What would sanitiser fail to do that detergent and warm water would do in cleaning glasses frame that isn't 'visibly soiled'? Update (from comment):

It's certainly possible that the manufacturer had that in mind when making their cleaning recommendation, but I'd like to think they would specifically warn against it if it was a common issue.

For an arbitrary glasses frame, specifically the earsocks, can regular alcohol/sanitiser replace detergent and warm water? Apparently some brands of glasses frames recommend really detergent and warm water. I mean, with alcohol and sanitiser, am I perhaps killing only 99% of the germs instead of 99.9% of the germs? (If we wanted planes to be safe "with statistical significance" that is 99% confidence level we'd have between 400 and 2500 crashes a day.)
I couldn't find any videos for this on youtube. Most of what youtube gives is cleaning ears or cleaning the lenses.
Edited to add: I got the following with my new glasses.

Kind of a hassle to do the recommendation especially that I've never cleaned glasses frames in my 13 years of wearing of glasses, except when they were, to borrow a term from WHO, 'visibly soiled':

Clean your hands by rubbing them
with an alcohol-based formulation,
as the preferred mean for routine
hygienic hand antisepsis if hands
are not visibly soiled. It is faster,
more effective, and better tolerated
by your hands than washing with
soap and water.

• Wash your hands with soap and water
when hands are visibly dirty or visibly
soiled with blood or other body fluids
or after using the toilet.

Alcohol is a substitute for soap and water for hands that are not 'visibly soiled'. Is there perhaps some kind of substitute for glasses frame?

The earsocks on Oakley brand sunglasses are made of a proprietary hydrophilic rubber called Unobtanium 1.  From what I can find, Unobtanium is likely a styrene copolymer 2, possibly a formulation called Kraton G 3.  Polystyrene is insoluble in water, but soluble in ethanol and 2-propanol (isopropanol) 4, which are the most common alcohols used in sanitizers.
So, as suggested by @Cell, soapy water is likely recommended by the manufacturer because it is unlikely to damage the glasses, whereas alcohol-based cleaners may degrade the soft rubber components.

https://www.oakleyforum.com/threads/how-to-restore-old-unobtainium-that-has-gone-sticky.10821/
https://www.oakleyforum.com/threads/rubbers.21973/page-2
https://kraton.com/products/KRATON_G.php
https://www.bangslabs.com/common-solvents-and-non-solvents-polystyrene


What does the term 'modified residue position' in phosphorylation mean? Does it mean the position of the amino acid in the protein sequence, or something else?

For example, I came across the phrase "S 368 phosphoryation" where S is the modified residue and 368 is the modified residue position. What does it all mean?

You are correct, the 368 stands for the position of the amino acid in the protein's sequence - this particular serine is the 368th residue in the protein counting from the amino-terminal end.


Do different people have the same number of mitochondria in comparable cell types? e.g. will a lymphocyte in one person have roughly the same number of mitochondria as a lymphocyte in another person.

".... The number and shape of mitochondria vary dramatically in different cell
types and can change in the same cell type under different physiological conditions, ranging from multiple spherical or cylindrically shaped organelles to a single organelle with a branched structure (a reticulum). The arrangement is controlled by the relative rates of mitochondrial division and fusion, which are regulated by dedicated GTPases that reside on mitochondrial membranes' In addition, the total organelle mass per cell can be regulated according to need.
For example, a large increase in mitochondria (as much as 5-10-fold) occurs
when a resting skeletal muscle is repeatedly stimulated to contract for a prolonged period."

Alberts, Bruce; Alexander Johnson; Julian Lewis; Martin Raff; Keith Roberts; Peter Walter, Molecular Biology of the Cell, 5th Edition.

As the Paragraph above explains, it can be assumed that due to different metabolism in different people, a specific number of mitochondria in the same cell types for different people may not be assumed.


Why do some moles grow longer and darker hair than the rest of the skin? In different parts of the body I have skin moles or in medical terms, nevus.
In some of them hair grow seemingly either darker/thicker (I'm not sure how much of the two) and notably longer. Here are pictures very similar to what happens. What is the reason behind this?

Before answering the question (about the hairs) I will first go in some detail about what moles actually are:

  Moles are growths on the skin that are usually brown or black.  They
  are formed by clusters of melanocytes, the pigmented cells responsible
  for your skin color.  Moles typically appear during the first 30 years
  of life, can be flat or raised, and can darken with sun exposure,
  puberty, or pregnancy.

There are no articles covering this topic in detail (most of them are about the skin cancer, if you are interested in this topic check out this article). However there are some medicial experts talking about the hair growth.

  Joshua Zeichner, M.D., Director of Cosmetic & Clinical Research at the
  Mount Sinai Hospital in New York City. "If the mole also contains a
  hair follicle, the hyper-pigmentation can cause the hair that comes
  out of it to be coarser and darker."

Junji Takano, a Japanese health researcher said the following about this topic:

  This is due to the fact that capillaries of a mole are growing rapidly
  and excessively, and this includes the hair follicles

Actually moles are benign tumors(wiki), the cells in the body in charge of normal skin color, are being produced at an extremely fast rate. Thus causing the melanocytes to form in clusters instead of spread out, causing abnormal skin pigmentation in some areas of the body(wiki). So based on the above quotes this "fast production" also affects the hairs which are present in this piece of skin. More interesting is that people hate these hairs (which make sense offcourse) but in most of the cases this is a sign that this mole isn't cancerous:

  A mole that has a hair growing out of it usually means that is was
  present since birth or at a young age and is typically normal.

references: first quote, second quote, third quote, last quote


can we say that pumps are carriers that need ATP? I know that pumps always use ATP , but i don't know what is the relationship between carriers and pumps .
are pumps a subdivision of carriers ?

Yes, you can consider pumps are carriers used for active transportation (needing ATP).

A carrier is a specific type of transport proteins. They differ from channels or pores in the fact that during a certain instant, carriers only have one side of the protein open1. While pores are continuously open, and channels are either open or closed2.

Carriers can be involved in active transport3 or facilitated diffusion (passive)4. But as you mentioned, pumps always are used for active transport. Pumps, as Bryan pointed out in the comments, are just a name given to some transport proteins that use active transport, but not all active transport proteins are labeled as pumps.

I hope this clarified things for you.


Are these claims of "revolutionising" understanding of human vision and hearing valid? I've started a hobby machine vision project (and posted some questions to this end on other SE sites) and on a side track, also been looking at relevant research in human vision (and partly, hearing).

I came across the work of one "James T Fulton" through an excerpt of a book which claims to have "revolutionised" our understanding of human vision and hearing.

Here are the respective links:

http://neuronresearch.net/vision/

http://www.neuronresearch.net/hearing/

I tried cross-verifying these claims via Google, but nothing turned up on searching either for the author or the book (apart from some Amazon links and very obscure references).

Considering the controversial natural of the claims made here, I would have imagined some level of debate, but the silence I found on the Internet is puzzling. Puzzling, because the sheer level of DETAIL in these books, prevents me from dismissing the claims altogether as well.

Can someone validate some of the content from these books so I can get an idea of the overall legitimacy of the work (and decide if I should continue reading, or not). Below might be a good link to start from:
http://neuronresearch.net/vision/pdf/11Biophenom.pdf

Adding a few examples:

The simplest one - is that the Principle of Univariance is not entirely correct. This is examined on pages 15 through 17 at this link (where I read it):
http://neuronresearch.net/vision/pdf/11Biophenom.pdf
There is this claim quoted verbatim from the site:
"The theory shows that the ARCHITECTURE OF ALL VISION IS TETRACHROMATIC. Although traditionally called trichromats, it is shown that HUMANS ARE BLOCKED TETRACHROMATS"
Caps in original. I just pasted it here to give an idea of the tone of some of the text.
This specific claim is "proven" here (in short):
http://neuronresearch.net/vision/files/tetracomparison.htm

And a longer form of the text is linked in the same page
There is also a theory proposed on why cochlea are coiled:
http://neuronresearch.net/hearing/pdf/coiledcochlea.pdf

Thanks!

OK, I'll field this one. I'll ignore any of the tell-tale signs of hokum such as writing in ALL CAPS.

Nevertheless, it's a lot of hokum. It's true that he goes into a lot of detail and I'm sure his math looks nice but the fact is that it's not grounded in reality. I would consider myself to be something of an expert (in training) in the field of phototransduction, so I'll focus on claims related to it. However, if he's as sloppy with the rest of the visual process as he is with phototransduction, then his claims are entirely bogus.  I'll just be working from the Synopsis section.

Where to start...How about the first sentence of the "Background" section:

  This work originated in the 1960's with the realization that rhodopsin, as then defined, did not meet the requirements for being a chromophore.  It was particularly deficient in the structural characteristics required of a good chromophore.

FALSE. Rhodopsin is not a chromophore and, to my knowledge no one has ever claimed it to be a chromophore. Rhodopsin is a protein. It is coupled with a chromophore, retinal, a form of vitamin A. OK, so if this is the foundation of his research, he is off to a bad start.

  The basic assumption had been that the residues of a destructive process could be easily returned to their original state and that state was a simple chemical bond involving only two components in a single molecule...It was assumed that one of the residues was the alcohol or aldehyde of Vitamin A. The other residue was assumed to be a protein and was given the name opsin. Valiant, but unsuccessful, efforts were made to define the nature of the molecule and achieve the formation of rhodopsin in the laboratory.

It absolutely is possible to reconstitute rhodopsin with the chromophore in the lab. This has been going on since at least 1983. Also, the crystal structure of rhodopsin, including the chromophore, was resolved in 2000.

  A new class of retinoids was defined by the author at that time, the Rhodonines. This class met the requirements of physical chemistry and photochemistry for a high performance chromophore. However, it was difficult to obtain acceptance of the Rhodonines as a replacement for Rhodopsin within the vision research community.

