text:
Database of predicted protein-ligand binding/docking score
Is there a database of computationally determined "binding scores" across protein-ligand pairs in the PDB?
My phrase "binding score" is deliberately generic, since any such score would be fine. In particular, some docking energy, i.e. scoring function, would be great. (Don't worry, I am aware that these docking energies are not perfect :) ).
I am looking for comprehensive coverage and the same score across bound pairs, meaning that experimental measures are obviously impossible; however, I am hoping there are people who ran some docking scoring function across all the protein-ligand pairs in the PDB, or at least some large number of them.
I am aware of the many database which hold experimentally determined binding data of protein-ligand structural complexes.
For instance, Binding Moad, Binding DB, PDB-Bind, and SC_PDB are all good for what they are meant to do.
However, they have (1) poor coverage (i.e. not all the complexes have affinity data or they don't include some complexes) and (2) use heterogeneous scores/measures (e.g. IC50, KD, etc...).
This is not the same as this question, since I am looking for comprehensive coverage and computationally determined scores, not experimentally determined ones.


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Why spermatogenesis is an independent process while formation of ovum is dependent on fertilization by sperm?
At the time of ovulation,secondary oocyte is arrested at Metaphase II and goes into the fallopian tube.If fertilization occurs, sperm binds with secondary oocyte and releases Anaphase promoting factor which leads to completion of meiosis II,ovum is formed and it subsequently gets converted into zygote.
My question is that why formation of ovum is dependent on fertilization by sperm and why formation of sperms is independent process? Has it some benefits for nature?

This can only be answered logically. Imagine bellow paragraph.
If secondary oocyte does not require fertilization for completing 2nd meiotic division then it will become an ootid (female gamete). Once formed lots of hormonal changes occur in female example individual's diet increase, mammary glands differentiate and all necessary changes for pregnancy which will be unnecessary at end of every month.
I hope u understood and comment if u want to ask about above imaginary paragraph.

Downvoters do not necessarily need to explain, in part because those explanations often result in rude comments like the one you just posted. Don't do that. You've posted a bunch of answers recently that are below the standards of the site and that's likely why you are getting downvoters. Please improve your answers as suggested by the post notices if you want your answers to be received positively.

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text:
Why haven't environmentally-reactive bodies developed as an evolutionary advantage?
Regardless of region, earth's tilt results in yearly seasonal changes, which organisms deal with through processes like migration/hibernation. Both seem like attempts to avoid the extreme fluctuations... so why haven't certain organisms developed environmentally-reactive bodies, changing with the seasons throughout the year (based on measures like temperature- I.E., additional fur growth during the winter), and why hasn't this continued as an evolutionary advantage to allow organisms to thrive in longer
environmental ranges (like staying in place instead of migrating) or even go a step beyond and take advantage of the qualities specific to each season?

What on Earth makes you think they haven't?  Certainly my dogs & horses grow much thicker coats during the winter, and shed them during the spring.  I believe that's true of many wild animals - e.g. fur trappers think winter pelts are better quality.  Also a number of Arctic animals change color, becoming white during the winter.

@jamesqf it's also true of humans. For example, small capillaries are rerouted away from the skin after spending time in cold weather and back towards it if spending time in the heat.

@jamesqf great information. Can you think of any reasons migration has been favored over more extreme body-variations regarding these seasonal changes? Is there an advantage to moving as opposed to staying put? Most animals are constantly on the move regardless and I assume that's an advantage in survival.

@Taytee: I think (I'm certainly no expert) that it'd mostly be a matter of food supply.  If you're a large grazing animal, in winter your food is dead grass under the snow, so it's economically beneficial to migrate.  (Also migration can be between elevations in mountain ranges.)  Likewise if you're a seed/fruit eating bird, or a nectar-sipping hummingbird. It's easier to go where there's food, than to try to survive a foodless winter.  Same reason bears &c hibernate.

@jamesqf totally makes sense! Animals likely migrated historically due to reasons along those lines, and since those specific species migrated and ended up in an acceptable environment again, it was never beneficial to develop a focus of seasonally-reactive biology. Interesting to note as well that it may be an early sign of animals engaging in a behavioral pattern to solve a problem instead of leaving it up to natural selection.

Hibernation itself is also a pretty good example of an environmentally-reactive physiology. It's not just behavior (sleeping longer), but a huge amount of metabolic and other changes (recycling urine in bears!).  https://en.wikipedia.org/wiki/Hibernation Without that set of body changes, the behavior would be harmful.

What you call environmentally-reactive is called phenotypic plasticity.

You could improve this question if you could give some evidence to support your assumption that this hasn't been favored over things like migration. I am pretty sure that's very simply wrong. I don't have numbers handy, but I would guess most species that live for a year or more have developed precisely the sort of thing you describe. Migration isn't as common as all that (I am ignoring hibernation since it is a perfect example of "environmentally-reactive bodies", pretty much the definition, actually).

This question shouldn't be closed. It has been answered in the comments.

As Jamesqf pointed out, food supply was likely a big contributor. As a general expansion onto that, I believe a sufficiently reasonable answer could be that animals likely found solutions (I.e. migration and hibernation) to deal could with seasonal factors out of their control (like lack of resources) before natural selection leading to more defined adaption could/would've taken place. Their behavior dealt with the problem- which leads to another interesting idea that it could have been an early sign of organisms using their intelligence to survive and change the course of natural selection.

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During the process of plasmid isolation, how can we be sure that only plasmid DNA has been isolated and there is no chromosomal DNA?
We separate the membrane and all other cell components, but how is it that only plasmid DNA is isolated and not chromosomal DNA?

It comes down to the size of genomic DNA (relatively huge) compared to that of plasmid DNA (rather small).
Cell lysis for plasmid extraction involves an alkaline buffer that includes sodium hydroxide and SDS. Both plasmid and genomic DNA denature in this condition. When the alkaline reaction is neutralized with potassium acetate, the fairly short plasmid DNA can quickly re-anneal, while the much longer and more complex genomic DNA tends to become tangled up with itself, which prevents sister strands from properly aligning and often results in protein-DNA binding interactions.
DNA bound to protein will then get pulled down during centrifugation, while soluble plasmid DNA remains in solution.
Qiagen and BiteSize Bio both offer some more description of the process:
https://www.qiagen.com/us/resources/technologies/plasmid-resource-center/key%20steps%20in%20the%20plasmid%20purification%20protocols/
http://bitesizebio.com/1660/plasmid-v-genomic-dna-extractionthe-difference/

It's also important to note that plasmids are cccDNA (covalently closed circular) which means that the two strands will be catenated upon denaturation. Basically, even though the strands are separated, they are still linked together.


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Non-splenic pools of erythrocytes?
In splenectomized animals, where could red blood cells be released from, to explain an increased hematocrit after exercise or muscular contractions?


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How to create a phylogenetic tree (using Maximum Likelihood method) in newick format for a Multiple Sequence Alignment file in FASTA format?
The file size is really big (26.7 MB). So, I am unable to use the online web tools, as they cannot handle such large input data.

Look into IQ-TREE. If you can work with R, I'd recommend phangorn to do the maximum likelihood analysis, and use write.tree() from ape to write the Newick tree(s).

RAxML (Stamatakis, 2014) would be a good place to start.

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What does a wing shake in crickets indicate?
What does it mean when a male cricket (Acheta domesticus) shakes its wings towards another male cricket? Is this an act of aggressiveness?

Could you elaborate a bit what you mean with shaking its wings? You mean chirping?


text:
The actual name of growth force
I see how large trees and weeds that are capable of splitting concrete, and realized that I have no idea what this phenomenon is officially called. Google was no help, suggesting root pressure, but that's an interior force for water and sugar transport, not what I was looking for. Is there a name for the act of plants growing through things like concrete and rocks on their own, independent of weathering?

