Circulation through the liver in light of drug metabolism I have a lingering question which stems from an answer that I gave to What hydrolyses aspirin within the digestive tract and blood stream?

When a drug or any other substance is absorbed into the bloodstream in the stomach or small intestine, it ultimately passes through the hepatic portal vein and into the liver sinusoids, where it is processed by hepatocytes and introduced into the general circulation via the vena cava.  In terms of metabolism, this is what causes a "first-pass" effect for drugs that are ingested.

For drugs that are delivered either by intravenous, intramuscular, or sub-lingually (as in the other Biology.SE question), this first-pass effect is avoided, and the drug is introduced into the general circulation without being metabolized by the liver first.

Even though the first pass is avoided, the blood in the body still makes its way back through the liver eventually via the hepatic artery, which is a branch off of the celiac artery.

The issue I still have is, does the incoming blood from the hepatic artery merge with the blood from the hepatic portal vein?  If not, does the blood from the hepatic artery still interact with the hepatocytes in some way? (it makes sense that it does, and I have also read that one of the main functions of the hepatic artery was to deliver blood supply for the liver's metabolic needs)  If this is not the case, where in the body would these drugs that were introduced via IV, etc., be metabolized?

Yes, the blood from the hepatic artery (proper) and the portal vein mix in the sinusoids of the liver. The hepatic vein supplies about 75% of the blood to the liver, and the hepatic artery the remaining 25%. Because the portal vein provides such a large part of the blood supply to the liver, then any disease that causes the blood to build up can cause portal hypertension.

The hepatic artery carries oxygen-rich blood from the heart. The portal vein is part of the portal system and connects the capillary beds of the gastrointestinal tract to those of the liver. Because of the larger volume through the portal vein, I think that each vessel carries about half the oxygen supply to the liver.

For drugs introduced through an injection, for example, metabolism occurs throughout the circulatory system and in the liver. Remember that it's all the same blood supply, but the first-pass effect just refers to the blood that goes to the liver before entering the systemic circulation (by which it can travel to its target).


Is it possible to determine what tissue a DNA sample came from based solely on its sequence? All cells have the same genome and differ only by the expression pattern. Is it possible to determine the tissue origin of a cell based on its DNA sequence using short tandem repeat (STR) analysis or copy number variation (CNV) analysis?

The answer is in the question but I suppose you wanted to ensure you were not missing some info.

Answer

The DNA sequence is the same in all cells of a multicellular organism. Only the expression pattern varies among tissues. It is therefore impossible to tell from the DNA sequence alone what tissue a cell come from.

It would be feasible by looking at the transcriptome or the proteome or eventually by looking at epigenetic modifications.

Potential exception

Of course, as you talk about CNV, if you consider that the number of chromosome is part of the info present in a DNA sequence, then haploid cells (spermatozoids and ovules) are an exception and you could tell them apart. Similarly anucleated cells would be an exception as they contain no nuclear DNA.

Further potential exceptions are explained by @tsttst in his comment.


Why is the Tm defined as the temperature at which 50% of dsDNA has changed into ssDNA? In molecular biology, Tm is defined as the temperature at which 50% of dsDNA is converted to its single stranded form. Intuitively it would seem that the melting temperature should have been defined as the temperature at which the entirety(100%) of the dsDNA converts into ssDNA. What is the basis of using this ratio, i.e, 50% in the definition of Tm?

If you search for DNA melting temperature plots you will see they have a sigmoid shape. It's common for those kinds of plots to be described by the 50% value for example the therapeutic index and the 50% lethal dose of a substance (LD50). This is because at really low and really high temperatures all DNA molecules become dsDNA or ssDNA respectively so that information is not really useful. You could maybe talk about the first temperature at which DNA becomes 100% denatured but the curves are highly nonlinear at that region so it's difficult to quantify. The 50% is an easy way to compare different molecules since that region is usually linear and easy to compare in a meaningful way (basically all molecules have the same ends of the sigmoid shape, but it's the middle part that changes the most).


DNA as a digital storage medium; sequences algorithmically avoided for safety reasons (or should be)? Safety for the environment is probably implicit here as well, but the focus should be on the people who may come in contact with large amounts of synthetic DNA used to encode information as a data storage medium.

The idea of using DNA as a digital storage medium is not new. Two papers are listed below but there are many others.

Recently the concept has been further highlighted by the news of a "movie" being encoded using CRISPR-Cas. A Harvard University video explains the process:

  In this video, Wyss Institute and Harvard Medical School researchers George Church and Seth Shipman explain how they engineered a new CRISPR system-based technology that enables the chronological recording of digital information, like that representing still and moving images, in living bacteria. Credit: Wyss Institute at Harvard University

  For more information, please visit: https://wyss.harvard.edu/taking-cells...

below: a GIF showing the original data, and the "movie" interpreted from the recording in DNA. From the Los Angeles Times:

  DNA DVR? Scientists have uploaded a short movie of a galloping horse into the DNA of living bacteria and were able to retrieve it with a 90% success rate. (Seth Shipman)

The immediate application in the Harvard Wyss Institute work seems to be (based on my understanding of the video) in-situ data logging, where information relevant to an experiment is recorded in the DNA of cells involved in the experiment. So the use of a moving image is a way to bring home the key point of "chronological recording of digital information".

Other uses involve the DNA itself, stored outside of living cells, as simply a mass storage medium.

QUESTION: I'm wondering if there are sequences that are likely to become algorithmically avoided as standard practice for safety reasons (or should be) when using DNA as a digital storage medium. The DNA may be handled by IT personnel rather than trained biologists, or shipped, or otherwise not be treated with the same diligence to safety that synthetic DNA is handled by researchers today.

Some other discussions of DNA as a storage medium:

Next-Generation Digital Information Storage in DNA, Church, Gao, Kosari, 2012. doi:10.1126/science.1226355

Towards practical, high-capacity, low-maintenance information storage in synthesized DNA, Goldman et al. 2013. doi:10.1038/nature11875

For further background on the temporally encoded data work, see the excellent answers to the question What does it mean to “write an image and GIF into the DNA of bacteria”?

edit: I'll quote a comment here just to make sure that the word safety isn't misinterpreted as data integrity or the safety of the bacteria:

  When speaking of safety issues related to the handling of biological or biomolecular samples, it's the safety of people that we worry about. Safety rules, safety procedures, safety courses, safety glasses, these are for the safety of the human, not the safety of the sample.

Yes, there could be sequences that a DNA based system could not store handle/very well: repetitive DNA sequences.

Not only do such sequences make a lot of problems during the sequencing ('reading of data'), but they are also more prone to form secondary structure elements like loops, since repetitive DNA can bind to itself in various different ways. This means that similar to natural occuring repeats they are more likely to mutate during DNA amplicifation (the number of 'copies' can quite easily change), which makes the 'data' more instable.

A possible way to solve this problem would be to use specialised data formats that avoid as much Repetition of data as possible (similar to how zip or jpg files work)

Otherwise I agree with Nathan, that DNA by itself is not dangerous (since it won't do anything outside of cells, and the bacteria used in molecular biology are generally harmless unless you start eating them in large quantities or otherwise getting them in your body). The possibility that the DNA could somehow code for toxic proteins is very very low, and you could just check that the 'data' in the DNA does not form a protein by chance anyway.


Are the asymmetrical positions of owl ears consistent across species with this trait? While at a raptor speech a while back ago the naturalist mentioned that owls have offset ears. One ear is located higher in the skull than the other. This is supposed to help the owl detect the location of prey due to the tiny time difference in which the sound reaches each ear. After doing some more research online, it seems that the offset ears are primarily found in owls that are nocturnal hunters. Specifically, I have found that Barn Owls left ear is higher than the right.

Barn Owl (Tyto Alba)-www.robinsonlibrary.com

Are the ear openings are always higher on the left for each species of owl that has asymmetrical ear openings? I would guess that they are predominately the same unless this characteristic had evolved in more than one instance.  Any additional information would be appreciated.

This is a good question indeed. If owls with asymmetrical ear canal openings have different arrangements, it would suggest that the asymmetry has evolved more than once and arrived at different solutions.

The Cornell Handbook of Bird Biology (2nd ed.) states that the Boreal owl right ear is positioned higher than the left. Ornithology by Frank B. Gill (2nd ed.) states that the barn owl left ear is higher than the right. If both of these reports are accurate, then we have two species that differ.

The Wikipedia entry on Sound Localization in Owls (section 3) also suggests that the asymmetry of different owl species may be a product of convergent evolution:

  For example, in barn owls (Tyto alba), the placement of the two ear flaps (operculi) lying directly in front of the ear canal opening is different for each ear. This asymmetry is such that the center of the left ear flap is slightly above a horizontal line passing through the eyes and directed downward, while the center of the right ear flap is slightly below the line and directed upward. In two other species of owls with asymmetrical ears, the saw-whet owl and the long-eared owl, the asymmetry is achieved by different means: in saw whets, the skull is asymmetrical; in the long-eared owl, the skin structures lying near the ear form asymmetrical entrances to the ear canals, which is achieved by a horizontal membrane. Thus, ear asymmetry seems to have evolved on at least three different occasions among owls.

(Emphasis added)

I presume the source of the Wikipedia information to be from Konishi, Masakazu and Susan F. Volman, 1994, though it is not cited in the relevant paragraph.

Perhaps some other ornithological journals will have more specific information, perhaps even allowing us to trace these separate evolved structures. It may even become a great thesis project!


Can an organism exist as a single cell but come together as multi-cellular during certain times? I am trying to remember a particular segment from a BBC special, about a single celled species. However, at certain times all the individual cells came together to form a structure, not unlike a mushroom, to scatter something like spores into the wind. Afterward, the individual cells separated and continued on as individuals.

Am I remembering this incorrectly? Is this even possible?

Welcome to Biology StackExchange.

  Am I remembering this incorrectly?

No, you're remembering it correctly.

I think you're talking about slime molds. You'll find more information on the wiki page

Is this the video you saw? These images are pretty cool.

  Is this even possible?

Yes (given that it exists). There is no way to correctly answer this question as it really is an open-ended question. But here are a few words that may push you writing further posts.