I have never heard of Rhodonines and web searches only result in his page. Due to his confusion of terminology, I don't know if he is proposing them to be proteins ("replacement for Rhodopsin") or simple chemical molecules ("a high performance chromophore"). If it were the former, one would wonder why Rhodonines were not identified in a comprehensive proteomics assay of the rod outer segment. One would also wonder why rhodopsin is so highly expressed in the outer segment (on the order of 1e8 molecules in mammals and 1e9 molecules in amphibians, more than any other protein in that compartment). If it were the former, one would wonder why there is an entire biochemical cycle dedicated to recycling retinal that takes place just outside the outer segment.

I'll ignore whatever physical state these Rhodonines are supposedly in since they don't exist. I'll also ignore this "Activa" thing. He owns a patent on it, which doesn't bode well for its existence in nature.

  The visual system is a very sophisticated system. It uses many of the most sophisticated methodologies known to man at the start of the 21st Century. Failure to recognize these mechanisms and methodologies leads to an inadequate understanding of the overall process.

I'll agree there, with the exception of the use of the word "methodologies"! This isn't engineering, this is biology.

  The visual system employs a number of time related processes that have not previously been addressed in the literature. To understand these processes, it is necessary to employ "complex algebra" in the differential equations arena. Employing these techniques provides the complete solution to the overall photoexcitation/de-excitation process within the Outer Segment of the photoreceptor

Phototransduction has a rich history of mathematical modeling. And yes, they involve "complex algebra in the differential equations arena." An excellent review of the first few decades of it can be found in the bible: Phototransduction in vertebrate rods and cones: molecular mechanisms of amplification, recovery and light adaptation. Since that publication, there have been two very nice lineages of models: one comprehensive one that focuses on the proteins (1, 2, 3) and one that focuses on spatial accuracy and stochastic interactions and gives more attention to second messengers (1, 2, 3).

  It has also been compounded by the historically poor preparation of the researchers in the field of mathematics.

I challenge him to read one of DiBenedetto's modeling papers and not glow in admiration of his mathematical prowess.

  The goal has been to present an overall view of the visual system in a defendable mathematical context and a global scientific framework. This goal has required the introduction of techniques and mechanisms not normally found in the literature of vision. This has been particularly true in two areas, the definition and detailing of the initial photodetection process and a similar detailing of the mechanisms of neural signal transmission. In both cases, the dominance of chemically based concepts is shown to have impeded progress. The description of the visual system, including the neural system, as an entirely electronic, more precisely electrolytic, based system leads to much greater insight into the operation of the visual system than any chemically based theory can offer.

I had to quote in full here. This is entirely bogus. The "initial photodetection process" (phototransduction) is entirely chemical in nature. All of the main players in the process are known and their interactions are largely well understood. Viewing the system as entirely "electronic" ignores the mountains of evidence of all of the proteins participating in it.

  Probably the most venerable is that of a dichotomy between types of photoreceptors, the rods and cones. The theory demonstrates in excruciating detail that there is only one functional type of photoreceptor cell and that it is associated with one of four types of chromophore. These chromophores are sensitive in the ultraviolet, the short, the medium and the long wavelength portions of the visual spectrum of light.

The problem with this is that if you look at a retina, you can see rods and cones. You can generate knock-out animals that have only one or the other. Those with only rods cannot handle bright visual stimulii, those with only cones cannot see in the dark. More damning is that you have two distinct phototransduction cascades, separated by evolution dating back to the origins of vertebrates. They share only a few proteins in common and otherwise have unique paralogs performing similar duties. You can isolate individual rod cells and, if you're clever and you have the right species, individual cone cells (they're much smaller and harder to harvest in animals like mice or cows). You can measure their electrophysiological characteristics and find that they are extremely different: cone responses are fast while rods can respond to a single photon of light. Their morphologies are completely different: the rod outer segment is filled with lipid bilayer disks, while that of the cone has a series of in-folds.

As for the whole tetrachromat thing, well, again I have to assume that he's referring to opsins when he talks about chromophores. Thanks to genomics, we can be confident that there are only three cone opsin varieties in old world apes (and one rod opsin). The rest of mammals only have two. If you get into other vertebrates, you'll find more...if you get into invertebrates, you'll find ridiculous numbers. There's not much to say here. A fourth cone opsin protein simply does not exist in the human genome.

So, that's just a quick overview. Do not worry about this guy's research. It is unsubstantiated and exists in a vacuum outside of the rest of the vision research world. I do wish that there were a way for him to work with others. I do wish there were a way for him to integrate current knowledge into his work. But the problem is that his work as it stands simply seems to ignore the wealth of data generated on the visual system and instead treats it as some theoretical circuit.


Why would there be a spike in coverage within a gene in RNA seq data? I'm looking at RNA seq data in Geneious for Salmonella typhimurium and I occasionally see a spike in coverage for a sequence of RNA within a gene. Why is there a section of the gene that seems to be transcribed much more often than any other part of it? The name of the gene in question is ftsI which is an essential cell division protein that may link upstream cytoplasmic cell division proteins with downstream periplasmic cell division proteins.

Without knowing how your libraries have been prepared and sequenced it is hard to tell if that is due to a technical or biological source.

However, there are a few bias sources in RNA-seq (which aren't an issue in DNA-seq)

One of them is that if you used a "random-hexamer" protocol, they're known to not be so random after all. See: Hansen KD, Brenner SE, Dudoit S. Biases in Illumina transcriptome sequencing caused by random hexamer priming. Nucleic Acids Res. 2010;38: e131.

You might also have a contamination from other species that would present a sequence identity for that part more specifically.


Why are pili more common in Gram negative bacteria than in Gram positive? Although pili have been observed in some species of Gram positive bacteria, the preliminary research that I have done indicates that pili are significantly more common in Gram negative bacteria.

Is this an accurate assessment of the current body of scientific knowledge? If so, do we know (or have any leading theories on) why this is the case?

Pili were at least discovered more recently in gram-positive bacteria.

Pili are formed differently in gram-positive and gram-negative bacteria.  Here's a pretty good review on the differences: http://www.ncbi.nlm.nih.gov/pubmed/18953686

Researchers seem to think that pili might be involved in adhesion/formation of biofilms (adhesion is important for pathogenicity).  Certain types of pili are specifically involved in gene transfer. This is a good review on pili and pathogencity in gram-positive bacteria: http://www.nature.com/nrmicro/journal/v4/n7/pdf/nrmicro1443.pdf. If you can't access it, let me know, and I'll do my best to summarize.

EDIT:

The Wikipedia entry for pilin interprets the second paper I linked as saying that pili are more common in gram-negative bacteria and that pili are implicated in pathogenicity.

Straight from the paper:

Prevalence:

  Over the past five decades, several distinct pilus types
  have been identified, most of which were described
  and characterized in Gram-negative bacteria.

Function:

  A common feature of Gram-negative pili, however, is their role in adhesion to eukaryotic cells. It has been
  proposed that bacteria use these structures to form an
  initial association with host cells, which can then be
  followed by a more ‘intimate’ attachment that brings
  the bacterium into proximity to the host-cell surface.

and

  Pilus-like structures on the surface of Gram-positive
  bacteria were first detected in Corynebacterium renale,
  by electron microscopy. More recently, surface
  appendages were reported to be present in Actinomyces naeslundii
   and were subsequently found in other
  species, including Corynebacterium diphtheriae, Streptococcus parasanguis (Streptococcus parasanguinis), Streptococcus salivarius
   and Streptococcus sanguis (Streptococcus sanguinis). Finally, in the past
  year, pili were also characterized in all three of the
  principal streptococcal pathogens that cause invasive
  disease in humans — group A Streptococcus (GAS; that
  is, Streptococcus pyogenes), group B Streptococcus (GBS;
  that is, Streptococcus agalactiae) and Streptococcus
  pneumoniae — in which they have been shown to
  have key roles in the adhesion and invasion process and
  in pathogenesis. [emphasis added by me]


How can 3' end polyadenylation protect cellular RNA from ribonuclease degridation? In this link, it states:

  It is worth noting that all intracellular RNAs are protected from RNase activity by a number of strategies including 5' end capping, 3' end polyadenylation, and folding within an RNA protein complex (ribonucleoprotein particle or RNP).

I do not understand how polyadenylation protects the intracellular RNA from ribonuclease. I always thought that polyadenylation was a way to mark RNA for degradation, not protect it from degradation. Perhaps it is speaking of protection from exoribonuclease only and not endoribonuclease?

Can someone explain this?

According to my book Molecular Biology Principles of Genome Function by Craig et al, eukaryotic RNA degradation does not have an initiation, as in bacteria where pyrophoasphate hydrolase hydrolyses the 5'-triphosphate to 5'-monophosphate, and is therefore the initiatior.

In eukaryotes the polyA-tail is shortened by a deadenylase enzyme complex which contains a 3'to 5' exonuclease called CCR4. But deadenylation of polyA-tail doesn't necessesarily need to lead to degradation since it is reversible by post-translational readenylation.

Poly A tail protects the mRNA by not letting the nucleases reach the mRNA itself. As long as poly A tail is degraded, its just fine, since it can readenylate back again. The figure below shows the degradation of mRNA in eukaryotes, which can be either in 5' to 3' direction or 3' to 5' direction.

What you are thinking of is ubiquitination of proteins, which is a post-translational process which can mark the proteins for degradation.


Is it a limitation of the eyes, or the brain, that we can't see a moving bullet? Are the photoreceptors in our eyes not fast enough to register the fast moving bullet, or is the brain not powerful enough to make sense of something happening that fast?

It's less a problem of speed and more of raw photon count. Assuming a brightly lit day, the bullet will move so fast that it doesn't reflect enough photons to register against the background. High speed images of bullets usually involve a very bright flash (and other controlled settings) for the camera to pick it up. (Also, a very short flash helps the bullet to appear stationary in the image.

On the other hand, seeing where your bullets are going is pretty useful. Therefore tracer bullets were created, which are essentially a pyrotechnic flare that you substitute in every 5th bullet, typically in machine gun ammunition. Proof that if you make a bullet bright enough, you can register it just fine.