Why do you think they are all that different?

a plant has the same pressure as 200m of water column in plumbing. that's about 10 times more pressure than a tap you can block with your thumb. it's called plants-popping-through-pavements or phytolithic perforation.

Turgor pressure is the force within the cell that pushes the plasma membrane against the cell wall.
It is also called hydrostatic pressure, the pressure measured by in fluid when at equilibrium.
It's term taught in biology class in school for plants that sag.
I saw a mushroom that had come through a new pavement once. it was cool.
pascal is the atmosphere at sea level:

The pressure inside phloem, the sap in a tree that rises, can be the same as trying to hold shut a hosepipe with your thumb, if the hosepipe water column is 200 meters high. that's why Sequoia trees are only efficient to about 110m high.


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How do rats open a walnut?
What techniques do rats use to open a walnut? What are the traces they leave in nature?
I have a book on traces that wild animals leave in nature, but it only explains squirrels (splitting the walnut in two halves, using their teeth as a lever) and mice (gnawing a hole into the hull of the nut). I am interested in the two common European species of rats, brown rat (Rattus norvegicus) and black rats (Rattus rattus).

In this article targeted at pet owners, it is implied that rats open nuts by gnawing on them (similar to mice, I presume). There don't seem to be scientific studies on the mechanics of how rats open walnuts. However this interesting study did find that consumption of walnuts improves brain function in aged rats, which is fascinating.
Based on this, I would expect the traces left behind in nature to be similar to those of mice, although the gnawed hole would potentially be larger given the relative difference in tooth size between the two groups.


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Extensions of proteins in SARS-CoV-2 variants
What lineages of the coronavirus SARS-CoV-2 occurring in the wild show some extensions, i.e., mutations of the stop codons to codons encoding amino acids (mutations to another stop codon don't count here).
By chance I found that the pango lineage B.1.1.318 has an extension of the accessory protein encoded by ORF7b.
Are there more such cases, and what lineages are affected?

Due to a 15nt deletion around the ORF7b stop codon B.1.1.318 has a merge of ORF7b and ORF8 giving ORF8: MKF 1:3 MIELSLIDFYLCFLAFLLFLVLIMLIIFWFSLELQDHNETCHAY


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Mutation profiles for Corona viruses in non-human hosts
In this question Mutation rate breakdown by original and mutated nucleotide for Coronaviridae mutation profiles for SARS-CoV-2 in humans are given. It is a known fact that mutation profiles are dependent on the host species and it was speculated that the Omicron variant of SARS-CoV-2 evolved at least partly in a non-human host based on its specific mutation profile.
My question is: What are some mutation profiles for SARS-CoV-2 in non-human hosts? All known non-human hosts count.

So, what have you found so far?

@bob1: No published numbers so far, some PCA plots showing different ellipses for mutation profiles for different species is all I have seen yet.

You should add the information you found to the question - prior research helps keep your question from being closed. Note that serial passage in animals in the lab is generally considered "gain of function" research, so won't have been done!

@bob1: There are data from natural occurring outbreak among animals (mink farms and white tailed dear come immediately to my mind), and also infection in other animals show typically mutations specific to that animal (hamsters are the animal model for Covid-19, to mention another species.

I second bob1: add the data to the question and explain why it is inadequate for your purposes within the question.


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Name of human language related gene
I'd like to know the name of a gene with the following description of effects:

Humans having two copies of this gene with a certain mutation aren't able to acquire human language, but otherwise their intelligence is not depressed
The human version of the gene differs significantly from the one found in the great apes
The human version of the gene was transferred to mice, and it was reported that the "voice" and the communication of the so-manipulated mice differs from the one of "wild" mice
If I remember correctly, the gene has the letter "x" in it like hox or pox or pax but alas, memory can be faulty

What is the name of this gene?
Bonus question: What are relevant publications concerning the gene described?

FOXP2? Three scholarly hits and the appropriate wiki entry on first 4 hits on Google. Googling is not difficult, and should really be tried before posting a question here. There's so much information out there! Google is really your friend. :)

@anongoodnurse You could make an answer out of your comment. It could be a 5 letters long answer :)

@Remi.b - lol, really? I'll take you up on that one. Ah, the minimum has beaten me.

Yep. The size does not matter :) See this query listing the shortest (typically two letters) accepted answers.

FOXP2, aka Forkhead box protein P2.


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Obtaining a mapping of RefSeq ACs to Uniprot ACs
I am trying to obtain a mapping for RefSeq Accession Numbers to Uniprot Accession Numbers.
I can write a script to do this for a list of RefSeq ACs like this:
#!/usr/bin/python

"""
Derived from:
  http://www.uniprot.org/help/programmatic_access#id_mapping_python_example
"""

import urllib
import urllib2

url = 'http://www.uniprot.org/mapping/'

params = {
    'from':'P_REFSEQ_AC',
    'to':'ACC',
    'format':'tab',
    'query':'NP_511114.2 NP_004295.2 NP_031465.2 XP_004934106.1',
}

data = urllib.urlencode(params)
request = urllib2.Request(url, data)

# Please set your email address here to help us debug in case of problems.
contact = "email@example.com"
request.add_header('User-Agent', 'Python %s' % contact)
response = urllib2.urlopen(request)
page = response.read(200000)
print page

I am curious if there is a way to request the entire mapping of human genes to proteins.
I have tried to configure a query from the Uniprot resources, but I can't see how to get RefSeq data from this tool.
http://www.uniprot.org/uniprot/?query=reviewed:yes+AND+organism:9606#customize-columns
I am happy to use a resource other than Uniprot.

You can use BioMart. Have a look at this answer.

You have a bunch of options:

You can use Biomart.
Biomart is a standalone tool, but also have a pyton and R libraries. So it gives you more options depending on your preferred programming language. This is a widely used tool and in general works well.

biomart http://www.biomart.org/
biomart python library
biomart R library (from bioconductor)
Biomart is widely used and have extensive documentation.

Use a python library called pyEntrezID
https://pypi.python.org/pypi/pyEntrezId/1.4.7
You can do all sort of conversions of ids, however I've never tried it.
You can try NCBI eutils or one of the Ensembl REST API endpoints


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Can iGEM distribution parts be directly PCR'd?
The iGEM DNA Kit Plate Instructions say that there is only 2-3ng of DNA per well, which is already miniprepped and in plasmids.  Then it says that "there is not enough DNA in each well to perform anything but transformations".
Couldn't PCR be performed on an amount of DNA that small, given appropriate primers?  Is transformation truly the only thing that could be done with that DNA?  If PCR could be done on the DNA, why might they suggest otherwise?

You probably could do PCR on that amount of DNA, but if you screw something up you don't get a second chance. Transforming bacteria and doing a miniprep turns your 3ng into a few micrograms, which is enough to tolerate a few mistakes.

A failed transformation would have the same bad result - no second chance - so that leads to the (obvious?) follow-up question: Is transformation a lot more reliable than PCR?

Transformation with intact plasmids is usually ok. I only have trouble with transformations when ligating a plasmid together. Remember these plasmids have all been transformed into bacteria, grown, and prepped, so they are intact and ready to go back into bacteria.

What's the approximate percentage of success in PCR and in transformation, in your own experience?  Thanks again.

Guessing a percentage is hard, there have been times when ligating a plasmid when I was glad to get 1 colony. If the plasmid was intact I can get a lawn of colonies if I don't remember to dilute the cells. I can't guess a percent for PCR but there are more things that can go wrong, primer design, reaction setup, purification, etc. Transformation has about 1 step, add DNA to cells, much smaller opportunity to fail.

Here is the feedback I got from iGEM HQ:

Yes, we estimate there would be a total of ~3ng (on average) for a part sample in a well, and assuming a suspension with 10ul, there would be more than enough for PCR reactions. However, transformations are recommended over PCRing directly from the kit, because you can now store that part long term in glycerol form and you can prepare more of that part easily.

