Why do hair on head not get pilo-erected? Whenever we have "goosebumps", there is a momentary piloerection, due to which hair on our elbows and legs get "erected" and "stand" almost perpendicular to the surface of our skin. But why do our "head hair" not get erected ?

Piloerection of head hair does happen as often as it occurs elsewhere on the body, but head hair length tends to make it difficult to see. Close observation, especially with short hair, should make it visible.

Piloerection of head hair is something more commonly felt by the person it is happening to rather than seen by others (or in mirrors); when you get that "goose-bump" sensation across your scalp, that will be due to pilo-erection.

(PS added) I haven't provided citations - this is not a phenomena that has had much specific academic research and I have not found any stating it occurs - or stating it does not occur (except in association with balness) despite looking, but is almost universally experienced, often without close examination or reflection about what specifically happens.

Citing references for baldness resulting in absence of piloerection on the scalp is not quite the same as a reference specifically stating it happens, but ... Professor Rodney Sinclair, head of dermatology at the University of Melbourne says - “You can’t get goose bumps on the scalp when you go bald and you can’t regrow hairs either because the follicles can’t regenerate.” ( https://www.futurity.org/goose-bump-muscle-1324242-2/ ) ( https://link.springer.com/article/10.1007%2Fs12565-016-0359-5 )


Is Norepinephrine beta2 adrenomimetic? I know that it has alpha1, alpha2 and beta1 effects.
It has beta2 receptor where epinephrine can effect.
However, to say that it is beta adrenomimetic, I am not sure.
That is ligand binding beta2 receptor causes a stimulatory effect.

Is norepinephrine beta2 adrenomimetic?

The answer can be found in PubChem, which is linked in the comment by anongoodnurse.

I would not say that

Norepinephrine is beta2 adrenomimetic

because norepinephrine has many roles such as neurotransmitter.
I would just say that

Norepinephrine is alpha, beta adrenoagonist.

More pieces of information about it from PubChem:


How spinal cord play its roles in human beings sex? I know most people can't enjoy sex if their spinal cord injured.

How spinal cord play its roles in human beings sex?

One of the major functions of the spinal cord is to serve as a "highway" for signals to travel between the brain and the sensory (and motor) organs. Thus, sensory the signals that are generated on the body during sex must travel up through the spinal cord in order to get to the brain, where it will be processed into a pleasurable sensation. If the spinal cord is damaged, the signals will not be able to reach the brain and thus there will be no generation of pleasurable sensations.

Here's an image that shows the general sensory pathways. You can see they travel from the sensory organ to the spinal cord, and up it to the brain.


What is the origin of prions? We know something about the origin of the first cell. But what do we know about prions? How did they originate?

The computational study by Ehsani et al., 2011, argues that an ancestor metal-ion transporter gene ZIP served as the initial template for the prion founder gene, where the same author produced a 2012 paper that said this was probably a product of a spliced LIV-1 ZIP transcript that became reverse transcribed and inserted into the host genome. Thus, evidence in part points to a retrogene origin for prions (mediated by a retrovirus, especially since the gene is integrated into the host w/ no introns). They go on to state that two genomic rearrangements spanning hundreds of millions of years serve as the basis for the prion founder gene: A cysteine flanked core element inserted into the ZIP ectodomain, and then the insertion of a spliced, C-truncated ZIP transcript.

I don't think the evolutionary origin of prions are very well understood, yet, but I will try to find more recent data on the subject.


dAT joining: please define I came across a reference to dAT joining in my reading of Genentech by Sally Hughes. The technique is described in passing as a technique for joining DNA fragments used around the late sixties to early seventies (likely prior and after, too, of course).

A quick query into earlier visits of the topic on the exchange returned no relevant results, but the results may have been have been obscured by the copious references to the neurologic "DAT" term (dopamine transporter).

Please provide a quick explanation to this concept/technique if you're familiar.

In the context of this book, dAT joining is a method used in molecular cloning to join two DNA molecules. Basically, terminal transferase is used to add polyA or polyT to the 3' ends of each DNA molecule. This creates cohesive ends which can anneal and then be ligated together, giving a covalently closed circular DNA molecule.

Image from: Jackson DA, Symons RH, Berg P. 1972. Biochemical Method for Inserting New Genetic Information into DNA of Simian Virus 40: Circular SV40 DNA Molecules Containing Lambda Phage Genes and the Galactose Operon of Escherichia coli. Proc Nat Acad Sci USA 69(10):2904-2909.

See also: Lobban PE, Kaiser AD. 1973. Enzymatic end-to-end joining of DNA molecules. J Mol Bio 78(3):453-460.

dAT joining can also refer to an assay of DNA ligase activity. Linear dAT oligomers are incubated with the ligase, which can circularize them and make them resistant to exonuclease digestion. This resistance to digestion correlates with DNA ligase activity.

Modrich P, Lehman IR. 1970. Enzymatic Joining of Polynucleotides. J Biol Chem 245(14):3626-3631.


Difference between CDS and cDNA What is the difference between Coding Sequences (CDS) and cDNA?

Are Coding sequences the sequences that is transcribed to mRNA and cDNA in contrast DNA obtained by reverse polymerization of matured mRNA?

The difference boils down to UnTranslated Regions. A CDS or coding sequence is the part of a transcript that is actually translated into protein. Therefore a CDS will (almost) always start with an AUG codon and stop at one of the three STOP codons (UAA,UGA,UAG).

The transcript however (note that I am referring to mature transcripts that have already been spliced so introns have been removed) will also contain the UTRs which are not actually translated into protein. A cDNA sequence is derived from the transcript by reverse transcription and will, therefore, also contain the 5' and 3' UTRs. For example, see this schematic diagram of an unspliced transcript:

The CDS of the gene depicted in image above will only contain the ATG, the STOP and the two green regions (exons). The cDNA will contain all that and, in addition, the two UTRs. Of course, both the cDNA and the CDS will not contain the introns.


identify some kind of vine I have found this plant in Trabzon, a city in Turkey. I found it near the highway. I assume it isn't planted intentionally, but maybe left after previous ornamantel plantings. It smells good I think. I am interested in it because of the nice scent. Please could you help me to find what species is this.

edit: and I forgot to add its fruits. I want to plant this vine, but if there are better varieties, I can plant them instead.

Sadly flowers lost their conditions because i collect them 2days ago. and i transported them in a plastic bag.

This is a clematis, probably clematis vitalba.

This plant is native to Europe and Turkey. It also occurs on the westcoast of the USA and Australia/New Zealand, but it is probably introduced there. Source occurences

Picture from Dutch wiki:

Many clematis species have a very nice smell, and both the flower and the fruit are also nice to look at. That is why clematis species are grown in garden often, with countless varieties. They differ in color (most are white, pink or purple), in flower size and in flower time (spring/summer).


Why do we find some things disgusting and others delicious? For example, why do I love paprika while my girlfriend hates it? Why do I find broccoli disgusting and she adores it? As humans, there are things we'd all agree on being awful, like rotten meat, for obvious evolutionary reasons - those things are damaging to our body and we should not eat those. But when asked about delicious food, everyone would pick something slightly (or completely) different.

I wonder, is it because our tongues are different and the food does indeed taste different, or is it our brains that interpret the same taste differently? Also, what evolutionary purpose does this serve? To me it only makes planning the dinner a pain without really adding anything to our lives.

Explaining phenotypic variance

You may want to make sure you have a good understanding of the concepts of the underlying variance of phenotypic variance (discussion linked to the concept of heritability) before reading this answer. In this post, I linked several sources of information on the subject.

Culture (environmental variance)

Variance in food preference is in part (in majority eventually) explained by cultural differences.

Genetic variance

I guess that very few people like the smell of rotten eggs. There is selection on taste and smell preferences. Those who don't like the smell of rotten food increase their chance to suffer from bacterial intoxication and mycotoxins. I remember from my Bachelor degree (can't find the study right now) Nestlé (among others probably) performed a genome-wide association study that showed genetic variance for food preferences.

Adaptation

There are probably many loci that are now fixed (not polymorphic anymore) that were at some point under selection as explaining variance for food preference. In other words, at a given locus there might have no more genetic variance as the current allele is well adapted.

By-products

Also I suppose that a part of the underlying genetic and environmental variance for the variance for food preference might be qualified as by-products. For example, it might be beneficial to appreciate a given smell because the smell when present in the sweat of a partner is associated with greater health. If this odour (or similar odour) happen to be present in food, then we may be indirectly selected to appreciate this food item as a by-product of the selection for recognizing healthy partners.


Which DNA polymerase can use a nick as priming site? Which DNA polymerase (commercially available) can initiate polymerization at nicks, without a standard primer?

My goal is to perform rolling circle amplification starting at a nick.

It sounds like you are looking for a DNA polymerase that can perform nick translation. NEB maintains a chart listing the properties of their polymerases, including nick translation and extension from nick.  Without additional details, it looks like Taq would work for your purpose.


Identify a bird by its feather Gray feather with red tip, about 5 cm (2 in) total length. It was found in Lexington, Kentucky (central western USA).

It seems to be the secondary feather of a Waxwing, a bird from the Genus Bombycilla, like Bombycilla cedrorum:

Cedar waxwing. Source: https://rctfan2.deviantart.com/art/Cedar-Waxwing-285656802

Actually, that red tip gives the bird its name (from the Wikipedia link):

  They have unique red tips to some of the wing feathers where the shafts extend beyond the barbs; in the Bohemian and Cedar waxwings, these tips look like sealing wax, and give the group its common name.

Therefore, the possible species are the Bohemian waxwing (B. garrulus)...

... and the Cedar waxwing (B. cedrorum):

However, since the secondaries of B. garrulus normally have a white area next to the tip...

... I'd guess that your feather belongs to B. cedrorum.

In conclusion

Besides the white patches in the feathers of Bohemian waxwings, OP just confirmed that the range of the Bohemian waxwing doesn't match. Therefore, this feather belongs indeed to a Cedar waxwing.


Do human visual functions degenerate due to genetic factors or by external factors? Does eyesight primarily deteriorate 'naturally' due to genetics (genomic/epigenomic factors), or due to external factors such as normal wear and tear, or disease?