Just a few words on the evolution of altruism

The main interest behind this life-cycle is that not all individuals reproduce. Some individuals form the stalk while others go through meiosis (see below on the life-cycle).

How unfair does it seem to those who form the stalk! Why would those individuals forming the stalk spend energy to help other individuals to reproduce?

Kin selection

Let's think about us, vertebrates, "real multicellular" organisms. The cell that is in your eye is never going to reproduce. Although it is spending all its energy into helping your ovules/spermatozoids to fuse. Why would this cell in the eye make such an effort? The genes in the spermatozoids/ovules are essentially the same as those in the "eye cell". Therefore, by helping your spermatozoids/ovules the eye cell is actually contributing to spreading copies of the genes that it is carrying. This is referred to as kin selection.

Slime molds and altruism

Now, the story is not exactly the same for the slime molds. The cells in the stalk can be quite different from those that are undergoing meiosis. Altruism can exist in a variety of different mechanisms and it would take several books to go over the literature about the evolution of altruism. Without knowing the literature specific to the slime molds reproduction, I just want to notice that the cell in the stalk will die anyway, whether or not it spend energy helping other cells reproducing. There is, therefore, no fitness cost into construction a stalk. Little population structure (causing higher relatedness within deme than among demes) could be enough to allow this behaviour to evolve.

Just a paper (that I haven't read) on the subject

Hudson et al. 2002

Genetics of the fruiting body

Interestingly, similar genes are being used in Dictyostelium discoideum (slime mold) to create this fruiting body than what is used in multicellular eukaryotes (ref.). Thanks to @Tim Cutts for this info.


Causes of Back Dimples What are the causes of the dimples commonly found above the buttocks?  They seem to be in line with the sacroiliac joints.  Do the joints have anything to do with them?

Back dimples or Dimples of Venus are created by a short ligament stretching between the posterior superior iliac spine and the skin. They are thought to be genetic.

Source and further reading: Kumar, Kanojia & Saili (2014) - Skin dimples


Reading annotations from a plasmid map Can anyone explain why inside plasmid mapping software the annotations are layered under each other, I am confused as to why there are essentially two layers within the map, for example in the image below.

The bottom red layer is annotated as "DsRed2" and the top yellow is "LacZ-DsRed2 fusion expressed in E. coli". Does this mean that the red layer is inserted into the original LacZ gene or some sort of mutagensis...? Any explanation would be real helpful.

Second Plasmid design

Third Plasmid

Keep in mind that the plasmid map is made by someone, and probably not perfect. They're also made by programs that let you annotate everything everywhere, even overlapping stuff.

In silico, I assume that the DsRed part and the Lacz parts were present, perhaps copied from some other plasmid map including annotation. After that, someone decided it was a good idea to annotate the complete ORF (in yellow).

What I think this means in reality (just guessing from the map, which is just coarse schematic picture): there's a part of Lacz still present in the plasmid (in pink, second lane) which is fused (in frame) to the DsRed gene (red). Together this gives the fusion gene marked in yellow. Also notice the part (terminator?) in pink that's in the third lane.


Is Batesian Mimicry a form a parasitism? To what extent is the species with real defenses harmed by the defenceless species? It seems like Müllerian mimicry would be an example of mutualism because both species would end up being eaten less by predators that only have to learn one pattern of warning symbols. But to what extent is Batesian mimicry a form a parasitism? It seems like predators who ended up consuming the harmless species would lose some of their conditioning to not eat prey that resembled it, thus harming the species that is actually protected.

How often might this happen in ecosystems where Batesian mimicry is present? Does the presence of a similar unprotected species cause the protected species to be a more common target for predators?

Difference between Batesian and Mullerian mimicry on wikipedia

In my own opinion, I would not classify this as parasitism, as more unpalatable species are eaten with Batesian mimicry (and eating causes death). Parasitic organisms often do not kill the host, whereas in this case, it does. However, you are correct in stating that a unpalatable species with aposematic coloring is detrimented by the presence of a palatable Batesian mimic.

Predators often recognize the aposematic coloring of an unpalatable or dangerous species. They "train" themselves not to eat that particular prey, as it is detrimental. The presence of a Batesian mimic which is palatable or not harmful, in simple terms, "untrains" predators of the harmful nature of that particular aposematic coloring. Predators are "confused", and are thus more likely to eat preys with that aposematic coloring, and results in more death of the species being mimicked, while providing protection to the species that is mimicking.

As far as I'm concerned, within an ecosystem, this phenomenon happens with any Batesian mimicry to some degree. Factors that may influence this degree is the recognizability of the aposematic coloring, as well as the ability of a predator to recognize this coloring.

I hope this clears things up.


Advice on Cell Biology texts by Alberts I am currently reading "The Chemistry of Life" by Rose. It's a great book (to me as a lay reader at least) and an interesting topic so I am interested in pursuing some of the further reading he suggests.

The first book he mentions in the bibliography is Alberts' "Molecular Biology of the Cell". Looking at the description and the reviews it seems that this is a pretty advanced bio-sciences graduate level text, and I am very much not that. I see that Alberts has also written "Essential Cell Biology" which looks more accessible. Before I buy this I wondered if anyone can explain the difference, which would be a better read for an enthusiastic amateur?

If it helps at all I am a science grad and I typically read authors such as Dawkins and Matt Ridley, but I'm looking for something a little bit more rigorous to expand my knowledge in cell biology.

Might as well make it into an answer. As I said in the comments, Albert's  "Molecular Biology of the Cell" is the classic textbook for Biology undergraduates. It has been so for decades now.

It starts from the basics and builds up. Anyone with a high-school science education and willingness to learn should be able to understand it. Just work your way through it :).


What nutrients can humans absorb in the mouth? For instance, I realise being able to absorb simple sugars in the mouth is pivotal in the rapid action of oral glucose gel. Thus I was wondering what nutrients in general can be absorbed directly within the mouth, and at what speed?

Quite a bit can be absorbed through the mouth. Most commonly, starches are broken down to maltose (two glucose molecules formed by a condensation reaction) and are easily absorbed by the bloodstream.

A lot of other factors balance into this, ie pH, lipid solubility, and molecular weight. Generally, if a substance is easily dissolved in saliva, it can be administered buccally or sublingually because the only remaining step is the diffusion into the subepithelial capillaries. In regards to speed, anything properly absorbed via buccal or sublingual administration goes to work much faster than a standard oral medication, and with a higher availability in the bloodstream. You are taking first pass metabolism and enzyme breakdown in the stomach out of the equation by diffusing the drug directly into the bloodstream.

There is quite a laundry list of medications that can be administered transbucally or sublingually, just a few of these:
Nitroglycerin
Acetylsalicylic acid (aspirin)
Glucose gel (as you mentioned)
Fentanyl (a narcotic painkiller)
buprenorphine (for opioid dependency)
Benzodiazepines (alprazolam, clonazepam)


Do Angiotensin II Receptor Blockers (ARBs) or other factors control the level of ACE2 expression? [coronavirus receptor] Because ACE2 is used by SARS-NCoV-2 to enter the cell, I am curious what factors determine its expression.  Interestingly, myocardial infarction increases ACE2 expression in the heart in an animal model ( https://www.ncbi.nlm.nih.gov/pubmed/15671045 ).  The paper found no significant effect from ramipril, an ACE inhibitor, but I don't think I can assume ARBs would work the same way.  (I am suspicious they might increase it based on the increase in the product Ang(1-7) level - https://www.nature.com/articles/hr200974 )  Note that soluble sACE2 can bind cells that did not produce it, by an RGD independent association with integrin beta 1.

Anything that influences the amount of ACE2 on cell surfaces is a useful answer.

I should follow up with some things I've found.  As a starting point, the normal expression pattern is available at https://onlinelibrary.wiley.com/doi/pdf/10.1002/path.1570 - note the staining of simple squamous epithelium in the alveoli and the endothelia of blood vessels.  Another paper details a sharp decrease in expression with age in rats, but I don't know if that extends to humans.

For regulation of expression, I was surprised to see that Google Scholar actually provides a very good assortment of search results, easier to work with than PubMed, which were topped by the MI regulation I described in the question.  Additionally https://onlinelibrary.wiley.com/doi/abs/10.1002/path.1670 (yes, that IS a different link) describes ACE2 expression in renal disease but not in normal kidney.  ACE2 expression correlated with proteinuria, but negatively with GFR. https://link.springer.com/article/10.1007/s00125-008-0988-x  There are discordant notes in some other situations: for example, subtotal nephrectomy decreased ACE2 expression in a way that was partially prevented by ramipril. https://portlandpress.com/clinsci/article/118/4/269/68827/Reduction-in-renal-ACE2-expression-in-subtotal

The mRNA and protein are both described in atherosclerotic lesions: https://onlinelibrary.wiley.com/doi/abs/10.1002/path.2357

In the lungs https://jvi.asm.org/content/79/23/14614.short describes a positive correlation with differentiation state in airway epithelium.  The regulation by HIF-1 alpha in hypoxia seems of special importance: https://journals.physiology.org/doi/full/10.1152/ajplung.90415.2008 but it is complicated (both positive and negative).

ACE2 is also expressed at high levels in placenta during pregnancy - at least in rats. https://journals.physiology.org/doi/full/10.1152/ajpregu.90592.2008

Last but not least, pharmacologic data is reviewed at https://link.springer.com/content/pdf/10.1007/s11906-008-0076-0.pdf which describes up-regulation of ACE2 by angiotensin II receptor blockers, ACE blockers, and mineralocorticoid receptor blockers.  This includes the common drugs lisinopril and losartan.  (see also https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.12573 ) Unfortunately the paper did not report substances inhibiting ACE2 expression.  But https://journals.physiology.org/doi/full/10.1152/ajpheart.00239.2008 reported that high glucose (!) or PKC inhibitors could reduce ACE2 expression.  (but the high glucose was causing kidney injury, which as described above could mean more ACE2...)  The anti-diabetes drug liraglutide increased ACE2: https://academic.oup.com/endo/article/156/10/3559/2422879  To top it all off?  SARS itself decreases ACE2 expression, and this might be part of the process injuring the lungs: https://www.nature.com/articles/nm1267

This is by no means a complete survey, and there is much I don't understand.  The relationship between ACE2 biology and the emerging COVID-19 risk groups seems apparent - as is the urgent need for research to determine which manipulations to ACE2 expression have positive versus negative effects on the prognosis of that disease.