So the reason to prefer transformation over PCR seems to be long-term storage and future amplification.


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How do we know for sure that Morus nigra (black mulberry) is tetratetracontaploidic (has 44 copies of each of its seven chromosomes)?
This answer to Is there any particular reason to choose strawberries for DNA extraction? explains that strawberries are octoploid. Wikipedia's Polyploidy and Morus nigra; Description both point out that Morus nigra or black mulberry is tetratetracontaploidic and cite two sources that both point to a third source in Plos One; Zheng et al. (2015) Definition of Eight Mulberry Species in the Genus Morus by Internal Transcribed Spacer-Based Phylogeny.
There, Table 1 includes KF784875, M. nigra with Chromosome number (Ploidy) of 308(44)*
So far I have not been able to find the author's meaning for the asterisk following the ploidy value, nor any further sourcing for the assertion of tetratetracontaploidy.
I am supposing that somewhere there will be some actual measurement, either using direct optical/floorescence or electron microscopy imaging or some clever molecular biology that established tetratetracontaploidy, but so far I can't find it.
Question:  How do we know for sure that Morus nigra (black mulberry) is tetratetracontaploidic?

 click for full size

Ref 8 in your linked PLoS article looks relevant; says docosaploid (308), lots of references therein on cytological studies.

@bob1 Yes, the title sounds promising doesn't it! However, I was disappointed after I read it. Perhaps you can find something there that I missed? https://www.jircas.go.jp/en/publication/jarq/18/3/222 Many of the interesting-sounding references in that 1985 paper are in Japanese. When I get to campus this morning I will try to access some of those references and the try to google translate them if they are text (and not images of pages of text).

There's ref 9: Seki H. “Cytological studies on mulberry, Morus. Part I. polyploidy of the mulberry trees, with special reference to spontaneous occurrence of triploid plants.” J. Fac. Textile and Sericulture, Shinsha Uni., Jpn, 20 (1959): 58-60. Can't find the paper yet though

The linked paper in the question has reference 8:

Toyo I (1985) Research of polyploidy and its application in Morus. Japan Agricultural Research Quarterly 18: 222–228. PDF here

This paper mentions a study by Seki in 1959 with the title Cytological studies on mulberry, Morus. Part I. polyploidy of the mulberry trees, with special reference to spontaneous occurrence of triploid plants. I was unable to find this reference in any usable form, but searches for it came across this paper:

Yamanouchi H, Koyama A, Machii H (2017) Nuclear DNA amounts of mulberries (Morus spp.) and related species. Jpn Agric Res Q JARQ 51(4):299–307 PDF here

This paper, along with reference to Seki (though not the one above), contains a couple of further references, one of which is relatively recent:

polyploidy can extend to docosaploidy (2n = 22x = 308) as in M. nigra
(Basavaiah et al. 1990, Darlington & La Cour 1947, Seki & Oshigane 1960).

Basavaiah et al is available online (PDF here) and is a cytological study of Morus nigra, which states:

During anaphase II, 154 chromatids were clearly discernible moving to the
respective poles (Figs. 9 and 10).

and supplies Figs 9 and 10 (screen shot from paper. See full reference below):

Full reference:

Basavaiah et al. (1990) Meiosis in natural decosaploid (22x)
Morus nigra L. Cytologia (Tokyo) 55, 505-509.

I managed to dig out the Seki and Oshigane paper via a Japanese website. The references in the various papers to this paper have the journal as J. Fac. Text. Seric. Shinshu Univ., which it turns out has the full name of Journal of the Faculty of Textiles and Sericulture Shinshu University. This lead me to the University's SOAR page and a text search for the article title (Note the name Morus nigra in the last link on the search) led me to the article itself in PDF form. The article is written in Japanese but has an English summary at the end, with the text:

（1）The chromosome number of the somatic cells of Morus nigra is 2n is 308 and 22x as the basic chromosome number of Morus is 14． This confirmed the reports of Thomas，Darlington and La Cour（1942)．

Seki, H. & Oshigane, K. (1960) Studies in polyploid mulberry
trees. (IV) Cytological and morphological studies on
Morus nigra L. J. Fac. Text. Seric. Shinshu Univ. 10, 7-13

To me this means they are basing the number of chromosomes on the genus as a whole rather than a measurement of the chromosomes in the species itself. You can also view the Darlington and La Cour reference from my first quote at Archive.org (1942 edition) which shows a chromosome spread with n=308 in plate IV(top)

Darlington, C. D. & La Cour, L. F. (1942) In: The handling of
chromosomes (2nd ed.) p92 & plate IV, George Allen and
Unwin, London

For once, the rabbit hole of link to link to link... worked!

That's such a beautiful series of meiosis micrographs in Basavaiah et al. 1990. There's also an archived copy in case that link breaks at some point down the road. Thank you for your successful rabbit hole exploration!

I've just realized this doesn't actually answer the question of n=22 tetratetracontaploidic, looks like it is publications from Janakai Ammal, a widely respected Indian woman cytogeneticist and Seki. I can't access either of the publications online though.

Oh, you mean we need confirmation of the 7 × 44 = 308, whereas the figure caption for Figs 1-6 gives us 14 × 22 = 308 instead? Fourteen chromosomes with 22 copies each? Yikes! Curiouser and curiouser!

@uhoh Yes, confirmation of the actual number of chromosomes, not the copies. The Yamanouchi paper says 2n = 22x=308, so 2n = 14, but confirming that it is actually 14 not 11 or 22 or even 77 (all being factors of 308), unless that number is based on a basal n for the genus. I can see Janakai Ammal working it out through careful analysis, she really was the expert on this at the time.

@uhoh updated with some findings.


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Where does Actino- come from in the genus Actinomycetota?
This comment under Bacteria trapped in crystal inclusions found 'alive' after 50,000 years - what were they eating all that time? links to Quintana, Badillo ann Maldonado (2013) Characterisation of the first actinobacterial group isolated from a Mexican extremophile environment. The term "Actinobacteria" seems to be synonymous with the phylum Actinomycetota.
According to van Bergeijk et al. (2020) Ecology and genomics of Actinobacteria: new concepts for natural product discovery

Actinobacteria constitute a highly diverse bacterial phylum with an unrivalled metabolic versatility. They produce most of the clinically used antibiotics and a plethora of other natural products with medical or agricultural applications. Modern ‘omics’-based technologies have revealed that the genomic potential of Actinobacteria greatly outmatches the known chemical space.

I have found Phylum Actinomycetota:

Etymology: Ac.ti.no.my.ce.to’ta. N.L. masc. n. Actinomyces, type genus of the phylum; L. neut. pl. n. suff. -ota, ending to denote a phylum; N.L. neut. pl. n. Actinomycetota, the Actinomyces phylum

But so far I have not found the origin of the "Actino-" part of the genus name.
Question: Where does Actino- come from in the genus Actinomycetota?
Is it perhaps related to actinide somehow?

This one is easily answered.
The Actino part of is derived from the first described genus in this group; Actinomyces and means "ray" as the formation of a colony has a light-ray-like appearance, as seen in this photo from Wikimedia:

Image attribution: US gov, Public domain, via Wikimedia Commons
Incidentally the "myce" part means "fungus", as it was thought from the appearance of the colonies, which sometimes show mycelia-like formations, that they were fungi, until later proven to be bacteria.

Interesting! So in a way "actino-" is sort-of related to actinides, since they also have rays (of emitted ionizing radiation).

@uhoh Yes, the word is the same. It's Greek and was more commonly used about 100+ years ago in the literature - a lot of early science fiction uses the term actinic.


text:
What is the role of various immune cells in demylinating neuropathy?
Is there a simple description or article of the life cycle of tcells and other immune cells and how they become programmed to attack the myelin of the nerves?
When I try to read through an article like this: http://m.neurology.org/content/56/1/74.full its pretty frustrating. I consider myself fairly technical but not versed in biological systems.