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


What are these pathways called in Biology? Considering the pentose phosphate pathway and the sulfate reduction pathway in bacteria;

What are these types of reactions called in biology? Bio degradation reactions or bio transformation reactions or something else? I wish to know whether there is a generalized names for these types of pathways.

Short answer
Assuming you wish to have a common name for both of these (widely differing!) pathways I basically agree with @Chris, and I would go for general terminology, namely metabolic pathways.

Background
The pentose-phosphate pathway is neither anabolic nor catabolic so those terms won't do. The pentose-phosphate pathway is, however, closely linked to general metabolism to supply the body with C5 sugars. So metabolic pathway sounds right to me.

The other pathway is a sulfate reduction pathway, which is an anaerobic respiration pathway that uses sulfate as the terminal electron acceptor instead of oxygen. It is an entirely different pathway. However, it too is neither catabolic or anabolic, but still closely linked to metabolism. Hence, metabolic pathway is applicable here too.


What are good data on the Human Metabolic Model and where can I get them? Trying to get a good SBML representation of the Human Metabolic Model for use in Flux Balance Analysis and drug targetting (i.e. gene knockout) simulations.

What are good sources for these data?

Thanks very much!

As far as I know, there is no one model officially known as "the Human Metabolic Model", but the Recon 2 model, described as a "consensus" model and the most comprehensive to date in Thiele et al. 2013, A community-driven global reconstruction of human metabolism (http://www.nature.com/nbt/journal/v31/n5/full/nbt.2488.html) is available at http://humanmetabolism.org/?page_id=75

Tissue-specific models are also available. See for example  Wang et al.:  Reconstruction of genome-scale metabolic models for 126 human tissues using mCADRE. BMC Systems Biology 2012, 6:153:


New infectious diseases appear mainly as a result of chance mutations in pathogen genomes? I am reading the book 'Homo Deus: A breief History of Humankid' by Harari. He mentions the following statement highlighted in the picture below (picture provided for context). I would be appreciated if someone could (1) explain the meaning of it (I have very little background in Biology) and (2) the reason behind it.

Mutations happen all the time when DNA is replicated. These random mutations are the building blocks for evolution under natural selection. So when a single nucleotide is changed, (or deleted or added), there are three possible outcomes. 1. the mutation is neutral, so nothing happens. 2. The mutation is lethal or mal-adaptive for the organism, in which case natural selection will remove the individuals carrying the mutation from the population, or 3. the mutation results in some change in function that helps the organism compete under natural selection. This 3rd kind is the rarest, but with pathogenic viruses and bacteria, with huge populations, the evolutionary test pool is much larger because there are so many new mutations being put to the test with every generation. So, for example, a mutation in a pathogen adapted to spread through chickens, could change the pathogen to be better adapted for spreading through humans.


Why are nucleic acids negatively charged at physiological pH? Why do nucleic acids and mononucleotides have a negative charge physiological ph?

The phosphate group/s present in the mononucleotide or nucleic acid result in the structure having an overall slightly negative charge.

Positively charged proteins that are also present in the cell such as histones help to keep the negatively charged nucleic acid stable 'in vivo'.


What tests can be performed to test the purity and quality of the raw peptide HCG (Human Chorionic Gonadotropin) What tests could be run to test the purity and type of HCG?

We are looking to purchase HCG from China but the purity and quality varies between labs, we are able to receive samples of the raw peptide and can use a contracted lab to perform tests but due to my academic background I have no clue which tests to request to determine the purity and type of the raw powder. The following is what we should be receiving from the labs in China.

Product Description
CAS Number: 9002-61-3
pI = 2.951
Extinction Coefficient: EmM = 3.88 (278nm)2
Synonym: Choriogonin, hCG
The molecular weight is approximately 37.9 kDa (with
approximately 31% carbohydrate by weight). The
theoretical molecular weight is 37.9 kDa based on the
native form, which contains 2 subunits. The α subunit
has a molecular weight of 14.9 kDa of which
approximately 10.2 kDa is for the polypeptide and
approximately 4.7 kDa for the carbohydrate. The
β subunit has a molecular weight of 23 kDa of which
approximately 16.0 kDa is for the polypeptide and
approximately 7.0 kDa is for the carbohydrate.3,

To answer Mad Scientists Question, the peptide is "supposed" to be CGA (1081) for use on humans. This is why it is so important for us to find a test that can define the qualities of the raw peptide.

A monograph from a pharmacopeia gives a good starting point for active pharmaceutical ingredient characterization. AFAIK there is no monograph for hCG nor your actual peptide of interest, but there is one for FSH (here for the european pharmacopeia monograph), which shares a subunit with CGA, meaning that modifications of it could suffice (though validating these modification will be a good amount of work, and will depend on the ultimate use for the peptide).
First, it is necessary to stress that even if the compound passes all assays, it would still be unsuitable for human use. It may be acceptable for animal experimentation. This is because the pharmacopoeia assumes a context where you have a non-adversarial relationship with your supplier, such that statement like "up to XX% remaining impurities" is an acceptable standard as the synthesis route & typical impurities are known. However, buying peptides from a random Chinese seller with no transparency on process is likely an adversarial situation.
Some keys to read the monograph:

Compound followed by the letter R ("water R", "glycine R"): these compounds have their own monograph. You could assay them accordingly, but for this use case understanding the R as "analytical grade" is possibly good enough.
"Follitropin CRS": chemical reference substance, a reference standard powder of follitropin obtained through reliable means (typically through EDQM for pharmaceutical purpose). Here also, substituting for an analytical grade standard from a reputable chemical seller could work.
Method followed with three numbers ("Bacterial endotoxins (2.6.14)"): reference a method monograph found in the given chapter/section. Apply methodology as described in the referenced text.

To adapt the assays to your peptide of interest, you need to understand which parts are specific to follitropin (and should be modified), and which applied to gonadotrophin-like peptides in general. For instance, for isoelectric focusing, the running conditions (pH, catholyte/anolyte) will be adequate, but the follitropin reference will be replaced with a CGA reference. On the contrary, the selective cleavage of peptide bonds assays is specific to the peptide, and will need extensive rework.


Identification of an insect from midwest US I have been seeing them more and more frequently indoors.  I am currently in the Midwest United States, weather has been unusually warm for December, and there are many trees nearby. Can someone please help identify this?

The pictures are of the same bug, but from different angles.

Brown marmorated stink bug (Halyomorpha halys):

See here, here, here or here for information.

These have become hugely invasive in the Northeast and Mid-Atlantic (and slowly Southeast) portions of the U.S. as well as along the West Coast.

The brown marmorated stink bug (Halyomorpha halys) is native to Eastern Asia, and likely 1st started spreading around the U.S. in Pennsylvania in the early 2000s.

Finally, you can see an image of the life stages of H. halys here.

Update:

Just for clarification, other brown stink bugs do exist and can be easily confused with H. halys. This article from UF IFAS, for example, demonstrates how to differentiate H. halys from Euschistus servus:

See here and here for additional ID tips and further reading.


How does the MMR vaccine affect lymph nodes in preventing measles? I am trying to understand this statement about the Measles part of the MMR (Mumps, Measles and Rubella) vaccine

  Measles prevention: MMR (AB protect during primary and secondary viremia)

Measles enters from respiratory tract, through mucosa of the upper respiratory tract. The virus passes into cervical lymph nodes. Now, starts first viremia (MMR somehow helping here) which lasts about 5 days. Then antibodies are secreted during 15 days which leads to rash lasting about 3 days.

I think this second viremia refers to the possible dissemination of the virus to other lymph nodes by blood.
This suggests me that the vaccine primarily have a mechanism that affects in the lymph nodes or generally in the lymphatic circulation.

How MMR vaccine affect lymph nodes in preventing measles?

Lets define viremia first: The primary viremia occurs in the cells which the virus enters first in the body. There it replicates to high titers before it leaves this cells, spreads through the body and infects other cells. This is then the second viremia.

For measles the primary viremia occurs in the respiratory epithelium and in the local lymph nodes. The second viremia then occurs in skin, conjunctiva, respiratory tract, and other distant organs. In this phase also the characteristic rash occurs due to a hypersensitivity reaction of the skin. For details see here and here.

The measles vaccine works like any other vaccine: By raising an immune response against the vaccination virus. This leads to a normal immune response which leads to the production of specific antibodies against the measles virus and also to immunologic memory. These antibodies are available to fight the virus when it enters the body of a vaccinated person. This also triggers the proliferation of virus specific memory B cells which then differentiate into plasma cells and produce vast amounts of protective antibodies. So there is no special mechanism involved here beyond immunologic memory.


Using decoy proteins to treat viral illness As a non-biologist, my understanding is SARS-CoV-2 uses it spike protein to latch on to the ACE2 receptor on cells in order to inject its genetic material into the cell.

Questions:

What would happen if you flooded a person with exogenous ACE2 proteins?
Would the virus attach to these decoy proteins and thereby save cells from being infected?
Would the injected proteins cause unwanted side effects?
Has this approach to treating viral infections been tried before?

Reference:
https://f1000research.com/articles/9-72

This is indeed a reputable strategy (#1,2,4) for rapid response to novel pathogens.  See https://phys.org/news/2020-01-scientists-decoy-molecule-neutralizes-arenaviruses.html and the open access article it cites https://www.nature.com/articles/s41467-019-13924-6

In the case of coronavirus, however, there is an issue (your #3) in that ACE2 is an enzyme that catalyzes the breakdown of a circulating hormone, angiotensin II, which is responsible for maintaining high (or normal) blood pressure.  So the "bait" used would have to be at least somewhat altered from this.  You would probably have to take into account how it affected other protein interactions such as with integrin beta 1 ... (see articles like https://europepmc.org/article/MED/14754895 ) to avoid getting caught up in speculation, it makes sense that a neutralizing protein might be made from part of ACE2 just as a neutralizing monoclonal antibody could be made, but you still have to have something specific before you can test for safety and efficacy.


Why would the Camargue horses have a white coat while the foal have a dark coat? The current issue of the magazine Lonely Planet India(Oct 2013) presents a photo of Camargue Horses which are white coated and mentions that they are born with dark hair. A search shows that the foal are either black, grey or brown coated and gradually turn white around the Third/fourth year.
What could be the possible advantage of that kind of difference between the young and the adult?

