Why do we need to amplify DNA sequences? I am learning about biotechnology. I have no education in biology or chemistry and am simply interested in the subject of biotechnology.

I am wondering why we need to have multiple copies of a piece of DNA in order to do something with it (ie. PCR)? Why is one piece of DNA not enough? Is machinery not precise enough to work with one piece of a DNA sequence in order to do something with it?

I can understand that an experiment may fail. In that case, make 8-16 copies for assurance. But why an extraordinary (billions) amount of copies? What practical use does it have? What applications require there to be an extraordinary amount of DNA to be succesful? Do the billions of copies just increase the speed of the experiment by being able to quickly "fish out" a piece of DNA? I just can't quite grasp the idea.

This is a question I also remember wondering about when I was younger in school. Now as a professional it's way too obvious to even explain. But i think it's an important and common question, which warrants an example or two from common daily lab practice.

Preface

You have to understand that DNA is a molecule. It's really tiny. It's not trivial to work precisely with it, nor detect it or discriminate two different pieces of DNA from each other, let along sequencing them. We make a lot of DNA through amplification so that we can prepare a sufficient amount to make reactions with.

Visualization

We usually make DNA visible by using chemical dyes that emit light (fluorophores) or incorporated radioactive pieces to make the DNA visible.

Here's a common case in the lab: we need to get enough DNA to use in subsequent reactions. When we work with DNA it is very rare that we obtain exactly what we want 100% of the time, or perfect yield. For example, we want to cut a piece of DNA once. But we have scissors (i.e. restriction enzymes) that will chop up the DNA multiple times, especially when we leave the reaction going too long. What we do is take 100 units of DNA, subject them to the reaction, and then view the results using electrophoresis using an agarose gel, for instance. We can then see 40 units of uncut DNA, 30 units of single cut DNA, and some 30 units of DNA cut multiple times (2+ times, so they are small fragments). We need enough single cut DNA to proceed with the next reaction, with full knowledge that there are no contaminating chunks of DNA. Typically there are many reactions in a row that we do to achieve anything in the lab. Cloning, in vitro amplification, sequencing, gene editing, preparing genes for transgenesis, creating RNAi probes, what have you.

More is better

Another case: if you want to know the sequence of DNA, you must sequence it. However, sequencing is imperfect and errors occur. To be sure, we re-sequence the same DNA many times to get a confident picture of what the sequence is like, beyond reasonable doubt. Sequencing DNA ten times is really more reliable than sequencing it once. This could be because of how the molecules behave in solution, or because of degradation, or tens of other things. You must understand this is also not specific to sequencing; a lot of reactions follow the same logic.

Amplification as a specification tool

By using primers in PCR, we can make sure we are obtaining what we want. In principle, this means that we can make a gajillion copies of something we are interested in (e.g. a gene), even from a single strand of DNA which may contain things we are uninterested in (e.g. the rest of the genome).

Some thoughts

This answer is certainly not extensive, but I hope it's a primer for you to understand that DNA work is just really smart nanotechnology, and we are not yet at the level of performing nanotechnology on single molecules, with full confidence, precision or efficacy. On the daily, we need enough to see it with our eyes so we amplify and react it with intercalating dyes to make them visible to the naked eye!


Is it NAD+ or NAD- or neutral NAD ? In glycolysis why NAD is positivly charged , why it's not neutral or negative ?

You are correct in thinking that because of the presence of the diphosphate linkage between the two nucleotides in NAD⁺, both of which will carry a negative charge at physiological pH, together with the positive charge on the nicotinamide N, it would be more chemically correct to write NAD⁻. However I think the idea of using NAD⁺ is to emphasise the N atom in the nicotinamide moiety, which is the 'active site' of the coenzyme.

As it says at the NAD⁺ Wikipedia page:

  Although NAD⁺ is written with a superscript plus sign because of the formal charge on a particular nitrogen atom, at physiological pH for the most part it is actually a singly charged anion (charge of minus 1), while NADH is a doubly charged anion.


Selective breeding fluorescent sheep - possible? I got into a small argument :-)

Friends of mine try to draw fat line between "natural" selective breeding and applying molecular biology (CRISPR/Cas9) to put new traits in existing species. The line of their argument is "GMO is something different, because you can't (in reasonable timeframe, ~1000 years) breed a sheep that will glow in the dark.

Intuitively I think that doing so is possible even without molecular tools to "write" new genes, just using things like horizontal gene transfer and "standard" breeding (I reserve right to use all modern knowledge and tools to plan and monitor progress). I don't have much to substantiate this claim though.

In your enlightened opinion, who is correct?

Natural horizontal gene transfer in higher animals is possible, but still very rare.
If any transfer happens then it's usually from micro-organsims (viruses/bacteria) or parasites to the host animal (or the reverse). Transfer of genes from any other source to animals is almost unheard of, because the transfer needs to affect the germline (sperm / eggs) to last more than a single generation and anything that doesn't live inside an animal is unlikely to get there.

Therefore your example of getting GFP (or any other fluorescent gene) into a sheep is highly unlikely$^1$, even with a 1000 year timespan.
You'd need a virus or bacteria that has a fluorescent gene and naturally infects/lives in/on sheep. However, no natural bacteria or viruses have a fluorescent gene in the first place (they almost all come from corals or jellyfish). Another problem is that just having a fluorescent gene somewhere in the DNA, doesn't mean the any part of the organism is fluorescent; once its in the gene pool this should be achievable by breeding though.

You'd have to wait for HGT of a fluorescent gene from a source animal/life form to bacteria. (Time estimate is super hard, you can maybe house some of these jellyfish in a fish tank regularly sequence the bacteria that live with them to see if HGT happened.)
Then the genes needs to be transfered to a bacterial/virus strain native to sheep (This is relatively easy/fast, since bacteria are quite proficient at HGT between each other)
Lastly you need a 3rd round of HGT from the bacteria to the germline of the sheep. (Again this might take 'forever': most mammals don't like bacteria or viruses living in or near their reproductive organs. Also at least from this point on animal experiment laws will become a serious hurdle to your project).

1) This is a researchers highly unlikely: without trying this, its not correct to say impossible, but the chances are so low that for all practical purposes it might as well be impossible.


Why are most fishes vertical? Why do most fishes have a "vertical" body shape instead of a "flat" one ?
Here "vertical" means that the body(from a front view) is roughly orthogonal to the horizontal plane, and a "flat" body shape means something like a frog's or a bird's with spreading wings.

PS: This question was raised when I was thinking how I can swim faster.

While the most popular image of a fish for many is as you say, a more "vertical" than horizontal body shape, however there are many different adaptations to body shape depending upon the lifestyle of the fish. An ultimate example would be the flat fishes, such as flounder and halibut, which lay on one side essentially flat on the ocean floor or other similar surface. These fish however have adapted to have both eyes on one lateral side. There do exist other fish, such as some angler fish, especially in the family Lophiidae, which are more wide than tall, and they sit on the ocean floor and use a lure like appendage to attract prey so that they can ambush it, using their fins more to walk along the bottom surface. The feeding/hunting style is also highly related to the body shape of a fish, some shapes are more suited for moderate constant speeds, while others are suited for short quick bursts. Generally though, flat fish are not well suited for swimming at the middle of the water column, giving them a smaller habitat in which to live, while the more commonly found fish body shapes are used by much more species throughout the water column.

More information from MEER:

More information regarding Fish locomotion on Wikipedia.


What is meant by “genes at the trunk of the evolutionary tree”? Recently I went through a paper about hepatocellular carcinoma in which they talked about trunk genes (p. 26, second paragraph):

  Branching tumor evolution complicates efforts to implement
  personalized medicine and suggests that targeted therapies might be
  directed to genes that are mutated at the trunk of the evolutionary
  tree. Transposons provide powerful tools for identifying trunk genes,
  as insertions in trunk genes are more likely to be associated with a
  higher number of sequencing reads.

I really don’t understand what are the trunk genes. Can anyone please explain them clearly.

Thank you

I think the article is using a phylogenetic tree to explain the stages of how the tumor has evolved.

According to Nature.com >>

  All trees have a shared 'trunk', which represents the complement of
  mutations shared by all malignant cells within the cancer.

Or simplified by Britannica.com >>

  Phylogenetic tree, also called Dendrogram, a diagram showing the
  evolutionary interrelations of a group of organisms derived from a
  common ancestral form. The ancestor is in the tree “trunk”; organisms
  that have arisen from it are placed at the ends of tree “branches.”

For a visual representation, this is a phylogenetic tree for evolution of breast cancer >>

Image Source: Phylogenetic Cancer Trees


Time from stimulus to gene expression My understanding is that gene expression, in response to some stimulus, generally occurs on the order of minutes. I'm curious about the extremes...the quickest and the slowest cases.

What is(are) the fastest time(s) recorded for genes being expressed in response to a stimulus? What are the slowest times?

The fastest I know of is the heat shock locus in Drosophila.  The transcription factor (HSF) accumulates within about 30 seconds, and RNA Polymerase can be seen to start accumulating within 3 minutes.

Katie L. Zobeck, Martin S. Buckley, Warren R. Zipfel, John T. Lis.  2010. Recruitment Timing and Dynamics of Transcription Factors at the Hsp70 Loci in Living Cells.  Molecular Cell 40(6): 965-975


what is knob heterochromatin? I am reading a paper which discusses Maize Genome Structure. Descriptions of the  structure is given in the papers introduction.
I know about heterochromatin "heterochromatin stains intensely, indicating tighter packing. Heterochromatin is usually localized to the periphery of the nucleus"
but, could someone explain what is knob heterochromatin?

thanks for help.

Here's a good summary of knobs, which says that they are "typically telomeric," "tandemly repeated DNA sequences [that] appear as distinct, heteropycnotic regions located at certain sites on specific chromosomes and look much like beads on a string" and are involved in:

increased recombination
neocentromere activity
preferential segregation
chromosome breakage and chromatin loss
sex differences in recombination

The introduction to this paper gives some of the same information.