Hi I don't think there is a simple way of describing the way the immune system works. However I'll give it a rough go. The immune system can be broken into two major categories, The innate immune system which does not need to learn about what foreign bodies are and works via physical systems such as the skin and molecular structures on cells such as PAMP-receptors (Pathogen associated mollecular pattern receptors) on Phagocytic cells (such as macrophages, neutrophils, ...) which innately recognize the bad guys which have characteristic non human molecular structures.
The other half of the immune system is called the adaptive immune system in which specialized cells T-cells and B-cells, rearrange their own DNA to create new and varied receptors which are specific for foreign antibodies.
T and B cells work together to recognize different sides(epitopes) of foreign mollecules (foreign peptides) and have to agree that the mollecule is foreign. A process of clonal selection and deletion of T-cells and B-cells in the thymus and bone marrow respectively can sometimes go wrong and this leads to auto-immunity. For example some B-cells which recognize self antigens might escape clonal deletion during their maturation process, and become later (many years ?) activated by a T cell which recognizes an adjuvant (close by aggravating molecule, such as a viral surface molecule).
Once the B-cells matures they can secrete self anti bodies.
Finally the innate and adaptive immune systems work together and shouldn't be thought of as separate. For example the complement system is part of the innate immune system as a molecular cascade amplifying immune system signals and works with both the adaptive and innate systems.
It would help if you can describe the specific type of autoimmune condition that you are investigating as there may be several ways that the immune system can become directed towards self.
There is a great online course from UC IRVINE and whose videos/lectures on the immune system available on youtube, you'll need at least 27 hours of good concentration, the autoimmune lectures are towards the last ones.
https://www.youtube.com/watch?v=gVCfC8WW4eU&list=PLIHnZ4fK_IyJaH2WNHIk2cFsnR2UM4z7t
My understanding is still evolving, however I hope this helps.

Nice answer. Please add some more references for ones who'd want further reading.

Wow - thanks for your answer! I just ran across this message - dont know how I missed it - but thanks!

I should add that I am trying to understand the steps that involve B-cells and why/ what caused the system to attack peripheral nerves. The condition is CIDP which has suddenly afflicted my wife. Perfectly healthy, no strange event, no fever/ sickness or other identifiable issue! Suddenly she start loosing feeling in hand and feet, progressing up the peripherals. Diagnosed as demyelinating by several clinics.


text:
question about fast/slow muscle twitch fibers
Here are my questions (I have several)
1) Are the fast twitch muscle fibers dominant or recessive as opposed to the slow?
2) Are people of mixed race/greatest genetic diversity in their background, tend to be the best athletes and the healthiest in general?
Allow me to clarify the first point:  Obviously no one in the world is either 100% fast twitch or 100% slow twitch.  Let's put this another way:  (and I'm just using random numbers here that are probably unrealistic, bear with me).  Let's say someone who is 80% fast twitch and 20% slow twitch has a baby with someone who is precisely the other way.  Would the child develop more of the fast twitch or more of the slow twitch?


text:
Histology tissue

Can anybody tell me from where is this tissue taken and in with techique is it colored please ?

Welcome to Biology.SE! What research have you done before asking it here?

I might as well be wrong, not being an histologist, but that's probably a classic: mammal liver tissue, (poorly) H&E stained, also showing Kupfer cells having phagocytosed something black (carbon particles from indian ink?).

It looks like a classic HE stain. (https://en.wikipedia.org/wiki/H%26E_stain)
Unfortunately I cannot help with identifying the source of the tissue as you have not specified a organism of origin.

Why did I get down voted? I identified the stain and provided a source. Also I simply pointed out that identification of the source of the tissue may depend on which organism it derives from. Please remember that histology is a broad field and covers both plants and animals! (https://en.wikipedia.org/wiki/Histology)


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What is R.ornitholytica? Is it a misspelling of R.ornithinolytica or a different species?
I'm trying to find out which of these is correct, or whether they are different organisms:
Raoultella ornithinolytica
Raoultella ornitholytica

I have come across both spellings in various articles, papers, etc.  They seem to be used interchangeably, but I'm not sure if they are the same thing, if one is a misspelling of the other, if they are equally acceptable spellings or if they are separate organisms.

I can't really be sure, but NCBI Genbank only "knows" Raoultella ornithinolytica, the variant ornitholytica does not exist there. So I would guess they are not separate organisms.

Thanks. Although this shows two results, I can't find them in the linked documents: https://www.ncbi.nlm.nih.gov/pubmedhealth/?term=%22Raoultella%20ornitholytica%22. I can't find any actual hits in any of the other databases there.

Probably someone misspelled the keywords for some articles including "ornitholytica". Nobody ever proofreads the keywords I guess.


text:
Are tergo-sternal muscles of cockroach involved in blood circulation?
Tergosternal muscles help in the blood circulation in a cockroach as well as in movement of the wings for flying. I came across a question that claims that these muscles are used in blood circulation as well. I can't seem to see a relation between blood circulation and these muscles.

Could you link to the question that you reference? Here's how!

It is not the tergo sternal muscles that are involved in blood circulation in cockroaches. Tergo sternal muscles help in breathing. It is the Alary muscles that help in blood circulation. The alary muscles are associated with all the thireen chambers of cockroach's heart on either side of it. The alternate contraction and relaxation of these muscles help to pump the blood.

Sources which support my answer:

Tergo sternal muscles are involved in respiration, Look into the book "A Dictionary of Entomology" pg 4, link
Alary muscles help in blood circulation, link

Please provide citations/links to the sources you used to help provide some credibility to your answer

@theforestecologist I have included suitable links in support of my answer please check them.


text:
What does "radiographic progression" mean in cancer?
I tried looking up the definition of the term "radiographic progression" using Google and medical dictionary, etc., but I couldn't find its meaning anywhere. All research articles that I found just use it, so I assume it is something common.
Please explain to me what "radiographic progression" means. I really appreciate it.

"Radiographic" refers to imaging modalities like x-rays, CT scans, MRI, etc.
"Progression" in medical terms is referring to progression of disease, where progression means advancing to the next stage, getting worse, etc.
Radiographic progression in the context of cancer would mean that based on X-rays, CT, MRI, etc, the cancer has gotten worse in some way. The exact meaning of progression has to be defined on some rating scale and will differ from study to study. Radiographic progression is not the only way to measure disease progression, other measures can also be used like symptoms experienced.

Thank you very much! I thought that was the case but I couldn't find the definition of the term anywhere so I was very confused.

@Paichu Yeah, I was pretty certain but to verify what I did was to find some journal articles using the term and saw how they defined it operationally, especially in contrast with other methods. I also never found a place where someone said "the definition of radiographic progression is _________" but from context it was easy to infer.


text:
Watering plants with soaked forest soil
I am thinking of mixing forest soil with water and water plants with that.
I was hoping that nutrients from soil would get released into the water, so in effect, fertilize the soil.
I am not sure if this works, since I am not aware in what chemicals P, K, Ca, Mg is "stored" in forest soil. If it is oxides that it should dissolve rapidly.
So, overall, is it beneficial to the plant to water them with water in which forest soil was dispersed?
Plant in question are tomatoes, peppers.

So basically you are trying to make your own liquid fertilizer. You might want to search DIY liquid fertilizer, compost sources are common. A small amount of soil is not going to contain much in the way of nutrients. I also recommend reading up on fertilizing practices and nutrient requirements of the plants in question as fertilizer burn is a real thing and if you are seeking multiple sources of fertilizer you can over do it.

forest soil can be very acidic indeed, its good  for alkaline/clay soils. pond/river silt and dung is much favored. typically place fist of dung beside plant roots to feed them, else mix in 1/4-1/3rd mammal dung depending on its strength/check multiple forest soil pots with tomatoes to see best dose results after 2-3 warm weeks.