Our own hair will also turn gray (indeed, yours seems to be on its way, if you don't mind me saying so) but there need not be an advantage to that; if it doesn't affect our ability to have successful children it probably doesn't matter much to evolution or selection.  When it comes to animals that interact with humans, though, many traits are selected for, even those without an advantage, in fact often we select for disadvantageous traits (if they were advantageous, we might not need to select for them in the first place).

As this 2008 paper from Nature Genetics goes into, the "graying with age [phenotype] is an autosomal dominant trait" overwhelmingly caused by "a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation".  To answer your question, though:

  The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals... The prestige of riding a white horse has thus led to selection of the Gray-causing mutation by humans; this mutation is by far the most common cause of white color in horse.

This phenotype is actually often detrimental, as white/gray horses can have eye problems and higher rates of skin cancer; Camargue's are particularly susceptible to melanomas, present in around 70% of horses by age 15.  There does seem to be some benefit, though, as the second paper I linked suggests these horses are subject to fewer fly attacks.

EDIT: I seem to have been unclear and you seem to have misunderstood my answer.  Let me break it down:

Camargue horses are gray.
Gray color is a simple mendelian autosomal dominant phenotype caused by a loss of pigment in adulthood.
Gray color is generally bad but sometimes good; either way, it's probably not a huge detriment.
Camargue horses are homozygous for gray color.
Humans have in the past selected for gray color in horses in general.

That is an example of why something negative or pointless might persist, as would a dominant inheritance pattern that is fixed in a population: negative traits that are only weakly deleterious have a non-negligible chance of fixation.  Asking what the advantage is is somewhat of a moot question because every single Camargue horse has the trait; asking what caused a seemingly-negative phenotype to become fixed is a good question, but likely an unanswerable one as it occurred long ago.

As a side note, how long a breed has been in an area does not simply imply breed purity.  Here's a quote from the International Museum of the Horse:

  Through the centuries many armies have passed by the Camargue, including the Greeks, Romans and Arabs. The horses brought with these armies influenced the Camargue over time. It has even been suggested that the Camargue has had some influence on the early breeds in Spain as armies took them back home.


How much time does it take for an evolutionary change to take place? I think I've read that in humans, it takes either 50,000 or 100,000 years for a mutation to fixate. But I've looked into the books I thought it mentioned it and I can't find it. I know there are theories that behavioral modernity has arisen before 40,000 years ago, and that modern humans evolved from Homo heidelbergensis, Homo rhodesiensis or Homo antecessor, some 100,000 to 50,000 years ago,  but I don't know if this implies the same. Anatomically moderm human . On the other hand, this other article (7 years old now)  says evolutionary change might take 1 million years (Not so fast).

How much time takes for an evolutionary change to take place in animals in general, but also in humans in particular? (if there is any difference between humans and the rest of the animals. I know mutations don't take the same time to spread in animals than in bacterias, for example)

How much time does it typically take for a new mutation to fix in an animal population?

The answer can really take any number. It will all depend upon the size of the population and the selection coefficient on the mutation. If we assume neutral mutations, then we can use Kimura and Ohta (1968)'s result. They showed that the expected time for a neutral allele to reach fixation (given that it will reach fixation) is

$$\bar t(p_0)=-4N\left(\frac{1-p_0}{p_0}\right)\ln(1-p_0),$$

where $p_0$ is the initial frequency and $N$ is the population size. Replacing $p_0$ by $\frac{1}{2N}$ and you get

$$\bar t\left(\frac{1}{2N}\right)=-4N\left(\frac{1-\frac{1}{2N}}{\frac{1}{2N}}\right)\ln\left(1-\frac{1}{2N}\right)$$

which can be simplified

$$\bar t\left(\frac{1}{2N}\right)=-4N\left(2N-1\right)\ln\left(\frac{2N-1}{2N}\right)$$

Stick in any $N$ you want and you'll get your answer. Of course, this equations assume panmixie. In absence of panmixia, then it all depends upon the interconnectedness of the different populations. If some population are perfectly isolated, then a mutation will never fix in the entire species.

How much time does it typically take for a new mutation to happen and fix in an animal population?

The time to wait for the mutation to fix is typically quite negligible comparing to the time it takes for this mutation to happen. Let $\mu$ be the mutation rate. The number of mutations happening each generation is $2 N \mu$ and assuming they are neutral a fraction $\frac{1}{2N}$ of them will fix. Hence, the expected waiting time is $\frac{1}{2 N \mu \frac{1}{2N}} = \frac{1}{\mu}$. In humans, the average $\mu$ is of the order of $10^{-8}$ per site but there is a lot of variation among sequences.

So, if your mutational target is only a single site, then the expected time to fixation of a currently non-existing mutation is $10^8$ generations! If you are considering the entire genome as you mutational target is the entire genome, your mutation rate is of the order of $10$ and the expected number of generations is only $\frac{1}{10}$.


Could viruses be used as antibiotics? Could we use viruses that only affect bacteria to act as antibiotics?

The more bacteria, the more times the virus divides, so the stronger it gets. Is this practical?

Could we use viruses that only affect bacteria to act as antibiotics?

Yes. The specific class you're referring to is called a "bacteriophage".

There's quite a bit of research going on surrounding phage therapy as a stand-in or replacement for traditional antibiotics. Here's a Nature Biotechnology article from 2004 that discusses your very topic.

It is practical, carries some risks (mutations being a known and accepted risk), and I wouldn't be surprised to see phages in practice now or sometime soon.


Are there any plants that parasitize on animals? It seems, fungi often infect animals, while plants it seems, never. Is it because the cellulose cell walls make them incompatible with animal tissue?

Yes! Here's a paper published August 2018
https://www.sciencedirect.com/science/article/pii/S0960982218308157


Self-thinning: slope of log (biomass) vs log (density) is -1/2 whereas slope of log (weight) vs log (density) is -3/2, why? In self-thinning or intraspecific competition (more relevant for trees I guess) why does logarithm of Biomass vs logarithm Density give you a slope of -1/2 whereas logarithm of Weight vs logarithm of Density gives you a slope of -3/2? Biomass is mass (or quantity) of an organism per volume(or area), weight is mass scaled by gravitational acceleration which is a constant, unless the organism you are dealing with is very very tall. So the plots can be shifted accordingly but shouldn't slopes be more or less the same ?

source: Ecology: Concepts and Applications
by Manuel Molles
www.mheducation.com/highered/product/ecology-concepts-applications-molles/M0077837282.html

.

Biomass here refers to the total mass of all the organisms in the population (in a unit of area), added together.

Weight here refers to the average weight or mass of an individual.

If biomass decreases, that could be because the individuals got lighter, or it could be because there are fewer of them, or both.

Added

I think I see what's happening.

Let $W$ be the average mass of an individual, $N$ be the number of individuals, and $B$ be their total biomass. Then of course,

$B=WN$

Let's start with:

$W$ is proportional to $N^{-\frac{3}{2}}$
$N$ is proportional to $N$ (duh). Let's rewrite that though, as:
$N$ is proportional to $N^1$

But that means:

$B=WN$ is proportional to $N^{-\frac{3}{2}} \cdot N^{1} =N^{-\frac{3}{2}+1} = N^{-\frac{1}{2}}$

Density increases with density (N). Weight per individual  decreases with the -3/2rd power (W). So their product, biomass decreases with the -3/2 + 1 = -1/2nd power  (B=WN).


Botany related question: liverwort sporophyte Is perianth part of the sporophyte or gametophyte in liverworts (Marchantiophyta)?

I think it should be a part of the gametophyte because it is formed from the fusion of leaves (which are haploid) and protects the archegonium and the developing capsule.

It also can be logically thought out. Since it develops before the sporophyte forms , it should be part of the gametophyte.


How do transgenic transformations cause off-target phenotypes? I read that transgene insertions can cause off-target mutations that result in a phenotype being overly ascribed to the transgene, e.g. the increase of lifespan being ascribed to Sir2 overexpression (Burnett et al, 2011, https://www.ncbi.nlm.nih.gov/pubmed/21938067). In that particular study, they outcrossed the transgenic strain several times with wild-type to remove these off-target effects, a mutation in Dyf2 being named in particular.

I have a poor background in genetics, so I don't really understand how transgene insertions can cause off-target mutations, nor how outcrossing can isolate the intended mutation.

The C.elegans used in the study you linked was originally made by Tissenbaum & Guarente using the gamma irradiation protocol.

In short, the protocol provides the injection of the desired DNA construct in the worm's gonad followed by gamma irradiation of the worms.

Upon radiation exposition, the genomic DNA of the worm will break at random sites and will undergo repairing by the appropriate cellular enzymes, during the latter stage the exogenous DNA can be integrated (ligated) into the genome. However, the genomic DNA can also acquire random mutations due to the radiation. This is how transgene insertions can cause off-target mutations in this case.

With other organisms or cells, the protocols are different. To engineer mammalian cells, for example, radiations are never used but still, you have to generate breaks in the genome to edit it. Depending on the method the "off-target rate" of a given experiment may vary, but it is never zero (not yet).


Do both ends of a muscle contract? I was under the impression that both ends of a muscle contract. For instance, the fibers of the biceps run parallel to the humerus so I thought they pulled toward the middle.

But now I'm confused because it sounds like the contraction of the fibers doesn't necessarily have to parallel the motion of the muscle itself. In other words, just because the fibers contract doesn't mean that the muscle lengthens or shortens in a particular direction.

Can someone clarify if muscles contract in both directions?

Or perhaps a better question is do muscle contract in a particular direction and is this the same direction that the fibers contract or does the muscle as a whole move in a different direction in comparison to the direction the fibers are contracting?

The muscular fibers (or more exactly the actin and myosin filaments) are contracted towards each other. This makes them "move to the middle" and you build up a force on both sides of the muscle. See this image (from the Wikipedia), which illustrates this process:

There is also an animated picture available, which illustrates this process even better (from here):

The process of the contraction applies a equal force to both endpoints of the muscle.