By normal wear and tear I include things like repetitive straining of the eyes by reading small text in a dim room night after night.

As a background to my question: By dissecting the causes of visual deterioration into genetic factors versus external factors I hope to relate those causes to the age of onset, and rate of decay of visual acuity.

Vision deteriorates for both reasons, but I'm not quite sure how to separate the effects of aging from wear and tear.

Cataracts are the leading cause of blindness in the world. Ways in which environment (which falls under the category of wear and tear in my book) affects cataract formation:

UV light: people living at high altitudes (e.g. Tibet) have more cataracts 2° to increased UV light than those at lower altitudes (sunglasses with UV protection delays the process)
lead exposure increases cataract formation.
infections in infancy and childhood (rubella, toxoplasmosis, other)

Macular degeneration is another cause of vision loss. Environmental factors include:

smoking: speeds up age related macular degeneration.
diet: diets low in antioxidants, and obesity increase degeneration.

Retinal damage caused by diabetic retinopathy:

Juvenile onset diabetes has long been thought to be associated with viral infections from coxsackievirus B, cytomegalovirus, adenovirus, rubella, and mumps.
Type II diabetes is influences by obesity, lack of exercise, certain medications, (nicotinic acid, some diuretics, anti-epileptics, psychiatric drugs, and drugs to treat HIV (can impair beta cells or disrupt insulin action); Pentamidine (used to treat a type of pneumonia) can cause pancreatitis and diabetes; glucocorticoids/steroid hormones may impair insulin action.

Corneal opacities:

infections: (Chlamydia trachomatis) bacteria that are spread by close contact with an infected person or by flies, especially common in Africa.
recurrent injury (soot and pathogens from indoor smoke, a dusty, windy environment).
vitamin A deficiency

Nearsightedness:
- near-point work: reading, working with a computer all day, etc.

Glaucoma:
- diabetes, obesity, near-point work, other.

Nonenvironmental causes would be genetics and illnesses associated with aging.

genetic predispositions associated with diabetes, nearsightedness and farsightedness
decreased lens plasticity with age
strokes secondary to hypertension, etc.
amblyopia (“lazy eye”), strabismus (when eyes are aligned in different directions), astigmatisms
hereditary causes of glaucoma and age-related macular degeneration
retinitis pigmentosa, (degenerative disease of the retina)
innumerable genetic disorders (Marfan's, Tay-Sachs, Albinism, Cone-rod dystrophy, various autoimune disorders, etc.
retinoblastoma
predisposition to glaucoma

 Focusing on Vision Through an Environmental Lens
 Glossary of Eye Conditions
 Causes of Diabetes
 Inherited Eye Disease


Cloning and Telomeres I read that the length of telomeres in Dolly was shorter, because the DNA was taken from an old sheep. Shorter telomeres may lead to early aging. What is happening now with cloning? Do we use a telomerase to restore the length in a donor cell?

No, it doesn't seem to be common practice. A telomerase treatment would probably do more harm than good, and may be completely unnecessary in the first place.
Betts and coworkers published a study in which they examined telomere length in cloned cattle. They found that while telomere length in cloned embryos does start out somewhat shorter than in naturally produced embryos, by the time that the normal processes of embryonic development were in full swing telomere length in cloned and natural embryos was equivalent.
Betts' results make sense in light of the fact that telomerase activity (and the activity of many, many related proteins) is normally upregulated in embryonic cells.
As for Dolly, while it is true that her telomeres were shorter than those of an average age-matched sheep at the time of her death, it's far from clear that those short telomeres had anything to do with her decline. Also keep in mind that she didn't just keel over suddenly in the night, she was euthanized. A subsequent autopsy showed that she had a form of lung cancer caused by a retrovirus common in sheep.
Edit: why were Dolly's telomeres shortened?
This is a good question, as the findings of shortened telomeres in Dolly's case do contradict the findings in the Betts paper. Clearly we need more citations:
-"Analysis of telomere lengths in cloned sheep." Shiels et al, 1999
This is the original citation for the claim that Dolly's telomeres were shortened. There isn't too much extra information to be had as it's a very short paper (1 page letter). They did look at other cloned sheep created from types of cells other than skin cells (as Dolly was) and saw the same kind of telomere shortening relative to controls. They also make a point of mentioning that Dolly's telomere length may be within the normal variation for sheep.
-"Remarkable differences in telomere lengths among cloned cattle derived from different cell types." Miyashita et al, 2002
The investigators found that telomere length in cloned cattle was strongly dependent on the type of cell from which the clone was derived. For example, clones made from mammary cells tended to have shortened telomeres, whereas those derived from muscle cells had normal length telomeres.
-"The analysis of telomere length and telomerase activity in cloned pigs and cows.", Jeon, 2005
This group found that cloned cattle had normal length telomeres, whereas cloned pigs had elongated telomeres. By way of explaining these results, they found that telomerase activity was upregulated in cloned pigs relative to control pigs, whereas telomerase activity in cloned cattle matched that of control cattle.
How should we take all of this information? At the very least we can say that telomere length in clones is highly dependent on species and on source tissue, and that telomere length can increase, decrease, or stay the same in cloned animals relative to control animals. Clearly telomere length in cloned animals is a fiddly property. It is very likely that it also depends on the exact details of the cloning protocol as it was carried out (i.e. how much did the experimenter's hands shake when they inserted the needle to suck out the nucleus?, etc.).
So I would say not to read too much into Dolly's shortened telomeres. They may have been a result of her being a clone, or they may have been a result of natural variation. In either case the shortened telomeres were not linked to her ill-health, and it's likely that small tweaks to the cloning protocol would eliminate any telomere length discrepancies in future clones.


Acquiring Covid-19 vaccination through kissing with viral vector vaccinated person The mechanism of COVID-19 viral vector based vaccines (AstraZeneca - Vaxzevria, Johnsen, Sputnik V - Gam-COVID-Vac, Johnson & Johnson - Janssen, etc. ) is delivering the genetic information of the corona virus through adenoviruses.
Would it therefore be possible to get "infected" by droplets (f.e kissing) with the manipulated adenovirus from a viral vector vaccinated person and consequently acquire the same vaccination?

No, this is not possible, as the vectors used for the vaccination cannot replicate anymore. Some of the genes necessary for this step have been removed from the viral genome to prevent the uncontrolled spread and replaced by the spike protein which is used as the antigen for the vaccination.
To replicate the virus in the production process, a special cell line with a plasmid carrying the genes necessary for the viral replication has to be used, afterwards the virus is purified and outside of these special cells not able to replicate.
For an overview about the adenovirus type 26 based vaccines, see here:

Vaccines based on replication incompetent Ad26 viral vectors:
Standardized template with key considerations for a risk/benefit
assessment


How does Acetaldehyde accelerate mitosis? I read that one of the ways alcohol is carcinogenic is via accelerated mitosis due to acetaldehyde, I was wondering what pathway caused this acceleration?

First of all Alcohol and Acetaldehyde are both cytotoxic. Along in our development we learned to deal with both substances, which is shown by specific metabolism pathways to break them down (for example alcohol dehydrogenase, acetaldehyde dehydrogenase, Cytochrom P450 and so on).

Alcohol and Acetaldehyde both have a negative effect on mitosis (which explains a good part of the negative effect which alcohol has on developing embryos).
Examples can be the following articles:

Acetaldehyde causes a prolongation of the doubling time and an
increase in the modal volume of cells in culture.
Alcohol inhibits cell mitosis in G2-M phase in cell cycle in a human
lymphocytes in vitro study.
Ethanol induces transient arrest of cell division (G2 + M block)
followed by G0/G1 block: dose effects of short- and longer-term
ethanol exposure on cell cycle and cell functions.
Ethanol induction of sister chromatid exchanges in human cells in
vitro.

Alcohol also has some effect on cancer - probably not by directly causing it, but at least as an additional risk factor. One article I found ("Alcohol and Cancer") mentions the following possibilities:

  The mechanisms by which alcohol consumption exerts its carcinogenic
  effect have not been defined fully, although plausible events include:
  a genotoxic effect of acetaldehyde, the main metabolite of ethanol;
  increased oestrogen concentration, which is important for breast
  carcinogenesis; a role as solvent for tobacco carcinogens; production
  of reactive oxygen species and nitrogen species; and changes in folate
  metabolism.

Using Pubmed you can find more articles on that topic.


Environment requirement for human life I was wondering, what are the humans needs to fulfill to achieve a human colonisation on mars ?

Let me explain, this is for role play game in a futuristic world where humans colonized mars.
That creates questions that needs answers for background purposes.
I saw like each another some scifi, read novels etc. But I'd like to know scientifically what could help us achieve that.

If this post doesnt have it's place here, do not hesitate to remove it.

In my mind :
breath
eat
drink
dont take radiations (at least not to much)
stay at the right pressure and temperature
any gravity issue on our body ?
try to avoid wandering naked in space

Any help is appreciated
thanks guys :)

Here is a good write-up for NASA of human needs in space, which applies to other planets, too.

Here is a table of contents with links to chapters that discuss relevant information for you.

The source is described so:

  Space Settlements: A Design Study, provides information on space
  settlement development and education and assists teachers and students
  in the NASA Ames Space Settlement Design Contest. The design study was
  the result of a 10 week program in engineering systems design held at
  Stanford University and Ames Research Center in the summer of 1975.
  Participants included professors, technical directors and students in
  a variety of disciplines from physical science and architecture to
  engineering and social science. The goal (see preface) was to
  construct a vision of how people might sustain life in space in a
  large colony.


In vivo, does it take energy to move double bonds from cis to trans in long chain unsaturated fatty acids In vivo, I understood that because all polyunsaturated fatty acids bonds are -cis they are crowded, kinking the molecule, and because of that, the oxidative enzymes cannot initially access them. They first have to be moved to the -trans side to allow the enzymes to act on the double bonds. So my first question: is ATP needed to move double bonds from -cis to -trans? And also, when the long-chain FA like EPA & DHA are oxidized, because of this energy expenditure to move them, wouldn't they yield less total bond energy when oxidized than if they were just oxidized in vitro, e.g. by heating?