I'm voting to close this question as off-topic because it is a better fit for Gardening.SE

You are thinking about something like "compost tea".
http://www.homecompostingmadeeasy.com/composttea.html
The problem is that a random piece of forest soil may or may not be rich in nutrients.  If that soil has water soluble nutrients in it, wouldn't the rain have already rinsed them out?
If you make tea out of compost, there has been no chance for rain to rinse out nutrients because the decomposed stuff has been in your compost bin.
Last piece: if you are making tea out of forest soil or compost, when you are done you will have a soaked clump of wet soil or compost.  What are you going to do with it?  Probably throw it on the ground somewhere.  It might make more sense and be much less messy to skip the tea step, put the forest soil or compost on the ground next to your plants, and then water them.


text:
What type of nutrients can be applied foliarly?
I am interested in what type of nutrients can you spray on plants? Which ones do get used by a plant and which ones make no difference.
By nutrients I mean general fertilisers N,P,K and also micro elements.

Stack exchange has a beta site on Gardening and 'general care and feeding of plants' is on-topic there. I think this is better suited there as the question is framed along the line of Gardening and not Biology.


text:
What is this pollinator's name?
What is the name of this bee pollinating a lemon tree?
Area: south-central Europe


text:
How is breathing involuntary if the muscles that control it are skeletal?
How is breathing involuntary if the muscles that control it are skeletal?  Breathing is involuntary. However, the muscles that control it are skeletal: intercostal muscles and the diaphragm. Are there other muscles involved? Is it that these skeletal muscles are being controlled and/or acting involuntarily?
Humans can both continue to breathe while asleep, and they can also intentionally take a deep breath.
How is breathing be an involuntary act, that can also be controlled?

There are other such muscles on "autopilot". Blinking is both voluntary and involuntary.

Breathing is controlled by both the Autonomic nervous system and the voluntary nervous system. You see this in instances where our breath rate increases in flight or fight situations glide to the secretion of Adrenaline and also when we intentionally increase the breathing rate when undergoing high levels of activity. This is due to the fact that the involuntary aspect of breathing is controlled by the medulla oblongata and the voluntary aspect s controlled by the cerebral cortex. The fact that it is controlled by skeletal muscles has nothing to do with how it is innervated. For example, Cardiac muscles are innervated by both the hearts own conducting system and by the Autonomic nervous system.
If you're wondering why the skeletal muscles dont get fatigued, it's because there is a small but significant rest period between each Breathing cycle (inhalation and exhalation). Therefore the skeletal muscles have a rest period. However if a high rate of breathing does occur for a sustained period, they will fatigue and that's why you get cramps after a marathon or a sprint.

Nice answer! Welcome. :)

I would argue that the problem here is more semantic than biological. We artificially classify processes into "voluntary" and "involuntary", but the reality is much more complicated. For example, is walking voluntary or involuntary? Well, if I decide to go walking, it may initially be voluntarily, but when I am walking, I am doing very little in the way of thinking about walking. Breathing is much the same way. There is BOTH a degree of conscious control from the cortex, and a basal regulatory system in the brain stem that keeps things going below conscious perception. Another way to look at this is that the conscious control from the cortex modulates the medulla based breathing system.

This could be a better answer without the (unrelated imo) philosophizing. "Involuntary breathing" is not semantic. We do it whether we want to or not; the brain will not allow us to forgo that activity. That makes it involuntary, and under the control of the ANS. There are also nerves in the CNS -> diaphragm that allow voluntary control, which can override the ANS to a point, but in the end, it's involuntary. Not semantics at all.


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What does it mean to combine in-solution capture of chosen RAD tags to target sequencing reads to desired loci?
The article about "rapture sequencing" found
here says:

"This protocol also recovers more unique (nonclonal) RAD fragments, which improves both standard RAD and Rapture analysis. Rapture then uses an in-solution capture of chosen RAD tags to target sequencing reads to desired loci. Rapture combines the benefits of both RAD and sequence capture, i.e., very inexpensive and rapid library preparation for many individuals as well as high specificity in the number and location of genomic loci analyzed."

My question is regarding the second sentence. What does it mean to combine in-solution capture of chosen RAD tags to target sequencing reads to desired loci? How do the RAD tags target sequencing reads, if that is what is being said here? How does this relate to combining the benefits of both reduced representation sequencing techniques, or am I missing the crux of the paper?

This method is essentially combining the techniques of RAD sequencing with targeted sequence capture. Both are reduced-representation DNA sequencing techniques, meaning that instead of sequencing all the DNA from a sample, only a portion of the DNA is sequenced. The main advantage is for studies that don't require a completely sequenced genome for every sample, allowing reduced sequencing for many samples and more effectively using limited sequencing capacity.
RAD sequencing reduces the sample genome essentially randomly, though the selection should be similar for closely-related individuals (it's based on the locations of restriction enzyme sites). Targeted sequence capture allows for specific genes or genomic locations to be sequenced, discarding the rest, but this requires some prior knowledge of the locations of interest (it anneals complimentary nucleotides to the region, similar to how PCR primers work).
This method first performs the "random" reduction of RAD, and then from those fragments captures the loci of interest (500 in the referenced article).
The authors claim this makes for easier library prep and cleaner results.


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How do I download entire human genome for local blast formatting and searching?
I'm trying to make a copy of the entire human genome for local blast queries on my machine.  I understand that I need to download it from the NCBI FTP server here...
ftp://ftp.ncbi.nih.gov/genomes/Homo_sapiens
After downloading it I need to format it into a database that blast can search.  I do this using NCBI's makeformatdb command.  It is run like this...
makeblastdb -in entire_human_genome.fasta -dbtype nucl -title human_genome -out human_genome.db

My question is...  Where do I get the fasta file containing the entire human genome?  Do I download the fasta files for all 22 chromosomes, the X chromosome, and then the Y chromosome and concatenate them?  Is there a fasta file on the site containing the entire genome?  A fasta file that is not partitioned by chromosome?

You can either download and concatenate the individual chromosomes from NCBI or make your life easier and download a single fasta file from Gencode (note that that's the primary assembly, if you want the one with haplotypes then it's here).
Having written all of that, the "human_genomic" files on the NCBI FTP server are the prebuilt blast databases for humans.

Just had a look at the prebuilt blast databases you linked to.  I would want the one named "human_genomic_transcript.tar.gz".  That is the largest one at 6.0 GB.  Is this the complete genome?

You probably want the 21 human_genomic.??.tar.gz files. They each contain subsets of the whole database. The human_genomic_transcript.tar.gz file is a superset of that, additionally containing refseq transcripts. See more details here.


text:
Why is ACE 2 located on the Alveolar side of Pulmonary Epithelium?
Location and Purpose of ACE 2.
Given that the primary purpose of the transmembrane enzyme ACE 2 is ostensibly to bind Angiotensin 1 and 2 in order to convert these to derivatives such as Angiotensin [1-7] in the case of AT2, and presuming that this function requires its expression in the endothelial cell membrane on the vascular side of pulmonary alveolar structures and indeed vascular endothelium generally (since Angiotensin 1 and 2 are circulating proteins), then what is its supposed purpose in the membranes of type 2 pneumocytes on the exterior side of alveolar epithelium where, if the presumption is correct, it does not bind AT2, and where it is peculiarly susceptible to destructive binding of the S1 spike protein of the SARS-CoV2 virus?
In the absence of a plausible explanation for that location of ACE 2, it might be possible, for example, to speculate rationally that part of that purpose, teleologically as it were, is in fact to bind that spike protein, in which case one is emboldened to inquire upon a broader evolutionary intention in such a relation between that virus and the human organism, and on the nature of that relation generally.
Part of this inquiry then requires further consideration of the extent to which ACE 2 receptors on the luminal side of vascular endothelium locally in the cardio-pulmonary vasculature and more generally are then implicated in the dissemination of the virus.  Part of this question involves the likelihood that some auto-immunity mediated by cytotoxic T-cells primed by mRNA vaccines to target the S1 spike protein might develop against AT2 itself by virtue of this common affinity for ACE 2; notwithstanding that such an effect has not been demonstrated in clinical trials of such vaccines to date.

