause a distant cells to divide in two resart the gradient, so that very precise distances can grow using very precise angles.
The research on genetics related to the dendritic morphogenisis in trees, neurons, lungs, ferns and other forms in nature, doesn't give a clear summary of the process that you thought it can.
There was a patent of a technology called "Fractogene" quoted by some serious research, and doesn't involve coherent propositions and sentences! if you can figure out what FractoGene was, please comment!
You'll find talk about P-cells, Cytoskeletons, Drosphila, Danio, meristems, concluding:
We expect that a new generation of data mining tools will be required to support recursive fractal geometrical, combinatorial, and neural network models of the genomic basis of morphogenesis.
A fractal can be written in 3 instructions (copy, advance, divide) so the cells only have to have 3 behaviours to create a fractal, it's very simple. Even H2O and NaCl can form dendrites similar to plant roots, so fractal genes have an fairly simple basis.
Dendritic gold:

dendritic copper:

dendritic manganese oxides on limestone:

Even pure water forms branches similar to trees. Something so simple to generate in nature is likely to have parallel evolution of many thousands or millions of genes that regulate the precise shapes of the fractals in many organisms.
What kinds of signalling hormone gradients and genes regulate branch and leaf vein angles are very obscure and I didn't find much about "branch angle gene regulation".
You'll find information like: "The plant hormones cytokinin, auxin and gibberellin are crucial during root development." cool description of plant hormones
Here's the best read I found on the subject:
https://dev.biologists.org/content/147/10/dev184499
The most confusing to read:
https://pubmed.ncbi.nlm.nih.gov/16527761/
I scanned through 15 research papers and very few claim to have found the mechanisms that regulate the morphogenesis of fractals in the natural world.

Firstly, it is necessary to note that fractals are not unique to live things: for example, a seashore is an example of fractal structure (with theoretically infinite length).
In regard to trees and broccoli, it is necessary to note that fractal structure maximizes the area, given the same volume, as opposed to other shapes (e.g., a spherical organism would have most of its cells inside the sphere), thus increasing the area exposed to sun and facilitating photosynthesis. As such, having such a shape increases the fitness of the organism, and almost certainly is encoded genetically as the result of natural selection. For example, see here.
Let me also bring the attention to the fact that fractals occur also on single-cell levels, such as the dendrites of a neuron.
Update
Fractals are more ubiquitous in live nature than it may seem at the first glance. The obvious examples are the shapes of trees, vascular systems (of trees and animals), neural networks, etc. Less obvious examples (because of being somewhat abstract) are metabolic networks, community food network patterns, and possibly ecen evolutionary patterns (depending on whether we believe that evolution has explored all the possibilities).
West an co-workers have used fractals to explain the scaling laws relating many biological quantities, e.g., such as basal metabolic rate and the lass or organism
$$
Y=Y_0M^{b}, b=\frac{3}{4}
$$
See here for general review and the references, but also the references by @John in the other answer. While purely geometric arguments would imply scaling laws proportional to $b\propto 1/3$ (since volume scales as length to the thirs power), the fractal nature of these networks allows to infer the correct exponents, $b\propto 1/4$.
The theory by West et al., is based on three assumptions:

networks are space-filling in order to service all local biologically active subunits;
the terminal units of the network are invariants;
performance of the network is maximized by minimizing the energy and other quantities required for resource distribution.

The third assumption, maximization of energy, is essentially the requirement of the maximum fitness. What appears to be somewhat fo an open question is to what extent the the living organisms evolve towards fractal structures or whether it is characteristic of all the living organisms, inherited from the most recent common ancestor.

What evidence do you have that fractals increase fitness? Given that this claim is at the center of the part of your post that actually answers the question, you need to provide support for this claim. Many plants, by the way, receive much more sun than they can use and therefore would not see any increase in fitness as you posit

@theforestecologist I have expanded this answer.


text:
Minimum and maximum exposure to virus
Is it possible to say that there is a maximum exposure time for the virus so that even an exposure time beyond that - will leave us with the same chances of infection?
If so, is there a way to estimate the interval between the minimum exposure time for infection and the maximum exposure time for infection and what happens inside?