Is ivy (genus Hedera) a shrub or an herb? It seems like the difference between a bush (shurb) and an herb is that a bush has a woody stem.

What does that make ivy (genus Hedera)? I know that ivy can get a pretty hard stem, does that count as woody? Is there something between a bush and an herb?

Woody plants are usually either trees, shrubs, or lianas. Ivies are lianas, they can have 40 years of woody growth rings and bark. The categories are flexible. It's an arbitrary division for convenience, it isn't that clear cut. Bamboos for example, are a woody grass.

https://weedwise.conservationdistrict.org/weeds/english-ivy#foobox-1/7/Untitled-4-copy.jpg

Does that count as a woody plant? yes it's a woody liana.


Why is the GenBank entry for the genomes of RNA viruses like coronavirus written as DNA? The reference genome in GenBank of the sars coronavirus from Wuhan is written in the following format:

attaaaggtttataccttcc

(The first 20 nucleotides)

Considering that coronaviruses are RNA viruses, the bases of which are adenine, cytosine, guanine and uracil, I was surprised to see the t symbol in the sequence, which stands for thymine, found in DNA, not in RNA. Additionally, no u symbols are present in the sequence.

So, what's going on here? Where did Thymine come from, why no Uracil?

It would appear that the current policy at GenBank is to represent all genomic sequences as DNA, even though this is not made explicit in any of the easily retrievable documentation on their website or in their publications. The way in which one determines the nature of the genome is from the first (LOCUS) line in the report, which, in the case of SARS-CoV-2 is:

LOCUS       NC_045512              29903 bp ss-RNA     linear   VRL 30-MAR-2020

The ss-RNA indicates a single-stranded RNA genome.

The only indication I could find that this might be GenBank policy was a reference to the fact that a separate RNA division of GenBank used to exist, but was discontinued in 1999:

  The RNA division of GenBank was removed in release 113.0 (August 1999). Sequences that were previously in the RNA division have been moved to the appropriate organismal division.

The genomes of certain RNA phages were originally sequenced as RNA (as were bacterial rRNAs and 18S rRNA) — that of phage MS2 was the first in 1976. The GenBank entries for these are currently in DNA format. Thus V00642.1 contains references to the 1976 MS2 paper by Fiers et al., but is in DNA format. As GenBank was not established until 1982 it is not clear whether the original entry in GenBank was in RNA or DNA format.

UPDATE 15.04.2020

I wrote to GenBank to ask them whether there was a specific policy and if so when it had been introduced. I had a reply from someone on their help desk to the effect that GenBank policy was that of International Nucleotide Sequence Database Collaboration, the shared rules of which includes table "7.4.1 Nucleotide base codes (IUPAC)". This states that "t" can represent thymine in DNA and  uracil in RNA. However my respondent could not find out whether this representation was used in GenBank for RNA viruses from the beginning or introduced later. As originally GenBank releases were on CD-ROM this is difficult to check.


Can genes be expressed sequentially? As I understand it, any gene on an exposed/unpacked region of a chromosome is continuously being expressed. Regulatory genes may increase or decrease the amount of protein synthesised due to its expression, but its expression is still fairly continuous.

Assuming I am correct, is there any regulatory framework by which genes are sequentially expressed. That is where the expression of one gene causes it to be turned off and another turned on?

For example, say some chromosome has genes A, B, and C. Is there a situation where gene A is expressed for some period, then gene B, and then gene C, but no more than one is ever expressed at once and they only are expressed in that order?

EDIT: I'll clarify that I don't expect genes which are suppressed to somehow still be accessible. Making them inaccessible is (as far as I know) how they are shut down. My point in mentioning how accessible genes are expressed is to highlight the uncontrolled nature of gene expression in relation to sequential gene expression and therefore to ask how the genetic machinery can get around this problem.

Simple answer: yes, this happens all the time.

A couple of notes:

Firstly, pretty much everything in biology is continuous. If a gene is expressed at a level of 1 protein per million cells, everybody would say it's not expressed, even though I guess you could argue the point. And don't underestimate how much regulation can affect expression -- you can easily have thousand-fold or million-fold differences between tissues and conditions.

Now, regarding the expression cascade: This is exactly what happens during the cell cycle. As the cell grows, there are genes that can sense the availability of nutrients and all the other signals that control initiation of cell division. Those then can turn on the genes first phase of the cell division cycle. Other regulators can sense whether that phase completed, and turn on the next set of genes, and maybe degradation signals for the genes from the first phase. And this then continues through the cell cycle.

Here's a figure from a paper that looked at gene expression in synchronyzed yeast cells (http://www.pnas.org/content/104/43/16892.full):


Sequencing two strands of dna My background is not genetics. 2.I am not interested in knowing how dna sequencing or genotyping is done. 3. I am interested just in the nature of the results as described here.

Now coming to the question: Humans have two sets of chromosome in each cell. So if I say sequencing chromosome1, what does that actually mean? Which of the two chromosome's gets sequenced? Of genotyping-do comparison take place between two+two=four chromosome1's? Or is my entire undertanding flawed?

I am interested just in the nature of the results as described here.

By aligning this sequence to all nucleotides of all organisms, we would realize that the given (short) sequence occurs in various organisms besides humans. Therefore it might come from a species with only one chromosome see NCBI Blast !

For the sake of the example, let's assume that the species had multiple instances of each chromosome (e.g. one by human mother, and one by human father), and look at "the results as described here". As no detail is given on the protocol, let's further assume the most common scenario - namely that there was no experimental distinction or separation of the individual instances of chromosomes.

Looking at the results, we would realize that is not "next generation sequencing", but Sanger-sequencing.

Now we look at the provided scheme again (note: this is not real experimental data): clearly the bands on the left side only occur for one letter/base, and at a given position of the sequence, there only is one very clear peak on the right hand side (as opposed to the possibility, to have multiple peaks corresponding to different bases).

We would have to conclude that every instance of the chromosome has an absolutely identical sequence. Thus we would conclude that it would not be important to distinguish individual instances.

But wait - aren't maternal and paternal chromosomes different? Absolutely, the given example however only looks at 25 bases rather than the full chromosome - and it would quite possible that they are absolutely identical. (note: there are various experimental techniques to select only specific regions of DNA or RNA for analysis).


Why does capsaicin irritate mammals and also kill fungi? Are the two related? From this article I heard about a study (search "Tewksbury") which concluded that chilies make capsaicin to discourage mammals from eating their seeds, since grinding by mammals' molars render the seeds unable to germinate. Birds, on the other hand, don't break open the seeds and spread the plants far and wide.

But, they also reference a different theory: capsaicin evolved to defend against a certain kind of fungi that infected pepper plants.

My question is: why does the same chemical do these two things? It seems like quite a coincidence, unless capsaicin has some general destructive properties. But Wikipedia's explanation talks about how capsaicin artificially stimulates a certain receptor in our mouths -- which sounds totally unrelated to fungi.

Recent study has shown that capsaicin indeed has antimicrobial properties. For example, see this article:

  Two pungent compounds found in Capsicum species (capsaicin and dihydrocapsaicin) were also tested for their anti-microbial effects. The plain and heated extracts were found to exhibit varying degrees of inhibition against Bacillus cereus, Bacillus subtilis, Clostridium sporogenes, Clostridium tetani, and Streptococcus pyogenes.

In one of the attempts to study its mechanism, a study on yeasts suggested that it works in following ways:

Detoxification of capsaicin by a PDR-type ABC
superfamily of multi-drug resistance transporters
Osmotic stress response and damages in membrane
structure caused by the capsaicin treatment
Genotoxicity of capsaicin to yeast cells
The effects of the deletions of the genes those were
induced by the capsaicin treatment
Mechanism of capsaicin in the growth inhbition to
yeast cells:

The DNA microarray analysis of antimicrobial
mechanism of capsaicin shows that capsaicin induced
an osmotic stress element, the key genes for membrane biosynthesis, and the PDR network and repressed the genes for ribosomal components
and cellular growth. The growth characteristics of
deletion strains suggest that PDR5 is important for
the resistance to capsaicin. These observations that
the PDR network may pump out capsaicin from cells
are the first findings. The contribution of the PDR
network also suggests that capsaicin enters to the
cells and capsaicin functions as a toxic substance to
the yeast cells. This toxicity is possibly to the
mebrane structure and/or as osmotic stress.

Full article (PDF) here.

Though in mammals, its mechanism of action is quite different; it acts on ion channels to give a burning sensation. See this article:

  The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to a receptor called the vanilloid receptor subtype 1 (TRPV1). TRPV1, which can also be stimulated with heat, protons and physical abrasion, permits cations to pass through the cell membrane when activated. The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the TRPV1 receptor, the capsaicin molecule produces similar sensations to those of excessive heat or abrasive damage, explaining why the spiciness of capsaicin is described as a burning sensation.

However, it is toxic for mammals too. Capsaicin is a highly irritant material requiring proper protective goggles, respirators, and proper hazardous material-handling procedures. Capsaicin takes effect upon skin contact (irritant, sensitizer), eye contact (irritant), ingestion, and inhalation (lung irritant, lung sensitizer). The LD50 in mice is 47.2 mg/kg.

Though its mechanisms are different, it performs quite similar functions: protecting the plant from predators and infections i.e. a defense system.

It seems like quite a coincidence, unless capsaicin has some general destructive properties.

It is neither a coincidence nor capsaicin has general destructive properties. In fact, capsaicin is being used as an analgesic too. See this article:

  Capsaicin is a chili pepper extract with analgesic properties. Capsaicin is a neuropeptide releasing agent selective for primary sensory peripheral neurons. Used topically, capsaicin aids in controlling peripheral nerve pain. This agent has been used experimentally to manipulate substance P and other tachykinins. In addition, capsaicin may be useful in controlling chemotherapy- and radiotherapy-induced mucositis.