I think you will find that just because a particular protein function is required at a particular surface of a cell, it doesn't mean that it is not also found on other cell surfaces...

@bob 1.. Yes, you may be correct; but truly, what is it doing there?  In this case, if the assumption is correct about the definitive function of ACE 2, then the very fact that it is also susceptible to destructive binding by the spike protein should militate against its persistence at such a site, just swinging in the breeze so to say; implying a real evolutionary disadvantage unless some higher consideration is afforded to the role of the coronavirus.  Of course, this requires a view of nature in general as precise and ruthlessly exacting with respect to intention, whatever that may be.

Almost all proteins are multifunctional, ACE-2 has functions in brain biochemistry, inflammation and immunology, cardiovascular... try this paper for basic information

@bob 1. Yes, I've read that paper. All those functions of ACE 2 you mention pertain to its effects on AT2 and AT1.  The issue though is not whether ACE 2 is multifunctional, which no doubt it is, but what its function is on the alveolar side of the pneumocyte membrane where, since it is unlikely to exercise the specific function of binding and modifying AT2, its role is in question. This is not an idle or inconsequential question since it is not outlandish to argue that at least part of its function there may be specifically to bind the SARS-CoV 2, and possibly other coronaviruses; therefore..

... therefore to imagine some useful function for these viruses -- indeed for viruses generally -- within the dynamic of human evolution.  Since this line of thought no doubt requires a challenging philosophical perspective upon reality which may or may not be valid, I would rather find some more concrete and immediate purpose for the ACE 2 at that alveolar site -- which is really why the question is asked.  Bear in mind too that until a few years ago, very little was known about ACE 2, and not much more now.

That paper covers it... it still involves the Ang pathway. There a section Direct Protective Actions of ACE2 on Lung Alveolar Epithelial Cells: ACE2 protects against lung injury by: (a) degrading Ang II, which is vasoconstrictive and proapoptotic for lung epithelial cells (Wang et al., 1999) and profibrotic (Li et al., 2008; Uhal et al., 2011), and (b) by producing the peptide Ang1-7, which inhibits the actions of Ang II through binding to the MAS receptor

@bob 1.  I've read the paper.  The point is that ACE2 can do none of the things you mention if it cannot bind Angiotensin because it is situated on the atmospheric side of the alveolar pneumocyte cell membrane.  Angiotensin 1 and 2 are circulating substances which are bound to ACE 2 on the luminal side of the vascular endothelium.  The question remains: if these assumptions about ACE 2 are correct -- and please correct them if not --, then what is the function of ACE 2 receptors on the atmospheric side of the alveolar cell membrane where it does not bind AT?  The best article I've found is..

.. M. Gheblawi: 'ACE 2: SARS-CoV 2 Receptor and Regulator of RAS', in which some of the physiological functions for ACE 2 to which you alluded are discussed; among which two may be relevant here: [1] the capacity to cleave proteins and [?] to facilitate amino acid transport across cell membranes (as an analogue of 'collectrin'); [2] the capacity to protect against dysbiosis of natural microflora, particularly in the gut but also possibly in the respiratory tract in cases in which such flora exists. Neither of these roles is very convincing however. What might SARS-CoV 2 be doing for us?

CoV-2; nothing, we have absolutely no seroprevalence before the advent of the virus in 2019. Other viruses possibly. Generally though ones which have co-evolved are no longer pathological or much reduced in pathology. ACE2 can do those things if there is some damage to the epithelium as would happen in an infection, releasing AT etc into the interstitial fluid. Check out any ISH staining for an epithelial ion channel and you will see some staining away from the surface on which they are active, despite having massive concs at the "correct" surface...

@bob 1.  Good.  There's probably part of an answer in there, with respect to the problem of interstitial AT which might conceivably be resolved by ACE 2.  I winder too whether ACE 2 is implicated in the reabsorption of the protein constituents of alveolar surfactant by the macrophages of type 2 pneumocytes since it is found in close association with those macrophages. Regarding any evolutionary benefit to humans of CoV-2 infection, it would consist in some facility of adaptation mediated by coronavirus infection generally, presuming that earlier coronaviruses have induced persistence of ACE2.

The problem is that ACE2 isn't the only receptor for CoV. There are a few other ones. MERS uses DPP4, HCOV-NL63 uses ACE2 also, but HCOV-229E uses APN, MHV uses CEACAM. Reasonable summary here

After some fruitful discussion in Comments with 'bob 1', and a review of several articles cited below, the likely answer to the question is that, in spite of the fact that ACE 2 expressed on the atmospheric side of type 2 epithelial pneumocytes cannot in the ordinary circumstance be exposed to circulating Angiotensin [1 or 2], its expression and activity appears to be strongly protective of lung tissue in conditions of inflammation or infection, as these two excerpts attest.  Whether this is due to the mitigating effect of ACE 2 during cell rupture or leakage of Angiotensin 2 into the interstitium or alveolar space is unclear, but would seem likely.
At the same time, as mentioned in the following, the fact that ACE2 has two distinct binding sites at this level suggests that its role is not restricted to that protective function generally; rather, more specifically its very presence as a portal with an allied tissue protective function presumably serves to mitigate the inflammatory effect of binding by SARS-CoViruses themselves, 1 and 2, notwithstanding the destructive effect on ACE2 of that process. This interplay between ACE2 expression and viral load/virulence may help to explain the widely varying clinical impact of COVID-19.
Article 3 further below suggests the manner in which such an interaction between host and virus would have evolved.
[a] Article 1 entitled' ACE 2: SARS-CoV 2 Receptor and Regulator of RAS' (Gheblawi etal.).

Lung epithelial cells express high levels of ACE2, which positively
correlates with airway epithelial differentiation. Involvement of ACE2
in Acute Respiratory Distress Syndrome [ARDS], which is triggered by
multiple diseases including SARS-CoV and SARS-CoV-2, has been
established in multiple animal models. ACE2 Knocked-Out mice exhibit
severe pathology of ARDS.
Additional ACE deficiency, or treatment with AR1R blockers of ACE2 KO
mice rescues them from ARDS implicating the benefit of ACE2 and the
critical balance of the protective versus pro-inflammatory and
fibrotic axes of the Renin-Angiotensin System [RAS]. These findings
are consistent with evidence of a beneficial effect of rhACE2 on
pulmonary blood flow and oxygenation in a pig model of
lipopolysaccharide-induced ARDS.  Age-related loss of ACE2 in the
lungs correlates with the increased mortality and worsened phenotype
in elderly patients with COVID-19.

[b] Direct Protective Actions of ACE2 on Lung Alveolar Epithelial Cells 2 [Article, 'ACE 2, Much More Than Just a Receptor for SARS-CoV2'].