No, on cannot say it this way, since further expose always carries a risk of getting infected.
However, one could argue that after certain time of exposure one is nearly certainly infected, so being exposed longer doesn't really change the result. This statement could be formulated more rigorously in terms of compartamental epidemiological models. If we take the figure for the SIR model in the linked article, we see that the number of the susceptible individuals (S) quickly drops about time 0.2-0.4, after which it is almost zero, i.e., there are almost no uninfected individuals in the population.

The numbers of susceptible (S), infected (I), and recovered (R) individuals can be normalized by the total number of the individuals in the population ($N=S+I+R$), and then interpreted as the probabilities of a person being uninfected ($p_S=S/N$), infected ($p_I=I/N$) or recovered ($p_R=R/N$). These probabilities will behave in time in teh same way as shon in the figure (but with different y scale), i.e., the probability of being ininfected would first be nearly constant, and then quickly decrease to nearly zero.


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What is this dark brown organism growing on a door frame?
A few brown spots appeared on a door frame and within 1 week it has grown to this size (~15cm). I have no idea what it is. How do I remove it completely? I worry that if I just wipe it off, it will just regrow from within the door frame. I've attached 2 pictures to assist with the identification.
Edit: I poked it with a stick and tiny white insects (~2mm) came crawling out of the structure.
My location: South India

Termites.
Photograph the insects and we will try to identify further. If the insects keep running, freeze some. This could be a big problem, so get good information soon.
Online I see this article that might help.
" An identification guide to the wood destroying termites of south India"
Journal of the Indian Academy of Wood Science
ISSN 0972-172X Volume 8 Number 2
J Indian Acad Wood Sci (2011) 8:148-151
DOI 10.1007/s13196-012-0028-9

Can termites be this small(~2mm) though? Unfortunately I can't get any more pictures because this is in my relative's house and I was just staying there for a while. I'll ask them to further look into this. Thanks :)

Ask them to trace the tunnel down to the nest, if they can.

@trinitrotoluene - if your relatives haven't got it resolved already, by the time termites are coming through the outside of wood, the internal is already overflowing with them and their tunnels. It is highly likely that they have a heavy infestation and will need an exterminator to get rid of them fully, then some serious repair work to trace, remove and replace the damaged wood.


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Deviation from Hardy Weinberg equilibrium (HWE)
I have a set of 10 genes, each gene contains around 15 SNPs. I have tested the deviation from Hardy Weinberg equilibrium (HWE) for all SNPs. All of the SNPs didn't deviate from HWE, except 5 SNPs in ABCG8, they had p<0.05. I have found different factors that can affect the HWE. My question: Why for the rest of the SNPs met the HWE, why only 5 SNPs in ABCG8 deviate largely from HWE?

Be careful with the claims based on p-values: a p-value allows to reject the null hypothesis, but not to confitm it. In other words, when $p<0.05$ one can say that HWE is broken, however $p>0.05$ does not mean that HWE holds - it could be still broken, but we cannot prove it.

I would quibble with @Vadim a bit- when you do 150 tests, you expect that $0.05 * 150 = 7.5$ SNPs to be $p < 0.05$, as under the null hypothesis, p-values from independent tests are uniformly distributed. P-values are a quite low standard of evidence except when they're very small. Having all 5 occur in one gene might be surprising, but nonetheless I would say that "rejecting" the null hypothesis based on it is a bit strong, as the observations are still pretty consistent with the null hypothesis (without seeing additional data).

@MaximilianPress I was talking about more basic difference about p-value and power, objecting the claim that the rest of the SNPs met the HWE. However I do agree with you that, given the large number of tests, even the five SNPs with $p<0.05$ are not a proof that HWE is violated.