Its mode of action is, seemingly, somewhat similar. See this:

  The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from
  nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the
  capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are
  defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies.

(P.S. substance P is a neuropeptide, a potent vasodilator & iniates expression of almost all known cytokines.)

Pay attention to the last line 'utility of topical capsaicin may extendbeyond painful peripheral neuropathies.' i.e. capsaicin may have more effects on body than known!


Organisms that do not wish to reproduce Are there any organisms that do not want to reproduce?
As humans, there are people who do not want to reproduce with the opposite sex. Do any other organisms replicate this behavior? Also, why does this behavior exist? If the end goal of an organism is to reproduce, why has evolution allowed organisms that do not want to reproduce to exist?

Animals and especially female animals might not "want" to reproduce when circumstances are bad for babies.  Pregnancy and rearing of infants is a big commitment of resources for female mammals.  If a female is under stress, or sick she might avoid having sex even though she could get pregnant because evolutionarily that was a winning strategy for her ancestors - committing the physical and nutritional resources to a pregnancy and fetus unlikely to survive current circumstances puts the mother and subsequent pregnancies at risk.

A more extreme example is the Bruce Effect.  Pregnant females exposed to the pheromones of a strange new male "decide" not to reproduce - their bodies resorb the fetuses.  Presumably this is because the new male is a risk to the fetus and they would do better calling off the doomed project, and possibly having a new litter with the new male if he shows up.

Weirder is the circumstance of parents that kill and sometimes eat their young.  That happens in mammals, birds, fish and others.  It is hard to see how this sort of thing advances genetic fitness - it seems like a crossed wire or misfire of some sort.  Certain animals, however, seem to do it all the time; hamsters come to mind.  Maybe stress causes weird behavior?  In any case this too would seem like a case of deciding not to reproduce.


Are Whales More Intelligent Than Humans? Are Whales smarter than Humans?
Their brain size leads me to think so.

The "wiring" of the brain is more important than the actual size. If only size would matter that basically humans would be rather unintelligent beings ( many many animals have larger head and brain than us). Intelligence is more related to the complexity of the brain (number and size of different brain components) and the number of connections between neurons. We humans are intelligent because we have high complexity compared to our brain size, our brain has more grooves therefore higher surface than a whale brain. So even though whales are quite smart they're not as smart as us.

EDIT: After getting a few comments I felt I need to clarify my answer, so here it comes: as pointed out by user137 humans have much higher brain-to-body size ration than whales and this is very important. What I was trying to explain (yet failed for the first time it seems), that mere physical size / volume is not that important. The level of development and complexity is that matters the most. Many parts of the human brain is found in lower order animals as shown in the image below:  (taken from http://en.wikipedia.org/wiki/Brain

The surface to volume ratio matters because the higher ratio implies a more complex brain structure. So while whales have a higher surface in absolute value (approx 2-3 times) yet their brain is larger by approx 5-6 times ( lots of comparison data here), thus we have higher surface/volume ratio (i left the ratio part out on my original answer). In the accepted answer on the question linked by Bez it is said that more grey matter in frontal lobe correlates with IQ. Now since grey matter is made of neuron bodies and (fewer)axons, this is quite straightfoward --> more neurons = more connections = higher complexity. But all that comparison was made between humans. So brain size differences between different individuals of the same species may contribute to individual qualities. Comparing mere physical brain sizes of different species is not straightforward because of different brain development levels and brain structure.


Could Cannabidiol steady a hand? Can Cannabidiol be used to steady shaky or nervous hand for precision work like surgery?

I have used it for shooting pool/billiards and I'm not sure if it is a placebo or it is helping? but I am more steady.

I have seen where Cannabidiol helps this man with Parkinson's stop shacking.
https://www.youtube.com/watch?v=rAdDdTZuNA8

I think this is a fantastic question.

As far as the Parkinson's application, it's definitely within the realm of possible. Taken form a recent review:

  Preclinical research in animal models of several movement disorders
  have shown variable evidence for symptomatic benefits but more
  consistently suggest potential neuroprotective effects in several
  animal models of Parkinson’s (PD) and Huntington’s disease (HD).
  Clinical observations and clinical trials of cannabinoid-based
  therapies suggests a possible benefit of cannabinoids for tics and
  probably no benefit for tremor in multiple sclerosis or dyskinesias or
  motor symptoms in PD.

Kluger et al. in Movement Disorder, 2015 (The Therapeutic Potential of Cannabinoids for Movement
Disorders)

As far as every-day hand steadiness, I haven't been able to find any good sources yet. I'll keep reading, and update this if I find anything interesting.


Theranos blood test's Specificity and Accuracy? I am studying the limitations of Theranos device.
They have 238 documents in Google Patents Search (Inassignee as Theranos), here.
Which patents are relevant for their device?
They have 70 tests which are not necessary to consider now.
Just the basics of the device.

My intuition says that it uses PCR to multiply the microliter of blood for the analysis.
What are limiations of multiplying so little blood?
I think this is where their engineering work applies.
What components do you need to multiply?
I think all is not necessary.
Otherwise, the specificity and accuracy can be difficult to hold.

How can Theranos blood test's be specific and accurate compared to conventional full blood test?
I suspect if you can do the conventional full blood test with Theranos device with the same accuracy and specificity as the conventional one.

Which patents are relevant for their device?

They currently only have about 27 issued patents (US)
Of those patents about 10 of them are related to network/internet/health record/algorithm (so not really about their device)
The remaining patents focus on a few areas: sample acquisition (getting the blood drop and handling of it), Patch based technology (before they pivoted), sample quality analysis (this is key to making sure the small sample is good quality), microfluidics/modular device (these are the patents relating to the actual testing and device)

What are the limitations of multiplying so little blood?

From a molecular standpoint (PCR) the smaller sample you start with, the less of the original nucleic acid template you have to start with.  Lower end PCR testing uses 10uL of sample.  This is ok when you are trying to bring molecular diagnostics to the point of care or developing markets, but the best PCR tests use 50uL of sample (more than a drop of blood which is traditionally 25uL or so),  regardless of how good your device is, at some point you start amplifying junk. The better the primers and other reagents the less junk you amplify, but at the end of the day you want more sample to be more sensitive.
From a NON-molecular standpoint (chemistries, cellular analysis, coag, etc.), they aren't/can't multiply the analyte of interest.  In these tests, they rely more on dilution or small volumes to perform detection.  This is where their ability to reliably dilute and correct for the dilution comes into play. Although there is certain limits to this.  Coagulation tests would not be representative if you diluted the sample so in this case they will have to rely on working with a small volume.  Cellular analysis can only be diluted so much as you get to a point where you miss important but less common cell types.  Take eosinophils (a type of WBC) while they can get to 15 or 20 percent of all WBC cell types, in general they only make up a couple percent.  Assume that 2% of all your WBCs are eosinophils.  If you only have 3500 WBCs per 1uL of blood (which is on the lower end of normal), you have approximately only 70 of these cells in that same volume.  If you dilute the sample so that way there is more of it available for other tests like electrolytes, but you still analyze 1uL, The number of those cells is even less.  If you had perfect detection you might be ok, but you generally want to analyze more blood so that statistics work in your favor and your performance goes up. Most of the other chemistries, proteins, and as mentioned earlier, electrolytes will probably be ok for dilution and detection and in fact this is why there are plenty of small devices already out there that use a drop of blood and perform the same tests.
Their issue in diluting or amplifying analytes of interest is that biology still is governed by the laws of physics and even though technology may allow you to analyze samples down to 10nL, that just isn't use full in biology, and limits their their capability to perform the supposed menu of tests from one microtainer of blood.  They don't publicize that they may need to draw a venous sample (needle in your arm) for some tests and depending on what tests you order, you may need a separate finger prick for each test.

How can Theranos blood test's be specific and accurate compared to conventional full blood test?

If they reliably control dilution of the small sample, they maybe able to provide high quality results for some tests.
Finger pricks actually can be easily skewed via technique.  Theranos has specially trained people to draw these samples, but it is time consuming >5 mins and until it is fully automated this is one variable that no matter how good sensors are, you can't correct for variation pre-analytically when you have that small sample.  Finger pricks also skew certain tests even when technique is good such as platelet and WBC values in the CBC.
I discussed the sample volume issue above regarding PCR amplification and how good tests use up to 50uL.  So if they compare to a 10uL test, they may be able to compete, but not full lab quality.
A lot of the future techniques they have regarding small techniques (in their applications) like their coagulation tests work great in an academic setting, but they fail to be able to handle the full range of blood samples they will see, so it will be interesting to see how that plays out.

Takeaway

Theranos is working on modular micofluidic devices/cartridges that will use small sample
There are certain biological limitations that stand in the way of them performing all the tests in their catalog with only a drop of blood
The FDA will eventually be requiring them to submit their tests for approval as they are currently doing tests that are available on commercially and FDA approved devices already (this makes sense because LDTs were never ment to be used in place of standard tests and equipment and since there is NO published data on their performance it can be worrisome to providers and payer)
Their true business plan has yet to be elucidated, but if they really did have a box that did all this, they would be selling them to physicians and clincs where those results could actually be used in diagnosis rather than 4 hours later.
I hope they succeed, but there is just way too much hype to buy in on it yet.

I am sorry I don't have sources, most of this is from intimate knowledge of the space and from the little info available on them so I could definitely be wrong on some of this.  I hope this helps!


If oxygen is such a good energy source, why do plants release it? Why do plants release excess oxygen, rather than consuming it entirely given it is an excellent energy source?

Short answer
Plants release O2, because it is not an energy source. Instead, it is used to free energy from energy-rich organic compounds.

Background
Plants are solar powered. They release oxygen as a waste product during carbon fixation. Carbon fixation is basically the storage of solar power into carbon-bonds in glucose, a process referred to as photosynthesis or the Calvin Cycle.