If this is true, then how much ATP is used to first get those double bond groups into the -trans position so the oxidation enzymes can reach them? And … thus could I state that in vivo breaking of long chain polyunsaturated fatty acids would not yield as much energy as would in vitro breaking of these bonds?

As I understand it the question refers to mammalian oxidative degradation of dietary polyunsaturated fatty acids, as the diet is the major source of such fatty acids. Its concern is with two different aspects of this process neither of which involve the use of ATP. The proposition in the final paragraph is therefore incorrect.

The first aspect is not explicitly stated, but seems evident in the mention of the crowding of fatty acids with cis double bonds and the repetition of “in vivo”. I would rephrase it as:

  How is the agglomeration of lipids disrupted so as to be available to
  the enzymes that degrade it?

This is as much physiology (not my field) as biochemistry, but there are many accounts available (e.g. this I found at random) regarding the emulsification of lipids by bile salts in the small intestine and their conversion to chylomicrons in the lymph and blood. The latter are either processed and stored in the adipose tissue and later oxidized when needed, or oxidized directly, in the mitochondria, especially of the liver.

The disruption of fatty acid aggregates is purely a physical process facilitated by the chemical environment in which they find themselves. This alone allows oxidative enzymes access. (In passing, I would say that it is difficult to conceive of a mechanism by which ATP could be used to disrupt a hydrophobic aggregate — see Appendix.)

The only stage at which ATP is required is the conversion of free fatty acids to fatty-acyl CoA by fatty acid thiokinase before reaction with carnitine and entry into the mitochondria in the form of acyl carnitine. In relation to the handling of hydrophobic molecules in a hydrophilic environment (or vice versa for membrane transport) it may be worth mentioning in passing that carnitine is a zwitterion.

The second aspect of the question is more straightforward. In chemical terms what the question refers to as “moving double bonds” is called isomerisation. So the question is:

  Does cis-trans isomerisation of unsaturated fatty acids require ATP?

This is described in standard biochemistry texts such as Berg et al., from which the diagram below is taken.

No ATP is involved.

Of course a reductase is required to catalyse the reduction of double bonds using NADPH as a reducing agent, regardless of whether they are cis or trans. As the related NADH can be oxidised in the electron transport chain to produce ATP by oxidative phosphorylation, this could be regarded as equivalent to using ATP. However this has nothing to do with the isomerisation.

Appendix: ATP and energy — concepts and  misconceptions

Although this question includes some chemically correct references (the need for cis-trans isomerisation for unsaturated fatty acids to act as a substrate for acyl CoA dehydrogenase), it does raises some suspicions of an incomplete grasp of the factors affecting the viability of biochemical reactions and the role of ATP. If this is correct — and shared by others — I suggest reading an account of how the concept that the Gibbs free energy change of a chemical reaction determines whether or not it proceeds, and how the negative free energy change in the hydrolysis of ATP can be coupled to reactions that have an (otherwise unfavourable) positive free energy change.

Two points relevant to the question are worth mentioning in this regard. Although ATP can be used to cause motion, this involves motor proteins like myosin, kinesin and dynein interacting with large molecular structures. Thermal vibration and thermodynamics are the normal drivers of motion in a cell. The second is that many biochemical isomerisation reactions have standard free energy changes close to zero as, in isolation, the alternative structures have similar energies. What normally prevents the reaction proceeding is the activation energy barrier for the interconversion reaction of one isomer to the other, which is where enzymatic catalysis is comes in. The actual free energy change depends on the concentration of reactants and products, so if the cis isomer builds up and the trans product is removed by reaction then the reaction will proceed in the cis-to-trans direction.


How a vegan can consume all the needed varied proteins / amino acids? I would like to ask if there are some proteins that the human body needs and can being endowed only from meat?

According this:

  Other protein sources, such as fruits, vegetables, grains, nuts and
  seeds, lack one or more essential amino acids. Vegetarians need to be
  aware of this. People who don’t eat meat, fish, poultry, eggs, or
  dairy products need to eat a variety of protein-containing foods each
  day in order to get all the amino acids needed to make new protein.

How a vegan can complete these missing proteins?

Proteins are made up of amino acids. It isn't particular proteins that are necessary in diet, but particular amino acids. For humans, these come primarily from breaking down the proteins in foods we eat.

Essential amino acids are the amino acids that humans cannot synthesize; other amino acids can be synthesized from these, but they do not need to be part of the diet. Not all sources of protein have sufficient quantities of all of the essential amino acids. When people refer to a protein source as "incomplete" they mean that particular source is low on one or more of the essential amino acids.

Meat products are typically "complete" because they contain all of the essential amino acids together. Therefore, if you subsisted on various foods but only got your protein from one animal source, you would be okay.

Some plant products do not have all the essential amino acids in large concentrations. However, if you combine protein sources from different "incomplete" plant sources that together cover these deficiencies, there is no disadvantage compared to a single "complete" source.

You also have a fairly substantial reserve of amino acids in the form of all the proteins in the body, which are constantly broken down and recycled. The daily protein intake is just a tiny fraction of the total amino acid content in the body.

Here is a paper that talks about some of these issues, and addresses some of the myths about balancing proteins. The quick summary is that problems develop if you get your sole protein from a source that is low in a particular essential amino acids over a long time period, but there is no need to ensure every meal contain all the amino acids.

It is possible for people on unusual protein diets, such as vegans, to develop a particular amino acid deficiency. There are many many guides on the internet for protein sources to mix to avoid this problem. A common combination is a legume (beans, peanuts) and a grain (wheat, rice). There are also some vegetable sources that provide complete protein nutrition - soy, for example, mostly works as long as it is not truly the only source.

References:

Young, V. R., & Pellett, P. L. (1994). Plant proteins in relation to human protein and amino acid nutrition. The American journal of clinical nutrition, 59(5), 1203S-1212S.


An alternate cure for AIDS? Is is possible to cure AIDS patients by using white blood cells of blood cancer, by fooling HIV to attack a false target?

Is it possible to wrap HIV in a physical boundary, such that it has no interaction out side the wrapper, so the functionality of the cell will not be affected by HIV?. Since all cells in out body are replaced within three years, after 3 years, the HIV affected victim will have fresh HIV free cells.

What would you choose when your treating physician gives you the option: leukemia or antiviral treatment? HIV is not lethal anymore these days, at the least life expectancy can be substantially prolonged. Admittedly, treatment is life long and not a cure, but you'll live.

Leukemia on the other hand, is life threatening and needs immediate treatment. Treatments for leukemia are primarily chemotherapy, and perhaps radiation therapy, biological therapy, targeted therapy, and stem cell transplant, all of which are by no means guaranteed to be curative.

But interestingly: a Berlin leukemia patient with HIV was actually cured after receiving chemotherapy and having received HIV-resistant stem cells to repopulate his white blood cells (Source: Medicine Net). The donor carried the relatively rare mutation called CCR5delta32. People with this mutation lack functional CCR5, the protein that HIV most often uses to enter cells.

Why is this not a standard treatment? The Berlin patient serves as a good example, because the patient suffered intestinal and neurological symptoms due to the chemotherapy. And besides being dangerous in itself, chemo is truly a grueling experience to go through. And in fact, this patient was the only instance in which this approach was followed (Source: Medicine Net).


What is the concentration of ATP in an average cell? Can someone give me some references showing the average concentration of ATP in a cell?

Answer

This article covers the energy charge and ATP concentrations of an array of muscle cells from many different organisms. Since many factors come into play (amount of glucose available, rate and regulation of glycolysis and cellular respiration, use of energy in metabolism, etc.) it is expected for the ATP concentration within the cell to vary significantly. The ATP concentrations reported span from approximately 1 to 10 mM.

References

 - Beis, I, and E A Newsholme. “The Contents of Adenine Nucleotides, Phosphagens and Some Glycolytic Intermediates in Resting Muscles from Vertebrates and Invertebrates.” Biochemical Journal 152, no. 1 (October 1975): 23–32.


How is HIV evolutionarily viable despite its extreme virulence? How does HIV survive natural selection? And how has it managed to kill far more than any non-airborne virus in recorded history?

Human Immunodeficiency Virus is a mutated form of Simian Immunodeficiency Virus. In simians (Apes and Monkeys, not including humans), SIV is not pathogenic, in most cases, however, when the mutated form made the jump to humans, it became highly contagious and virulent. You can find a basic description in the wikipedia article here: Simian Immunodeficiency virus.

As for your second question, I would likely say that influenza has killed more humans in total than HIV, so you would have to provide a reference for your claim.

However, because HIV is a retrovirus that incorporates into the genome of the immune cells of its host, it can survive in the body for long periods of time in a dormant state. A person may not know they are infected for months or years, and they can pass the virus on to other people. Slow killing viruses such as HIV are very dangerous, as they can be transmitted to large swaths of the population before people are aware they are sick.

Update:

Based on comments, there may be a misunderstanding of the term virulence. From The Karolinska Instetutet medical subject heading (MeSH) definition:

  The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.
  -The Karolinska Institutet; Virulence

The emphasis is mine, but virulence also refers to the ability of the virus to infect its host, and does not necessary lead to the hosts death. The virus that causes the common cold is highly virulent, but for almost the entire human population it causes nothing more than discomfort.

A virus like Ebola on the other hand is highly virulent in both senses of the term. The reason that there are far fewer cases of Ebola is that it kills the human host so quickly, that an afflicted person will on average only go on to infect about two other individuals, mainly because victims 1) die quickly, 2) are only contagious after symptoms manifest themselves, and 3) requires direct contact with the infected person's bodily fluids.

Contrast that with Influenza which a single person can infect tens to hundreds of people and is contagious before they are displaying symptoms and spreads it with casual contact, or as stated above, with HIV, where a person can be contagious for weeks, months, or even years before they are aware that they are infected, and you see why HIV is very sustainable in the Human population.

HIV also has the added weapon in its arsenal that it can lay dormant in cells for long periods of time so as to escape the detection of the host immune system, and as the disease attacks and kills immune cells, when the dormant virus activates again there are far fewer specialized cells to address the active infection.