Update: a NEJM podcast today described this biology as 'complicated' link.  It is clearly of interest, but still under investigation.  For example, losartan is presently the subject of two clinical studies news, presumably these ClinicalTrials


Evolutionary selection pressure for human hair patterns? Are there hypotheses or conjectures that postulate any selection pressures or benefits that account for the patterns of non-pubic human hair?  Particularly:

Humans do not grow notable (i.e., non-vellus) body hair until puberty.
Terminal body hair growth in adults is not only sexually dimorphic but also peculiar in its patterning:

Source
As with any trait: it is quite possible that the evolution of human hair patterns had no selective significance.  It could also have been the result of a sexually-selective feedback loop, and therefore are an arbitrary sex trait.
I am looking for hypotheses or conjectures that suggest some objective benefit to terminal body hair.  I struggle to imagine one particularly because of the sexual dimorphism in adult hair patterns:  E.g., if facial hair provides some benefit to men, why would it not provide the same one to women?
If we stipulate that the pattern is only fully expressed in males then it is still peculiar: For example, I can't see any functional characteristic that would make hair on the front torso beneficial while not conferring a benefit if present on the shoulders or top of the torso.

At least some of it is a side effect of the way human skin develops. Humans actually have the same number and density of hair follicles as great apes, it is merely that our hair develops as short vellum hair rather than the thicker, longer hair of great apes. This is a side effect of the same genes that control eccrine sweat gland development, turning on the genes causes the skin to develop more sweat glands at the cost of reducing hair thickness across the body. For humans, a primarily tropical species, having sweat glands was evolutionarily more useful than being hairy, so we largely traded hair for sweat glands. As a result, the distribution of hair across our bodied may be at least in part a side effect of where it would be most useful to have sweat glands. Hair is typically retained in the armpits and groin because it helps trap odors that may elicit sexual signalling.
Hormones may also play a role. Testosterone has been linked to changes in hair development, and may actually be related to male-pattern baldness.


What is the cause of the spots on this leaf? On a hiking trip to the Alps I found trees whose leaves showed those spots you see on the picture. I am curious about what the cause is.

Higher resolution pictures of front and back side.

This is a "Tar Spot" disease usually found in Europe and North America. It mostly affects the Maple tree leaves. Tar spot is caused by 'Rhytisma acerinum' a plant pathogen fungus. This pathogen does not seem harm to tree but disturbs the leaves as it finds a suitable condition in summer with bit of wetness. It enters the leaves through stoma and then creates yellow lesions of various sizes over the leaf area which later gradually turns into brown-black tar colored spot. It reduces the photosynthesis process of leaves and thus creating more wide dark spots on the leaves. After sometime the leaves will fall.

Entire detail is available in the Wikipedia link with the detail of the pathogen. (Add some more info if you find this detail not enough)


Why do plasmids replicate on their own? I know how plasmids can replicate independently of the main genome and know that they confer various properties to the bacteria and are useful in conjugation.

My question is - what is the advantage of plasmid replicating on their own? (Would there be any disadvantage if they were controlled by the main genome instead?)

In plasmids with high number of copies, the plasmid needs a certain density to be able to supply its function. If a given cell contains a few dozens of plasmid mollecules, and this is its optimal density, the easiest way to achieve this is to downregulate the replication by its own presence or the presence of one of its components. This also allows a random segregation during cell division, due basically by simple diffusion. It's also easier for the plasmid to achieve its optimal density once it has enter in a new cell by conjugation or transformation.

Plasmids are also subject to selection, so it is reasonable to assume that the more independent and more contagious a plasmid is, the bigger its presence in the population. In fact, it is a reasonable hypothesis to assume that many viruses are parasitic plasmids (many viruses in fact have a similar genomic structure and share many traits with them).

However, in plasmids with low number of copies the replication events can be dependent of the genome replication as you describe (despite the fact that many plasmids of this kind still regulate its own replication by itself). In this case, though, the line between plasmid and chromosome is less clear. In some organisms some big plasmids seems to form part of the genomic organization in the whole strain, and they usually contain important genes. This plasmids behave just like regular chromosomes, and they segregate by the same mechanisms the rest of the genome use. For those plasmids the terms minichromosome and megaplasmid are used, and the choice usually depends of the kind of genes it contains.


Ethanol production by fermentation? As bacteria are involved in the production of ethanol through fermentation and ethanol is also used as antiseptic that kills bacteria, so how and why bacteria are involved in the synthesis of such alcohol which is lethal for itself(bacteria)?

Yeast can produce up to 16-17 v/v% ethanol without dying according to this article. Yeast is a primary industrial ethanol producer, it produces ethanol even under aerobic conditions, in contrast to bacteria that usually ferment sugar to ethanol under anaerobic conditions. Bacteria can also withstand up to several percent v/v concentration ethanol in their media. Check this paper for details. They produce ethanol because it is a natural byproduct of their cellular metabolism. Under anaerobic conditions sugar as the primary energy source cannot be oxidized and utilized as well as in aerobic conditions.

  Alcoholic fermentation converts one mole of sucrose into two moles of ethanol and two moles of carbon dioxide, producing two moles of ATP in the process.

from: http://en.wikipedia.org/wiki/Ethanol_fermentation

Anaerobic bacteria follow this path because fermentation of ethanol does not require oxygen. This byproduct is secreted from the cells. In natural environments ethanol either dilutes in the media bacteria live in or can be taken up by acetic acid bacteria and used as an energy source.


Can ampicillin resistant bacteria survive penicillin plate? in my molecular bio class we were asked a trick question:

If the bacteria has a plasmid with that grants it ampicillin ressistance, can the bacteria survive if placed in penicillin?

I gave it  a thought and said that it cant, since amp differs from pen by an extra amino acid that could harm the bacteria, the answer corresponds with the class material but amp is known as the broad spectrum antibiotic.... so should i go with the  class flow  lured by the experimental assumption and assume it dies  or persist on whether it will survive? i'm really confused at this point, any input is appreciated

Short answer: Your assumption is wrong and bacteria, which are resistant to penicillin are are also resistant to ampicillin.

Long answer: There are different classes of antibiotics, which have different mechanisms of action. Penicillin (and also ampicillin) belong to the class of beta-lactam antibiotics which are an irreversible inhibitor of the bacterial transpeptidase, which is needed for the proper formation of the bacterial cell wall.

There is a number of different natural occuring penicillins as well as some which have been generated by modifications of the general structure. The general chemical formula for these is shown below (from the Wikipedia article), the different penicillins differ only in the "-R"-group shown in the molecule (in the upper left):

If you now compare Penicillin G (which occurs naturally and is still used) and ampicillin side-by-side, you will see the the difference is not very big, basically only one amino group:

Penicillin G on the left, Ampicillin on the right.

The difference of this one amino group makes ampicillin more polar and allows it to penetrate the cell wall of some gram negative bacteria (the main action goes against gram positive bacteria).


Why do some tissues have insulin-dependent glucose transporters and others not? Insulin upregulates GLUT-4 glucose transporter insertion in skeletal muscle and adipose tissue. But there are many tissues in the body that use insulin-independent glucose transporters (like GLUT-3 in the brain). Would there be any disadvantage to have the entire body use insulin-independent transporters like GLUT-3? Why involve insulin in this? Wouldn't the concentration of glucose in the blood regulate the influx of glucose via concentration gradients anyway?

Summary

The whole point of hormones is that they allow the organism to control the metabolism of tissues in an integrated manner, rather than each tissue acting independently. Insulin, glucagon and epinephrine are classic examples of this in relation to carbohydrate metabolism. In the fed state, the fasted state and in stress situations it is appropriate for different tissues to respond in different ways. The presence or absence of a hormone receptor — together with the enzyme complement of the tissue — achieves this. Allowing all tissues to have only GLUT-3 (or all GLUT-4) would mean they would all respond to changes in glucose availability in the same way — a totally inappropriate situation for the organism, with potentially disastrous consequences.

More Detailed Answer

Insulin is an indicator of the fed state. In such circumstances there will be a surplus of glucose and it is of benefit to the organism for it to be taken up by muscle and adipose tissue for storage as glycogen and fat, respectively. Conversely it is important that in starvation blood glucose is not so utilized, but spared for those tissues for which it is vital in any conditions. (Muscle can utilize other metabolites such as fatty acids.) Hence, for these tissue allowing glucose transport to be controlled only by blood glucose concentration would not produce a sharp cut-off and result in deny this resource to those vital tissues which cannot replace glucose by other energy sources.

The tissues you mention such as brain (and erythrocytes) depend absolutely on glucose, irrespective of whether the organism is in the fed or fasted state. If they had only an insulin-dependent transporter they would be starved of glucose during the fasted state, with lethal consequences. The insulin-independent transporter allows continued transport down the glucose concentration gradient, even as the blood glucose concentration falls.

Note that blood glucose concentration in the fasted state is maintained by the liver, so that this tissue has an insulin-dependent transporter, not to allow glucose uptake, but to allow the glucose produced by gluconeogenesis to be transported out into the blood.

Further Reading

I would hope that the logic of my answer will be sufficient convincing, but it is good practice in Biology-SE to provide references to support one’s arguments. Section 30.22 of the online edition of Berg et al. discusses the metabolic profile of different tissues and includes some discussion of glucose metabolism and glucose transporters. (The liver glucose transporter is actually different from that in nervous tissues, as is that in erythrocytes — see Wikipedia article.)


Segmentation in Platyhelminthes My text book says:

  Platyhelminthes are unsegmented worms.

Moreover, tape worm (Taenia solium), which is segmented, is one of the examples of Platyhelminthes.

My question is: why a segmented worm is included as an example in Platyhelminthes (unsegmented worm)?

The confusion here is quite common (at least it was quite common among my students): the "segments" in a tapeworm like Teania, properly called proglottids, are not really segments, or metamers.