@Vadim ok, that makes sense. I agree with your overall point about p-values used to confirm the null hypothesis, I think I was just worried about the other side of the issue, which wasn't clear. I think that you actually addressed the question quite directly and accurately! I would suggest making it into an answer, actually.

A significance test (i.e., p-value) allows us to reject the null hypothesis, but not to confirm it. In other words, when $p<0.05$ one can say that the conditions for HWE are not met, however $p>0.05$ does not mean that HWE holds - the conditions might still not be met, but we cannot prove it. Thus, by making statements such as All of the SNPs didn't deviate from HWE and the rest of the SNPs met the HWE one may be committing Type II statistical error.
As @MaximilianPress correctly pointed out, in this case one should not be making any statements about the SNPs with $p<0.05$ either, due to the high possibility of False discovery. Indeed, a p-value gives us the probability that the data would be at least as extreme as was observed, even though the null hypothesis is true. Given $N=150$ SNPs one expects about $$N\times\alpha = 150 \times 0.05= 7.5$$ statistically significant outcomes to occur by chance, even if the HWE holds. That is, one could be also committing the Type I error of rejecting the null hypothesis, when it is true. To exclude this error one needs to use a more stringent test, e.g., Bonferroni correction, i.e., testing against the significance level $N$ times smaller than the current $\alpha=0.05$:
$$
\alpha\longrightarrow\frac{\alpha}{N}=\frac{0.05}{150}\approx 0.0003
$$


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The exact points of muscle attachment and the "equal and opposite force" that skeletal muscles apply
I've been trying to make a simple simulation of the human body executing some motions in Mathematica (the details are irrelevant), but I need to know some more information about muscles and how they exert forces. To simplify the problem/question that I am asking, take just the bicepts for example. Suppose that you have just the chest, upper arm, and forearm attached, and ignore the rest of the body (and by that, I mean either remove or treat it as rigid, with the exception of the joints in question, which would therefore be just the shoulder and elbow joints).
One relevant idea that I should point out is that I'm simulating the guy basically jumping, and, whilst in the air, your body is in an inertial frame, meaning that Newton's Third law applies. Under the assumption of a constant moment arm, the usual simplifying assumptions that are made here, etc.. (actually, see the hyperlink below), does contracting JUST your bicepts cause an equal and opposite force at the shoulder, or just the elbow, and is this typical of muscles in the human body?
When the bicepts contract, if they're attached to the shoulder/chest they will (theoretically) pivot the upper arm towards you, while if they're attached to the upper arm they may pivot it backwards, the other way (I think). If they're attached to the upper arm, then the diagram here is essentially what I'd use, but if the muscles went all the way through to connect I'd have to basically "add" an additional segment to the diagram depicted in the link, and the muscle would pass directly over the upper arm, instead, for the purposes of contraction, attaching your forearm directly to your shoulder. This is why I think it's a problem of where the muscles seem connected.

Which of these is a more accurate representation of how human muscles accurately attach things, and therefore exert equal and opposite forces when they contract (and is what I've said so far even correct??)? Alternatively, how accurate is the image depicted in the hyperlink in the above paragraph?

Thank you in advance, so so much
Added TLDR; does (-from a conceptual viewpoint-) flexing purely your bicepts function to bring your forearm and UPPER ARM closer together, or is it really bringing your forearm and SHOULDER closer together? Is this how muscles work in general?

Does it help you to envision muscles (with tendons) as springs? The third law applies to the forces at the two connection points, like with any spring.

@BryanKrause kind of, I think that's a clarifying question though. I guess that what I'm asking is more like where the springs are attached; for example is the equal and opposite force at the other end of the spring exerted on the upper arm or shoulder; one moves the shoulder, the other moves the upper arm, too.