Another thing is it is the comorbidity with other diseases that often results in the death of a patient with an HIV infection. AIDS results from other diseases having the opportunity to go unchecked after HIV has decimated the host immune system.


Is end-systolic volume (ESV) the same as residual volume? I am reading this site and my study materials.
The end-systolic volume (ESV), 50-60 ml, is the volume of blood found in ventricles after systole and contraction of ventricles.

I think ESV is the same as residual volume because residual volume is always the volume found in ventricles.

Is ESV the same as residual volume in normal physiological situations?

The ESV is the residual volume of blood remaining in the ventricle after ejection.
It is the minimum volume of blood in the ventricles (residual volume).
Note that you can also have residual volume of air in the lungs after exhalation.


What is the tRNA gene copy variation between different yeast strains? I just started working on predicting steady-state protein levels from different codon usage bias measures. I have whole-genome sequences (it's NGS data) from different strains of S. cerevisiae and S. paradoxus and I began to wonder if it's possible that different strains of the same species could have different copy numbers of tRNA genes? If so, would this be detectable in the sequencing data (presumably the reads were mapped onto a reference genome so maybe this copy number variation would be lost)?

I'd take that computational angle and run the sequence data through tRNAscan-SE (Lowe & Eddy, Nucl Acids Res 25: 955-964). Ideally, you'd install this locally. This tool is what the UCSC folks use and it has been the best known, most widely used tRNA predictor for years. It's what we all used on Arabidopsis thaliana genome annotation back in the late 1990's.

There is also a genomic tRNA database that may have many of the predictions you seek, at least for some of your species/strains.


What is the reaction mechanism of dopamine hydroxylase converting dopamine to norepinephrine? The reaction is basically shown below. Dopamine hydroxylase is an enzyme, so I'm not sure if we can have a theory based on organic chemistry. On the other hand, maybe there is a theory that involves structural biology?

Evolutionarily speaking - the enzyme has evolved to add OH to the beta-carbon rather than somewhere else. I'm really wondering what in the enzyme's shape makes the OH added to the beta carbon, rather than somewhere else. In other words, what is the structural mechanism behind substrate specificity?

There are various studies on the mechanism of action of dopamine beta-hydroxylase (DBH).

This review (sorry, non-free article) by Kaufman and Friedman was written less than 10 years after the discovery of the reaction of conversion of tyrosine into [nor]adrenaline in the adrenal gland:

DOPAMINE BETA-HYDROXYLASE - Kaufman S., Friedman S. - Pharmacol Rev. 1965 Jun;17:71-100.

It makes for an interesting read, as they start detailing the history of our knowledge on adrenaline synthesis (well, at least at that point in time!), the various hypotheses and models that were thought of, experiments with radioactive labeled precursors and so on.

They then procede to talk about the mechanism of the enzyme. Without going too much in detail, they report experiments showing that oxygen, ATP and Mg++ stimulate dopamine beta-hydroxylase enzymatic activity, with the following note on Mg++:

  [...] Mg++ is required for the uptake of catecholamines by the adrenal vesicles. EDTA inhibits the uptake of the precursor, hydroxytyramine, but does not inhibit the enzymatic conversion to norepinephrine if the vesicles are intact.

They also list the requirement for two cofactors: ascorbate and copper

  The first indication that Dopamine-beta-hydroxylase is a mixed-function oxidase was the demonstration of a requirement for ascorbate. It was found that this reducing agent
  could stimulate the hydroxylation reaction even in adrenal particles, and the requirement for ascorbate became more pronounced as the enzyme was purified.

Bringing to the reaction:

  Dopamine + ascorbate + O2 → L-norepinephrine + dehydroascorbate + H2O

For the Cu:

  Only recently, however, was the enzyme obtained in a pure state and the metal characterized by direct analysis. The metal is copper and it is present in a concentration of 0.65 to 1.0 ug per mg enzyme (4 to 7 moles of copper per mole of protein). It can be removed by treatment with concentrated potassium cyanide. This copper-free enzyme is inactive but can be reactivated by addition of Cu.

They then proceed to detail some basic mechanism of action, which I will not report here for briefness.

A few years later, researchers from the same group authored a book chapter for the American Chemical Society entitled:

The Mechanism of Action of Dopamine β-Hydroxylase - Kaufman S., Bridgers W.F., Baron J - in Oxidation of Organic Compounds, Chapter 73, pp 172–176, 1968 - Chapter DOI: 10.1021/ba-1968-0077.ch073

From the abstract (I do not have access to the full text of this):

  Dopamine β-hydroxylase catalyzes the side-chain hydroxylation of dopamine and other phenylethylamine derivatives. Ascorbic acid serves as a specific electron-donating cofactor. The enzyme from bovine adrenal glands contains Cu2+ and a smaller amount of Cu+. When the enzyme oxidizes ascorbate to dehydroascorbate, most of the Cu2+ is reduced to Cu+. Added substrate is hydroxylated, and Cu+ is reoxidized to Cu2+.

To get to some more recent years...

In this review

New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. - Prigge ST, Mains RE, Eipper BA, Amzel LM. - Cell Mol Life Sci. 2000 Aug;57(8-9):1236-59.

A mechanism for Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) is proposed, and

  Since PHM is homologous in sequence and mechanism to dopamine beta-monooxygenase (DBM; EC 1.14.17.1), the enzyme that converts dopamine to norepinephrine during catecholamine biosynthesis, these structural and mechanistic insights are extended to DBM.

A structure of PHM along with a modeling of DBH is shown in Fig 14. You can see the two catalytic copper atoms and the possible binding of dopamine to the site.

They also show a mechanism of action for PHM. Essentially, through the oxydation of ascorbate the Cu++ becomes Cu+ and can then bind an oxygen molecule that will be used to hydroxylate the product:

Finally, a detailed computational model of the enzyme, and its active site is shown in this paper:

Structural Insight of Dopamine β-Hydroxylase, a Drug Target for Complex Traits, and Functional Significance of Exonic Single Nucleotide Polymorphisms - Kapoor A, Shandilya M, Kundu S - PLoS One. 2011;6(10):e26509. Epub 2011 Oct 20.

The active site is shown in Fig. 7, where you can clearly see the two copper atoms in purple and green, the most important aminoacids at the active site and two water molecules in red:

Active site of DBH http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0026509.g007&representation=PNG_M

Figure 10C shows the interaction of dopamine with the aa of the active site (Fig 10A and B show superposition between rat and human enzymes and Fig 10D shows the interaction of a drug with the enzyme):

Residues important for catalysis http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0026509.g010&representation=PNG_M

Finally, a remark on your question. You say:

  Evolutionarily speaking - the enzyme has evolved to add OH to the beta-carbon rather than somewhere else.

As I said somewhere else: not everything has an evolutionary explication, and evolution is not finalistic. This specific enzyme structure appeared at some point and it was evidently working fairly well, and at the time the rest of the pathway may or may not have been like it is at present, but the important thing is that the enzymatic network managed to work together. It could had well evolved to hydroxylate another position, but probably in that case we would have different enzymes downstream. The important thing to remember is that the enzyme did NOT evolve with the finality of oxydating the beta carbon.


Is the eukaryotic nucleus composed of a single or double membrane? I know that it is usually considered a double membrane like those surrounding mitochondria and chloroplasts, but I read a review that stated "according to topological details it is actually a single lipid bilayer; this distinction is important"1.

Could anyone please explain how this is true and why the distinction is important? And why this topological analysis wouldn't apply to other membranous structures in the cell?

The nucleus is topologically single membrane but functionally, and as visualized, double membrane.  Naturally, this is a bit confusing.

First consider the mitochondria and plastids.  One of these organelles has two entirely separate lipid bilayers, one of which is nested inside the other.  If you start inside the organelle and draw a line to an external point, the line will pass through two lipid bilayers (assume there are no membrane folds to be encountered), first through the nested one and then through the entirely separate outer bilayer.

The nucleus at a gross level appears to be structured similarly.  A line from the interior to the exterior will usually pass through two lipid bilayers, one that is the inner wall of the nucleus, then through the outer wall.  This may seem like the inner wall is separate from, and nested inside, the outer wall, but it is not.  As nicely illustrated in your reference (Martin 2005), the two walls are continuous with each other and not nested.  Because of this, a line from nuclear interior to exterior may in fact not pass through any lipid bilayers; it may pass though a nuclear pore.  Topologically (mathematically) speaking, the two walls are one surface, and the "inside" of the nucleus is on the same side of the surface as the outside.  (The topological interior is perinuclear space and the interior of the endoplasmic reticulum.)  Functionally though, the structure acts as a double membrane since it physically constrains its contents.

The distinction is not very important for most biological contexts, but for a few purposes needs to be considered.  The main reason to pay attention to the distinction is that it probably is related to the evolutionary history of the nucleus: it is likely to have evolved from a single bilayer somehow.  In contrast, the mitochondria and plastids, with nested bilayers, evolved from two bilayers, one from a separate cell and one from an enveloping piece of a host cell.  This is why the distinction is important in the cited paper, which concerns the evolution of the nucleus.


Pronunciation of technical vocabulary All knowledge of biology I have comes from online and after speaking for a brief period of time with someone from a biological education it is very clear that I have no knowledge of the pronunciation of all the necessary jargon I have learnt.

For example: Chordae Tendineae, Squamous Suture, Loop of Henle

How have people overcome this issue? I have searched online for pronunciation videos and whatnot, but very often they pronounce them differently to each other and it is impossible to know who is correct. I also do not want to learn the IPA for English.

I would try to use the audio features of dictionaries on the internet.

Ideally you would buy a good scientific dictionary app with audio pronunciation for your iPhone, just as I have for foreign language dictionaries on mine. However, the scientific offerings I found on the app store did not fit the bill (there may be something hiding there that I missed), so I looked on the web, and what I found was:

The Science Dictionary

Now this appears not to be an actual dictionary itself, but an aggregating site. So when I searched for Chordae I got several options, mainly from Wikipedia, which did not provide audio pronunciation, but also from

Dictionary.com

which did — for both the singular (which is what is the listing) and the plural.

Dictionary.com doesn’t always provide audio pronunciations. When I tried squamous suture there was only a definition — but there were individual pronunciations for squamous and suture.