According to Hickman et al. (2001), in the chapter 17, Segmented Worms:

  Body segmentation, or metamerism, in annelids is not merely an external feature but is also seen internally in the repetitive arrangement of organs and systems and in the delimiting of segments (also called metameres or
  somites) by septa. Metamerism is not limited to annelids; it is shared by
  arthropods (insects, crustaceans, and others), whose metamerism may be
  homologous to that in annelids, and also by vertebrates, in which it evolved independently.

Some pages before, in chapter 14 (Acoelomate Bilateral Animals), the authors say:

  Some zoologists have maintained that the proglottid formation of cestodes
  represents “true” segmentation (metamerism), but we do not support this view. Segmentation of tapeworms is best considered a replication of sex organs to increase reproductive capacity and is not related to the metamerism found in Annelida, Arthropoda, and Chordata (see pp. 193 and 371).

I'm citing Hickman, but all zoology books I'm aware of (Ruppert-Fox-Barnes, Brusca & Brusca, etc...) will say the same: segmentation is synonym of metamerism, and Plathyhelminthes (including Teania) are not segmented animals.

Source:

Hickman, C., Roberts, L., Larson, A., Ober, W. and Garrison, C. (2001). Integrated principles of zoology. 1st ed. Boston: McGraw-Hill.


Why does wood become darker when it ages? I have lots of pieces of pine furniture which have different colours depending on how old they are. So, I just wondered why that is. I guess it has something to do with structures and chemical compounds that were already in the wood when it was still alive, so I hope this is not off-topic here.

What processes take place in dead wood when it ages?

What determines the colour it will have? For example, pine and spruce wood looks very similar when freshly cut, but will develop very distinct colours afterwards.

Is there also wood that does not become darker?

Is it something to do with the processing of wood, or will that happen to any stick you leave lying around in your room (so it doesn't rot)?

While most wood we see comes from stain or oils, wood left on its own will darken.  As far as this article suggests, this is caused by the polymerization of polyphenols from lignin into tannins which are dark red or brown in color when they are highly polymerized.

The specific content of the lignin in different woods will affect the density, strength and color of the wood.

This woodworking reference shows that intense UV exposure to wood will darken it to give it an aged look.


Complementarity Determining Regions (CDRs) Complementarity determining regions (CDRs) are part of the variable domains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively, where these molecules bind to their specific antigen. (source: WIKI, with a minor change)

Now does this mean that this CDR is the paratope? As it has the same functionality as paratope, to bind to epitope of the antigen. So is CDR a type of paratope?

(I have not studied biology since last 8 years and now I am going through it because I need it for my research. So if someone can describe it in simple language it would be very helpful)

The paratope is the part of an antibody that binds the epitope on the antigen. The CDRs (heavy chain CDRs shown below) are part of the structure of the variable domain, and contain the hypervariable regions that bind to the epitope.

From Wikimedia

The actual paratope is within the hypervariable regions, which are within the CDRs - the paratope is not necessarily made up of the entire CDR region, and in fact may only be composed of amino acids contained within one or two of the three CDRs on each antibody chain (heavy and light).

If you're in the market for a good introductory immunology text, I highly recommend Janeway's Immunobiology. An earlier version is also available on the NCBI Bookshelf.


Identifying a spider very similar to a brown recluse I took this pic tonight when I saw what I thought to be a Loxosceles reclusa or brown recluse. But when I looked closer, the typical pattern on the back of its cephalothorax seems to be upside down! I tried to compare with lots of pics and I was not able to identify this one. Plus, its abdomen is kind of velvet greenish.
Could anyone help identifying this spider please? Last precision : the body size (excluding the legs) is around 1cm.
Thanks Folks!
Photo taken on June the 24th 2018 around 10pm in Toronto, South Ontario, Canada.
PS: Even if one of its leg is fully missing, it was still running very quickly...

I think this a nice male Cheiracanthium inclusum, the familiar "yellow sac spider" (outdoors edition).  The abdomen is what you would expect, the very long first pair of legs, the obvious eyes at the front of the head (middle two of the top row).
I'd feel more comfortable if I could see the usual very dark 'face' and chelicerae, but the angle of the photo is such that it might be just hidden.  The carapace pattern looks interesting, but it may well be that the flash of the photo is giving us a different look there.

Here's the link to the Bug Guide page, with a representative photo of a similar male:

https://bugguide.net/node/view/80427


Is this a stag beetle? Just saw this beetle on my window.
The coin is an American dime.
Location is Shenandoah Valley,
in central Virginia, U.S.A.

This is indeed a Stag Beetle (Family Lucanidae); in particular a member of the genus Lucanus.  Looking at the bugguide.net page for the genus here your specimen is most likely Lucanus capreolus, though Lucanus placidus also looks possible -- the two species are very close in appearance, though the former does seem more likely based on distribution.  Consulting The Generic Guide to New World Scarab Beetles here confirms that L. capreolus is featured here -- the femora (the first long segment in the leg, and the first we can see -- look at the right front leg) are bicolored (darker at the tips) -- the femora of L. placidus would be solid dark brown to black.


What's the difference between stabilizing selection and balancing selection? I came across these terms in Darwin's "Origin of Species" and I wasn't sure what the difference is.

Usual meaning

Usually, Stabilizing selection is a concept that applies to a phenotypic trait while balancing selection is a concept that applies to a given locus.

Balancing selection can either be due to negative-frequency dependence selection or due to overdominance (=heterozygous advantage at a single locus).

What Darwin may have meant

Because Darwin didn't know about genes, he was necessarily not using the term balancing selection as I am using it. I can think of several more or less related pattern of selection that might fall withing the definitions for "stabilizing selection" and/or "balancing selection". Maybe he meant "frequency-dependent selection", "positive selection for an intermediate trait", "varying selection through time (temporally heterogenous environment)" and "varying selection through space (spatially heterogenous environment)". Eventually again, that might mean "positively correlated traits that undergo opposite selection pressure (or the opposite)" but that would definitely be surprising.


Design arbitrary degenerate primers (with non-binding criteria) I would like to design a number of arbitrary degenerate primers (primers with variable bases, e.g. NGATWGCTSATNGC) for a TAIL-PCR.

I would like to be able to specify the following parameters for the design function:

Annealing temperature (ideally 44°C)
Degeneracy (how many variations of the AD primer there are (ideally 128 or 256)
Binding frequency on (mouse) genome (ideally 1/3000) - though this may be contingent on the degeneracy, and vice-versa.
Non-binding area (of course I would not like any variation of the primer to bind to the known-sequence area in between my specific primers and the unknown area which I want to sequence)

Any ideas of any tools that can help me with the above steps? For Primer design I have used eprimer3 thus far (with invariably satisfactory results) - but it seems to not support the concept of arbitrary degenerate primers.

Ideally, if I had a function which could sort out the first of the above criteria, I could use Biopython and BLAST to script the rest myself. Though the binding frequency would take hours if not a day or two, for BLAST to determine it. It would greatly help if anybody already wrote something more elaborate for this.

If you already know the basic sequence i.e. the fixed regions in the primer; for e.g. the known nucleotides in the sequence -  NGATWGCTSATNGC, then you can implement your algorithm like this:

Fix the max length of the primers. Lets say 20nt.
Generate all combinations of primers (20nt): that is pretty straightforward. You will have  4N × 2(R+Y+S+W+K+M) × 3(B+D+V+H) number of combinations, where each alphabet denotes number of such instances. Chek this site for the nucleotide codes.
Calculate the Tm of the primer-template pairs. UNAfold has a nucleotide hybridization Tm calculator. You can specify parameters like salt concentration etc. There are other such tools too. These can be run on the commandline.
Discard all primers have Tm below the acceptable limit.
For those that exceed the acceptable Tm, keep dropping a base from the 3' until the Tm reaches within the range.
If primer length goes below 14nt then discard the primer.
Now with all these selected primers check for parameters like self hybridization, GC clamp etc (OPTIONAL). You can use primer3 for these purposes by running it on the primer_check mode.
Download the nr/nt BLAST database.
Adjust BLAST parameters for short nucleotide search: Decrease the word length, increase e-value cutoff etc (See this biostar post and BLAST help).
BLAST your primers against the database in plus-minus mode.
Worry only about cases where there is significant alignment at the 3' of the primer as only these can cause extension.

These instructions can be automated using any language or shell script.

Questions on script writing would be off-topic in this site. You can ask specific doubts about coding in stackoverflow.


Problem on finding sequence of Taq polymerase As i know, Taq Polymerase can be found in Thermus aquaticus, so i do a search for protein list of Thermus aquaticus and have this : http://www.ncbi.nlm.nih.gov/genome/proteins/1724?project_id=55053 . After filter for 'polymerase' i found a lot of protein named polymerase :

DNA polymerase beta domain protein region
DNA polymerase I
DNA polymerase III, alpha subunit
DNA polymerase III, beta subunit
DNA polymerase III, delta subunit
DNA-directed DNA polymerase
-.....

I don't know what they mean and which is the protein i'm looking for ?

After click on one of them i have the sequence not in A-T-G-X format :

ORIGIN
        1 msgvdallll gvelsraiit aysvyaivli lggflarlpt rweervealg gsfylagvil
       61 wryyaggday dldlflrasg mallvlprlv rvvlreyggg r

What does it mean and how to working with it ?

According to the paper here "Taq polymerase" is the DNA polymerase I from Thermus aquaticus. (Incidentally the paper has the complete sequence of the gene in question.)

You can find a protein sequence entry at NCBI here. This shows the sequence of amino acids in the protein, not the DNA sequence of the gene. Several lines from the top you will see:

  DBSOURCE    locus TTHDNAP accession D32013.1

with the last word highlighted as a link. Follow that link to the DNA sequence. That entry includes the line:

  CDS             1..2499

which tells you that the initiator ATG of the gene is right at the start of the sequence shown, but that the 3026 bp sequence includes a lot of downstream DNA. If you click on CDS on that line it will highlight the coding sequence in the DNA.

A very cursory comparison of this sequence with the one in the paper that I linked to suggests that this is the same gene.