Muscle groups can be really complex, but individual muscles really aren't. I think you just need an anatomy reference and look where the tendons are anchored for any particular muscle you're looking at. It won't be attached to the "upper arm" or "shoulder" but to a specific place on a specific bone which will produce a specific degree of motion.

For major muscles you can probably find enough just on Wikipedia.


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In human anatomy / biomechanics, what is the motion called when the arm swings sideways so the elbow moves in an arc of 90 degrees?
In human anatomy / biomechanics, what is the motion called when the arm swings sideways so the elbow moves in an arc of 90 degrees?
So e.g. if a person was to elbow somebody behind them , or if somebody had their arm out and then swung it keeping it parallel with the floor.
Like in this video
https://www.youtube.com/watch?v=IOh2-4WWzEE

It’s humeral retroversion at a 90 degrees abduction angle with extended elbow and slightly internally rotated shoulder.

Shoulder Horizontal Abduction/Adduction.
https://www.youtube.com/watch?v=R3xJDsJ_Nw4&ab_channel=InteractiveBiology
"the motion of bringing the arm across the chest is called shoulder or glenohumeral horizontal adduction. Glenohumeral horizontal adduction is demonstrated starting from 90? of shoulder flexion
with the arm slightly away from midline in abduction as seen from a front or anterior view."
Abduction would be away from the midline/body. i.e. the outward direction.
Adduction would be towards the midline  i.e. coming across/towards your body.
Starting and staying at 90 degree shoulder flexion.
Google shows this from oxfordreference.com
"Horizontal adduction
horizontal adduction (horizontal flexion)
Movement of the arm or thigh in the transverse plane from a lateral position to an anterior position. ..."
So it's also known as Horizontal flexion and horizontal extension.
as shown here https://www.youtube.com/watch?v=c0JxEZ87W40&ab_channel=BlakeMartin


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Potential obstacles to growing nanoelectronics within living cells?
Say there was a nanotechnology allowing to "grow" and wire up electronic components/sensors measured only a few nanometers in cross-section, though spanning in length across microns. Say this was possible inside living cells (for the purpose of monitoring or even controlling living tissues at individual cell level).
Would such a technology be doomed in the bud simply because cells will immediately deploy antibodies to fight the foreign objects off, and either succeed in it (rendering the growing of said components impossible) or die if they can't succeed in it? Or are there chances to get the cells ignore the electronic components and live with them happily?
What are any other potential obstacles to this sort of technology from biological perspective?

This is an opinion-based question because it is asking about a hypothetical situation. From the [help/dont-ask], avoid asking subjective questions where […] you are asking an open-ended, hypothetical question: “What if ______ happened?” We expect answers to be based on verifiable facts and references, along with subject-related expertise.

@MattDMo I am actually seeking facts and references, obviously not in relation to nanoelectronics in cells (unless such things exist) but in relation to implantation of foreign objects in cells in general (which, hopefully, is already not hypothetical). The reference to nanoelectronics is more of an indication of where the question is coming from rather than requirement for answers to reference it.

This question is still hypothetical, because to my knowledge no one has implanted materials of the type you're describing into animals (which you need in order to elicit an immune response. The devil is in the details here, and we simply don't have the information necessary to answer this question in anything other than a hypothetical manner... which is off-topic.

@MattDMo An answer along the lines "no one has done anything like that yet so the science does not know the answer as of today" would be a good answer then. When the time comes, it would be updated accordingly.

I think this is a really timely and interesting question. Here is a link to the online version of an article that appeared in Sci Am last month. It may be of interest to you and shows that nanotechnology is advancing pretty rapidly in this arena. Perhaps it can help you to narrow down your question and to rewrite it into an answerable format.