To release the solar energy from glucose it has to be burned (oxidized). Oxidation of glucose can be realized via the the citric acid cycle (or Krebs cycle) and electron transport chain to generate ATP. O2 only comes in in the very last step by acting as the final electron acceptor to produce H2O (Fig. 1.)

Fig. 1. Electron transport chain in mitochondria. Electrons are sent through a chain of proteins that drive hydrogen transport out of the mitochondrial space. ATP-synthase uses the proton gradient to generate ATP. Source: Davis University College

Hence, O2 is not the source of energy, it is merely used to free it from energy rich compounds such as glucose. Because it is so abundant in the atmosphere, it doesn't make sense to store it.

Reference
- Berg et al., Biochemistry. 5th edition. New York: W H Freeman (2002)


Does capsaicin in food kill bacteria? Do foods like spicy peppers have less bacteria on their interior due to their capsaicin content? Probably not, but it seems like they could. Or I guess in other words: does capcaicin provide any benefit from anti-bacterial properties?

In 2014, a review article was pushlished by the Department of Food Science and Nutrition at the University of Minnesota-Twin Cities, one that outlines  studies that (collectively) target the top 14 food-borne pathogens in attempts to identifying any potential antimicrobial properties of chili peppers, given that chili peppers can contain high amounts of capsaicin.

From the abstract of the article:

  Chili peppers are used worldwide in foods for their pungent flavor, aroma, and to prolong food spoilage. With capsaicin contents ranging from zero to millions of Scoville heat units, the different varieties offer a wide range of options for people all over the world. In addition to their use in cuisines, chili peppers have been explored for their antimicrobial and antifungal properties.

..

  This review goes over some relevant research that has already been done in this area. In addition it lays the ground for the new research that is emerging testing new varieties of chili peppers for nutrient content, flavor profiles, and for antimicrobial activities against numerous human pathogens.

The fourteen pathogens that were targeted and tested against were chosen due to their high risk of harm to the general public, most especially pregnant women (according to the FDA). To name a few that are well known, there's: Clostridium botulinum; Escherichia coli; Salmonella (enteritidis and typhimurium); Staphylococcus aureus; and Listeria monocytogenes.

After reading the conclusions of several studies that were provided by the review article (as well as the conclusion of the review article itself), it would seem that the current (as of 2014) consensus is that the efficacy of capsaicin (in chili peppers) as an antimicrobial agent is still to be determined. Of the (multiple) studies that were considered, collectively they produced quite mixed results. The reason for this is because each study has their own method for testing the antimicrobial activities of capsaicin, which makes the comparison of results between tests difficult to perform with confidence.

  There are a variety of methods for testing the antimicrobial activities of chili peppers. These methods strongly affect the observed levels of inhibition. Various reasons may contribute in the differences between results, including inconsistency between analyzed plant materials.

..

  In these experiments, crude extracts of chili peppers were used; no
  separation of pepper components was done. Based on the data, it seems that capsaicin had a lesser antimicrobial effect compared to other components of chili pepper extracts. Therefore, future studies should try to determine what compounds in the chili pepper gives the spice its antimicrobial properties, and to do so purification of the extracts is necessary. Capsaicin gives chili peppers the ‘hot’ sensation, which some people might not like. It would, therefore, be beneficial if there is another substance in the pepper that could be used in the food industry as a preservative without the pungent taste and hotness.

So, it would seem that, since the idea of using capsaicin as an antimicrobial agent is (fairly) new, there hasn't been a defined method for testing, and because of that, definitive conclusions aren't able to be made yet.


Can I find out what resistance bacteria has based on strain? where do I look for that info? I have a list of strains across various organisms for example:

Escherichia coli - ATCC 25922, CGSC 6152, W3110RL.

Pseudomonas aeruginosa - ATCC 27853, PAO1, APAE1111.

I'm failing to find any resistance information on these strains, as in what strain is resistant or susceptible to what antibiotic. Is there a way to find out?

Thanks.

If database and literature searches fail, you can plug the GenBank accession numbers for your genomes into the CARD Resistance Gene Identifier. It takes either protein or nucleotide sequences, though nucleotide seqs. undergo ORF calling first. For example, plugging in NZ_CP009072.1 for E. coli ATCC 25922 gives 7 perfect hits to known antibiotic resistance genes. Granted, carrying the genetic determinants of resistance is different from phenotypic resistance, but it's a place to start.


Effect of ethanol and detergent on cell membranes problem I am currently writing my biology report for an experiment I did on how ethanol and detergent affect the cell membrane. For my ethanol experiment, all went as expected. However, for my detergent experiment, the results seemed quite strange. The absorbency rate was higher for the 20% and 40% detergent than it was for the 100%. It seemed as though the results were backwards. I'm really confused.

What might have happened? Was it just an experimental error or is there a reason behind this? Can you also please explain to me what detergent does to a cell membrane exactly?

Detergent and membranes
Moderate concentrations of non-ionic detergents facilitate lysis of cells. This can be exploited for extracting soluble proteins, often in their native form (ThermoFisher). Detergents affect the membrane at concentrations lower even than those that cause an increase in membrane solubility (Ahyayauch et al., 2010). Two ways this manifests is an alteration of the flip-flop effect (the lipid action caused by flipases) and leakage.
Note that the relationship between detergents and membranes aren't mechanistically well understood, and there aren't yet good general mechanistic rules that explain the relationship between concentration and permeability.
Your experiment

The absorbency rate was higher for the 20% and 40% detergent than it was for the 100%. It seemed as though the results were backwards.

It depends on your specific experiment, but typically the higher concentrations will more readily lyse the cell/make them more permeable. It's hard to say exactly what went wrong here without more information. Unless you were using an exotic detergent, it is quite likely that there was an experimental error and the test should be repeated. Alternatively, the results have been misinterpreted and indeed at lower concentrations, there was no cell lysis, and at 100% there are no cells left intact or something along those lines.


Is sperm contagious? A person may have a cold or any other disease that is an airborne-infection.
Is their sperm also contagious? Should the person take any precautions?

I'm unsure about the use of the word "contagious" here. If you would describe it as an organism "catching something" from another only once, this answer applies (vaguely perhaps).

One example of "contagious" sperm: sea urchins spray their sperm (called milt) into the surrounding water, so that it can hopefully fertilize roe, which are fish eggs. The eggs are also expulsed for some species, but for others they stay on the surface of the female sea urchin, as this Wikipedia article explains.

  The gonads are lined with muscles underneath the peritoneum, and these allow the animal to squeeze its gametes through the duct and into the surrounding sea water where fertilization takes place.
  ...

  In most cases, the eggs float freely in the sea, but some species hold onto them with their spines, affording them a greater degree of protection.

Thus, it's entirely possible for a female sea urchin to be bombarded by free-floating sperm, to ultimately fertilize the eggs on its surface. I don't know if one would strictly consider this a contagion, but it's what I initially thought of after reading the question.

When referring to sexually transmitted disease however, sperm in itself is not contagious, as it would require the pathogen to "tag along with it" in whichever environment (whether it be airborne or aquatic). Also, if considering impregnation as "contagious", physical contact would certainly be required.

In short: For humans, no. For sea urchins (and likely other aquatic animals), sort of.


What is the difference between organelle membranes? Cells and organelles are contained in lipid bilayers. I'm particularly interested in eukaryotic organelle bilayers and the biophysicochemical differences between them.

Many papers assume a difference in membrane characteristics and some like Anderson et al., 2007 have categorised the relationship between these characteristics and protein function in depth.

Do any reviews or comprehensive studies exist in the field that compare the thickness of the membrane, the rigidity of the surface, any differences in lipid entropy, or the overall charge inside and outside across different types of organelle membranes?

Great question. Turns out, there is some information about it.

For example, consider following resource: Membrane Protein Lipid Composition Atlas. Published by University of Michigan, it provides information on, primarily, protein content of different membranes from different species, but also has a list of lipid content.

Just as an example, consider following difference between membranes of mitochondria in yeast:

Now, concerning your interest in biophysics. To my taste, starting with just bulk lipid composition is a good first approximation. Although you also want to know about lipid raft formation and density/distribution of proteins. Next step, probably, will be symmetry considerations, that is, difference between sides of same membrane. You can imagine membranes with same bulk composition, but because of different lipid position (in/out) properties will be different.

It seems you can assess raft composition based on membrane lipid composition. Membrane capacity also is a property of membrane content.

Following quick walk through this Google Scholar search provides even more links between biophysical properties and lipid bilayer composition. However, it might be challenging to find exactly what you are looking for.


Meaning of 5’–3’ in relation to ORFs I was reading a paper in the journal Molecular Basis of Disease, which stated:

The ORFs are arranged as replicase, and protease and major S, E, M,
and N proteins which follows a typical 5’—3’ order of appearance, are
considered are as considered as major drug/vaccine targets.

(Naqvi, et al., 2020)
I'd like to know what the " ' " means; if it means inch, or something else like minute. I am doing research so I don't know what units are being used.
Source
Naqvi, A. A. T. et al., 2020. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1866, p. 165878.

I assume you are referring to the "typical 5’—3’ order of appearance".
The correct way to pronounce these is with the word "prime", that is, "Five prime to three prime". These are not units but refer to the directionality of RNA/DNA and the numbers five and three refer to specific carbon atoms arranged in the sugar molecules that make up the RNA/DNA backbone.
RNA/DNA are typically "read" (and always written) from the 5' to the 3' end of the molecule by molecular machinery in the cell, so that's usually the order we read the sequences as well. "5' to 3'" in molecular biology effectively means "beginning to end".


What is LD50 for 25i (25I-NBOMe)? Firstly I would like to apologise if this is not correct place to ask this question, as it can be seen more as chemistry and not biology question.

I was looking around for data on psychedelic substance called 25i (25I-NBOMe) . It was fist synthesized in 2003 and is somewhat 'new'. I have found some data on overdoses and they are few, however I could not find any specific data on mortality to dose rate nor on LD50 (Dose where 50% of people would die). Wikipedia is quiet in this regard.
Judging by the dosage it being active in sub-milligram doses (600–1,200 µg) it should not be very lethal compared to most, should it?