Book about ordination in ecology This is a question I posted on Cross Validated few weeks ago but no response has been given so far.

I am looking for a book that would cover a lot of different ordinations techniques (indirect gradient analysis e.g. PCA, CA, DCA, MDS, nMDS but also direct gradient analysis e.g. CCA, CCorA, RDA) with applications in ecology (with R would be better) and mostly focusing on these methods.

I think " Numerical Ecology " by Legendre & Legendre (https://www.elsevier.com/books/numerical-ecology/legendre/978-0-444-53868-0#) would be relevant but it seems to cover a very extensive number of topics. Any other idea ?

I took a class in ordination methods a few months ago and found the following books helpful in better understanding the various techniques:

Multivariate Statistical Methods: A Primer by Brian Manley https://www.crcpress.com/Multivariate-Statistical-Methods-A-Primer-Fourth-Edition/Manly-Alberto/p/book/9781498728966

Correspondence Analysis in Practice by Michael Greenacre (this is somewhat more in-depth for forms of CA) https://www.crcpress.com/Correspondence-Analysis-in-Practice-Third-Edition/Greenacre/p/book/9781498731775

Multivariate Statistics for Wildlife and Ecology Research by McGarigal, Cushman, and Stafford https://www.springer.com/gp/book/9780387988917

Numerical Ecology is really excellent, even if it covers a broad number of topics. I focused on the ordination methods and found it to be very straightforward. Check out the McGarigal et al. book if you are interested in seeing examples of application in ecology.


evolution and mutation of microrganisms against medicines? I presume microorganisms would have very short life span and they would multiply more creating millions of their kind. Is it really a threat to consider when we use anibiotics and other stuff more making these creatures becoming resilient to the medicines. On the other hand bodies becoming dependent on the medicine making us weaker .we clean our office spaces homes etc with bleaching agents, acids killing microorganisms and thus making our body unaware of these and letting these organisms survive and create more deadly strains.

I believe there are examples like malaria microbes becoming resistant to quinine perhaps many more.  If someone tries not to take medicines when he suffers from common cold and small fevers and let the body fight but is it right to do so considering that mecines are available and one should take them.

There is an article also published today.

A few throughts about this: Microorganisms have a short life span but they replicate very fast with a short generation time. So this create vast amounts of "offsprings" with some mutations naturally occurring. Due to this large numbers the chance of developing resistances is much higher than for slowly replicating species.

This is especially true, when the selection pressure is high, as this is the case when you treat with drugs which usually kill these microbes efficiently. When people are not taking these drugs (antibiotics for example) according to the necessary scheme, the concentration of the drug in the body is lower than necessary to kill of all microorganisms. This leads to the survival of microorganisms which are a bit adapted to survive the drug and so on.

The real problem are people who are not following their treatment regime necessary and thus causing resistancies. A case for this is tuberculosis. Regarding taking medication: Always take them when necessary and leave them out when not. A simple cold for example can not be treated antibiotics since it is viral, the secondary middle ear infection usually can.


Autoimmunity - negative selection of T-cells - APC Through negative selection of T-cell in the thymus T-cells lose the possibility to react to antigens which are "body own" -> self antigens.
Though there are more than just this negative selection for preventing T-cells recognizing own antigens some T-cell become self reacting.
This T-cell in our case cd4 T-cells can recognize antigens presented on MHC II complexes by APC cells.

And the question is:

Who presents the self-antigens to the wrong selected CD4 T-cell, which leads to autoimmunity? How does the APC cell get this self-antigen in the first place?

Since you already know that the repertoire of T cell receptors is developed in the thymus, the missing half of the story in the context of antigen-presenting cells is that MHC complexes do not discriminate between self, foreign and mutated self peptides. The take home point is that selection in the thymus is meant to produce a repertoire of T cells which can overcome this fact.

In all healthy tissues, nucleated cells express class I MHC molecules loaded with self-peptides. A T cell probably isn't going to respond to it, however, because trafficking of T cells into tissues requires signals such as cytokines and chemokines. The T cells circulate to and from the lymph node T cell zones.

In the context of inflammation and cellular injury, self proteins may be released into the extracellular space where they're regularly cleared by macrophages via endocytosis. The extrinsic antigen presentation pathway loads peptides onto class II MHC molecules. In this very context, T cells are trafficked into distressed tissues by activated endothelium, where they interact with tissue APCs. Autoreactive clones that escaped thymic selection have the opportunity, then, to react to self antigens, ignoring regulatory or suppressor cells (ref).

Not just self-peptides, however, but also potential self-antigen mimics that take well meaning T cells directed against bacterial peptides, which happen to closely resemble a self antigen, and pit them against your own tissues (example). Unlike autoimmune T cells that have escaped selection and attack your cells, this invites T cells that have gone through the proper channels to do so as well.

See Cellular and Molecular Immunology, 8th ed. for an even better overview of T cell-based autoimmunity.


Why do birds legs' not get frostbite? In a nature documentary I watched a while ago, there was a scene where a flock of flamingos slept in a lake that froze overnight. Each morning they just had to wait until the lake defrosted sufficiently to release them so they could get on with their day.

How do they not get tissue damage etc doing this?

Birds have a few adaptations and behaviors to keep their legs warm in cold weather:

Blood vessels (veins and arteries) run very close together or are intertwined:

The arteries and veins intertwine in the legs, so heat can be transferred from arteries
back to veins before reaching the feet. Such a mechanism is called countercurrent exchange. Gulls can open a shunt between these vessels, turning back the bloodstream above the foot, and constrict the vessels in the foot. This reduces heat loss by more than 90 percent. (Wikipedia)

Birds have specialized scales on their feet and legs which act as an insulator.

Birds often alternately tuck their legs into their body feathers to minimize heat loss. (Audubon)

Other survival mechanisms such as shivering and torpor come into play with extreme cold.

Other sources: Mother Nature Network. I don't have my texts handy, but can highly recommend Manual of Ornithology: Avian Structure and Function by Noble S. Proctor and Patrick J. Lynch.


What makes a gene dominant or recessive We all carry two copies of each gene (outside of male sex chromosomes).  If the two differ from each other often one is dominant and one recessive.  How does this mechanism work on a molecular level?  What mechanism determines which gene gets expressed?

On the molecular level, genes most often encode proteins which perform some function for the cell: For example, they could be enzymes and catalyze chemical reactions. They could also have some structural function, such as make up the "muscle" part of your muscle cells... You get the idea.

In the most simple case, the dominant allele encodes a protein that can perform its function. For example, the dominant allele for the CFTR gene encodes a channel that can let chloride into and out of the cells. The recessive allele, on the other hand encodes a protein that cannot do its job correctly (this also called a loss-of-function mutation). So if you inherit a functional copy from one parent and a non-functional copy from the other parent, you will still have one copy of the protein that can do its job. Only if you get a nonfunctional copy from both parents will you have a recessive condition called cystic fybrosis.

On the molecular level a gene can also encode a dominant-negative variant of a protein. In this case the protein cannot do its job and also prevents the functional version of the protein to do its job too.

A third way this could work is by a gain-of-function mutation. In this case, the gene encoding a protein acquires a mutation that gives a new function to the protein. For example, in Huntington's disease, the mutant Huntingtin protein acquires the ability to clump together in large plaques, which are poisonous to some neurons in the brain. Since it takes only one copy of the protein to perform the new function, the gain-of-function allele is a dominant one.

These are only a few examples that deal with simple dominant and recessive inheritance. Most often there are more complex mechanisms of inheritance at play.


Identifiying a conserved residue in multiple PDB structures I have a few hundred PDB structures of the same protein, and I need to identify a specific conserved residue in all of them.

Originally I wanted to extract the sequences from the PDB files with BioPython, align them and then use that alignment to identify the residue number in each PDB for my conserved residue.

But it turns out that is a bit harder than I expected. Parts of the sequence are often missing in the PDB. I don't see an obvious way to get a proper sequence out of the PDB files. Then there is the issue of mapping the conserved residue number back into the PDB file.

Is there any easier way to do this? It doesn't have to be BioPython, though that would be nice.

My approach to this problem would be to use VMD (Visual Molecular Dynamics), where you can load multiple PDBs, perform structural and/or sequence alignment and analyse residue conservation within one program.

VMD is a powerful molecular visualization program for displaying, animating, and analyzing large biomolecular systems using 3-D graphics and built-in scripting. It is probably an overkill for what you want to do, but I find it rather intuitive to use and powerfull. I also has an amazing documentation and many step-by-step tutorials, starting from this basic introduction.

What you will specifically need for your problem is a MultiSeq 2.0 plugin that you can find under Extensions->Analysis->MultiSeq in new versions of VMD. It is a bioinformatics environment that allows you to load, display, and analyze both sequence and structure data for your proteins within a few mouse clicks. It also has a great set of tutorials to help you start! What you might find interesting for comparing many similar protein structures is an option to create, view and manipulate phylogenetic trees.

Here is step by step tutorial on comparing structures and sequences with MultiSeq.

Here you can find original publications for both VMD and MultiSeq:

VMD:

  Humphrey, W., Dalke, A. and Schulten, K., VMD - Visual Molecular
  Dynamics., J. Molec. Graphics, 1996, 14:33-38.

MultiSeq:

  Roberts, E., Eargle, J., Wright, D. and Luthey-Schulten, Z.,
  MultiSeq: Unifying sequence and structure data for evolutionary
  analysis. BMC Bioinformatics, 2006, 7:382.


How much of the Neanderthal genome is living on in humans? I've understand that outside of African, most ethnic groups carry some (4% or less) Neanderthal DNA.  So en masse, across all living humans, what percentage of the original Neanderthal genome is still alive in human decedents today?