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Evolution at a glacial pace: how does it work?
Some trees are very long-lived, such as the Great Basin Bristlecone Pine and the Giant Sequoia (up to 4,800 years old).
How does natural selection and evolution affect such long-lived organisms?  Their DNA has remained unchanged for thousands of years.  Mutation can't hope to change the DNA of the entire tree.
I don't understand how they can hope to be able to adapt to a changing environment.  And yet the    Sequoioideae subfamily has existed since at least the Jurassic, so they must have a winning strategy for survival.
Please help me understand how a species such as this can adapt.  And what natural pressure would select for such longevity?

For some clarification, evolution isn't observed within individuals; it's observed in populations, and over multiple generations.

@Harris has correctly noted that evolutionary time is better measured in generations, rather than absolute years. You also have mentioned the Jurassic period - that is 200 million years ago - this is still hundreds of thousands of times longer that the lifetime of Sequoia given in your question (could you provdie a reference for this number?)

@Harris I am not quite sure what you mean by 'evolution isn't observed within individuals; it's observed within populations' - could you clarify that?

@user438383 The question seems to frame this as individual trees' DNA changing to adapt, which is not a typical context to consider evolution in.

Consider that a long-lived individual can produce offspring - in this case, seeds - over many years.  In the case of the Giant Sequoia, seed production can begin as early as 10 years, and is heavy from about 150 years, which means about 2000 years or more of producing genetically diverse seeds, of which only a few individuals will survive.  https://www.srs.fs.usda.gov/pubs/misc/ag_654/volume_1/sequoiadendron/giganteum.htm


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Bug identification request
Can anyone please offer a suggestion of what the insect below is?  It is about 3mm in length, and I saw it on my kitchen counter.  I live in an apartment, 9th floor of a highrise.  It is January 5 (winter), 2021, in Ottawa (-3C outside).
I suspect that is might not be relevant, but last month, I saw what might be Dermestid lavae.  The beetle below, however, doesn't look like a Dermestid beetle
Thanks.


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Predicting how proteins will be cleaved
Is it possible to predict how proteins coded from mRNA will be cleaved?
The reason I was interested in this is because I did some initial work to translate the raw Coronavirus RNA sequences, which you can see here: https://github.com/imranq/coronavirus. The background section below has more information on my approach.
With the "naive" approach to translate coronavirus RNA, using AUG as the start codon, I am able to identify 7 out of 24 proteins from Zhang lab sequences. However, I also did some string matching between my amino acid sequences and the Zhang lab final amino acid sequences. After doing that comparison, I see I have 21 out of 24 protein sequences coded in uncleaved protein sequences.
It would be nice to get to the final 24 proteins straight from the mRNA strand. Please help. Thanks!
Background
Here is the series of steps I used to convert coronavirus RNA into proteins.
1. The raw RNA sequences are here (sourced from the NIH):
https://github.com/imranq/coronavirus/blob/main/data/rawrna.json

2. The script to translate the RNA is here (assumes AUG is the start
codon):
https://github.com/imranq/coronavirus/blob/main/scripts/translate.js

The translated protein sequences are here:
https://github.com/imranq/coronavirus/blob/main/data/processed/translatedProteins.json

3. The script used to generate a comparison between the translated
proteins and the known protein sequences is here (using levenshtein
distance as our difference metric):
https://github.com/imranq/coronavirus/blob/main/scripts/compareTranslated.js

The data generated from that script is here
https://github.com/imranq/coronavirus/blob/main/data/processed/translatedComparison.json

4. Then we detect cleavage in proteins by running a sliding window
across RNA segments between the known and translated proteins. The
script to do so is here:
https://github.com/imranq/coronavirus/blob/main/scripts/detectCleavage.js

4. Finally we merge the datasets we generated from translation and
protein complexes into one dataset, translated proteins and protein
complexes matched to known proteins.