Where could I get data on LD50 for 25i (25I-NBOMe)?

Cimbi-5 or 25i (25I-NBOMe) is a class 2C psychedelic drug.(wiki site.)

Lethal dose or LD50 of "Cimbi-5" is still unknown.

Though you can predict approximate the LD50 by structure computationally.


Size constraints on CRISPR guide RNA I had a quick questions on the size limitations of a CRISPR guide. More specifically on the shorter end. Can I make a guide that is say 7-10bp and still have an active complex? I transfect using an RNP system.

Just curious.

Thanks in advance.

You can definitely make such gRNA, but chances of off-targeting increases as you decrease the size of gRNA. It is always better to have 17-20 bp gRNA. However, you can check off-targets of a gRNA through several online tools.


Semantics Question: epigenetic mark on a person's DNA? In an article on biomarkers of child abuse, the author referred to an "epigenetic mark on a person's DNA". It's a popular science article, so the language may reflect a combination of the journalist's scientific competency and his or her desire to communicate complex topics efficiently to a lay audience. Is that an example of such language?

My understanding was that anything in the realm of "epigenetics" is happening to something other than DNA. Is it technically correct to refer to an "epigenetic mark on a person's DNA"? Correct enough? Only potentially misleading? I'm trying to wrap my head around the whole epigenetics concept.

We may restrict your definition of epigenetics as heritable changes in an organism's phenotype that occur without a change in the sequence of DNA bases. That is, changes to the DNA molecule itself is permitted, as long as the sequence of ATCGs are not affected.

In this sense, it would not be wrong to refer to an "epigenetic mark on a person's DNA". For example, a mechanism of epigenetics that does directly change the DNA molecule would be something like DNA methylation.


Why isn't the upper limit of pain lower in humans? From what I understand, pain is an useful mechanism that signals us that something is not quite right with our body (in particular, we're under attack). It's good - it alert us and tells us that we got to do something (stop the threat, or run away, etc). From Wikipedia:

  Pain motivates the individual to withdraw from damaging situations, to
  protect a damaged body part while it heals, and to avoid similar
  experiences in the future.

However, there are damages that cause too much pain. If you are stabbed in a particular place, you will most likely have so much pain that you simply can't fight back or run away. The shock makes it incredibly hard to do something or even think properly.

So my question is: is there a reason why pain can elevate to such high levels? I'm just assuming that if we had some sort of hard limit on the amount of pain we receive, we could perform better in several dangerous situations. In other words: instead of hurting so much that we can't even think properly, it hurts enough to let us know we are in grave danger but still capable of assess the situation and perhaps even act accordingly.

Obviously some physical damages will render you unable to act anyway. Like, damages on the spine that may cause your limbs to malfunction. But I mean damages such as a large open wound on the abdomen: if that didn't hurt so much, I'd imagine you could probably stand up and run away (you'd probably bleed out but at least you'll have a chance to escape the threat).

My guess is that it "cannot be helped". Pain are signals from different parts of the body to the brain, and once a signal is sent, the brain has no choice but to process it accordingly.

You are assuming that fighting back with a bad wound would be more useful than dropping to the ground. That is not always the case.

Dropping to the ground and ceasing activity is very adaptive in almost any situation involving potentially significant blood loss. Becoming prone or supine prevents loss of consciousness, the most critical aspect of survival. Decreased movement is also likely to decrease the rate of blood loss (though not in as significant a manner as consciousness).

Certainly with a significant abdominal wound, running would increase cardiac output, which would increase bleeding. Is running from a traumatic event advantageous if you pass out before escaping? On the other hand, lying prone and holding the wound (instinctive) may reduce bleeding and prolong consciousness and life.

What "cannot be helped" (like withdrawing a hand from a flame) is usually advantageous.

An infant's cry changes during circumcision (an involuntary reaction to pain). The cry in turn naturally produces a visceral reaction in nearby adults that compels action (causes a state of strong sympathetic nervous system activation.) The adult either avoids the cry by trying to distance themself, or responds by coming to the infant's cry.

The infant cannot help changing the intensity of the cry with intense pain. If a "certain level of pain" was as far as one could feel, the baby might not elicit the sense of urgency in adults which it does.

Newborn pain cries and vagal tone: parallel changes in response to circumcision.
ASSESSMENT OF INFANT CRY: ACOUSTIC CRY ANALYSIS AND PARENTAL PERCEPTION


Are all healthy animals more likely to defecate near the end of a rest-cycle? Just what the title states.
It stems from observation & personal experience that a person/dog/cat/monkey is more likely to relieve oneself immediately after it wakes up from the peak-sleep cycle of it's body-clock. Is this observation true? What causes this behaviour ?

I think we can actually go farther than mere behavioral argumentation. The separation of the autonomous nervous system into parasympathetic and sympathetic is, one the one hand, associated with the sleep/wake cycle, on the other with parasympathetic/sympathetic activity (low/high epinephrine secretion). This duality certainly applies to all vertebrata (i.e. big animals), as fight & flight is associated with all vertebrata, see e.g.

http://en.wikipedia.org/wiki/Fight_or_flight_response

In other words: from the existence of fight or flight in all vertebrata I infer the existence of a dual autonomous nervous system (parasympathetic and sympathetic) in all vertebrata, although there may be other proof. Since in sleep the parasym. NS is active, the bowel moves. Conclusion: the bowel moves in the sleep of all vertebrata.


How significant is RNA degradation with removal of cap/polyA's in eukaryotes, or UTR's in prokaryotes? Question is rather self-explanatory, but segmented into two parts. I'm attempting to make use of a repression system that employs cleaving RNA at specific areas with ribozymes with the intent of degrading (or just inactivating) them.

This scenario seems more likely in eukaryotes, as they have capped 5' UTRs and a polyA tail at 3' UTRs that lend to RNA stability. How quickly and how much will an uncapped RNA degrade? What about the lack of a polyA tail?

Since prokaryotes lack these structures, I am restricted to the use of UTR regions in my particular instance. Is there any similar mechanism, whether in general or for specific proteins, that will allow me to exploit a UTR region for RNA inactivation in prokaryotes? Please keep in mind adding synthetic sequences to these UTR regions is certainly a possibility.

Removal of 5' cap is essential for degradation by 5'→3' exonucleases such as Xrn1/2. Xrn1/2 is constitutive and degradation of uncapped RNAs would be quite fast (don't have a reference for the exact lifetime). Deadenylation generally precedes 3'→5' degradation by exosome but I am not sure if that is a prerequisite. However tailless mRNAs can be stabilized by tethering Pab1p (Poly-A binding protein) to the 3'UTR. See this paper.

Figure 4 of the linked paper.

  Tethered Pab1p stabilizes mRNAs that do not receive a tail. (A)
  Strategy. The HDV self-cleaving ribozyme was inserted into the 3′ UTR
  of MFA2/MS2 RNA, yielding an mRNA without a poly(A) tail (A0) in vivo.
  (B) Oligo(dT) cellulose chromatography. RNAs were extracted from cells
  carrying the ribozyme-containing construct depicted inA, or the
  control plasmid used in previous figures. RNAs were fractionated by
  oligo(dT) cellulose chromatography, then analyzed by Northern
  blotting. The ribozyme-containing RNA is not retained by the column,
  whereas the control RNA is retained. (T) Total RNA prior to
  fractionation; (+) retained by the column; (−) not retained by the
  column. The mRNA runs slightly faster in the oligo(dT) retained (+)
  sample than in the total (T) RNA, because less RNA is loaded per lane.
  (C) S1 nuclease analysis. The 3′ end of mRNA prepared from a strain
  carrying the ribozyme-containing RNA was determined by S1 nuclease
  mapping. The position of undigested probe (65 nucleotides) and of the
  protected species (43 nucleotides) are shown. The prominent 3′
  terminus lies at the expected position for ribozyme cleavage. (D)
  Decay of ribozyme-cleaved RNA by a transcriptional pulse-chase
  experiment and Northern blotting. The turnover rate of
  ribozyme-cleaved reporter mRNAs was determined in strains with (left)
  or without (right) MS2/Pab1p. Time (in min) following transcriptional
  repression are given directly at top; half-lives are at bottom. (E)
  Quantitation of results. Amounts of mRNA were normalized to the level
  of 18S rRNA, at bottom of each lane in D. (•) MS2/Pab1p; (○) vector
  alone.

Prokaryotic UTRs do not have any general paradigm. To have a controlled inactivation of a mRNA in a prokaryotic system you can use riboswitches or  cis-repressive RNA (RBS complementary RNAs). RNA-guided RNA degradation is also possible in prokaryotes using the CRISPR-Cas system. See this paper. Proteins Cmr-1,2,3,4 & 6 are required for this activity.


How conscious are mammals that mating leads to pregnancy and offspring? Does a pregnant female mammal know that its pregnancy is the consequence of a previous mating? Or are humans the only mammals which are conscious of it?

I have trouble citing the exact source now as it's in one of my books at home, has 'sex' in the title (Sex in History), and I'm at work and can't Google that. But needless to say, the book made mention of studies of isolated, modern human tribes where it was evident that the people of the tribe had not made the connection between pro-creation and child-birth. Rather, intercourse was often tied to specific rituals that had a side effect of birth.

So there are a few things that one can extrapolate from this:

Pre-historic humans may have often not been aware that sex led to procreation
From that one can extrapolate further that no animals have this awareness either, as we are the most intellectual species on the planet

Further, the evolutionary development of sex points to this too. The ultimate cause of child-bearing is propagation, but the proximate cause of child-bearing is pleasure. Before life could be aware of the connection, there needed to be a reason to have sex, and so we would have developed in a way that encouraged pro-creation for no other reason than we liked doing it. Eventually we were bound to connect the dots, but we're oriented for this behavior regardless.