In addition to its protective role in the cardiovascular system, ACE2
has a direct protective role in alveolar epithelial cells. In the
lungs ACE2 has numerous physiological functions, most of which are
protective against lung injury. Similar to the endothelial site, ACE2
degrades the octapeptide Ang II by removing a single amino acid from
the C-terminal end of the peptide to generate the heptapeptide Ang1-7.
Our laboratory and others have shown that ACE2 protects against lung
injury by:  (a) degrading Ang II, which is vasoconstrictive and
proapoptotic for lung epithelial cells (Wang et al., 1999) and
profibrotic (Li et al., 2008; Uhal et al., 2011), and (b) by producing
the peptide Ang1-7, which inhibits the actions of Ang II through
binding to the MAS receptor (Gopallawa and Uhal, 2014).
In support of this protective role for ACE2, pharmaceutical
preparations of recombinant ACE2, when administered to experimental
animals, protect against lung cell death, inhibit acute lung injury
and prevent lung fibrosis after chronic injury to the lungs (Li et
al., 2008; Rey-Parra et al., 2012).
As further evidence, the application of a specific competitive
inhibitor of ACE2, DX600, to primary cultures of isolated ACEs
increases the level of Ang II released into the serum-free culture
medium by autocrine mechanisms, reduces the amount of released Ang1-7
and, importantly, induces apoptosis inhibitable by the AT1 receptor
blocker (Menter et al., 2020). Thus, functional ACE2 normally
expressed by alveolar epithelial cells can be viewed as a critical
survival factor for these lung cells. In addition, the enzymatic
product of ACE2, the Ang1-7, itself protects against lung cells death
by antagonizing that actions of Ang II (le Tran and Forster, 1997).
If Ang1-7 is applied to cultures of lung epithelial cells, it can
prevent lung cell death in response to either Ang II or the ER stress
inducer MG132 (Nguyen and Uhal, 2016). The Ang1-7 receptor MAS and the
JNK-selective phosphatase MKP-2 appear to be critical in this
protective action of Ang1-7 response, because iRNAs or antisense
knockdowns of MAS or MKP-2 can eliminate the ability of Ang1-7 to
prevent lung cell death (Gopallawa and Uhal, 2016). Indeed, Ang1-7
itself and congeners of the peptide, such as cyclic Ang1-7 (Gopallawa
and Uhal, 2016), have already been shown to protect the lungs in
preclinical models of acute lung injury.

However, the not unrelated possibility also remains that since there are two distinct binding sites on the ACE2 found in these alveolar epithelial cells, one of which is the catalytic site implicated in its modifying effects on Angiotensin, and the other, the N-terminal protease domain which specifically binds the spike protein of coronaviruses, SARS-CoV2 in particular, at least part of the role of this binding domain has persisted for the purpose of facilitating entry of coronaviruses, more especially with as little immediate inflammatory damage to the portal as possible.
From the same article mentioned 1, the key observation is as follows;

ACE2 has an extracellular facing N-terminal domain and a C-terminal
transmembrane domain with a cytosolic tail. The N-terminal portion of
the protein contains the claw-like protease domain (PD), while the
C-terminal domain is referred to as the Collectrin-like domain. The
receptor-binding domain (RBD) of SARS-CoV-2 binds with the PD of ACE2,
forming the RBD-PD complex distinct from the ACE2 catalytic site.

This observation may suggest a type of evolutionary symbiosis between coronaviruses generally, SARS-CoV2 in particular, and the human organism which has adapted to permit the entry of those viruses via the N-terminal protease domain which is evidently distinct from the ACE2 catalytic site.  Naturally this sort of speculation presupposes that the role of this protease is not restricted to some ordinary physiological function, such as enhancing reabsorption of surfactant by alveolar macrophages for example.
Here it may be interesting to insert an excerpt from another article 3 from 2012 quoted below and dealing with the original SARS-CoV.
Article 3, 'Evidence for ACE2-Utilising Coronaviruses in SARS in Bats'.

In 2002, severe acute respiratory syndrome (SARS)-coronavirus (CoV)
appeared as a novel human virus with high similarity to bat
coronaviruses. However, while SARS-CoV uses the human
angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry, no
coronavirus isolated from bats appears to use ACE2. Here we show that
signatures of recurrent positive selection in the bat ACE2 gene map
almost perfectly to known SARS-CoV interaction surfaces. Our data
indicate that ACE2 utilization preceded the emergence of SARS-CoV-like
viruses from bats.
Cell-surface receptors often play a key role in defining viral host
range. New diseases can emerge when existing viruses evolve the
ability to bind the ortholog of their cell-surface receptor in a new
species.  Indeed, the principal genetic component defining host range
in coronaviruses is the spike protein on the surface of the virus and,
in particular, its receptor-binding domain (RBD).
It is believed that the severe acute respiratory syndrome (SARS)
epidemic resulted from the zoonotic transmission of a coronavirus from
bats to humans. The central role of the RBD in the SARS-coronavirus
(CoV) zoonosis was crystallized in an experiment in which a bat
coronavirus became infectious in primate cells when it was altered to
contain the RBD of human SARS-CoV.
Over long periods of time, co-evolutionary dynamics can develop
between viruses and their hosts. For example, host populations will
experience natural selection for receptor mutations that reduce virus
interaction affinity, and viruses will, in turn, be selected for
mutations that increase affinity with new receptor variants. This
back-and-forth selection will result in the rapid evolution of both
the host receptor and the virus surface protein.
The protein evolutionary rate can be analyzed by studying the rates of
accumulation of non-synonymous (dN; changing the encoded amino acid)
and synonymous (dS; silent) mutations in the underlying gene. Most
genes retain far fewer non-synonymous mutations than synonymous
mutations (dN/dS ≪ 1) because protein-altering mutations tend to be
deleterious.

These are some further pertinent extracts from the article 1 by M. Gheblawi etal. entitled 'ACE 2: SARS-CoV 2 Receptor and Regulator of RAS'.

Knowledge of the underlying biology and physiology of ACE2
(angiotensin-converting enzyme 2) has accumulated over the last 20
years since its discovery and has provided a major stimulus to further
our understanding of the renin-angiotensin system (RAS).  ACE2 has
distinct roles ranging from catalytic activities with various
substrates, as functional receptors for severe acute respiratory
syndrome coronaviruses (SARS-CoV), and as an amino acid transporter.
ACE2 functions as a master regulator of the RAS mainly by converting
Ang (angiotensin) I and Ang II into Ang 1–9 and Ang 1–7, respectively.
Whereas somatic ACE contains 2 active sites, ACE2 possesses only a
single catalytic domain. Both ACE and ACE2 act as zinc
metallopeptidases but of differing substrate specificities defining
their distinct and counterbalancing roles in the RAS.  Whereas ACE
cleaves C-terminal dipeptide residues from susceptible substrates (a
peptidyl dipeptidase), ACE2 acts as a simple carboxypeptidase able to
hydrolyze Ang I, forming Ang 1–9 and Ang II to Ang 1–7.
ACE2 does not cleave bradykinin, further distinguishing its
specificity from that of ACE while it is also insensitive to
conventional ACE inhibitors. The C-terminal domain of ACE2, which has
no similarity with ACE, is a homolog of a renal protein, collectrin,
which regulates the trafficking of amino acid transporters to the cell
surface, endowing ACE2 with multiple and distinctive physiological
functions. It is the multiplicity of physiological roles that ACE2
plays that has allowed it to be hijacked by SARS-CoV-2 as a receptor.
ACE2 is expressed in the vascular system (endothelial cells, migratory
angiogenic cells, and vascular smooth muscle cells), heart (cardiac
fibroblasts, cardiomyocytes, endothelial cells, pericytes, and
epicardial adipose cells) and kidneys (glomerular endothelial cells,
podocytes and proximal tubule epithelial cells). ACE2 is also
expressed and functions in the local RAS of the liver (cholangiocytes
and hepatocytes), retina (pigmented epithelial cells, rod and cone
photoreceptor cells and Müller glial cells), enterocytes of the
intestines, circumventricular organs of the central nervous system,
upper airway (goblet and ciliated epithelial cells), and alveolar
(Type II) epithelial cells of the lungs and pulmonary vasculature.
The entry of both SARS-CoV and SARS-CoV-2 into cells is facilitated by
the interaction between viral S-protein with extracellular domains of
the transmembrane ACE2 proteins, followed by subsequent
down-regulation of surface ACE2 expression.

From the same article, the following details of intestinal expression of ACE 2 may or may not suggest a similar role in pulmonary epithelium.