The data generated from this algorithm is located here
https://github.com/imranq/coronavirus/blob/main/data/processed/mergedProteins.json

At the end of this pipeline, we get 21 out of the 24 proteins matched straight from RNA.
References:
Here are the papers / articles I researched to answer this question
Turning Genome Data into Proteins
Khan Academy Genetic Code: https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/translation/a/the-genetic-code-discovery-and-properties
Zhan Lab - SARS CoV 2 - Nucleotide, Coding Region, and Protein sequences https://zhanglab.ccmb.med.umich.edu/COVID-19/
More in the readme here: https://github.com/imranq/coronavirus/blob/main/README.MD

Your question is very broad, and a bit unclear. Yes, the recognition sites of many proteases are known, so it is possible to predict where a particular one may cleave a protein substrate. Some searching in PubMed and Google Scholar should be informative in that regard. But I'm not sure what, if anything, you're expecting us to do from there.

Thank you Matt. I guess I was looking for any research ideas that could help understand rna to protein better. It seems like it’s a harder problem than I thought and warrants further research.

The cleavage site of the PLpro is obvious from https://www.ncbi.nlm.nih.gov/nuccore/NC_045512.2, it is L(N/K)GG.  For the 3CLpro it is more complicated and a paper says it is (small amino acid)-X-(L/F/M)-Q↓(G/A/S)-X. Also you need to implement the ribosomal frameshift and detect the correct start codon from the secondary structures. This is solely for ORF1ab.

Thank you that is helpful. I'm not sure what the notation " L(N/K)GG" means however. Also what is a ribosomal frameshift? I thought the start codon was largely the same across mRNA.


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Why don't the cell organelles settle down in the cell under the influence of gravity?
In cuboidal or columnar cells or cells of any other shape the nucleus and the other organelles and inclusions remain suspended in the cytoplasm. Why doesn't gravity affect them ?
Could this be because all organelles are of colloidal size ?
Or is it the result of being held in position microfilaments and other cytoskeletal structures that facilitate cytoplasmic streaming ?

It's the cytoskeleton - cells are surprisingly full of it.

okay thanks....got it


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Does a critical mass of infected individuals exist after which mutations will overtake vaccination attempts?
As we know, all organisms have a probability to undergo mutations when they replicate. For every infected individual with the Covid-19 their bodies are environments in which the SARS-CoV-2 may mutate beyond existing vaccines.
Therefore, as the number of infected individuals increases, there will come a point where mutations in the SARS-CoV-2 would occur faster, perhaps even concurrently in different countries, than vaccines may be developed and deployed to stamp out the virus once and for all.
So my questions are as follows: is there a critical mass* of infected people, beyond which our existing vaccine development & deployment time frames will not be able to cope with? Do we have an estimate of this number?
*I understand this is not a single, fixed number but a fuzzy, probabilistic range.

Whoever downvoted it, it would be nice if you explained to a new poster here why instead of being a silent and unhelpful critic.

I didn't downvote - but I think your question could be a bit more focused. It might be better off sticking to a specific scientific question at the beginning and removing any reference to 'What should we do next..?' - since that part is more opinionated and unrelated to biology.

OK will edit accordingly, thank you for your feedback.

I agree with @user438383 - the question actually gave me an idea for a more pointed question.

@MeEngineerTrustMe you seem to be conflating many different concepts in one place. Viruses are rather different in terms of what may happen to them, you may want to take a look at my post here: https://biology.stackexchange.com/a/97324/59521

Also note that not all mutations will be able to circumvent the effects of vaccination. Some mutations may not cause changes in the protein at all, others may keep the protein structurally similar to an extent such that they are still recognizable by antibodies etc. To answer your question one needs to know the mutation rates of sars cov2 and I wasn't able to find any specific study on it.