Action of Ebola Viruses This video suggests that the first cell to be the victim of viral infection of ebola is the dendritic cell which acts as the leader of immune system cells.But I am unable to understand how the dendritic cells get infected if they are the leaders?

Viruses can infect any cell:

  a virus must have a host cell (bacteria, plant or animal) in which to live and make more viruses. Outside of a host cell, viruses cannot function.

Source

This includes the dendritic cells:

  Dendritic cells are antigen-presenting cells of the immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers. They don't actually release any antibodies.

Source

Quite simply, at the beginning of an infection, the viruses / bacteria will be destroyed by macrophages.

The dendritic cell will "pick up" some of the leftover pieces.

When it finds a T-Cell that has the same configuration, it orders lots of identical T-Cells to be made. These T cells have multiple jobs, one of which is activating the B cells. It is the B cells that release the antibodies.

So Ebola.

If the dendritic cells are "invaded", then the only line of defence is the macrophages. This is often not enough to stop an attack, and it multiplies out of control.

The reason the Dendritic cells can be invaded is because they are just as vulnerable as other cells. They haven't activated the T cells, and they haven't activated the B cells, so there is nothing protecting them.

Images Source (YouTube video)


What is the difference between Reservoir and paratenic hosts? Paratenic host

'In parasitology, the term paratenic describes a host that is not necessary for the development of a particular species of parasite, but nonetheless may happen to serve to maintain the life cycle of that parasite' until they are transferred to an obligatory host.

(from Wikipedia and Parasitology: A Conceptual Approach book)

Reservoir host

  Reservoir hosts are such animals which accumulate in themselves the invasive larvae of the helminthes and contribute to their transfer to the definitive host, not being however an obligatory condition for the complition of parasite ontogenesis.

(from Proceedings of the First International Congress of Parasitology: Roma, 21-26 September 1964)

The source however says that Reservoir host is same as paratenic host which contradicts other sources
(like General Parasitology by Cheng) which says:

  Reservoir host is an animal that becomes infected and serve as a source from which other animals can be infected. (the only difference I presume is that it may or may not be obligatory)

In many other books (book 1 & 2) a parallel definition is mentioned that a reservoir host is a host that harbors parasite until their transmission to human beings.

This inturn brings forth another question, is a reservoir host a biological vector then?

So the question : Are paratenic host and reservoir host same or different?

P.S. I don't know what the standard books on parasitology are which could have solved this issue. Reference to one such book will be really appreciated.

Reservoir host: The host of an infection in which the infectious agent multiplies and/or develops and on which the agent is dependent for survival in nature; essential host for maintenance of the infection when active transmission is not occurring.
Paratenic host: A host in which a parasite survives without undergoing any additional development (a transport host only)
Source: Diagnostic medical parasitology, pg 1161

and

Any animal that harbors an infection that can be transmitted to humans is called a reservoir host, even if the animal is a normal host of the parasite. Source: Pg no:4

So, we can conclude that paratenic host is different from reservoir host due to following differences:

Paratenic host don't harbour infective stages , if they harbour them, then they would be called as reservoir host but not paratenic host( see second definition)

No development takes place in paratenic hosts, whereas in reservoir host development and multiplication takes place( see 1st definition).

Is a reservoir host a biological vector then?

I too asked the same question, its answer is here.


Why is it that I can understand speech through one ear better than the other ear? First, I do a lot of music so I'm used to pick up details in sound and I have had hearing tests showing that my ears are quite well balanced, for my age, without any dead spots.

When I am in a social situation, I will hear people's voices equally well on both sides, however I will 'understand' dialog better on one side.

I remember reading many years ago that this is normal and there is a known reason for it, but I can't really find much about that topic.

Does anyone here know why this is happening?

I remember reading many years ago that this is normal...

Indeed, this is normal and quite expected: understanding one's voice is a brain task, not an ear (sensory organ) task, and if there is difference in the parsing capabilities between the left and the right hemisphere (which is the case, as we are going to see soon), the stimuli captured by the right ear will be treated differently from the stimuli captured by the left ear.

To understand what's happening here we have to know two things: the Wernicke's Area and Dichotic listening test.

The Wernicke Area, quoting Wikipedia, is...

  ...located in the posterior section of the superior temporal gyrus (STG) in the (most commonly) left cerebral hemisphere. It is involved in the comprehension or understanding of written and spoken language (in contrast to Broca's area that is involved in the production of language).

Thus, in most people, the left hemisphere is responsible for (most of) linguistic capabilities, both producing language (Broca's area) and understanding language (Werneck's area).

Now comes the dichotic listening test. In the dichotic listening test, two different stimuli are presented to each ear. The results of the test indicate that there is preference for the information captured by one of the ears.

According to Freberg (2010):

  Dichotic Listening Is Related to Hemisphere Lateralization for Language: When conflicting information is provided to the two ears, the person who has language lateralized to the left hemisphere will show a preference for the word heard by the right ear. The information presented to the right ear will reach Wernicke's area in the left hemisphere faster than the information presented to the left ear. (emphasis mine)

Here is an image explaining the test (click for a larger size):

As you can see, there is a advantage to the right ear. According to Hugdahl et al. (2003):

  In the present paper we report on speech perception in left (n=16) and right (n=10) frontal lobe nonaphasic patients compared with healthy controls (n=26). [...] The results showed significant differences between the left and right lesioned patients in their performance on the dichotic listening test. While the right lesioned patients and the control subjects had a normal and expected right ear advantage, the left lesioned patients performed almost at random with regard to the right and left ear stimulus. (emphasis mine)

Sources:

Freberg, L. (2010). Discovering biological psychology. 1st ed.
Hugdahl, K., Bodner, T., Weiss, E. and Benke, T. (2003). Dichotic listening performance and frontal lobe function. Cognitive Brain Research, 16(1), pp.58-65.


UK - What type of spider is this? Location: East Anglia, UK.

Approximate size (including legs at full span; like in the image): about 3cm.

It appears to be a Noble False Widow Steatoda nobilis

From http://britishspiders.org.uk/wiki2015/index.php?title=File:Steatoda_nobilis.jpg

It apparently is thought to be introduced to the UK, and there are some reports that the bite has caused some issues for some people.

https://en.wikipedia.org/wiki/Steatoda_nobilis


Confusion about how to compute probabilities for linked genes I am confused about how to compute probabilities for linked genes.
The problem that I am solving is this:

P generation: AAbbddEEff X aaBBDDeeFF. If A and B are 40 centimorgan apart, what is the probabilty to get aabbddeeff in F2?

Here is what I have:

F1 is: AaBbDdEeFf.
The next cross it goes through is this: AaBbDdEeFf X AaBbDdEeFf.
To compute this cross, I drew the 2 chromosomes for AaBb (in coupling), and then the probability for a is 0.5 (A or a) and the possibility for no recombination is 0.6. So 0.5 x 0.6 = 0.3. The same goes for b, so aabb is: 0.3 x 0.3 = 0.09.
For ddeeff: 0.25x0.25x0.25 = 0.015625.
Multiplying these gives 0.09 x 0.015625 = 0.00140625.
Extending that and for 2 gametes gives this: (0.00140625)^2 = 0.00197x10^-3.

But the correct answer is not what I have computed, but instead is 0.000625.
I'm really confused with this question. If we know that only 2 of the 5 genes are linked, is it still correct to multiply: 0.09 x 0.015625 = 0.00140625?  Maybe I should use a Punnett square somehow? Because in that case, the probability for a recessive homozygous is 0.0625 but I'm not sure it fits to this question.

0.000625 looks right to me.  On one chromosome, you have a 50% chance of a.  Then you have a 40% chance of b (if and only if a crossover occurs).  These multiply out to 20%.  You multiply that by 50% for three unlinked genes to get 2.5% abdef.
Your approach was correct overall, but you used a 60% chance of b, so your final answer was too high by (60%/40%)^2.  Don't let capital and small letters trick you - ab comes from a recombined chromosome.


While someone's ears pops with pressure, can he/she hear other sound at the same time? I know that after or before someone's ears pops because of pressure changes, he/she can hear the sound such as laughter. But can these two things ("her ears popped with pressure" and "she can hear the laughter") happen at the same time?

Yes, of course they can. What happens when your ears feel 'full' like on an aeroplane is that the air pressure in the middle ear is different from the air pressure outside. When you 'pop' your ears, you push open the Eustachian tubes that connect the middle ear to the throat and make the pressure equal. No matter what the air pressure, the air still conducts sounds. The difference is that your ear drum moves a bit less if the middle ear pressure and outside pressure is different, thus why sound is muffled before you pop your ears.


Could we transmit smells electronically? We can encode sound and images in radio waves and send them, but presumably there's some physiological reason that we can't easily make a picture or video of a smell. Could we realistically break smells down into "primary scents", in analogy with "primary colors" and encode the information for easy reproduction?

There are only three kinds of optical receptors in the eye, but more than 900 kinds of olfactory receptors. Thus you can encode pictures with the three primary colors, but there is no small set of primary scents.

To transmit a smell via "primary scents", you'd have to create an artificial nose that monitors the response of each of the olfactory receptors, and then at the other end release a chemical mixture that has the exact same response pattern. (You won't find a one-to-one mapping of chemical compound to receptor.)


Fate of antigen-presenting cells after antigen presentation to Helper T cells In many texts, the Antigen-presenting cells (APCs) that initiate helper T cell responses are often "forgotten" after their antigen presentation function is discussed.
I have been wondering how the antigens in these cells are destroyed since they are complexed to MHC II protein (not MHC I).
Yes, the macrophages can receive additional signals from already activated helper T cells to destroy the pathogens harboured in their cytosol, but what about B cells and Dendritic cells which lack such abilities?