(Loop of Henle was also there with pronunciation. Perhaps going directly to dictionary.com is your best bet.)

Rider and caveat

As @JM97 mentioned in a comment, some entries in the free dictionary have audio pronunciation, although others do not. There may be other on-line facilities that do likewise. However with any on-line dictionary one should ask oneself how reliable is the pronunciation; and it is difficult to tell because one doesn’t know how it is done in the way one does with a primary dictionary with a print reputation.

For example, take the pronunciation of the word "caeca". The open dictionary pronounces this in a classical Latin style with a hard C, whereas dictionary.com. pronounces it in a mediaeval Latin style with a soft C, the way it is pronounced by scientists I know who dissect it.


What is the efficacy of an Ebola antibody response There is contradictory (~?) evidence in the literature that antibody responses against Ebola are effective in clearing the virus and protecting the patient. Some time ago, I wrote a bit about the literature on this in my blog (which you can find here) that one of the primary problems faced in developing an effective antibody response against Ebola is that antibodies may actually be hijacked by the virus in order to mediate entry (Takada et al).
My question is, has this observation been supported? And, if so, how do more recent vaccines address / avoid this problem?

Although there are a handful of papers suggesting that antibodies can enhance Ebola infection, in practice Ebola vaccines seem to be highly effective both in animal models (e.g. Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses, VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain, Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus) and, probably, in humans (Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial).

If antibodies can enhance infection, how could vaccines protect?  That's not as contradictory as it sounds.  In general, antibody-mediated enhancement of infection only works under specific conditions.  Even with Dengue, the poster child for ADE, it only occurs during a specific window of antibody titers and affinities.  Ebola is probably much less adapted to needing ADE than Dengue, so it's likely that you'd only get ADE in a very narrow range of antibody titers, affinities, and perhaps targets.  So if vaccines induce high titers, high affinities, and/or a particular set of antigenic targets, ADE may never kick in -- it may be a lab curiosity that isn't relevant in the real world.

(Alternatively, it may be an issue down the road, say if vaccine-induced immunity fades in a specific way that allows it. I don't know of any evidence suggesting this would happen, but I'm not an Ebola researcher.)


What causes the characteristic 'gleam' in the eye of a living being? The title is pretty much what I seek to know.
Unless the other person is play-acting, one can often make out the eye of a living person has a shine-of-life to it; a cadaver does not. Similarly the gleam appears brighter when a person is feverish, or excited otherwise ... or has some infection in the eye itself.

What causes this gleam? Is it merely nervous electricity at work that disappears when the system is shutdown/crashed?

Not being an opthalmologist, if one happens along and gives a better/correct answer, listen to them.

Otherwise, let's take a moment to look at the eye:

What is not pictured here is the saline-like solution that keeps the conjuctiva moist. If we include the lubrication in all of the surfaces which interact with light, our list would look like this:

Lubrication
Conjuctiva
Cornea
Anterior aqueous humour
Iris
Posterior aqueous humour
Lens
Vitreous humour
Retina
Fovea

Out of that list, the Iris, Retina, and Fovea are designed to absorb light; not reflect it. The Vitreous humour merely serves as a medium for light to pass through and probably would not reflect light on its own. The same is true of both aqueous humours - they do not modify the light so much as serve the eye structurally.

That leaves us with the Lubrication, Conjuctiva, Cornea, and Lens - surfaces which also interact with light, but act to some extent to reflect or modify it as well. The Cornea is what's actually operated on when a person undergoes corrective surgery; a pattern is etched into the Cornea which redirects light similar to the person's previous prescription and giving them better vision.

Now, because you mention the difference between an excited person and presumably someone at their normal state, it's worth to note (when dealing specifically with the eye) a very common side-effect of psycho-active drugs and emotional states (particularly fear and interest/curiosity) is the change in pupil size when lighting conditions don't change:

The reflection is different depending on the size of the pupil, and I would venture to guess the pupil size difference between someone who's excited or manic (whose system is flooded with endorphins) and the person at normality is part of what you define as 'gleam.'

The other situation you draw a difference between is a dead person vs. a living person. Before rigor mortis sets in, the relaxed state of the ciliary body is to stress the suspensory ligaments - resulting in pupil dilation. In addition, and I think this is the most important distinction: dead people don't blink. The act of blinking spreads the lubrication on the surface of the conjuctiva, and can be mimicked with tear-drops for people with dry eyes. Because the lubrication acts as another surface to reflect light (similar to having a thin layer of water on a surface), the dead person's eyes will have less of a "gleam" than a living person's.

So, to sum up: The "gleam" in a person's eye is probably due to hydration and/or pupil dilation. Pupils will dilate at lower light levels, under the influence of certain drugs, or when showing interest. Hydration is constant, except when the lubrication is not produced in the quantities necessary or when the person is unable to blink ('dead' in your example).


What could cause spiral tree growth? While hiking through one of the areas burned in the 1988 Yellowstone fires, I noticed that some of the trees appeared to have grown in spiral patterns.

Most downed trees have crack patterns that imply straight growth, but some look like the one in the picture.  The direction shown in the picture seems to be more common, but it's not universal, and it doesn't appear to be related to location -- another picture I took shows two adjacent logs that spiral in opposite directions.

The two commonly put-forward explanations for spiral growth of tree trunks related to stress-loading and damage-tolerance.

The stress-loading explanation states that spiral-grained trees flex more than straight-grained trees before they break. Flexibility under stress-loading is useful in areas with heavy snowfall (as the tree can flex until the snow falls off) and in areas with heavy wind (as the tree can flex in response to wind-buffeting instead of breaking).

The damage-tolerance explanation states that in trees with straight grain, the leaves (or needles, etc) have water delivered to them, via the xylem, from the roots on the same side of the trunk. In spiral-grained trees with several years of growth, water and nutrients from a given root can be transported to branches on all sides of the trunk. Therefore in spiral-grained trees, if one section of the tree's root system is damaged, it does not necessarily mean that a corresponding part of the canopy will have to die off.

Kubler (1991) discusses both the stress-loading and damage-tolerance explanations in much more detail, if you're interested in further reading.


Is it possible to express a mutant gene only in a specific tissue? Imagine that someone tries to develop a knockout mouse for a gene, but this result in lethality for the homozygous.

Is it possible to express that mutant gene only in a specific tissue of interest to get a idea of which phenotype it produces? Does someone know an experiment which used this idea or something similar?

It is called conditional mutation.

You flox (put lox sites around) gene of interest and express Cre recombinase driven by tissue-of-interest-specific promoter.

Illustration from here:

Using chemically-activatable variant of Cre recombinase (cre-ER) you can create knock-out in some cells of tissue of interest, not every.

Addition: a bit weird but still useful method is to produce KO by means of CRISPR/Cas9 system. Tissue-specific expression of Cas9 protein together with gene-specific sgRNA will likely produce KO in mosaic fashion. One of positive sides is that such approach requires only one transgenic line, e.g. Tg(promoter:Cas9;sgRNA)

Addition: (via WYSIWYG's suggestion) you can express shRNA or other gene transcription-interfering product from promoter that only active in specific tissue/specific period of time. And beauty of genetic/bioengineering is that you can combine several methods for additional control, robustness, efficiency etc.

Taken from here:

Inducible and sell-specific gene KO with shRNA

For further reading:

http://cre.jax.org/introduction.html

http://link.springer.com/protocol/10.1385/1-59259-065-9:477#page-1

Update

I re-read OP question and, as commented to it, feel some confusion. So I would like to mention as well way to express mutated gene in specific tissue that, when expressed constitutively (all the time, everywhere), is lethal. Imagine some very strong oncogene. Or something like cell-toxic protein, e.g. chemically-activatable nitroreductase or light-activatable Killer-red. Or it might be mutated version of your favourite synaptic protein that, when expressed in all neurons, causes severe lethal phenotype.

What you do, is create transgenic animal with transgene-GFP fusion (nitroreductase, KillerRed, etc) that has floxed stop-codons in front, and cross that animal with transgenic with tissue-specific CreER (for example). What you get is animal that, when injected with tamoxifen, start to express mutated gene/toxic protein in tissue of interest. Then you are sure that only GFP-positive cells express that gene. That is how you "express that mutant gene only in a specific tissue of interest to get a idea of which phenotype it produces".


Do flies actually take off backwards? I've been told that flies take off backwards, but I haven't really been able to prove it to myself. The closest I've gotten was noticing that they fly into window glass back-first, with their heads pointing up. Is that how they take off?

From this video demonstration in caltech, you can clearly see that Drosophila can fly forwards as well as backwards using high fps video image capture and it even does unexpected behaviours in times of perceived danger/threat.


In which direction does ATP synthase rotate? I heard about the rotation of ATP synthase in a biochemistry course. The professor said it will rotate counterclockwise. Is that true? If so, what mechanism defines its direction?

Short answer
The direction of rotation depends on the viewing point of the observer and the reaction catalyzed by the ATP synthase. When synthesizing ATP, and viewed 'from the bottom' (observer faces the intermembrane space looking into the mitochondrial matrix) it rotates clockwise.

Background
ATP synthase is a membrane bound enzyme with two large subunits; F0 and F1. F0 is inserted in the membrane and funnels H+ ions from the intermembrane space into the mitochondrial interior (Fig. 1). The stalk region connection F0 and F1 contains the γ subunit, which basically forms a rotating shaft powered by the flow of H+. This causes the entire F1 unit to rotate during ATP synthesis.

Now importantly to know before continuing; enzymes basically work two ways, as they merely establish equilibrium. As such, any ATP synthase is also an ATP hydrolase. When it synthesizes ATP, the γ subunit runs in clockwise direction when observed from the “bottom” (the side closest to the F0 and the membrane, see Fig. 2). When it hydrolyzes ATP (e.g., under non-physiological laboratory conditions) it runs counter-clockwise as the reaction, as well as the movement of the γ subunit reverses (Nakamoto, 2008).