Epidemiological modeling
If a virus is able to change so that it renders previous vaccination inefficient, reinfecting those who were previously vaccinated, one could describe this process using epidemiological SIS model (Susceptible-Infected-Susceptible) or its modification that includes a vaccinated group (like SISV model), and indeed estimate how quick should be vaccination in order to eradicate dthe virus before everyone gets infected. One could even add a D (deaths) compartement and study whether the virus may lead to extinction of the huiman species (unlikely, since the survival rate is very high).
Real viruses
In reality we are not dealing with such a situation, since there is no reason to think that mutations make SARS-CoV-2 able to overcome the immune defenses (although they do make it more contagious and more dangerous to non-vaccinated individuals).
To clarify the issue let me outline the scenarios where viruses do escape vaccine resistance.
Influenza
Flu is known to be susceptible to vaccination, and this is a lasting vaccination. What makes this virus to come back every year is gene reshuffling, where it exchanges some of its several genes with similar viruses living in animals (the roles of some of these animals in flu outbreaks gave rise to such names as swine flu, * birs flu*, etc.). This means that every few years we are dealing with an essentially new virus (rather than a virus that has accumulated many mutations), which is not visible to the antibodies created by previously administered vaccines. In this sense, one cannot exclude a possibility of a new coronavirus causing a pandemic in a decade or so, just like the current outbreak follows similar ones due to SARS in 2002 and MERS in 2012.
HIV
HIV is know to adapt very quickly to the new antibodies, evading the immune defenses. This makes it impossible (or at least very difficult) to develop a vaccine against this virus. However, HIV is much less contagious than flu or coronavirus, since it needs to infect specific cells/tissues. In orther words, it is stopped by the barriers of the immune system other than those boosted by vaccination. Coronavirus is a much simpler virus than HIV and will never reach the same degree of sophistication via mutations.
Bacterial pathogens
Bacteria are known for routinely developing resistance to antibiotics, which has been somewhat of a hot issue in terms of antibiotic development. They however share the same weakness as HIV - being less contagious (and far more complex).
To summarize, the devil is in the details: the scenario outlined in the question is good for science fiction, but it has very low probability to be realized in real life.

Thank you for your explanation!

@user1136 Thanks, I corrected it.

We also have the example of several highly contagious viruses which were widespread prior to the development of vaccines, yet which are now eradicated, or nearly so.  E.g. smallpox (eradicated), polio (eradicated except in a few countries), and measles (which would probably be eradicated if it weren't for the anti-vaxers :-().  So while it's possible for a virus to evolve to evade vaccines, that's the exception rather than the norm.

@jamesqf excellent point ! Thanks.

I'm going to answer this one with a No.  Outside of a simple simulation with very unrealistic constraints, we can't know the basic parameters to generate such a number.  From an omniscient point of view there would be some number where this becomes inevitable, but from that point of view we could say it is inevitable or impossible right now.  Some aspects to consider:

The viral mutation rate can vary, depending on the sequence (and mutations) of the RNA-dependent RNA polymerase.  That rate is presently considered slow.  There is a limit (mutational load - most mutations are undesirable) to how much that rate could increase, but the limit depends on how people react to the virus, how they are treated, and so on.  If one virus is in a position to infect many cells and people, it can tolerate a higher rate of errors.
The virus can invade animal reservoirs, such as minks and cats.  We do not know all the animal reservoirs, and given the scarcity of human testing, our understanding of these other reservoirs must be quite limited.  We can't predict what adaptive mutation the virus might undergo to adapt to known, let alone unknown, hosts.
RNA viruses can undergo template switching in which the 'front' of one virus is appended to the 'back' of the other.  (This can be called 'recombination', though it is different from recombination in normal human cells - see this paper)  The odds of this happening may depend more on where, how, and in what species the viruses interact, than on the number of people infected.
On the plus side, there are conserved amino acid positions at which mutations will be poorly tolerated, which may be recognized by a sufficient fraction of the vaccine-induced antibodies.  We can't necessarily predict whether neutral mutations presently arising will permit further mutations at residues we think are well conserved.

We really have no way of knowing whether such a point of no return has been passed already, except by an empirical approach - waiting to see whether very different Covid strains emerge from hidden animal reservoirs or rare recombination events in humans.