Even though individual humans only have around 2-5% Neanderthal genome, it's not the same 2-5% across people. In total, at least 20%, and perhaps as much as 40% of the Neanderthal genome could be recovered from modern human populations:

  We identified Neandertal lineages that persist in the DNA of modern humans, in whole-genome sequences from 379 European and 286 East Asian individuals, recovering more than 15 gigabases of introgressed sequence that spans ~20% of the Neandertal genome

--Resurrecting Surviving Neandertal Lineages from Modern Human Genomes

However, there are stretches of the human genome that are almost completely devoid of Neanderthal genes. These include male-fertility associated regions (leading to the suggestion that male sapiens/neandertalis hybrids may be been subfertile or sterile):

  Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

--The genomic landscape of Neanderthal ancestry in present-day humans

And some brain-specific regions (suggesting that those are uniquely human):

  Regions depleted of archaic lineages are significantly enriched for genes expressed in specific brain regions ... A large region depleted of archaic sequence spans 11 Mb on chromosome 7 and contains the FOXP2 gene (Fig. 4B), which has been associated with speech and language

--Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals


What is the difference between different brain regions The brain is separated into different regions, and different regions perform different tasks. Well, what are the differences between these regions on the cellular/systemic level. The brain is made up of neurons and other cells, but how come one part is used to process sound and another is used to process, say, smell? Are they like different computer circuit boards - using the same components but are wired differently?

And anyways, why did evolution not come up with a brain that uses the entire brain to process something, would that not be more efficient?

The wiring is different as you mentioned. However, perhaps the most important is the brain knows where it's input is coming from. The brain knows where each fibre innervates and thus can compile and present this data to our conscious mind. We show if we stimulate the brain directly, than we feel a sensation in the part of the body that portion of the brain is responsible for. Plasticity means our brain can change what feeds into where, this is most commonly where we learn a motor skill. If we play the piano for example the part of the cortex feeding to this area increases.

Another way is the type of chemical transmitter and receptor. Dopamine is primarily used for things that cause us pleasure for example. However dopamine can affect our movement if it is secreted in from the substantia nigra, as this feeds into the motor cortex. Furthermore, neurotransmitters can be excitatory or inhibitory and this is an analogue rather than binary signal. All of these fine tune, and the position at which they inhibit and the location and the feedback from which they obtain their signal all indicates from where the brain is getting the information or to what it is responding to.

In summary it is wiring, signalling and location. However the components are incredibly similar but it isn't the small differences that have a profound effect.


Transfer of electrophoresis bands to MS I have a lab question that is confusing me. Just to be clear this is a homework question but I've done some extensive research and can't find what seems to be a "good" answer.

The question is this:
List the steps in order that need to be taken between gel electrophoresis band excision and MS?

The only things I can think of are cleaning the salts out of the sample if salting out was used and removing any detergents that were used like SDS. The question seems to imply that there is a specific order or steps required leading me to think there is something I am missing. Any thoughts appreciated.

You have to remove the salts, remove the dye, digest the protein, extract the digested peptides from the gel etc.

For details, see this protocol.


Why is my blood group O -ve? My parents have B +ve blood group in fact my brother also have B +ve blood group, then why my blood group is O -ve ?

Humans are diploid organism. So humans have two copies of every chromosome and gene.

When a person has B blood. We mean that the blood cells of that person expresses  the B antigen.

To produce the B antigen you will need at least one allele for the B antigen. Hence the B antigen phenotype can have a genotype of BB or BO.

Now if two people have the genotype of BO have children, a punnet square will show they they have a 25% of having a child with BB genotype, 50% of having a child with BO genotype and 25% of having a child with OO genotype.

Phenotypically, it means that there is 75% chance of having a child with B blood. And 25% chance of a child with O blood.

A similar system also occurs with rhesus +/- system. A person with +ve blood can have a genotype of ++ or +-. If two people with the genotype of +- have children together, there is a 25% chance that their child will have -- genotype and be rhesus -ve.

The two systems work together. So two people with genotype of BO blood type and +- rhesus antigen having children together, they can have a child with O blood and rhesus negative with a probability of 1/16 (6.25%)


Deeper Learning in Physiology? I am a Pharmacology and Toxicology major at a large state school. I was only required to take physics I and II. (algebra based)

At first I thought that was fine, but I soon began to realize that I can't just memorize like my professor and book asks me too, but I need to go in-depth.

So my question is this, I am looking for a way to learn the "physics and chemistry behind physiology" or deeper that what we are taught?

For example, say we are taught that atherosclerosis can cause aneurysms and that aneurysms can rupture.

But what we aren't taught is that blood flow through a closed vessel is constant, so any dilatation in the mid-length will increase the cross-sectional area and decrease the fluid velocity to maintain flow.

In accordance with Bernoulli's principle, the decrease in velocity is met with an increase in pressure, which increases wall tension. Vessel integrity is already compromised from the three layer degradation. So now you start to see this great positive feedback loop whereby atherosclerosis damages the vessel wall causing it to dilate, which increases the pressure, which causes it to dilate further, which damages the vessel wall further, etc, etc, until the aneurysm finally ruptures. (I did not write this example, but it is an example of how I would like to learn it.  I would like to know how the author of that explanation came to that conclusion or what kind of book would explain in heavy detail.)

The question I am asking how can I learn the "science" behind the physiology?  I'm a type of learner that needs to know the how and why.  Will I need to take more physics classes?

** Sorry if I posted in the wrong section, I am new to stack exchange!

It is very easy, use google + pathophysiology and read some articles in the actual topic. There are a lot of pathophysiology books as well (some of them pretty expensive). Another way to do an online course.

Just a simple search about your example:

  It is known that AAAs are characterized by destruction of elastin and
  collagen in the media and adventitia, loss of medial smooth muscle
  cells with thinning of the vessel wall, and transmural infiltration of
  lymphocytes and macrophages. Atherosclerosis is a common underlying
  feature of aneurysms. However, atherosclerosis is not the primary
  driving factor in the development of AAAs. Atherosclerosis is a
  disease that is widespread throughout the vasculature, however
  aneurysms only form in specific locations and only in certain
  individuals. Additionally, atherosclerosis is primarily a disease of
  the intima, while aneurysm formation primarily affects the media and
  adventitia.

2009 - The Pathogenesis of Abdominal Aortic Aneurysms


Which animal species are known not to murder (a targeted attack leading to death) members of their own species? Is there any evidence to suggest that some animal species do not murder  (a targeted attack leading to death) members of their own species? If so, which are the relevant species?

Here are a few suggestions:

Any coral
Any sponge
Blue mussels
Sheep
Dugong
brown-headed cowbird
Blue whale
Common earwigs
Plasmodium falciparum (causing malaria)

If by the use of the term "evidence", you are expecting a peer-review paper that discuss the matter, I am afraid you wont find any as it is not really a question of interest to researchers. If you can prove wrong any of the above suggestions I will be happy to remove it (and eventually add some others).


Why is melanin black? I understand that the function of melanin is to protect individuals from sunlight, and that people living in sun exposed areas are darker due to increased production of melanin. But why is the melanin pigment black in color? Wouldn't it have been more useful if melanin was white?

From my understanding, black absorbs more sunlight than white, so if melanin is black, it will tend to absorb more heat (which isn't a good thing in areas with a lot of sun exposure). This will lead to production of more melanin (tanning).

Instead, evolutionarily wouldn't it have made more sense if melanin were white, since not only would the pigment protect the person from sun exposure, but also prevent more sunlight from being absorbed?

Let's do a quick mind experiment. Imagine a ray of UV light hitting a white molecule in the skin. White generally reflects light, so that UV light would bounce off, and potentially could hit something much more critical. Black, on the other hand, absorbs light, so the energy in the UV light would be absorbed by melanin rather than other, more sensitive molecules. According to this article:

  eumelanins are capable of dissipating >99.9% of absorbed UV and
  visible radiation through nonradiative means.

Eumelanins are the most commmon type of melanin. Incidentally, not all melanin is black.

Another quick note, somewhat relevant: Try not to think of evolution as having a goal or purpose. Melanin being black is a result of random changes that happened to result in a beneficial phenotype. It didn't conclude that something was needed to counteract UV light and try to reach that goal.


How does species diversity vs Earth total biomass relate? Are there any laws/theoretical foundations about how diversity of species relate with total biomass on Earth?

While there is a lot of esoteric sort of talk "humanity dis-balances the live on the Earth", I thought, there are formally seen the following hard facts (correct me if I am wrong):

biomass of human species and species we need (plants/cattle etc) is increasing;
diversity of species is decreasing

So it looks like some sort of global system change (correct me if I am wrong), but how does biology science discuss them (in case my inquiry can be anyhow scientifically formulated)?

I don't work in ecology, but my first thought is that I would not expect any relationship whatsoever between diversity and biomass. Biomass simply means the combined mass of all life on the planet. If that mass consists of one extremely fat goat the size of the moon, or several trillion different organisms doesn't make a difference, mass is mass.

Now, it is undoubtedly true that loss of diversity is a huge issue. However, the way this works is usually that we replace the local ecosystem with its several, varied species with a monoculture. For example, grasses like wheat and barley are taking over the world. Destroying a forest to plant wheat might easily result in no net change in biomass or even a net positive, but it will certainly be a significant loss in the diversity of the local ecosystem.

Finally, humans are a teeny tiny part of the world's biomass, most of which consists of unicellular life, plants and insects:

Note that the axes in the image above are logarithmic. You can get a clearer image, perhaps, from this:

(both images taken from Bar-On YM, Phillips R, Milo R., The biomass distribution on Earth, PNAS, 2018 Jun 19;115(25):6506-6511. https://www.pnas.org/content/115/25/6506)

See how all animals, let alone humans, are just a tiny part of the image on the right? That gives you a pretty clear indication of just how irrelevant we are in terms of global biomass. So yes, diversity is indeed decreasing, but there is no reason to think that the accumulated mass of living organisms will decrease, only the diversity of said mass will decrease.


Can viruses protect themselves against restriction enzymes? Restriction enzymes cut the DNA of bacteriophages. Have bacteriophages evolved any mechanism to protect themselves from it ?

I guess you are talking about the restriction modification system, not restriction enzymes in general (which are used a lot in the lab, for example).
If so, this paper might help answer your question.