In Janeway it's being said without further explanation (I will edit and add reference)   that B-cells and macrophages "become targets" of cytotoxic T-cells after these killer cells have become activated, have been primed. However, this answers your question only if presentation on MHCII (not I) implies that presentation on MHCI has occurred as well. Only then APCs that present to T helper will be targeted by cytotoxic T cells and die. According to my basic knowledge that is the case with Dendritic cells and Macrophages. According to the explanatory text of your question Macrophages only receive signals to kill pathogens they include. Your inference may be correct that they cannot become target of T-cytotoxic cells. It is beyond your question to ask if Macrophages always do get that signal. If no that puts them into the same category as Dendritic APCs.
Understanding that there exists a signal to survive (destruction of phagocytoses pathogens) leads the way to understanding that there is cell death without killing by Tc cells:  cells that present antigens to T helper cells will "apoptotically" die because they have been infected, if not killed by immune cells to prevent the production and shedding of virions. According to my basic knowledge it is coherent  that a cell presenting is a cell sentenced to apoptosis. Killing by T cells is killing at an earlier stage only.
However, I found no reference that explicitly confirms that - maybe with very few exceptions -  that B cells do present on MHCI, to the contrary I found reference - I promise to add this one link quite soon - that explicitly states that B cells only endocytose debris, "protein" (in the sense of protein vaccination) i.e. isolated antigen, not whole virous. Thus, any antigen they present would be on MHC II, not I, as the antigen is not "endogeneous", not produced by the B cell as it has not become infected. This inference from basic textbook knowledge is supported, in this context, by the fact that B cells, just as T cells - which they are thought of as of one and the same category, the Lymphcytes - should not be killed after presentation (whereas T8, cytotoxic T cells do not present at all) as parallel to killing of T cells they still have their job to do: presentation activates the B cells which start to divide and produce antibody.
Consequently, it matters if a B cell not presenting on MHCI, thus not being killed by Tc cells, is sentenced to apoptosis and cell death because it has engulfed the antigen. In my opinion B cells - and I will add any reference to the contrary - not even need, as Macrophages, a signal to survive, as they cope with antigen alone and there is no interference with their regular by viral infection. (However cells hosting active HIV produce protein for viral ends for a long time before they finally die, but this is different.)
To sum up:

Dendritic cells present on MHCII and I, hence killed  by Tc cells or dying by apoptosis

Macrophages present on MHII and I, but according to textbook different to Dendritic cells have the option or are programmed to receive a survival signal to consume the pathogens they harbour

B cells present on MHCII and, according to my understanding: maybe, on MHCI, which would put them too in category 1: same fate as Dendritic cells, however basic knowledge coherently applied speaks in favor for B cells regularly not presenting on MHCI, not getting killed by Tc cells and not undergoing apoptosis as not "infected" by whole virus

So my own personal answer on B cells based on basic textbook knowledge and lack of explicit statements to the contrary might be very different from the answer regarding dendritic cells (and macrophages, see explanatory text of your question).
The B cells do not die after presenting to T Helper cells.


Exclusive microtubule minus-end labeling Like the title explains I am looking for a way to exclusively label microtubule minus end in vivo. Looking through the literature I could not find any techniques yet. Do you have an idea?

γ-Tubulin is specifically localized to the minus end of microtubules. GFP labeled γ-Tubulin can be used to label the minus ends in-vivo and without the requirement of staining. Fan et al have developed a phage display antibody specific to α-Tubulin that can be used to visualize minus ends. See the figure below.

The image is an electron-micrograph but it is certainly possible to do a fluorescent microscopy after IHC staining.


How to find miRNA binding sites on a specific gene? I am trying to find miRNAs that bind to the 3'UTR of a specific gene. What is the best way of doing that (that is, with a good scoring analysis that is most commonly used by researchers in this area)? I would also like to know the other possible methods if there are multiple ways of doing this.

There are some tools for predicting the binding:

TargetScan (based on seed match [primary], extra pairing, sequence context 1 — nucleotide composition around the site etc [secondary])
miRanda (based on hybridization stability and seed match[primary] and sequence context [secondary])
PicTar (adds a layer of evolutionary conservation criteria)

1 Context means the position of the target site in the 3'UTR and the surrounding nucleotide composition (which is also considered an indirect metric of secondary structure)

miRanda and TargetScan also have classes called conserved and non-conserved targets. miRanda reports miRSVR scores and TargetScan reports context scores but these measures are based on few experimental results and may not always be meaningful. miRSVR is based on change in target expression upon miRNA overexpression/knockdown. It also uses metrics for target site context. Context+ score of TargetScan includes many metrics which include target abundance and conservation along with the regular context scoring. Some of these metrics may be more useful than the others. But scores based just on miRNA OE/KD experiments can be misleading- especially if target expression is quantified just at the RNA level. Target abundance also varies between different cell types. For more details on these metrics refer to the papers corresponding to these tools.

There are some experimental procedures for target determination which mainly involve Protein-RNA crosslinking followed by immunoprecipitation of Ago and subsequent quantification by RNA sequencing. See HITS-CLIP and PAR-CLIP. These techniques do not really find the targets. All they do is to correlate the levels of miRNA and their predicted targets attached to Ago (you won't exactly know if the ternary mRNA-miRNA-Ago complex really formed or not).

CLASH is a more recent technique which tries to address this issue by ligating mRNA with miRNA. This way you can capture the miRNA-mRNA interaction. However, I am a little skeptical of CLASH; I myself was working on this principle some time back and faced this one challenge. CLASH roughly involves the following steps:

Crosslink protein-RNA
Immunoprecipitate Ago
Use RNAse to digest unbound regions of mRNA (and make it small enough for a short read sequencing experiment)
Ligate miRNA and mRNA bound to Ago using RNA ligase
Degrade Ago using protease
Sequence the miRNA-mRNA ligated pair

My doubt was how would miRNA and mRNA be ligated when the footprint of Ago is bigger than an miRNA (reported ~50-60 nt in HITS-CLIP and PAR-CLIP). When the RNA is nuclease protected then how can it be accessible to ligase. When I was thinking about it then I thought that a partial protein degradation was necessary (after RNAse step and before ligase step) to give some space for ligase to act. Eventually I did not work on it further. Three years later CLASH paper was published and I was happy that someone made it work. But the ligase issue was not addressed (It seems to have worked but I don't know how!!).

To test the predictions you can use a reporter assay (such as GFP or Luciferase) with the 3'UTR cloned downstream of the reporter. These can have artifacts too. Overexpressing the miRNA should be avoided and seed mutations should be done to ascertain the targetability.

Another technique to determine a target mRNA is to mask its predicted miRNA binding site and see the effect on the expression. This has been done in zebrafish using morpholinos complementary to target sites but not on other models AFAIK. This seems to me as an elegant assay- no overexpression and you can precisely determine the target site.


Are genotypes with the same two alleles equivalent even if the alleles come from different parents? I am looking at the following question

  If $m$ alleles may occur at a given locus, how many distinct diploid genotypes are possible at that locus?

The obvious answer is that there their is $m$ possible paternal alleles and $m$ possible maternal alleles so the solution is $m^2$. However this considers inheriting allele $a$ maternally and allele $A$ paternally as the same as inheriting $a$ paternally and $A$ maternally.

If they are considered distinct we have double counted all matchings apart from matchings where the same allele is inherited maternally and paternally so I think the answer to the question if $Aa$ is the same as $aA$ would be $\frac{m(m-1)}{2}+m$

My question is which if any of my interpretations is correct?

Thanks in advance

If you have genomic imprinting then $k^n=m^2$ (with k=m and n=2 because of diploidy) is correct as inheriting a from the father and b from the mother (i.e. ab) is not equivalent to inheriting b from the father and a from the mother (i.e. ba). For 3 alleles (a,b,c) you have 9 possible genotypes (aa,ab,ac,ba,bb,bc,ca,cb,cc).

Under no genomic imprinting, ab and ba are equivalent. This is equivalent of calculating the number of elements of a triangular matrix which is $\frac{(m+1)*m}{2}$. So for m=3, you have 6 possible genotypes (aa,ab,ac,bb,bc,cc), for m=4 you have 10 possibilities (aa,ab,ac,ad,bb,bc,bd,cc,cd,dd) etc...

I hope this helps. Your formula is actually equivalent.


Measuring reverse transcriptase activity in E. coli Goal: To quantify the HIV-1 reverse transcriptase (RT) activity for a number of mutated RTs.

Idea:

Put RT into a vector in E.coli.
Deliver GFP mRNA to E.coli.
RT will process the mRNA.
The resulting DNA will be integrated into E. coli.
RT activity correlates with the GFP we observe.

First question: Does this logic make sense?

Second question: An alternative procedure?

the devil is in the details here - the logic is okay, but there is no experiment here. Too many unanswered questions.

Are you doing anything specific to see optimize RT activity?

How are you preventing your GFP mRNA from being turned into protein, producing much larger signal than you will ever see from RT activity?

Once its integrated into the chromosome, how will this gene be expressed when it has been suppressed in all these other stages?

How do you know that the plasmid isn't just being incorporated into the chromosome by some other means?

Where is the RT coming from ?  E coli doesn't have the gene. this experiment is very likely to give no results.

When/how does this RT work?  If its some sort of phage RT ( i don't know if there are such things) any sort of viral RT will probably kill the cell the way normally it would.

so many questions before this could work - need to do some homework here.


Are Night Parrots (Pezoporus occidentalis) really extinct? This incredibly rare animal has been reported to be extinct since 1990, however several cases has been raised that night parrot was spotted in the areas of Australia. What is the cause of their extinction, or in the first place, are they really extinct?

As per Wikipedia it is listed as endangered having been downgraded from critically endangered due to the spread in sightings over the years over a large area. Sightings have been rare with a reported sighting on 12th April 2005 and a dead specimen found in 2006 The first photos and a 17 second video of the bird was taken by a wildlife photographer John Young in 2013. Details can be found in this link.