Trypsin and Cell Surface Receptors Can adding Trypsin to mammalian cells affect the expression of or hydrolyze cell surface receptors?

Yes. Trypsin cleaves proteins and can do so quite indiscriminately if left on for very long. Trypsin is primarily used to cleave the proteins that cells use to adhere to each other and the plate in culture. It can cleave other membrane bound proteins as well, including receptors.

https://jbiomedsci.biomedcentral.com/articles/10.1186/1423-0127-17-36


Is fat distributed proportionally around the body? One guide I have been using to tell me if I really am gaining a lot of weight is a ring around my 2nd last finger on my right hand, if I can slip it on and off without any resistance then I'm fine, however I've been basing this from the notion that if I gain weight it's proportionally distributed around my body, as such, if I get fatter so do my fingers

So I am wondering, is fat distributed proportionally around the body (ie. if your waist gets bigger then your fingers will get bigger along with it)?

@fileunderwater's suggestion to use a scale is probably the best answer you could get, but looking at this broadly, the answer is no.  The oft-referenced apple and pear shapes are indeed very real and have medical consequences.  One of the issues is that there are sex differences in fat distribution.  There is no evidence I can find that finger fat is a good correlate of overall body fat, although admittedly yours could be.  It is also likely a function of how much overweight you were when you began the "experiment" i.e. the relationship probably isn't linear.

That being said, in men the ratio of the length of the second and fourth digits are otherwise meaningful.


Is this how female and male gametes look like in plants? In the red box, the pink one is female sex cell I presume and the blue one is a male sex cell.

http://prntscr.com/dsii2x Am I right? or are these chromosomes.. I'm confused.

This is law of segregation.

The comments are very unclear and your interpretation of the figure seems very wrong (no offense). You should have a look at an intro course (such as this one by Khan Academy) as asking such intro questions here will require for one to rewrite an entire course.

The pink and blue thingies on the image are chromosomes, not gametes. A gamete is a haploid cell (we can see 4 of them at the bottom of the figure). One chromosome (say the pink one) has been inherited by the mother of the individual and the other chromosome (say the blue one) has been inherited by the father of the individual.

Let's assume that the segregation we see on the figure happens in a female individual. So, on the figure we see female diploid cells and female haploid cells. The female haploid cells are called ovules (there is a bit of oversimplification here). You can imagine the same process of segregation could occur in a male individual. The male haploid cells are called spermatozoid (there is a bit of oversimplification here). The male and female gametes might fuse to become a zygote which will develop in a new fully grown individual. The colors of the chromosomes in this scenario indicate whether the chromosome originally come from the grandmother or the grandmother of the zygote.


How do I get a brighter DNA bands I've been trying to a good contrast for my DNA bands, however I haven't been so successful. I've been running the ladders only to make sure I get a good contrast before further experimentation.
I created the gel using 70mL 1X TAE buffer, 0.84g of agarose (so about 1.2% gel), and 28ul EtBr.
I set the electrophoresis box at 90V for about 1 hour hoping to get a better gel but the results came out looking the same as if I had ran it at 110V.
I've attached a picture of my gel. It was taken with a DSLR, no flash, 20 seconds exposure time.
Any tips would help. Thanks

I normally use 1-2 ul (depending on whether my gut tells me I have a lot of DNA, or a little that day) in a 70 ml 1% gel (which is probably 60-65 ml after boiling in the microwave). I have no trouble whatsoever seeing ladders and DNA samples of down to 100 ug in wells not much bigger than about 4 mm.

Here are the factors that you can manipulate to alter the brightness:

Amount of EtBr. More is brighter. (However, you already use a lot - using less may even be better because it would reduce background while still saturating the DNA with EtBr)
Amount of DNA. More is brighter. To avoid guesswork, use a ladder and consult the instructions in its manual or spec sheet. They usually have an example picture of a gel, and say exactly how they obtained it.
You messed up. Do other people in the lab get good gels? Ask them to do the protocol with you.
Sample preparation. Are you using a loading dye in the correct amount? Is the DNA diffusing out of the wells? Are you spilling a lot of it when you load?
Band width. Obviously if you load the same amount of DNA in a well 4 times as wide, it will be 4 times fainter.
Strength of UV light. Many illuminators have a knob to adjust the intensity, people turn it down to avoid damaging DNA when gel-purifying restriction fragments. You can also play with intensity, gamma and exposure in a geldoc machine.
Quality of EtBr. I've never actually had this happen, but your stock may be bad for some reason. Ask another lab for a ul or two to easily control for this.
Quality of DNA. Obviously, your sample must actually have DNA in it, and not be degraded. You can check amount and purity easily with a spectrophotometer, but it will not tell you if the DNA has been digested into its component nucleotides (that is usually checked with a gel).
Amount of gel. The crucial variable is obviously not total amount of EtBr, but concentration. Less gel, brighter bands - but you seem to be using a standard gel amount.
Quality of gel. Again, never had this happen, but try making the gel with someone else's reagents.

I can see that you have a ladder in the middle, so at least some DNA is definitely there.

Also, keep in mind that off-the-shelf cameras are not good at imaging the EtBr fluorescence, because the wavelength is a bit unusual. The nice pictures you see in papers are taken with a specialized geldoc machine or a camera with an appropriate filter.


Discrepancy in time for genetic differences between human and chimpanzee to accumulate Genetic differences between human and chimpanzee include ~50,000 amino acid changes, ~30,000,000 point mutations in non-coding sequences, and millions of insertions, deletions, inversions, genomic rearrangements, and transposable element movements [1]. The vast majority of these genetic changes are neutral [2] [3]. For neutral mutations, the expected number of generations required to reach fixation in the population is the reciprocal of the mutation rate per site per generation [4]. This holds irrespective of selection at other linked loci, changes in population size, or almost any other conceivable complication [4]. The human mutation rate, μ, is ~10-8 per site per generation [5]. Although μ can be orders of magnitude greater at certain sites, the fact that, as cited above, millions of neutral mutations occurred in the human line since its divergence from the chimpanzee line indicates that at least thousands of mutations occurred at the average rate of 10-8 per site per generation. Since the expected number of generations required for any one of these mutations to reach fixation in the population is the reciprocal of μ, this number equals ~108 generations. Since a generation is ~20 years for humans [5], the time required for any one of these thousands of neutral mutations to reach fixation is ~109 years.

According to the currently-known fossil record, the human line diverged from the chimpanzee line between 6 and 8 million years ago [7].

How is this major discrepancy between population genetics and the fossil record to be reconciled?

References

[1] Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005)

[2] Harris, E. E. Non-adaptive processes in primate and human evolution. Am. J. Phys. Anthropol. 143 (Suppl. 51), 13–45 (2010)

[3] Vallender, E. J., Mekel-Bobrov, N. & Lahn, B. T. Genetic basis of human brain evolution. Trends Neurosci. 31, 637–644 (2008)

[4] Lanfear et al, Population size and the rate of evolution.  Trends in Ecology & Evolution, January 2014, Vol. 29, No. 1, Pages 33-42

[5] Kong, A. et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature 488, 471–475 (2012)

[6] Walker, R. et al. Growth rates and life histories in twenty-two small-scale societies. Am. J. Hum. Biol. 18, 295–311 (2006)

[7] Levin, N. Annual Review of Earth and Planetary Sciences, 43: 405-429 (2015)

Good literature work here and good question +1! In short, your main mistake was that you based your calculations on a single site and not on the whole genome. More info below.

Genome-wide vs sites specific mutation rate

The statistic of $10^8$ generations that you computed is the average rate of fixation of new neutral mutations per site. As considered the genome-wide statistic between humans and chimpanzee, you have to scale your predictions up to the entire genome. There are about $3 \cdot 10^{9}$ nucleotides in either the human of the chimp genome. That would result in a genome-wide mutation rate of $U ≈ 2 * 10^9 \cdot 10^{-8} = 20$  (the two is because mammals are diploids). Hence, the rate of fixation of 0.05 generation.

So, the expected time it would take for $30 \cdot 10^6$ new mutations to fix would be $30 \cdot 10^6 \cdot 0.05 = 15 \cdot 10^5$ generations. Because, such mutation can happen in either lineage (humans or chimps), we have to divide this number of 2 leading to $7.5 \cdot 10^5$. With a generation time of 20 years, that would take $1.5 \cdot 10^7$ years or 15 million years.

15 million years? Why not 6-8 million years as expected from fossil records?

Most of the discrepancy is probably due to vague approximation made in the computation. For example, you assumed a mutation rate of $10^{-8}$ while in reality, the average mutation rate is rather twice as large (Nachman et al., 2000, Kong et al., 2012, Wang et al., 2012, Rahbari et al. 2016).

Doubling this mutation rate would divide by 2 our expectation of 15 million years leading to an expectation of 7.5 million years that perfectly match the fossil records!

There is however another source that may cause an overestimation of the time needed... You assumed the absence of incomplete lineage sorting or in similar words, you assumed that the standing genetic variance in the ancestral population negligibly affected divergence among the two lineages. However, these discussions are for another time!


Can a virus infect a virus? As far as I know a virus can infect any cellular organism from a bacteria onwards, including protists, algae, plants, and so forth.
But can a virus infect a virus?

No, it cannot. Viruses infect cells, in order to use the cellular machinery to replicate themselves - viruses themselves do not possess such a machinery, so speaking of one virus infecting another is meaningless.
This does not mean that viruses do not interact: when two viruses co-infect the same cell, the progeny virions may contain parts of the genomes of both viruses. This is how genetic recombination occurs in HIV.
An even more famous example is gene reshuffling of influenza viruses, where an animal virus exchanges its genes with a human virus, producing a new human strain. In the popular culture some of these a famously named after animals whose virus contributed or animals where the reshuffling has occured (bird's flu, swine flu, etc.)
Update
It is worth mentioning the satellite viruses, which are viruses that lack the proteins necessary to catalize the replication and possibly even the genes coding for their capsid proteins (in which case they are more properly called satellite nucleic acids rather than satellite viruses). These viruses are dependent on a helper virus to carry the missing genes. This is not characterized as parasitism, but it is rather close.
Update 2
A special type of satellite viruses, called virophages, actually do exhibit characteristics of parasitism in respect to the helper virus:
Unlike satellite viruses, virophages have a parasitic
effect on their co-infecting virus. Virophages have been
observed to render a giant virus inactive and thereby
improve the condition of the host organism.