I have not read through it totally, but at least some viruses trigger the downregulation of restriction enzymes to make them cleaving their DNA less likely. Restriction enyzmes are also quite selective for the site they cut at, so single nucleotide changes at this site, might, if the phage is lucky, not change the function of the encoded gene, but keep the restriction enzyme from binding (and thus cleaving) at that site. Mutating helps a lot. And it is fast in those little critters.


Understanding mRNA vaccine for COVID As I've learned, mRNA helps us to produce virus spikes proteins to induce learning of the immune system.
But then, I remember to have read that the coronavirus has some trick to pretend to be "food" to our cells, that is it has some lipid element. So it can entry the cell easily. But this was not same part as the spike protein, right? (otherwise it would have been contradictory with the mRNA approach?)

You have it wrong. Coronaviruses are part of a family of viruses that are called "enveloped viruses". These all have an "envelope" comprised of a lipid layer derived from the host cell as the virion exits. The envelope is distinct from the spike. The spike protein is produced by the virus during replication and is not found naturally in a host cell.
This does not pretend to be "food" at all, but it can help evade host immune responses by hiding the other virion capsid proteins.


regenerative capacity of human body Is liver the only internal organ in human body with regenerative capacity? How about endometrium?and what is the difference between regeneration and renewing?

I'd say renewing refers to a constant process wheras regeneration applies to wholesale rebuilding due to trauma.

For example, your skin is constantly "renewed" by the undermost cells, adjacent to the basement membrane, dividing to produce new cells that migrate outward. These cells are modified to protect and eventually slough off to feed the mites in your bed. Ditto to cells lining the stomach which are replaced/renewed about ever three days due to abuse of stomach acid and salsa.

Humans can regenerate much of the last joint of a finger, bone and all. I'm not sure if this is age dependent nor how much of the knuckle needs to remain. Search "regeneration of fingers in humans" to find many references to this.


Current understanding of abiogenesis I am trying to understand the current work on abiogenesis in biology, e.g. primordial soup, the Miller-Urey experiment, etc.

How has our understanding of abiogenesis been revised since the Miller-Urey 'primordial soup' hypothesis?

Our understanding of how life began on earth has indeed advanced substantially since Haldane, Oparin, Miller, and Urey. To learn about the latest ideas, I can't think of a better place to start than this excellent video series with Nobel Laureate Jack Szostack, who is currently doing some of the leading work on the subject.


epiphyte mats in tropical forests I read in an ecology text book ("Ecology: Concepts and Applications" (7th edition) by Manuel Molles) that trees in tropical forests can be sustained despite the poor soil is because they extract nutrients from epiphyte mats. Trees send roots from trunks and branches to get nutrients from epiphyte mats that are located high up in the canopy. I would like to visualize these roots. Are there any pictures available (conveniently in the Internet) showing these roots?

Or are these roots usually located beneath epiphyte mats (e.g., very short) and cannot be seen unless we remove epiphyte mats?

Adventitious roots into epiphyte mats aren't all that uncommon, and aren't restricted to the tropics. They can occur in old growth forests in the pacific northwest (my neck of the woods). A well-developed bryophyte mat in a single upper canopy tree can store up to six metric tons of water, plus all the mineral nutrients from atmospheric deposition. For the tree, it's a huge advantage to be able to tap into that epiphyte mat rather than rely on bringing up water from their subterranean roots. As far as visualizing it goes, yes, you would have to remove the mat to see them, but they look very similar to subterranean roots. Not sure if this is helpful, but I like to think of it like this: when a new meristem is formed, it's basically undifferentiated, and if there's sufficient water and mineral nutrition it can develop into a root (or a shoot if it's getting sunlight). The tree doesn't care if that's below ground or in the canopy.


Identifying a weird Texas tree I recently saw this tree in Texas, with many bees on it. I think it attracts   bees. However it didn't have any specific smell, so I don't know why there were so many bees (they were bee for sure). I tried to identify the leaves but couldn't. Dear experts: could you please identify this tree?

That looks like a live oak covered with oak galls


How to produce and isolate an enzyme? I have recently learned that one of the best ways to isolate a protein in industry is via Chromatography. What are other ways enzymes are isolated in industry? Are there other ways?

Chromatography is one of the best ways to isolate a protein, full stop. It is extremely widely used in both academia and industry.
Before we get into the details, though, a definition is in order. Chromatography is a means of separating components of a mixture using a mobile phase (liquid or gas) traveling though a stationary phase (a solid, gel, or very small beads, frequently with something attached to them). Chemical and/or physical interactions between the components of the dissolved mixture and the stationary phase cause those components to migrate at differential rates, separating them out from each other.
There is a huge variety of protein-stationary phase interactions that can be utilized in chromatography. Microscopic beads made of different substances can be used to create a matrix of pores where larger proteins will migrate more quickly than smaller ones. Epitope tags such as Myc or FLAG can be recombinantly added to a protein's sequence and purified using beads that have epitope-specific monoclonal antibodies covalently bound to them. The tagged protein is "grabbed" by the antibodies while the rest of the mixture washes through, then the binding is reversed by various chemical means that interrupt the protein-antibody interaction, such as high salt concentrations, varied pH levels, or chaotropic agents and the concentrated protein collected all at once.
Sometimes it is known that a certain class of proteins (such as antibodies, for example) will bind very specifically with another protein or protein fragment (in this case, the bacteria-derived Protein A). That protein is covalently bound to beads and used to purify and/or concentrate all antibodies in a solution, regardless of the antibody's specific target. Protein A binds to a section of an antibody known as the Fc region, so that sequence is sometimes fused to a non-antibody recombinantly-expressed protein so that it can be easily purified by this method. Antibodies that are specific for the protein of interest itself can be used for purification.
Many other chemical reactions can be harnessed to cause a protein of interest to bind to a stationary phase substrate and later eluted by reversing or inhibiting the chemical reaction. One example is purification based on electrical charge, called ion-exchange chromatography. If it is known that a protein has an overall positive charge, negatively-charged beads can be used to bind it (and all other positively-charged proteins in the mixture). Once washed, the protein(s) can then be eluted by changing the pH, hence neutralizing their overall charge and breaking the ionic bonds which bound it to the stationary phase. Positively-charged beads can also be used to purify negatively-charged proteins.
There are many other strategies besides the ones I've highlighted here – the term chromatography encompasses a huge range of possibilities for protein purification. I would say that in the majority of large-scale industrial purifications, combinations of different types of chromatography are the only methods used. There are of course other methods involved in the manufacturing of a protein therapeutic, such as cell lysis, filtration, concentration, dialysis, formulation, etc., where chromatography is not used, but for purification it's typically the only one. One reason for this is automation. Chromatography columns can be loaded, washed, eluted, cleaned, and regenerated without the need for any human interaction other than to provide the necessary buffers and materials. It can often also be scaled up quite a bit from benchtop to manufacturing suite, allowing for more material to be processed per batch. And, once everything is tweaked and optimized, you can get extremely pure material out of it.
There are some other protein purification methods, such as organic extraction, density centrifugation, and differential precipitation/solublization, but these are typically (but not always) used more in research and development than manufacturing, for various reasons. You don't want toxic organic chemicals like phenol, chloroform, ether, etc. involved in your manufacturing process if at all possible, because it takes a lot of work to prove to the FDA that all traces have been removed at the end. Centrifugation is not very scaleable, and is rather difficult to automate. One of the issues with precipitation is ensuring that re-solublization is both complete and consistent between batches. The amount of work that goes into validating manufacturing processes for injectable drugs and getting FDA approval is absolutely mind-boggling. Trust me :)
Hopefully I've answered your question! Please let me know if I missed anything or you want to know more about something.


Do prokaryotic chromosomes have centromeres? I found this here.

Eukaryotic chromosomes are always linear. ... In contrast, prokaryotic chromosomes are either completely devoid of centromeres or carry the so-called “plasmid centromeres” which are not essential (with a few exceptions, such as Caulobacter) (57,–60).

What does it mean by prokaryotic chromosomes carry "plasmid centromers"?
Their chromosomes carry the centromeres of plasmids? Do they have centromeres or not?

No, prokaryotes do not have centromeres.  They do, however, generally have a somewhat analogous structure used during cell division to partition the replicated chromosomes and plasmids between the two daughter cells. The analogous place on the chromosome or plasmid is the parS element, a DNA sequence on the chromosome or plasmid which is part of the parABS system.  This system, consisting of two proteins (parA and parB) along with parS, forms a mechanism to segregate the copies of a chromosome or plasmid for the daughter cells.
parS is usually called a "centromere-like" site, but is sometimes referred to as a "plasmid centromere”, which is why the quote uses the phrase so-called “plasmid centromeres”.


How did the introduction of artificial light changed the life cycle of a plant? Plants in urbanized areas are constantly exposed to artificial light after sunset. In their natural habitat there is a more distinct day and night cycle.

Since light is an important factor in a plant life cycle, I wonder if the introduction of the artificial light forces any changes in the life cycle of plants in urbanized areas?

According to this study, artificial lighting similar to that provided by streetlights in the UK can reduce flowering in at least one plant, which also affects the aphids that feed on it.

This article discusses it in more general terms - night lighting doesn't affect photosynthesis, but can affect the length of day/night perceived by plants and alter growth accordingly. There are two examples given of how it is harmful:

Young trees grow longer and don't enter dormancy, making them increasingly susceptible to cold temperatures.
The stomatal pores of leaves remain open longer, making some trees more susceptible to pollution and water stress.


Why can't you just take a vitamin? Why you need a healthy diet on top of that? From what I understand, your body needs certain amounts of vitamins and minerals to maintain health. Why can't we just take enough pills to obtain these vitamins and minerals?

I think the piece of missing information here is the distinction between macronutrients and micronutrients. The info from Mayo clinic quoted in the another answer addresses some reasons why whole foods might be better than pills for obtaining micronutrients (i.e. vitamins and minerals).  While this may be true, most of it remains to be conclusively demonstrated (arguably). However, one clear reason “why….you need a healthy diet on top of that” is (unarguably) to obtain the fat, protein, and carbohydrates that your body uses to create energy. Unlike the minerals that act as cofactors, these macronutrients are the substrate. They are broken down to create the ATP that keeps everything running and they are built up to create the very structure of the body.