According to Birdlife.org the reason for its population to decrease significantly include predation by feral cats and foxes, altered fire regimes, competition for food, degradation of habitat near water by stock or rabbits, and reduced availability of water as a result of over-use by feral camels.


Which part of the brain needs to be shut down to lose conciousness? Whether it is mechanical (trauma), chemical (anaesthesia) or electrical - which part of the brain is shut down to cause loss of consciousness?

There is no widely-accepted neurological structure that mediates 'consciousness.' Even if some structures have been shown to be necessary for consciousness, they have not been shown to be sufficient. This is true with anesthetic mechanisms as well -- their ability to paralyze and block pain signals is fairly well-understood, but the mechanism of loss-of-consciousness is still unknown.

Still, 'consciousness' has to be there, somewhere between being awake and being dead, states which anesthetics can readily bridge (review):

  Nevertheless, at some level of anesthesia between behavioral unresponsiveness and the induction of a flat EEG [indicating the cessation of the brain’s electrical activity, one of the criteria for brain death (22)], consciousness must vanish.

Later in the same review:

  The evidence from anesthesia and sleep states (Fig. 2–3) converges to suggest that loss of consciousness is associated with a breakdown of cortical connectivity and thus of integration, or with a collapse of the repertoire of cortical activity patterns and thus of information (Fig. 2). Why should this be the case? A recent theory suggests a principled reason: information and integration may be the very essence of consciousness (52).

This is consistent with my own take. Consciousness itself is the subjective experience of 'brain,' so it can't be lost, just poorly integrated.


how to clone a gene fragment in two direction as sense and antisense in vector I have a sequence ATG GGG CCC TTT AAA TAA and want to use it as antisense RNA in my vector. How should I clone it? I am confused with the direction of my clone. I looking for the direction and sequence of the clones.

Tour sequence's complementary is TAC CCC GGG AAA TTT ATT. Together they form a DNA strand. Now replicate this and then, after transcription of both the DNA you get the RNA sequence you wanted. Use it as sense or antisense.


Lyonization and X-linked disorders? Lyonization or X-chromosome inactivation is the conversion of all but one, X-chromosomes in Females into non-coding heterochromatin (i.e. deactivated) leading to the formation of one or more Barr bodies. The selection of the X-chromosome to be inactivated is different in different animals. In female Marsupials, the inactivation is always of the Paternal X-chromosome while in placental mammals, the selection is random. (Although the extent of lyonization is not completely random and varies directionally with age).

My question is

  If the X-chromosome to be inactivated is randomly selected in
  placental mammals (including humans), then why don't the females
  heterozygous for a X-linked recessive disorder do not show the
  phenotype of the disease though the functional gene is equally likely
  (as compared to the defective) to be the one to be lyonized?

There are some evidences of genes escaping inactivation and managing to exhibit themselves but I don't think they can account for all the recessive x-linked disorders.

The simple answer is that which X chromosome is inactivated varies in different cell lineages, so typically a female will have cells exhibiting either wild-type or mutant phenotypes. It was Mary Lyon's observation of mosaicism in heterozygous mouse coat colour that gave the phenomenon its name. So in the case of a recessive disease there will be a phenotype, but in many cases the 50% of cells expressing the normal gene will provide sufficient functional cells to get by. From the Wikipedia article about Mary Lyon:

  Her research has allowed us to understand the genetic control mechanisms of chromosome X, which explains the absence of symptoms in numerous healthy women that are carriers of diseases associated with this chromosome.

Edit - response to comments:

Plug, I et al. (2006) Bleeding in carriers of hemophilia. Blood 108: 52-56

Abstract:

  A wide range of factor VIII and IX levels is observed in heterozygous carriers of hemophilia as well as in noncarriers. In female carriers, extreme lyonization may lead to low clotting factor levels. We studied the effect of heterozygous hemophilia carriership on the occurrence of bleeding symptoms. A postal survey was performed among most of the women who were tested for carriership of hemophilia in the Netherlands before 2001. The questionnaire included items on personal characteristics, characteristics of hemophilia in the affected family members, and carrier testing and history of bleeding problems such as bleeding after tooth extraction, bleeding after tonsillectomy, and other operations. Information on clotting factor levels was obtained from the hospital charts. Logistic regression was used to assess the relation of carrier status and clotting factor levels with the occurrence of hemorrhagic events. In 2004, 766 questionnaires were sent, and 546 women responded (80%). Of these, 274 were carriers of hemophilia A or B. The median clotting factor level of carriers was 0.60 IU/mL (range, 0.05-2.19 IU/mL) compared with 1.02 IU/mL (range, 0.45-3.28 IU/mL) in noncarriers. Clotting factor levels from 0.60 to 0.05 IU/mL were increasingly associated with prolonged bleeding from small wounds and prolonged bleeding after tooth extraction, tonsillectomy, and operations. Carriers of hemophilia bleed more than other women, especially after medical interventions. Our findings suggest that not only clotting factor levels at the extreme of the distribution, resembling mild hemophilia, but also mildly reduced clotting factor levels between 0.41 and 0.60 IU/mL are associated with bleeding.

Bimler, D & Kirkland, J (2009) Colour-space distortion in women who are heterozygous for colour deficiency. Vision Research 49: 536-543

from the Introduction:

  About 15% of women are heterozygous for some form of colour vision deficiency (CVD). That is, they possess a genetic abnormality on one of their two X chromosomes, affecting the photopigments (opsins) which subserve colour vision. The retina of a heterozygous woman is a mosaic in which some cone cells express the aberrant gene while others express the normal copy, depending on which X chromosome is active (inactivation of one X chromosome occurs randomly in retinal stem-cells at some stage of fetal development). The normal cells are sufficient to provide full trichromatic vision.


How long does a signal from the brain take to reach the limbs? If the brain sends a signal to move what's the time it takes the signal to travel via neurons to motor neurons in hands, arms and legs?

How fast do those signals travel?

Speed of transmission is going to vary depending on the neuron fiber subtype.

Specifically, the biggest gains will be seen with cross-sectional area (feel free to ask why on physics.stackexchange.com) and neurons with myelin sheathes (fat wrappings which affect saltatory conduction rates).

You're specifically asking about Efferent neuron transmission rates, but here's a general idea:

Keep in mind that the entire circuit (from pre-motor cortex to muscle spindles) will involve several different types. In-general, your central nervous system (brain, brain-stem, spinal chord) are A-alpha, and if I recall correctly - the somatic nervous system (the voluntarily-activated neurons throughout the rest of your body in the PNS [peripheral nervous system]) are A-delta. If I'm wrong, somebody please correct me.

On average non-voluntary reflexes (which is actually information going to the CNS, being processed, and then going out to the motor neurons) take about 0.3 seconds. However, the average human can blink in about 0.1 seconds, which is probably a better measure.


Can a virus be transmitted from a sweating person out to another person? In the sport of Jiu-Jitsu, close contact with many partners is common. Many times these partners are sweating profusely (Yuk), which in turn drips on the other person sometimes into the eyes, nose, and yes mouth. I am just wondering if viruses can enter in this way.

Sweat per se, at the source, is not likely to be contaminated with bacteria or viruses. However, that's a moot point, because as soon as it's produced it's on contact with the sweaty person's skin, which is invariably coated with bacteria and potentially with viruses. Sweat can therefore act as a medium for transferring infectious agents between two hosts.

Examples of this are described in Contact transmission of vaccinia virus from smallpox vaccinees in the United States, 2003–2011:

  Among adult male cases, the most frequently reported activities associated with vaccinia transfers were wrestling, grappling or sparring (n = 18) [12,18–20]; household interactions (e.g., sharing towels, clothing) (n = 6); unspecified “contact” (n = 4); and football or basketball (n = 3).

(Vaccinia virus is the vaccine for smallpox. As such it's far less dangerous than smallpox itself, but as an ancient vaccine it's also much more dangerous than the vast majority of modern vaccines, and exposure to large concentrations of the virus in an uncontrolled setting is potentially risky.)


Rattlesnakes developing stronger venom I have heard that rattlesnakes are developing stronger venoms causing more people each year to die from rattlesnake bites.

But why would a snake that is already very venomous need to develop stronger venoms? I mean for the venom resistant ground squirrels couldn't the snake just wait longer or maybe strike more than once before it eats?

And I could see this going to venom overload in the next few centuries. If rattlesnakes keep developing stronger venoms at the pace that they are then rattlesnakes could become as venomous as a cobra or worse. Along with that it might rattle less and less until it just stops using the rattle.

Is is because of the fact that we are developing stronger pit viper antivenoms(mainly by injecting rattlesnake venom, copperhead venom, and cottonmouth venom into an animal with a stronger immune system like a horse and after a while, getting the antibodies needed for the antivenom) that rattlesnakes are developing stronger venoms?

I did find an article which mentions the venom strengthening:
http://www.sciencedaily.com/releases/2012/06/120605102638.htm

It may be an evolutionary bonus. Snakes with the most potent venom may leave fewer survivors, particularly with something like humans who would hunt down a snake if they could find it. A snake which leaves fewer survivors may be better able to escape. It may also have more successful hunts which may have been what lead them to become poisonous to begin with.

Unlike the antibiotics arms race against bacteria, it's unlikely that antivenoms are the cause of more dangerous snakes.

As far as "centuries from now" we really can't hypothesize whether more potent venom will continue to be a more helpful evolutionary trait. More potent venom doesn't have an infinitely continuing effectiveness. After a certain point, whatever bitten isn't any more dead with a stronger poison.


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

The incubation period is the time it takes from the infection of a patient with a disease until he develops symptoms. How fast this happens depends on the disease.

According to the references the main difference is that SARS 2003 replicates in the lung/lower airways, while SARS-CoV-2 also replicates in the upper airways and sheds high viral loads there early in the course of the disease.

Since both diseases are transmitted by droplets, it is much easier to have a sufficient viral load in infected cells from the upper airways compared to the lower ones.

References:

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