The direction in which the rotation takes place is dependent on the steps involved (Fig. 3). In this figure, ATP hydrolysis is shown and that can be compared to burning fuel in a combustion engine. Now the direction of H+ reverses, against its concentration gradient and needing energy (the road speeding below a car if you like). Because ATP binding, hydrolysis and release of waste (ADP + Pi) each cause a 120o turn of the rotor, the F1 subunit rotates one full turn in each cycle (Yoshida, 2001). During ATP synthesis the opposite direction is established, as waste (ADP + Pi) is taken in and phosphorylated to ATP, during which the flow of H+ reverses (akin to a car going downhill, only combustion engines cannot generate gas from carbon dioxide and water, unfortunately).

Fig. 1. ATP synthase subunits. source: Penn State University

Fig. 2. ATP synthase. source: Noji, 2004

Fig. 3. ATP synthase compared to a combustion engine. A combustion engine converts fuel energy into rotation of a rotor. It can drive the intake of the fuel gas, compression, ignition and exhaust sequentially just by a simple rotation of the central rotor (right panel). The F1 gamma-subunit has and three reaction chambers (the catalytic beta-subunits (left panels). The three reaction sites each go through three cyclic steps in a 120° phase difference to cause rotary motion, very similar to a combustion engine. source: Yoshida, 2001

References
- Nakamoto, Arch Biochem Biophys (2008); 476(1): 43–50
- Noji, Biohistory journal (Winter, 2004)
- Yoshida, Nature Rev Mol Cell Biol (2001); 2: 669-77


gene manipulation books for beginners Are there any introductory book to explain gene manipulation in yeast for non-biologist?

I had a look at this book and now I have some ideas. I like to read another book at the same level which is more applied/practical. I find this book chapter useful too, but I find it a bit more difficult to follow. Also video lectures are appreciated.

I think that the information you are looking for could be covered on this website:https://www.addgene.org/protocols/

Not only has addgene a protocol section, it also has an education section for understanding the concepts of genetic/molecular cloning: https://www.addgene.org/mol-bio-reference/

The material is for biologist, but should be relatively easy to understand for you are starting.

They also have a nice ebook which should cover some of the topics you asked: https://info.addgene.org/download-addgenes-ebook-plasmids-101-3rd-edition

Hope that helps!


Do viruses or bacteria have a flavour? My 9 year old niece asked me this when I was explaining some stuff to her about the coronavirus. She asked "What does this virus taste like? Can I tell whether my sandwich is contaminated for example?"
That sounded like a silly question and I immediately responded by saying that they are too small to have any taste, and even if you manage to eat a whole lot of viruses it would taste like water.
The day after, I searched a bit just to make sure that I haven't fed the wrong information to the kid. As I expected, there wasn't a single page mentioning this question (except this quora post with a vague answer). Now it may sound like I am overthinking and the question is too naive and isn't worth the time, but then again, I thought what's the harm in asking?

Has there been any research on the likely taste or maybe smell of a specific virus or bacteria?

So I think this is a more conversational kind of question. I will address some misconceptions you have, and I will try to keep it brief, considering the nature and depth of your question. One could comment on the question very deeply, so I'll stick to addressing some misconceptions.

  Can I tell whether my sandwich is contaminated for example?

Usually you can taste contamination because of the (action of) metabolic products of microorganisms. You do not taste nor smell the microorganism directly; you taste their metabolites or the effect of their presence, such as products of fermentation, or oxidized molecules which are normally not present because air does not penetrate through e.g. apple skins. Take filamentous fungi, for instance; they release enzymes that act on complex carbohydrates to break them down. You cannot taste the cellulose which makes up the majority of a stalk of celery, but you may be able to taste its broken down products once a fungus has begun to digest it prior to absorbing its nutrients: sweet glucose, sucrose, trioses, some acids. It depends on the food and the extent and kind of contamination.

  they are too small to have any taste and, even if you manage to eat a whole lot of viruses it would taste like water.

You can taste molecules which are far smaller than a virus. Indeed, pheromones and volatile or sticky chemicals and all that jazz are definitely much smaller than viruses. Viral particles themselves may actually be too big to taste, because your sense of gustation and olfaction depends on the interaction between tastant or odorant molecules and corresponding receptors, which are situated on the membrane of sensory neurons (nerve cells which are responsible for detecting and relaying information to the brain about the outside world). These receptors harbor ligand-binding pockets that are too small to capture entire viruses. This does not rule out the ability for you to taste broken bits of viruses, but I think this is unlikely or coincidental (i.e. the particle may bind to receptors weakly and not very well).

  it would taste like water

Water is a requisite for taste and smell, things have to be dissolved in water for you to be able to detect them. Water by itself has no taste! Only impurities, oxygenation and carbonation and mineral content give water flavor. I understand that you factor in temperature and texture into the 'perception of water', but these are not gustatory phenomena and use different mechanisms of detection.


Hypovolemia and orthostatic hypertension What is the physiological mechanism behind the occurrence of orthostatic hypertension in the presence of hypovolemia?

The pathophysiology of orthostatic hypertension has not been elucidated. It is believed it involves activation of the sympathetic nervous system [1], vascular adrenergic hypersensitivity and diabetic neuropathy [2]. High levels of plasma atrial natriuretic peptide and antidiuretic hormone were observed in children [3].

Hypovolemia causes:

baroreflex-mediated increase in muscle sympathetic nerve activity [4]
release of epinephrine and norepinephrine [5]
activation of renin-angiotensin axis [5], thus increasing ADH levels

All these reactions result in vasoconstriction and blood pressure raising. But not up to absolute hypertension.

  Orthostatic hypertension is diagnosed by a rise in systolic blood pressure of 20 mmHg or more when standing [6].

This is possible. A raise of 20 mmHg from hypotension could result due to vasoconstriction.

References:

Fessel J, Robertson D. Orthostatic hypertension: when pressor reflexes overcompensate. Nat Clin Pract Nephrol. 2006 Aug;2(8):424-31. doi: 10.1038/ncpneph0228. PubMed PMID: 16932477.
Chhabra L, Spodick DH. Orthostatic hypertension: recognizing an underappreciated clinical condition. Indian Heart J. 2013 Jul 5;65(4):454-6. doi: 10.1016/j.ihj.2013.06.023. PubMed PMID: 23993009.
Zhao J, Yang J, Du S, Tang C, Du J, Jin H. Changes of atrial natriuretic peptide and antidiuretic hormone in children with postural tachycardia syndrome and orthostatic hypertension: a case control study. Chin. Med. J. 2014 May;127(10):1853-7. PubMed PMID: 24824244.
Ryan KL, Rickards CA, Hinojosa-Laborde C, Cooke WH, Convertino VA. Sympathetic responses to central hypovolemia: new insights from microneurographic recordings. Front Physiol. 2012 Apr 26;3:110. doi: 10.3389/fphys.2012.00110. PubMed PMID: 22557974.
Wikipedia contributors, "Shock (circulatory)," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Shock_(circulatory)&oldid=612494727 (accessed June 26, 2014).
Wikipedia contributors, "Orthostatic hypertension," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Orthostatic_hypertension&oldid=603984647 (accessed June 26, 2014).


Are there lifeforms that have more than 2 sexes? Are there any lifeforms on earth that have more than male and female biological sexes?

If so, are all three mates required for reproduction or is there something else going on?

If not, why not? There are species that have one sex and there are species with 2 sexes. I get some of the basics of why there are two instead of one, but would those benefits not be even greater if there were three sexes?

  NOTE: I am of course only talking about sexual reproduction. I have no intention or desire to talk about transgender or LGBT issues nor am I wanting to make any points on the issue. This is solely a question about sexes in biology and not human social constructs.

Also, I am a computer programmer, not a biologist. Please forgive me for not knowing any of the terminology.

There exists something like multiple sexes in fungi, but it's a bit complicated.

First of all fungi don't actually have anything that represents the two classical animal sexes, phenotypically their reproductive cells are all equal (they have isogamic reproduction).
However there can be certain alleles in some fungi species (sometimes multigenic, sometimes not), that restrict sexual reproduction to other fungi with a different variant of that allele, these alleles are therefore called mating types. It is however important to note, that almost all fungi can also reproduce asexually (by basically cloning themselves).
In general all of the mating type systems always require only 2 individuals to (sexually) reproduce, it just can't be 2 individuals with the same type.

In their simplest form mating types resemble the male/female sex we often see in animals: for some fungi (e.g. yeast) there exist exactly 2 forms of the mating type allele (called a and $\alpha$), so basically they have '2 sexes' (though genetically/biologically the difference is MUCH smaller).

There are however also much more complicated mating type systems:
Some species of the Basidiomycota or Agaricomycotina groups have a tetrapolar mating type, which is composed of 2 independent alleles (with 2 variants per allele this would already results in 4 different 'sexes'). Additionally they can have many more than 2 forms for each of the alleles (up to hundreds), which leads to (ten-)thousands of different mating type combinations (or 'sexes').


Do whales ever just hang out on the surface breathing? You only ever hear of whales surfacing for a brief second to exhale/inhale before they dive back down. But do they ever just stay at surface level, laying there with their blow hole up in the air, continuously breathing for a while? One would think that might be a relaxing experience for them?

Whales often hang out on the surface for a while, for a number of reasons. Sometimes it is for curiosity, sometimes to socialize with other whales, and sometimes simply to rest.  The particular sort behavior that you are describing sounds like logging, where the whale basically rests, often for an extended period of time, with its back slightly out of the water, looking sort of like a floating log.


Pedigree - Dealing With Unknown Parent Genotypes I'm dealing with a pedigree problem, and I'm having some trouble dealing with problems of unknown parental genotypes (where there are multiple possibilities). This is not a homework question; it's an exam practice problem.

The question asks: Suppose brother and sister 6 and 7 are mated. What is the probability that their first pup will be albino?

The answer choices are 1/4, 1/8, 1/16, 1/32, or Not Enough Info.

Here's my attempt at the problem:

Since #2 is black, and some of its offsprings ended up sepia, #2 must carry the sepia gene (since the male mate is cream, and sepia is dominant over cream). So, we know that #2 is $Cc^k$.

Now, the male mate can be either $c^d c^d$, or $c^d c^a$.

This means that in order for the offspring of #6 and #7 to be albino, we need:

1) Male parent needs to carry the albino gene (i.e. male needs to be $c^d c^a$).