  The energy that is consumed in the form of food or drinks can either be stored in the body in the form of fat (the major energy store), glycogen (short-term energy/carbohydrate reserves), or protein. . . to be used by the body to fuel energy-requiring events. *

These are called macronutrients because they are required in gram quantities — hundreds or even thousands of times more massive than the requirements for most micronutrients. As such, they don’t fit in a pill. As tragic as it is, we must keep eating.

*Gibney, M. J., & Nutrition Society. (2009). Introduction to Human Nutrition. Chichester, West Sussex, U.K.: Wiley-Blackwell.


ExAC Browser: What does a "dubious variant annotation" mean? I am studying a protein in the ExAC browser. However it is flagged with a "LoF flag". What exactly counts as a "dubious" variant in ExAC.

I couldn't find any further information neither at the variant's page nor in the FAQs.

Link to ExAC browser.

Link to variant site (This is a bad example, because there is a multi-allelic warning, but this is the variant shown in the picture)

Further links to variants with LC LoF flag:

14-45636336-C-T

14-45636346-C-CTA

Briefly speaking you expect more or less uniform coverage for reads. So if you see a systematic difference in quality scores or coverage for minor and major alleles or for forward and reverse strand, it could be an SNV, but most likely it is a technical issue. That's a 'dubious variant'.

A lot of such biases are described in "Genotype and SNP calling from next-generation sequencing data":

  Other types of filtering based on deviations from the HWE — generally
  low-quality scores, systematic differences in quality scores for major
  and minor alleles, aberrant LD patterns, extreme read depths, strand
  bias, and so on — can also help to improve the accuracy of genotype
  and SNP calling. The appropriate filters depend on the sequencing
  protocol and the upstream analyses. For example, a site with strand
  bias (where a disproportional number of plus and minus strands are
  observed) could be an indication of a problematic site that is more
  error prone and should be filtered out. However, if the sequencing has
  been performed on captured sequences, such as those used for exome
  capturing, then the bias might not be an indication of a problematic
  site but rather an artefact of the capture array.

Update
I've just received an answer from ExAC:

  The "LC LoF” means that the variant was marked as a low confidence
  loss of function variant. If you click on the “Transcripts” dropdown
  on the variant page it will show the reason why the variant is of low
  confidence for that transcript. In this case it was flagged as
  “END_TRUNC”. An explanation of the LoF filters can be found here:
  https://github.com/konradjk/loftee


Presence of reaction module in bacteria but not in Eukaryotas (human) From the statistics page, I found that the Module-M00008 is present only in bacteria and not Eukaryotes. Why so? I noticed that all the compounds necessary or the reaction are present in human body and also all the enzymes required for the reactions are present in human body too. Then why does that reaction not happen in humans?

That module represents Entner-Duodoroff pathway, which is an alternative pathway to the Embden-Mayerhof-Parnas pathway of glycolysis.

Entner-Duordoff pathway exists only in prokaryotes.


Aspirin - does it inhibit enzyme of thromboxane? This is a diagram a friend showed me about the drug aspirin, where we were arguing which enzyme it prevents.

Aspirin is known to inhibit the production of prostaglandins. However, it also serves fit as a purpose to inhibit production of thromboxane.

My question is, does the drug inhibit enzyme a to prevent the production of both thromboxane and prostaglandins, or only enzyme B?

Aspirin and some other NSAIDs inhibit cyclooxygenase which is the first enzyme in the prostaglandin/thromboxane biosynthesis pathway if you consider first substance is arachidonic acid (a fatty acid). Generally, arachidonic acid is present in the form of a phospholipid, and if you consider that in the pathway, substance-Y is arachidonic acid and enzyme-A is cyclooxygenase.

  From: Heckmann, Lars-Henrik, et al. "Outlining eicosanoid biosynthesis in the crustacean Daphnia." Front. Zool 5.11 (2008).


Book recommendations for evolutionary models I was recently working on getting a statistical model of a DNA sequence. To do this I found that understanding evolution quantitatively seems to be quite important. I would really appreciate any book recommendations on the basics of evolution.

I come from an Electrical Engineering background and have a limited knowledge of evolution and biology.

You either want a introductory book in evolutionary biology or a book that offers mathematical models of evolutionary processes.

In my first class of evolutionary biology I had this textbook: Futuyama, Evolution I think it gives a good start to the field and offers a good overview of the difference subfields.

If you think you already know enough about the concepts selection, genetic drift, molecular evolution, etc… and you want a book that provides mathematical formulations of evolution, then you might want to have a look into the field of population genetics. On this post you'll find some book-recommendations

If you are particularly interested into molecular evolution, I'd suggest: Yang, Computational molecular evolution

Maybe you are particularly interested into the statistical methodology used in DNA annotation or in phylogeny. Then…. I don't know! It's not quite my field!


miRNA_ID to GENE_SYMBOL conversion I have a list of miRNA IDs and a list of mRNA IDs and they are from Mus musculus species. I have converted the list of mRNA IDs to gene symbols by a list of data that was exist in NCBI and miRNA IDs list to gene symbols using Diana but I got in trouble because gene symbols on NCBI didn't match with the gene symbols that exist in Diana site. I think the problem is that naming of gene symbols doesn't follow a specific rule in different databases and are not standardized. Can anyone tell me a good way to transform both mRNA & miRNA lists to a platform for example unigene that would be unique in all kinds of databases?

For mouse gene names and other details you should refer to the mouse genome informatics database (it is a standard organism-specific database like flybase [Drosophila], SGD [yeast], etc).

However, it is much better to work with RefSeq IDs. Moreover, miRNAs are seldom referred to, using their gene names. Always stick to the miRNA naming convention that is described in miRbase.

I am not sure what you are actually interested in. If you intend to map miRNAs to their targets then you can use one of the standard gene names along with the RefSeq ID. If you are using miRanda or TargetScan to predict the targets then these programs return different identifiers for the target gene including its official gene name.

In general, for ID conversion, I would prefer BioMart.


Could the Warburg effect be used to starve cancer cells in situ? What is wrong with the following chain of reasoning?

Nearly all cancer cells rely on high rates of glucose uptake (upto 200 times more than normal cells). This is known as the the Warburg effect.
There is only one cell type in the human body that is obligated to use glucose - red blood cells (erythrocytes).
Starve cancer cells of their only energy source by inducing hypoglycaemia in the patient, preserving red blood cells using, for example, erythrocytapheresis or an oxygen-carrying substitute.

I understand that to completely eliminate a tumour such a regime would need to be in place for an extended period, but would like to know why such a treatment isn't feasible in theory?

The human body needs energy (ATP) for even the most basic function. I guess when you decrease glucose levels (which is broken down for ATP), you will be in affect taking away the ability of the body to function normally by depriving it of energy. This is my theory so I would be happy to if someone with more information on the topic could tell me if I am right or wrong.


What does it mean to perform in vitro experiments with mutant bacteria? I came across the following sentence while reading the paper:

Nanchen, Annik, et al. "Cyclic AMP-dependent catabolite repression is the dominant control mechanism of metabolic fluxes under glucose limitation in Escherichia coli." Journal of bacteriology 190.7 (2008): 2323-2330.

  These in vivo flux data are qualitatively corroborated by in vitro
  enzyme activities in the Crp and Cya mutants, which exhibited
  significantly reduced activity of the key glyoxylate shunt key enzyme isocitrate lyase ...

My understanding of in vitro experiments is: those performed in artificial set up , possibly only with part of the cell, where the complete cell is not potentially alive. For, example we can test the inhibition activity of a particular enzyme by a metabolite.

In the paper cited, experiments from which flux are derived (chemostat) are considered in vivo. What would it mean to say the enzyme activity was tested in vitro on the mutant? When we say the response of the a single gene knock out mutant, the cell should be intact except for lacing one gene, which would mean that the response is in vivo.

Please help me if I am misunderstanding some thing.

Answer clarified based on comment by @DurgaDatta

  What would it mean to say the enzyme activity was tested in vitro on the mutant? When we say the response of the a single gene knock out mutant, the cell should be intact except for lacing one gene, which would mean that the response is in vivo.

The knockouts were performed inside the E. coli cells and, as you noted, the flux measurements were in vivo (in the cell) inside of the chemostat culture. They identified two mutants, Crp and Cya, that yielded much higher biomass. On page 2326, the authors write,

  In the Cya (encoding adenylate cyclase) and Crp mutants that lack the cAMP-CRP complex, in vivo glyoxylate shunt activity was essentially abolished....

I am not familiar with these genes but the implication is that the wild type regulators have the cAMP-CRP complex. Because this complex is missing from the mutants, the enzymes no longer function the same. However, it would be possible that some type of interaction of the mutants with other enzymes caused the observed result in vivo. They therefore verified the result by extracting the Crp and Cya mutant enzymes from the cells and assaying their enzyme activity in isolation from the other enzymes (in vitro). The technique is explained in the answer by @dgg32.

In your comment to that answer, you ask.

  what difference does it make whether the enzyme was taken from wild-type or the mutant one, since it is the same enzyme?

It is the same enzyme in name but not in function. The mutant enzyme lacks the cAMP-CRP complex so it cannot perform the same function as the wild type. In vitro, they first showed that mutant enzyme activity was altered relative to the wild type.  They then added the wild type enzyme to the in vitro test and restored normal wild type activities:

  To verify that the observed changes were not due to polar effects of the still present marker gene or secondary-site mutations, we complemented the Crp mutant with the plasmid-based Crp gene and cultivated the complemented mutant under the same chemostat conditions. In vitro enzyme activities demonstrated that both the isocitrate lyase and isocitrate dehydrogenase activities were restored to the wild-type level

Yes, this was performed inside the chemostat cultures but only with the enzymes, not the living E. coli cells.