First discovery of long-term depression? LTP was first described by Tim Bliss and Terje Lømo in their paper Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path.

When was LTD first described? By whom?

The process of long-term depression (LTD) was first discovered in the cerebellum by Ito et al. in 1982:

Ito M, Kano M. Long-lasting depression of parallel fiber-Purkinje cell transmission induced by conjunctive stimulation of parallel fibers and climbing fibers in the cerebellar cortex. Neurosci Lett. 1982;33(3):253-8

Ito M, Sakurai M and Tongroach P. Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar Purkinje cells. Journal of Physiology 1982; 324: 113–134.

Check this source.


Why are there so many medicinal plants? Question

Quite a few plant species can be used for medicinal purposes wiki. As an example, Filipendula ulmaria is rich in acetylsalicylic acid (aspirin).

An allele that produces a substance which is beneficial for a predator should not get fixed in the population! Why are there so many drug-like plants?

Thoughts

Here are some (intuitive, unclear or far-fetched, non-exhaustive and non-exclusive) hypotheses I can think of:

Because plants want their seeds to get ingested in order to propagate
Is it because there are so many substances that affect our homeostasy that many plants are toxic and many are healthy just by chance. Containing healthy substances are not adaptations but by-product of evolution.
The substances that are beneficial for us actually evolved to repulse predators. These substances are toxic at high dosage and therefore are efficient against predators that are small or eat a lot of plants (herbivorous). These substances at low dosage might actually have a benefical effect. For example a substance that make blood thicker is very toxic except if you eat just a bit of it while bleeding.
We (primate or whatever taxon you want to consider) evolved in order to get advantage of the surrounding envirronment. Sbstances that were neutral became beneficial. The advantage of being sensitive to various products cause that, by chosing our food source, we can heal. Therefore, by evolving sentivity to various substances, our behaviour can act as a reinforcement to immunity (and other anti-illness system). If this is true, we might expect that the frequency of presence of a plant species affect the probability that out homeostasy get affected when eating it.
Lineage selection. Lineages that produce substances that are active in predators body in a way or another are undergoing many various selection forces because of these substances. Therefore they get a higher speciation rate than other lineages.
Keeping some non-herbivorous species in large population size (by helping them) is the best way to keep herbivorous species in small population (because of territory competition, predators relationships, etc... )

Perhaps the question may also be phrased, "Why is it common for plants to produce chemicals that possess pharmacological or toxicological effects in man and animals?", and to that question it is often reasoned that plants, being sessile and otherwise defenceless food sources for predators, produce compounds that affect the physiology of animals in such a way as to make it not beneficial for a predator to consume them, which is close to your 3rd hypothesis. Remember that pharmacological benefit is largely anthropocentric, and relative at that. For instance, a plant compound that lowers blood pressure could be used as treatment of hypertension, but if the plant were to be consumed in its native state in appreciable quantity, it could put the eater into shock, cardiac arrest, etc.

Most pharmacologically active compound from plants comprise a class of compounds known as secondary metabolites: metabolic intermediates that are not appreciably involved with functions of growth, respiration, etc. (often interpreted as evidence for a defence mechanism).

Try this wikipedia article and see what you think: http://en.wikipedia.org/wiki/Plant_defense_against_herbivory

The major classes of secondary metabolites in plants are: terpenes, which are polyisoprenoids, phenolic compounds, including the polyphenolic compounds, which are a popular study in natural products research, and alkaloids (along with other nitrogenous compounds).


Loss of function in inflammation The Wikipedia-article about Inflammation says

  The five classical signs of inflammation are heat, pain, redness, swelling, and loss of function (Latin calor, dolor, rubor, tumor, and functio laesa).

What does 'loss of function' mean? And how does it occur?

TL;DR: It originally referred to abnormality in "secretion" by the inflamed tissue and later became used to mean any abnormality at all.

This fifth cardinal symptom of inflammation seems to be rather mythological as laid out in detail by Rather (1971, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1749862/?page=3). This source explains that the term seems to have been invented at some point in the 19th century without proper definition. Later authors seem to have interpreted it as basically just meaning "not functioning properly" (although this is literally the definition of unhealthy as opposed to healthy, and not specific to inflammation).

According to Rather, the original source of the confusion may have been the phrase: "...heat, redness, tumour and pain; to which should be added an alteration or suspension of the natural secretions of the part." by Macartney in 1838 (page 8 of the same document). Various versions of mentioning a fifth cardinal symptom that involved altered function made their way through pieces of writing, until it received the Latin term "functio laesa" in the late 19th century (Rather cites a piece from 1882), lending it credibility as an established concept. The passage by Macartney was later cited by Marchand in 1924, who was trying to clear up the confusion around who established the four and potentialy fifth cardinal symptoms of inflammation. Marchand rephrased it into a "fifth cardinal symptom the alteration or disappearance of normal secretion (thus a functio laesa)", trying to explain what, according to Macartney, is the fifth symptom, and adding why it could be called a "loss of function".


Is the knee locking mechanism present in animals? We study in human anatomy that when the knee is in full extension, the femur slightly medially rotates on the tibia to lock the knee joint in place. This reduces the work required to be done by the hefty thigh muscles. This happens in the knees in humans since they are the weight bearing joints.

So, is the mechanism of locking present in other animals? If yes, is it even in the fore limbs or just the hind limbs?

Yes, the mechanism of patellar locking does occur in quadrupeds too. Although they are 4 limbed, a major portion of the weight is borne by the hind limbs. This is known as the stay apparatus and includes the mechanisms of Patellar locking, reciprocal mechanism and check apparatus.

On the other hand in the forelimb, although there is no locking mechanism as such, there exists a neat difference from the human anatomy. Human forelimbs are majorly adapted for manipulation but for quadrupeds, they are weight bearing. There exists what is called the stay apparatus - which includes the suspensory apparatus and the check apparatus.

For a detailed explanation for the interested reader, heres a helpful link - https://en.wikivet.net/Stay_Apparatus_-_Horse_Anatomy


What is this growth on a Rosa rugosa stem? I saw many of these on my big old Rosa rugosa bush yesterday. What are they?

This looks like a gall. At first I thought that it was the common rose bedeguar gall, also known as Robin's pincushion gall which is caused by Diplolepsis rosae, a small wasp. However, there is a related wasp, the spiny rose stem gall wasp Diplolepsis spinosa, which attacks Rosa rugosa so I imagine this is what you have here.

Incidentally, you are probably wondering what bedeguar might mean. According to the OED it derives from a French word bédégar which in turn comes from the Persian bād-āwar ('wind-brought’).


How to increase pheomelanin production? How can you increase the pheomelanin production in your body, while decreasing the eumelanin production? In other words, shifting the balance towards pheomelanin.

From what I see, sulfur and cysteine can help with this. MSM and glutathione caps can be a good way to do this, since these are used for skin lightening.

But is there another way? Something more scientific? Like deactivating the MC1R? Is that even possible?

Thank you!

Since Eumelanin is the protective form of melanin and there is some research available that Pheomelanin contributes to the generation of reactive oxygen species which are harmful to the cell (see reference 1, which contains a lot of further references on this topic), I don't see any reason to do so, but ok. Additionally removing Eumelanin from your skin will lead to a higher risk for skin cancers as Melanoma. Let's think through this:

If we look at the biosynthesis pathway of the Melanins, they both start with the same two reactions (see the figure from here):

The routs parts at the DOPAquinone, which in the presence of Gluthathione or Cysteine goes into the pheomelanin direction. The concentration of Cysteine available to the cell needs to be higher than 0,76 µM (see references 2 and 3 for details), otherwise the reaction goes exclusively into the Eumelanin direction.

There are some skin whitening (or better lightening) products available which contain L-Cysteine or GSH. This will work to some extend, but once the level drops enough, the ratio will shift back to the more natural ratio between Eumelanin and Pheomelanin. There is also no data available on the risks of doing this, so I would strongly advocate against it. See the review in reference 4 for details and additional references on this topic.

If you now think, ok, taking some pills is enough, I would call this a false hope, since this process is highly regulated. This happens on one part through external signaling through the MC1R receptor (which as you already mentioned is of importance here) and also through the availability of key enzymes in the process as well as stability of them and their regulation.

Signaling through the MC1R receptor is highly important for pigmentation and also the amount of enzymes available (the transcription factor MITF is regulated by it). If the signaling is strong, the cysteine storage is soon depleted bringing on the production of Eumelanin. If this signaling is weak
this will not happen and the production of pheomelanin is favoured. Mutations in MC1R are the reason for people having red hair and and fair skin. See reference 5 and 6.

Interfering with the signaling cascade which is activated by MC1R is certainly not a good idea either, since this will interfere with other processes in the cell as well. These pathways are also disregulated in cancers, so I would not touch these.

Summarizing I think there will only be a way of influencing this by taking some supplements, but how safe this is, is unknown. All the other possible ways are certainly more dangerous.

References:

How does pheomelanin synthesis contribute to melanomagenesis?: Two
distinct mechanisms could explain the carcinogenicity of pheomelanin
synthesis.
Rate constants for the first two chemical steps of eumelanogenesis.
Chemistry of mixed melanogenesis--pivotal roles of dopaquinone.
Systemic skin whitening/lightening agents: What is the evidence?
UV signaling pathways within the skin
The melanocortin-1 receptor: red hair and beyond.


16S sequencing: pooled or individual samples? I am planning to run 16S sequencing on a set of individuals to explore microbial diversity. The question I am facing is: should I sequence them individually or I pool them (for example 5 individuals = 1 sample)?
I was just thinking on advantages and disadvantages of both methods:

1) individual. I can get the diversity of each individual, in that way I know the proportion of individuals which have a particular species of bacteria. The cost are higher since I need more samples with respect to the pooled way, but the reads/sample needed should be lower (since this number increases with the microbial diversity).