2) Male parent needs to pass on the albino gene to both #6 and #7.

3) #6 and #7 both need to pass on the albino gene.

I think the probability that the male is $c^d c^a$ is $\frac{1}{2}$, since the male parent can be either $c^d c^a$ or $c^d c^d$.

If we draw out a punnett square, the probability that the albino gene gets passed onto 1 individual is $\frac{1}{2}$ (since we already know the offsprings are sepia, we only need to consider the genotypes that contain $c^d$).

The probability that #6 and #7 pass on the albino gene is $\frac{1}{4}$.

This led me to think that the final probability is then P(male parent has albino gene) * P(#6 inherits albino gene) * P(#7 inherits albino gene) * P(#6 and #7 pass on the albino gene), which is $\frac{1}{2}$ * $\frac{1}{2}$ * $\frac{1}{2}$ * $\frac{1}{4}$, which gives us $\frac{1}{32}$, but I do not feel confident in my answer. Specifically, I do not know how to account for the fact that the male parent can be either $c^d c^d$ or $c^d c^a$.

Is my thought process correct? If not, where in my logic did I go wrong? Thank you for your help.

Based on the information given in the pedigree, you can actually be certain that #2's mate has a genotype of CdCa because of the following:
Two of 5's siblings are albinos. Since albino is a recessive trait (lowest in hierarchy of dominance), both parents (4 and 4's mate) must have the Ca allele. Let's call 4's mate "8". Since 8 has the Ca allele, at least one of 8's parents must also have the Ca allele. Since you have already (correctly) determined that #2 is CCk, #2's mate must have the Ca allele, and must therefore have a genotype of CdCa.

Thus you can eliminate the extra (1/2) from your calculation, making the answer (1/2) * (1/2) * (1/4), or (1/16).


Why does sequence of amino acids presented on the Catalytic Site Atlas from a given protein differs from the sequence on the RSCB Protein Data Bank I wanted to compare the amino acid sequence of enzymes for this project I'm working on and need to compare them at their catalytic site. For that, I went to the Catalitic Site Atlas to get the information on the catalytic site, but since they don't offer an easy way for me to download the structure data programmatically I downloaded it from the RSCB PDB by downloading the fasta sequence. When checking for the catalytic sites it wasn't matching what the CSA was telling me and that's when I realized that they are different files. Take for example the 3nos, the CSA presents the following sequence:

MGNLKS...

While the PDB presents the following sequence:

PKFPRV...

Why aren't they the same sequence if it's the same protein?

Sorry if it's a noob question, I'm not a biologist, just a computer scientist who happens to like bioinformatics.

Important info:

The CSA data comes from here while the PDB data comes from here

Crystallography results (pdb files) almost always contain a truncated sequence.

Both ends of a protein are often flexible (even in a crystal) and don't result in enough data for a good fit. The corresponding residues are removed from the model and the sequence, and you're left with only the residues that show a defined electron density.


How exactly can a drug affecting squalene epoxidase affect the methylation cycle, necessitating the use of 5-MTHF? I found a case report in which the authors say that Terbinafine might have possibly affected the methylation cycle in a patient, necessitating the prescription of 5-methylfolate to correct the imbalance. I tried googling to find some description that would include the interaction of ergosterol synthesis and methylation cycle, and found nothing.

Maybe I was not googling the right words.

I can't seem to find how exactly we can affect the methylation cycle by affecting squalene epoxidase (the target of terbinafine, the drug used by the patient in the case report).

The article quoted is titled Antifolates and MTHFR (Trachtman and Pagano, 2015)

Preamble

I have tried to follow the logic of the rationalization of the clinical case described in the report of Trachtman and Pagano, but have failed. I suspect from the quality of their biochemical illustration (arrows leading from compounds to enzymes, and talk about ends of cycles) that they do not have a clear idea themselves. However, having done the literature search, let me set out the picture as I see it, in the hope that this may enable someone else to see a connection I may have missed.

Anti-fungals inhibit the erosterol biosynthesis pathway in fungi

As the poster states, anti-fungals such as terbinafine do act by inhibiting the synthesis of ergosterol, which is a cell-membrane steroid, unique to yeast. Of relevance to this analysis, there is a methylation reaction in this pathway, that lies after the target of terbinafine, squalene epoxidase:

Methylation step in ergosterol synthesis (from Uniprot)

Inhibition of ergosterol synthesis can affect S-adenosyl methionine in yeast

The only experiments that I can find linking ergosterol synthesis with the methylation cycle in yeast do not involve anti-fungals. Rather, they involve yeast with mutations in the genes encoding enzymes of ergosterol synthesis. In a study performed by Shobayashi et al. (2006), mutants of the gene, Erg6, encoding the methyltransferase, resulted in the accumulation of S-adenosyl methionione (SAM). Clearly there are other methylation reactions in the cell which utilize SAM, but this suggests that the ergosterol synthesis pathway is so active in yeast that its disruption affects the concentrations of intermediates of the methylation cycle.

What is the relevance of this to methylation in humans?

Although the situation described above confirms a connection between the methylation cycle and ergosterol intermediates in yeast, as mentioned in the original clinical report, it is difficult to see how it relates to human metabolism. This is because, although squalene epoxidase does exist in man, the ergosterol synthesis pathway and the methylation step catalysed by the methyltransferase (the erg6 gene product) do not. In any case, inhibition of a methylation step would result in an increase in SAM, whereas just the opposite appears to be the case in the patient.

Final observations

The clinical report is of one patient with a mutation (MTHFR) in the methylene tetrahydrofolate reductase gene, which would reduce his ability to regenerate the methionine and S-adenosyl methionine needed for methylation. L-methylfolate greatly reduced his symptoms. Nevertheless, this report is for a single patient, whereas “The gene mutation known as the MTHFR affects approximately 45% of the US population”. If MTHFR were the only factor involved in this case one would expect other reports of adverse reaction to terbinafine. In the apparent absence of such reports one suspects that in this patient the affect of terbinafine — whatever it may be — involves some other, yet undiscovered metabolic interaction.


How do you store membrane proteins? We're producing some membrane proteins and they aren't amenable to freeze thaws even when we add glycerol. The proteins are solubilized in detergent above the cmc so they should be in micelle form in solution. Currently, they are being held at 4C. I'm curious what is the best way to store them for long term use?

I work with membrane proteins and in my experience some proteins can be frozen and thawed without any problems, other proteins just don't like that. It's linked to the stability of the protein. If you really need to freeze the protein you may think about playing around with different detergents to see if you can improve the stability of the protein.

General rules:
- freezing membrane proteins at -80°C without glycerol
- avoiding protein freeze-thaw cycles, making aliquots before freezing
- keeping them at 4°C only for short term use
- after concentration always spinning the protein (10 min at 100k for example) to precipitate aggregated material. Aggregation causes aggregation, so you want to get rid of it.


Do any organisms recycle their own waste internally? I thought of this question yesterday and it turns out it's surprisingly hard to Google.

All organisms recycle their waste internally. Every cell of every living organisms is constantly breaking things down and re-using the components so produced. But you're presumably wondering about things such as carbon dioxide, urine and faeces? These are not recycled because the benefits of doing so are not worth the costs.

Let's consider carbon dioxide as an example. We know that carbon dioxide can be usefully converted into energy-holding molecules using readily available sources of water, oxygen and sunlight. So why do animals** "wastefully" breathe it out? Because the energetic benefits of respiration are high compared to the energetic benefits of photosynthesis and so photosynthesis is unable to make a useful contribution to the overall energy balance of an animal while the costs of the effectively photosynthesising are quite high (e.g. having leaf-like protrusions, synthesizing chlorophyll and so on).

In fact, it must always be true that there are processes which are not energetically worthwhile because of entropy. An organism that could perpetually recycle its waste would be a perpetual motion machine.

** - and many microbes and, in fact, plants - although their intake of carbon dioxide is typically higher over the solar cycle.


Is bootstrapping an acceptable way to determine standard error for binding constants? I'm measuring binding constants my system and I appreciate the usual methods of using replicates to measure standard errors and using those errors to calculate propagation of error. I'm curious if bootstrapping is a reasonable alternative to calculate uncertainty?

My understanding of bootstrapping is that you may estimate variance (and thus standard error of the population mean) iff your measurements are independent and have the same population distribution, in which case a number of sampling-with-replacement calculations can be done. I suspect that this method of estimation would be less desirable with small n values because of the effect that outliers or large standard deviations may have on the calculation. If you have a large dataset then it shouldn't be an issue.


What constitutes as the death of a bacteria? I've read that some bacteria can survive a long time without food.
What constitutes the death of a bacteria ?
What process needs to take place for it to be considered dead?

When you talk about organisms like fungi and bacteria which can have a dormant form, and viruses, "dead" becomes somewhat harder to define. In fact, it has not been definitively defined for bacteria.

I would have guessed "when they are permanently unable to reproduce", but I may be wrong.

From one source[1]:

  The observed coordinated gene expression continued even after cell death, in other words after all bacteria permanently lost their ability to reproduce. Transcription of a very limited number of genes correlated with cell viability under the applied killing regime. The transcripts of the expressed genes in living bacteria – but silent in dead bacteria-include those of essential genes encoding chaperones of the protein folding machinery and can serve as molecular biomarkers for bacterial cell viability.

From another[2]:

  it is a challenge to determine if bacterial cells are dead, or viable but non-culturable (VBNC), and what is an agreed upon correct definition of dead bacteria.

Some viable but nonculturable cells (VBNC) can be "resuscitated" into dividing cells. [3]

Also4,

  However, the simple binary definition live/dead probably does not accurately describe the complex physiological states possible with microbial cells.

Unfortunately the actual conclusion is behind a paywall.

Finally, another country heard from5 :

  Programmed cell death is a gene-directed process involved in the development and homeostasis of multicellular organisms. The most common mode of programmed cell death is apoptosis, which is characterized by a stereotypical set of biochemical and morphological hallmarks. Here we report that Escherichia coli also exhibit characteristic markers of apoptosis—including phosphatidylserine exposure, chromosome condensation, and DNA fragmentation—when faced with cell death-triggering stress, namely bactericidal antibiotic treatment.

So, perhaps the answer is, a bacterium is dead when it is unable to reproduce, cannot be resuscitated, gene expression has ceased, and shows characteristic markers of apoptosis

[1] Transcriptional activity around bacterial cell death reveals molecular biomarkers for cell viability, Remco Kort, Bart J Keijser, Martien PM Caspers, Frank H Schuren and Roy Montijn, BMC Genomics 2008
[2] Can dead bacterial cells be defined and are genes expressed after cell death? Trevors JT1, J Microbiol Methods. 2012 Jul
[3] A matter of bacterial life and death Gregg Bogosian, Edward V Bourneuf
[4]Advances in microbial food safety: 23.
[5] Antibiotic-Induced Bacterial Cell Death Exhibits Physiological and Biochemical Hallmarks of Apoptosis, Daniel J. Dwyer, Diogo M. Camacho1, Michael A. Kohanski, Jarred M. Callura1, James J. Collins, Molecular Cell, Volume 46, Issue 5, 8 June 2012, Pages 561–572


Why is it that I can only detect smells if I breathe, and not when I hold my breath? At school we're told that the receptors for smell (olfactory receptors) are present in the Schneiderian membrane. But I've noticed that I'm only able to detect smells only while I breathe and not when I hold my breath.

I even tried an experiment to confirm my observations and the results were positive. I placed an open bottle of really strong perfume fairly close to my nose, and lightly inhaled. I could easily detect the smell. But as soon as I hold my breath I'm not able to smell it anymore, even though I placed the bottle right under my nose I wasn't able to smell anything. Immediately I moved the bottle away, walked into another room and took a breath, and the smell of perfume was so strong it made me choke.

I guess this 'experiment' of mine contradicts what we've been taught. That Olfactory receptors present in the nasal passage simply pick up traces of molecules (in this case, perfume) and this is perceived as smell, since by keeping the bottle right under my nose the perfume would've already diffused into the air in large quantities and would've already entered the nasal passage, yet I was unable to detect it.

So my question stands, 'Why is it that I can only detect smells if I breathe, and not when I hold my breath?'

The olfactory epithelium is located in the highest part of the nasal cavities, overlying the cribriform plate of the ethmoid bone.  In order for you to smell something, the odoriferous molecules have to travel the length of the nostrils (which are a pair of very narrow passages which also happen to be filled with hair) and up though the full height of the nasal cavities, having to pass three sets of baffles (known as the nasal conchae) on the way.

When you take a breath, your lungs and inspiratory muscles form a suction pump which pulls air through the nostrils up into the nasal cavities; some of this air, along with any odoriferous substances contained therein, is swirled up to the top of the nasal cavities, where the olfactory epithelium is located.

In contrast, when you're holding your breath, there is no significant air movement through the nasal cavities, and even airflow contained entirely within the nasal cavities is considerably obstructed (thanx to the aforementioned hairs and baffles); therefore, for any odoriferous substance (such as the perfume you're probably sick of smelling by now) to reach the olfactory epithelium, it has to diffuse all the way from the tips of the nostrils to the top of the nasal cavities on its own.  This is a much slower process, and, therefore, it takes rather a while to notice anything smelly when you're holding your breath - even if it's, literally, right under your nose.


Do Osteichthyes fishes have any cartilage? Higher vertebrates, such as mammals, birds, reptiles and amphibians have both bone and cartilage.

But do Osteichthyes fish (Bony fish) have any cartilage? Or do they only have bones?

I've searched the web but I could not find anything helpful.

Yes, Osteichthyes do have cartilage. For example, Ancient origin of lubricated joints in bony vertebrates shows images of cartilaginous tissue in the joints of several bony fish.  More generally, cartilage is required for normal bone development, and Osteichthyes are no exception (e.g. Distinct patterns of notochord mineralization in zebrafish coincide with the localization of Osteocalcin isoform 1 during early vertebral centra formation).


Why does the SARS-CoV2 virus not remain infectious forever? Or does it? Given that the majority of biologists do not currently consider viruses to be alive, a virus can never die.  It can, however, get destroyed by long exposures to soapy water, alcohol, and apparently certain frequencies of UV light.

Why is an individual SARS-CoV2 virion not infectious forever?  Or is it?

Would it help to think a little differently? Rubber bands (for example) aren’t alive either, but there are several ways they can be destroyed, including physically pulling them apart or just by having them exposed to air enough. Viruses are the same, conceptually.

Soap works in part by dissolving the layer of fat that keeps the virus together. It also ends up surrounding dirt so that it doesn’t stick to your skin and can be washed away with water. (These mechanisms take some time to work so that’s why people are recommended to wash their hands for 20+ seconds.)

As for when a virus is just on a surface, logically we know that how long a virus remains viable depends on both the air and the surface because the science reports different numbers depending on what the humidity is and what the surface is like. One helpful source notes:

  Similar molecules appear to interact more strongly with each other than dissimilar ones. Wood, fabric and skin interact fairly strongly with viruses.

  Contrast this with steel, porcelain and at least some plastics, such as Teflon. The surface structure also matters. The flatter the surface, the less the virus will “stick” to the surface. Rougher surfaces can actually pull the virus apart.

  The surface of fibers or wood, for instance, can form a lot of hydrogen bonds with the virus.

  In contrast, steel, porcelain or Teflon do not form much of a hydrogen bond with the virus. So the virus is not strongly bound to those surfaces and is quite stable.


Why don't neurons die during a stent procedure in the brain? Stents are used to provide scaffolding to the blood vessels. When they are used in arteries or arterioles in brain, won't neurons die because of lack of oxygen during procedure?

I am assuming you are asking because of occlusion during balloon angioplasty. If not, please clarify.

Ischemic stroke occurs when a blood vessel to the brain is occuluded by a clot or some other emboli or poor perfusion due to atherosclerosis (a type of narrowing of the vascular lumen). Given enough time, ischemia can produce tissue death, called infarction. It is possible to suffer an ischemic stroke (or ischemia to any tissue) without substantial infarction if reperfusion occurs quickly enough.

Time to tissue death

For stroke, the catchphrase "time is brain" is often used to indicate the importance of occulsion time in stroke. Cell death is not instant upon loss of oxygen, but rather occurs throughout any extended reduction in blood flow as well as during reperfusion.

The brain is more sensitive to ischemia than other tissues like the heart, but there is still a window in which little to no damage is done. By 5 minutes, however, neuron death can begin.

Balloon Angioplasty

When using balloon angioplasty (including during balloon delivery of stents), a single vessel is occluded for ~30-180 seconds. It is also possible for multiple individual inflations. Importantly, this time range is normally kept less than the ~5 minute range for damage to occur.

Embolic protection

One of the dangers during balloon angioplasty is the release of particles from the vascular wall that is being opened up. Those particles can cause distal embolisms. In other organs like the heart, this problem is fairly minor, because only small amounts of myocardial tissue are expected to be impacted which will not have a major impact on heart function. However, loss of small regions of brain could have significant impacts on patient recovery. Therefore, embolic protection strategies are sometimes employed which include devices to block distal flow or capture emboli. The use of these devices is very case-dependent, because if there is already a significant blockage it may not be possible to use particular devices for a particular case.

In any case, pharmacological protection with drugs like aspirin and clopidogrel are standard for interventional angioplasty procedures.

Balloon alternatives

Balloon-mounted stents are standard for coronary procedures, but in the periphery, including carotid and neurovascular implants, there are other stent types, such as nitinol, a shape-metal alloy of nickel and titanium. These are also known as self-expanding stents. They are deployed by removing a protective sheath and they open up on their own. Thus, there is no total occlusion during a nitinol stent deployment. However, balloons can still be used with nitinol stents to open up the original blockage, because the nitinol stents themselves don't "push" nearly as hard against the walls.

In my opinion, the major benefit to nitinol stents is not that occlusion isn't necessary for their deployment, but rather that they are not sensitive to crushing. With a regular stainless steel stent, external pressure would permanently deform the stent. In the heart that isn't a problem, because if someone is poking you in your myocardium you have bigger problems. However, the carotid arteries are fairly exposed in the neck, and a regular metal stent in the neck could be compressed and deformed. Instead, nitinol will snap back into position, like the underlying tissue.

Neurovascular circulation redundancy through collaterals

Although any ischemic tissue can eventually develop collateral circulation pathways to bypass the occlusion (assuming partial and not total occlusion, sufficient to keep the tissue alive in the meantime), the neurovascular system is unique for the high degree of redundancy present even in normal individuals with no blockages. Therefore, occlusion of a single vessel even permanently may not cause substantial symptoms. Of course this will vary from patient to patient and depends on the patency of collaterals, overall vascular health, and specific anatomy at the site of treatment.

Caveats

Of course there are risks in any surgical procedure. It is unlikely that there is zero neuronal death during any neurovascular procedure. Rather, these procedures are used when there is already significant risk or imminent damage without intervention; the intent is to create as little damage as possible while either solving an acute problem that is much worse, or reducing the likelihood of future infarction events.

References

Kulik, T., Kusano, Y., Aronhime, S., Sandler, A. L., & Winn, H. R. (2008). Regulation of cerebral vasculature in normal and ischemic brain. Neuropharmacology, 55(3), 281-288.

Lee, J. M., Grabb, M. C., Zipfel, G. J., & Choi, D. W. (2000). Brain tissue responses to ischemia. The Journal of clinical investigation, 106(6), 723-731.

Mousa, A. Y., Campbell, J. E., AbuRahma, A. F., & Bates, M. C. (2012). Current update of cerebral embolic protection devices. Journal of vascular surgery, 56(5), 1429-1437.

Pan, Jie, et al. "Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies." Neuroradiology 49.2 (2007): 93-102.

Saver, J. L. (2006). Time is brain—quantified. Stroke, 37(1), 263-266.

(disclaimer: I worked for a major manufacturer of intravascular catheters and stents for about 4 years. I was last employed by that company ~8 years ago and no longer have any financial relationship with that company. Everything in this post represents my own personal views. I am not a medical doctor; this information should not be taken as medical advice. Only your doctors/interventionalist can give appropriate medical advice according to your specific case)