2) pooled. I have only a general proportion of diversity in the pool (I can't assess how many individuals have a peculiar becterium). The cost are lower due to small amount of samples, but reads/sample should be higher due to more than one individual pooled (?).

Can someone help me? Are my assumptions right or I am missing something?

Ultimately, it depends on what insights you are trying to glean from your sequencing data, but from a purely scientific perspective, there's almost never a reason to pool samples in the the way you described. You pro-con list is not far off, in terms of information lost or gained, but I think it overlooks some of the down-stream consequences of losing that information on your analysis. For one thing, pooling limits your ability to make biologically or statistically meaningful comparisons. For example, if your individual samples are pooled by country of origin prior to sequencing, you have no way to estimate varation within those pooled samples. Because of that, not much can be said about any observed difference between countries beyond simple descriptions of richness and taxonomy. Treated as individual communities, you can look for differing trends, make meaningful beta-diversity comparisons, and actually analyze them with statistics. If you have environmental data, you might even be able to do some meaningful ecological analyses.

Second, as you mentioned, a pooled sample should theoretically have more diversity than the individual samples it was pooled from (at least it should have no fewer unique sequence variants than the richest of the pooled communities), but pooling could also mask community diversity. If one of the pooled samples has a particularly high abundance community that is dominated by just one or two organisms, it could create the appearance that some organisms at moderate abundance in other more diverse communities are actually vary rare, or non-existant. Even at a much greater depth of sequencing, diversity metrics accounting for abundance lose value, since any outlier sample could skew pooled results, creating a false impression of overall community profile.

Lastly, all of the cost-savings assumptions in your post are going to depend on the sequencing center you use and how they bill samples, so there isn't really a straight answer to give. But I will say that the per-sample cost of Illumina 16s amplicon sequencing is pretty cheap (especially compared to the cost of collecting insects from 5 different countries). And because of how sequencing is performed, pooling samples might not even save you much money. Sequencing is often billed per sequencing kit or per lane of sequencing used, not per individual sample you send. So, unless you have someone to share your sequencing run, it's possible that you'd pay roughly the same amount for 5 samples as you would for 95, with only minimal cost savings on library prep and extraction kits.

To summarize, pooling samples reduces your effective sampling effort and limits your potential scope of inferrence. The only valid reason I can think of for pooling samples in such a way would be if you cannont isolate enough bacterial DNA for sequencing from any one individual (which could be the case, depending on what type of insects you're working with). Like I said at the start, though, it really depends on what you want to learn from your 16s data. If the microbiome comparison is crucial to the outcome of your study, I'd suggest sequencing as many individual communities as possible, or at least a subset of individuals from each country (depending on how many you collected). If you don't plan on doing much analysis beyond describing microbial richness and maybe some taxonomic classifications, maybe pooled samples are sufficient for you needs.


What do sphingolipids do in humans? I want to know the significance of sphingolipids in human.
I have learnt that sphingomyelin is the most significant type of sphingolipid in human.
Also that the sphingomyelin serves as a structural constituent of myelin sheath of nerve fibres.

Is that all? I need to clarify this. Please help me. Thank you

It turns out sphingilipids have many functions in humans, many of which might still remain unknown. I will discuss here only the general, known functions  of sphingolipids, not about specific sphingolipids (as it'll make the answer too long).

Sphingolipids are believed to protect the cell surface from harmful external factors by forming a mechanically stable and chemically resistant outer leaflet of plasma membrane lipid bilayer.
Certain complex sphingolipids are known to be involved in cell signalling and cell recognition. It has been suggested that ceramide on the cell surface of one cell can be recognized by proteins on another cell's surface. Also, antibodies have been created which recognize the ceramide on a cell's surface1. All this suggests that sphingolipids play an important role in cell-cell interactions which lead to cell recognition and cell signalling.
Some simple sphingolipids, like ceramide and sphingosine-1-phosphate, have recently been shown to be mediators in signalling cascades involved in apoptosis2, proliferation3, necrosis4, inflammation5, autophagy6, senescence7, etc.
Ceramide-based lipids self-aggregate in cell membranes and form separate phases less fluid than the bulk phospholipids. These sphingolipid-based microdomains, or lipid rafts were originally proposed to sort membrane proteins along the cellular pathways of membrane transport8.
Studies indicate that proper sphingoid base synthesis is required to control protein phosphorylation events that are crucial for endocytosis and overexpression of protein kinase C1 (PKC1) and PKH1 or PKH2 (ortholgues of mammalian protein-phosphoinositide dependent protein kinase 1 or PDK1) restores the actin localization defects in the lcb1-100 mutant9,10. A suggested pathway representation would be like this11:

Decreased levels of ceramide and increased levels of sphingosine-1-phosphate are known to be mechanisms of tumor progression and drug resistance in cancer cells, and are hence being targeted in pharmacological experiments as possible cancer cures12.
Sphingolipid (mainly sphingomyelin, ceramide and gangliosides) reorganization and interaction with proteins within cellular membranes is suggested to cause many neurodegenerative disorders13.
Sphingolipids are also known to play an important role in microbial pathogenesis since in the context of bacterium- and virus-host interaction, the host is typically the source of sphingolipids, whereas in the context of the protozoan- and fungus-host interaction, both host and pathogen sphingolipids are involved14.
Sphingolipids also act as immune response modulators. Exogenously added sphingolipids (especially sphingosine) changed the receptor expression in immunological synapses, including CD3, CD4, CD8, CD45, CD54, etc. disrupting T-helper cell differentiation and prevelance of Th2 cells over Th1 cells. Sphingolipids activate macrophage function via elevation of receptor F4/80 expression and chemokine production. Fumonisin B1 regulates memory cell formation and secondary immune response, and inhibits the DNA synthesis in normal lymphocytes in response to mitogenes, more effective in T cells compared with B cells15.
Sphingosine-1-phosphate (S1P) level in lymphoid tissues, especially in thymus, is lowered as compared to blood. This creates S1P gradient that attracts lymphocytes and promotes S1PR1-dependent egress into the blood. When T cells are ready to exit the thymus and enter the blood, S1PR1 is re-expressed so that T cells can respond to the chemotactic effect of high S1P levels in circulation. When T cells re-enter the blood, S1P downregulates S1PR1. Increased lymphoid tissue S1P. blocks egress of lymphocytes by disruption of the S1P gradient or desensitization of S1PR1 on T cells. See the diagram below for representation16:

References:

 1. Gerrit van Meer, Sandra Hoetzl, Sphingolipid topology and the dynamic organization and function of membrane proteins, FEBS Letters, Volume 584, Issue 9, 3 May 2010, Pages 1800-1805, ISSN 0014-5793, https://doi.org/10.1016/j.febslet.2009.10.020.

 2. Hannun YA, Obeid LM (July 2002). "The Ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind". The Journal of Biological Chemistry. 277 (29): 25847–50. doi:10.1074/jbc.R200008200

 3. Spiegel S, Milstien S (July 2002). "Sphingosine 1-phosphate, a key cell signaling molecule". The Journal of Biological Chemistry. 277 (29): 25851–4. doi:10.1074/jbc.R200007200

 4. Hetz CA, Hunn M, Rojas P, Torres V, Leyton L, Quest AF (December 2002). "Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase". Journal of Cell Science. 115 (Pt 23): 4671–83. doi:10.1242/jcs.00153

 5. Snider AJ, Orr Gandy KA, Obeid LM (June 2010). "Sphingosine kinase: Role in regulation of bioactive sphingolipid mediators in inflammation". Biochimie. 92 (6): 707–15. doi:10.1016/j.biochi.2010.02.008.

 6. Lavieu G, Scarlatti F, Sala G, Carpentier S, Levade T, Ghidoni R, Botti J, Codogno P (March 2006). "Regulation of autophagy by sphingosine kinase 1 and its role in cell survival during nutrient starvation". The Journal of Biological Chemistry. 281 (13): 8518–27. doi:10.1074/jbc.M506182200

 7. Venable ME, Lee JY, Smyth MJ, Bielawska A, Obeid LM (December 1995). "Role of ceramide in cellular senescence". The Journal of Biological Chemistry. 270 (51): 30701–8. doi:10.1074/jbc.270.51.30701.

 8. Brown DA, London E (June 2000). "Structure and function of sphingolipid- and cholesterol-rich membrane rafts". The Journal of Biological Chemistry. 275 (23): 17221–4. doi:10.1074/jbc.R000005200

 9. Friant S, Zanolari B, Riezman H. Increased protein kinase or decreased PP2A activity bypasses sphingoid base requirement in endocytosis. Embo J. 2000;19:2834–2844.

 10. Friant S, Lombardi R, Schmelzle T, Hall MN, Riezman H. Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast. Embo J. 2001;20:6783–6792.

 11. Rao, Raghavendra Pralhada, and Jairaj K Acharya. “Sphingolipids and Membrane Biology as Determined from Genetic Models.” Prostaglandins & other lipid mediators 85.1-2 (2008): 1–16. PMC. Web. 5 May 2017.

 12. Oskouian, Babak, and Julie D. Saba. “Cancer Treatment Strategies Targeting Sphingolipid Metabolism.” Advances in experimental medicine and biology 688 (2010): 185–205. Print.

 13. Elena Posse de Chaves, Simonetta Sipione, Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction, FEBS Letters, Volume 584, Issue 9, 3 May 2010, Pages 1748-1759, ISSN 0014-5793, https://doi.org/10.1016/j.febslet.2009.12.010.

 14. Heung LJ, Luberto C, Del Poeta M: Role of sphingolipids in microbial pathogenesis. Infect Immun. 2006;74(1):28–39. 10.1128/IAI.74.1.28-39.2006

 15. Sphingolipid modulation of immune cell function: The Association of the Sphingolipidologists

 16. Maceyka M., Spiegel S. Sphingolipid metabolites in inflammatory disease. Nature. 2014;510:58–67. doi: 10.1038/nature13475.


How the pattern of fertilization path is determined before the cell division to form the blastocyst? Is it individually specific? After sperm meets ovum,the inactive nucleus starts following a particular path inside the zygote rather chase a path.This path is biologically known as fertilization path (as mentioned in an article of a local magazine named "science reporter"). But my question is how the pattern of the path is determined?  I came to know from the article that for every individual this particular path is very specific. Is it true?  If so then what does that specific path determine and why is it specific for every individual?

First of all, the more commonly used term is "copulation path," and I don't ether is used as a formal biological term, but rather in models for the public.  The term that is used in literature is "pronuclear fusion" for the process as a whole, and I don't know of a more technical term for the path itself.  Your inability to find information may have been linked to terms used.

Anyway, the copulation path doesn't have as much variability as the penetration path, which is what determines the copulation path.  The copulation path tends to be a relatively straight line between the two pronucleoli, dictated by and pushed along the cytoskeleton (Lian et al, 2014).  It is worth noting that it is often not the shortest straight line (think of the number of lines between a smaller sphere and a larger one), but still a relatively straight line.  People tend to care about this, because what ever the copulation path, it sets the axis of division, which can effect in vitro fertilization techniques, particularly in plants.

Getting at what I think you are trying to ask, the penetration path is variable because it is an oscillatory phenomenon.  You actually have to move back in the fertilization process to the sperm impact angle (Hedrih et al, 2015 is the coolest model I've seen of this) to see how this can change.

To understand oscillatory phenomenon in general, you need to understand that a lot of the processes in biology are driven by the chaotic (used in the formal since) vibrating or shaking of molecules and fluid microcurrents.  This means that we can not know (regardless of how sensitive we measure) the conditions specific enough to create the specific path.  These things are not tied to genes or to the person in general (perhaps exuding of mutations/disorders that effect the morphology of sperm or egg).  Rather it is specific to any single fertilization reaction simple because of chance/chaos.


Does the Heart Require Gold? I distinctly remember an episode of NOVA from the early 1980’s that concerned itself with gold. One of the points that was made was that there are trace amounts of gold in the human body, specifically in the heart, and without this gold our hearts wouldn't beat. I've never been able to find another citation of this. Is this true?

According to this source, gold is not a necessary trace element for living organisms.

Would have been cool, though...


How to incubate freeze dried culture? I have a freeze dried culture of staphylococcus aureus; how do I incubate it?

Can I just mix it into Luria broth and just keep it in the incubator?

Many micro-organisms do not tolerate freeze drying (you should freeze them using cryo-protectants). Apparently Staphylococcus can tolerate it. You don't directly put the dried cells in the medium. First you have to rehydrate the cells using the medium and then transfer them to the culture vessel. See the following instructions from ATCC:

  The preferred method for long-term preservation of bacteria and algae
  is freeze-drying; however, some bacteria do not survive freeze-drying
  well and are frozen instead. For freeze dried cultures, using a single
  tube of the recommended media (5 to 6 mL), withdraw approximately 0.5
  to 1.0 mL with a Pasteur or 1.0 mL pipette. Use this to rehydrate the
  entire pellet, and transfer the entire suspension back into the broth
  tube and mix well. The last few drops of this suspension may also be
  transferred to an agar slant. Alternatively, algal cultures must be
  initiated on agar plates. Please note that anaerobic bacterial
  cultures must be rehydrated in an anaerobic environment; the viability
  of the cells decrease rapidly if the vial is rehydrated in an oxygenic
  environment.

  Incubate cultures under the appropriate conditions. Given proper
  treatment and conditions, most freeze-dried cultures will grow out in
  a few days. However, some may exhibit a prolonged lag period and
  should be given twice the normal incubation time before discarding as
  nonviable.

If you had received the cells from some repository or a vendor, you would have also got an instruction manual on how to revive the cells and what media to use. It is best to follow the specific instructions given in the manual.


When does protein folding begin? I had always assumed that protein folding is an independent activity that occurs after translation is complete. However, recently, I learned that intermolecular forces begin shaping the peptide bonds as they exit the ribosome, while translation is still occuring.

This leads me to ask: when do the "stages" of protein folding take place? What is a general "timeline" for protein folding? For example, when do secondary and tertiary structures begin forming? Or, when do things like chaperones bind and act?

When does protein folding begin?

With reference to time you have asked, it can be after the translation has occurred (called Translational protein folding) or while translation is still occuring (called Co-Translational protein folding). Here is the link to an article for basic understanding of co-translational protein folding.

There is a lot of debate on the true time. Experimentalists have amassed extensive evidence over the past four decades that proteins appear to fold during production by the ribosome. Protein structure prediction methods, however, do not incorporate this property of folding (reference).

If you are looking at particularly some organisms it is advised to refer to the research articles related to them.The primary mechanism is the interplay between several non-covalent interactions such as hydrophobic effect and hydrogen bonding in a cooperative manner (they also follow basic rules of thermodynamics) which leads to a marginally stable tertiary structure.

When do secondary and tertiary structures begin forming?

Ofcourse, after Primary structure forms.The alpha helices/beta sheets then fold in a cooperative manner to form a tertiary structure.

One point to note is that, slight variations in these cooperative act causes misfoldingng of proteins which may cause certain diseases.


Observed to Expected CpG Observed to Expected CpG is calculated as below :

Obs/Exp CpG = Number of CpG * N / (Number of C * Number of G)   where N = length of sequence.

I also don't understand the expected CpG which is:

Expected =  (Number of C * Number of G)/ N

Can someone give an example or intuition for the above formula ?

First, count the number of each nucleotide in the sequence, and divide that by the total number of all four nucleotides in the sequence.  For the C. elegans genome these frequencies will be approximately:
A = 0.32
C = 0.18
G = 0.18
T = 0.32
These frequencies should sum to 1.00.

If you select one nucleotide at random from that DNA sequence then those frequencies become the probabilities for selecting a specific nucleotide at that site.  So very roughly you would be twice as likely to get back an A or a T (compared to a G or a C).

Next count the number of each of the 16 possible dinucleotides (e.g., AA, AC . . . TG, TT) in that DNA sequence and divide the numbers by the total number of nucleotides in the sequence.  That will give you the observed frequencies of the dinucleotides. CG (or CpG in your post) is one of these.  If CG occurs proportionally to the frequencies of C and G then if you picked a random dinucleotide from the sequence you would expect the probability to be 0.18 * 0.18.  You can do this same calculation for all of the dinucleotides in a genomic sequence and compare the observed frequencies to the expected frequencies.

If every site is truly random in the sequence then the observed dinucleotide frequencies should be identical to the expected frequencies, and this would be a zero order Markov chain.  In fact, genomic DNA is usually not accurately modeled as a zero order Markov chain.


How long would you expect a designed plasmid to remain in a population of E. coli after transformation? When transforming E. coli with a genetically-modified plasmid, how quickly/often is this plasmid "lost" because of mutation, or horizontal-transfer, or "dilution" over reproduction over several generations?
How often are inserted plasmids lost/mutated/diluted in E. coli? How long would you expect to observe the plasmids' output after transformation?

There isn't a simple answer.
There are a lot of factors which can influence how stable a plasmid will be. I'll describe what the main factors are, but to work out exactly how stable your plasmid is, unfortunately you'll just have to test it. I've given links to some studies which do this at the end.
Copy number
Copy number refers to how many copies of your plasmid are present in each cell. This can range from 1-10 for low copy number plasmids, to 300-500 for high copy number plasmids. Generally, low copy number plasmids can be lost easier than high copy number plasmids as there is a higher chance that the plasmid won't be present in one of cells after division. (https://www.nature.com/articles/s41598-017-05219-x)
Plasmid Size
Very large plasmids (in the mega base range) tend to be less stable than smaller plasmids as organisms, especially E. coli, can struggle to replicate them. This means that over time, less of the plasmid will be present in your system. (https://pubs.acs.org/doi/10.1021/acssynbio.0c00008)
Selection marker
Typically, synthetic plasmids will have a selection marker encoded which is used to provide selective pressure for keeping the plasmid. The exact marker used can affect the stability of the plasmid, as some are more effective than others. This paper has a good comparison of two different markers and measures the stability of plasmids for each: https://bmcbiotechnol.biomedcentral.com/articles/10.1186/1472-6750-8-61.
Burden
Plasmids normally contain an insert which encodes your system. Some inserts will have relatively low burden on the cell (for example low expression of a small protein). Others may involve high expression of many proteins, or proteins which are toxic to the cell. Mutations are much more likely in high burden plasmids compared to low burden plasmids. This is because cells containing plasmids with mutations which reduce/stop expression will have a much higher fitness advantage over those cells with unmutated plasmids. Other time, these mutated plasmids will become dominant and eventually you will lose your original plasmid. There's some good reading about cell burden here (https://2019.igem.org/Team:Austin_UTexas/Measurement) and here (https://pubmed.ncbi.nlm.nih.gov/25849635/).
This is anecdotal, but I've managed to run 24 hour experiments with plasmids about 5kb in size containing a low burden insert and without using any selection marker without seeing plasmid loss. I've also had trouble even cloning plasmids of about the same size but with antibiotic selection and a high burden insert without any mutations occurring. So it really does depend on what your plasmid is and what it's expressing.
Measuring plasmid stability
Here are some examples for how you can measure plasmid stability:

https://link.springer.com/protocol/10.1007/978-1-4939-9877-7_16
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966108/ - This paper describes plasmid stability mathematically
https://academic.oup.com/femsle/article/232/1/45/490969


Are lanternfish real? Is there a real lantern fish existing in the world? If yes, kindly share a picture if one exists. I searched online for images, but most of them seem to be fake. The pictures I have seen on the internet were of a fish with a hanging lantern over its head. Are these possibly real pictures?

Fish you are referring to by description "fish with a hanging lantern over its head", are not lanternfish. Fish with "lantern" bait above head are members of group of fish named anglerfish (Lophiiformes).

You can find more information about them here: https://en.wikipedia.org/wiki/Anglerfish

Lanternfishes or myctophids are smaller fish that use bioluminecence for communication during mating season.

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


What insect is in this photo? Found in Russia, in the kitchen. It is about 1–2 cm length.

This is an immature "True Bug", order Hemiptera. You can tell this from the general shape of the wings, and from the big "beak", a feature of the Hemiptera.

Within Hemiptera, it's possible that with those enlarged front legs, it could be an Assassin Bug, family Reduviidae.