ACE2 As a Chaperone Protein for the Amino Acid Transporter, B0AT1
(SLC6A19).
B0AT1 is highly expressed in the intestines and kidneys with function
in the absorption of neutral amino acids. The ACE2-B(0)AT1 complex is
assembled as a dimer of heterodimers, with the collectrin-like domain
of ACE2 mediating homo-dimerization. ACE2 has a RAS-independent
function, regulating intestinal amino acid homeostasis, expression of
antimicrobial peptides, and the gut microbiome.  ACE2 is necessary for
the expression of the Hartnup transporter in the intestine, and the
differential functional association of mutant B(0)AT1 transporters
with ACE2 in the intestine regulates the phenotypic heterogeneity of
human Hartnup disorder.

Evidently ACE2 facing the gut lumen also serves to inhibit dysbiosis, and although it is considered unlikely by researchers to exert any corresponding function in the generally aseptic lower respiratory tract, it may play some such role in the upper tract.  Altogether, it is an extremely interesting enzyme, a zinc metallo-enzyme no less, whose importance is yet to be fully appreciated.

Nice synthesis of the current research. Looks like it could be an interesting PhD topic for someone. BTW, you might want to format the excerpts as blockquotes to make it more clear which bits are from papers and your comments.


text:
Speed of Brain Waves
Given that brain waves are characterised as such by virtue of the wave-like properties of 'electrical activity' in the brain, what is the speed of such waves; and how does it differ from neural conduction rates in peripheral nerves ordinarily in the range ~50 cm/sec.  (Oddly I have had difficulty locating an answer to this question elsewhere).

It of course quite depends on which waves you are studying. One cool recent example from the Sejnowski group at the Salk Institute show these circular brain waves occurring during sleep, which complete within ~70msec travelling a loop of ~30cm... http://www.salk.edu/news-release/princess-leia-brainwaves-help-sleeping-brain-store-memories/ (Original paper: https://elifesciences.org/articles/17267)

Consider the simple case of 'alpha waves', with a frequency ~8-12 Hz.  What is the speed of propagation within the brain and presumably in its 'white matter'?.

@jeremiah See the answer by baca - when people refer to "brain waves" they are talking about oscillations in a recording, they are wave-like in time, not necessarily space. If they travel in space, too, that's a separate property.

@jeremiah That's right, as baca and Bryan have explained, these 'alpha waves' to which you refer are activities within a frequency band recorded from collective ensembles of neurons (e.g via EEG) where these oscillations might indicate a degree of coherence in a population.  The circular brain wave I mentioned above I thought was one of the better examples of a wave I could find (in a more normal sense of the word) where excitation spreads through space and a speed could theoretically be calculated.

Excellent and very helpful answers.  My interest is more in the spatial aspect, or I suppose, the co-ordinated relation in sequential activity between or within areas of the cerebrum--but is at this stage still ill-informed.  The implication of pyramidal cells seems interesting.

@jeremiah Yes, the coordination of waves throughout the brain is fascinating. You asked a good question and I wish I could have provided you with more well-studied examples.


text:
Carbohydrates- D-Glucose & L-glucose , alpha and beta
What's the difference between D-glucose & L-glucose ?
Yes , I know that L-glucose is an isomer of D-glucose . But what differences do they have ? They are the same , they are glucose .
Similarly for alpha and beta glucose ?
Sorry I just started learning on carbohydrates and I'm a little confused about these 2.

Welcome to Biology.SE! What research have you done before asking it here?

They are not the same. Because they are enantiomers, they do not have the same shape. Because they do not have the same shape, enzymes in metabolism that have evolved to use D-glucose cannot work on L-glucose.
L-glucose is not synthesized by organisms because life on earth shares a lineage using the R-enantiomer, so organisms don't encounter it, so there is effectively zero selective pressure to evolve the ability to metabolize L-glucose.
For alpha and beta glucose, see this question on Chemistry.SE; those terms refer to anomer forms of glucose that can interconvert in solution. Given enough time, glucose and similar molecules in solution will form an uneven but consistent ratio of alpha and beta forms.


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Non competitive inhibitors and Uncompetitive
Non competitive inhibitors affects the function of enzymes and slows the rate of reaction. Can I say the same for uncompetitive inhibitors ? Because Vmax decreases and it takes longer to form products .
However when I plot the graph both gradients needs to be the same ? So I'm a little confuse here to whether for uncompetitive inhibitors, it does affect the function of enzymes and slow down the rate of reaction .

I am not really sure to understand completely your question, but both non competitive and uncompetitive inhibitors affect the rate (Vmax) of the reaction by decrease it. In fact in both case, the enzyme (E) takes longer to transform the substrates (S) in to products (or to release it).
To better allow you understand I put below two mechanism of action for uncompetitive inhibition and non competitive inhibition.
Uncompetitive inhibition

Uncompetitive inhibition is unique in that the inhibitor binds to the enzyme-substrate complex. This could imply that the binding site for the inhibitor is accessible only after the enzyme has bound to its substrate. This reduction in the effective concentration of the E-S complex increases the enzyme's apparent affinity for the substrate through Le Chatelier's principle (Km is lowered) and decreases the maximum enzyme activity (Vmax), as it takes longer for the substrate or product to leave the active site.

Non competitive inhibition

Non-competitive inhibition models a system where the inhibitor and the substrate may both be bound to the enzyme at any given time. When both the substrate and the inhibitor are bound, the enzyme-substrate-inhibitor complex cannot form product and can only be converted back to the enzyme-substrate complex or the enzyme-inhibitor complex [...]
This type of inhibition reduces the maximum rate of a chemical reaction without changing the apparent binding affinity of the catalyst for the substrate.

Hope this could help.


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Uncompetitive inhibitors
In Uncompetitive inhibitors , the Km decrease .
With uncompetitive inhibitors , the affinity of the enzyme for the substrate (E+S) increases .
I've searched up on the net and it says that the substrate has now been taken up to form E-S and E-S-I , therefore consuming more substrate than the original inhibitor-free equilibrium .
E + S -> ES (equilibrium position shifts to the right)
I've read up on all these and more doubts form in me .
Why is substrate needed to form ESI ?
I understood what it meant by equilibrium position will shift to the right . It is harder to form E + P as more substrate will form ESI.
Thanks !

u should add the link where u read that the substrate is required for the intermediate complex formation otherwise the question is unclear.

An uncom-petitive inhibitor doesn't compete with the natural substrate of the enzyme for active site i.e. it binds at a site distinct
from the substrate active site and binds to the $ES$ complex.

$K_I$ is the equilibrium constant for inhibitor binding to $E$ and $K_I^{'}$ is the equilibrium con-
stant for inhibitor binding to $ES$. Uncompetetive inhibitor lowers the value of $V_{max}$ and $K_m$.


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In SDS-PAGE, why are the sample buffer and running buffer different in concentration?
I'm currently trying to understand the concepts of SDS-PAGE. Every protocol I've read says to use 5X for sample buffer and 1X for running buffer, but I don't really understand for what reason? What are the negative consequences if I don't?

Please give the composition of your buffers. You can't expect us to know what they are and if we don't we can't give an answer to your question that is of use to anybody.

The reason why the sample buffer is more concentrated (typically 2x or 5x depending on your protein concentration) is its dilution when you mix it with the sample. You mix 4 parts of your sample and 1 part of 5x sample buffer, so that the final concentration of this buffer is 1x.
If you use 1x sample buffer together with the same amount of sample, the final concentration of the sample buffer would be 0.5x, if you do the same 4+1, it would only be 0.2x in the end.
This dilution is too strong and the buffer will not fulfill its purpose, the complete denaturation of all proteins in the sample, so that their distribution on the gel depends only on their molecular weight and not also on their tertiary/quarternary structure.
Using a 5x buffer allows you to add a lot of sample when diluting it to 1x without changing the concentration of the protein too much. It also allows to load larger amounts of sample compared to 2x buffer, interesting when the protein concentration is low.
The running buffer is not further diluted by adding sample, so that it has to be diluted to 1x in order to have the right ionic strength. Since these are often used in big quantities in the lab, it is more convenient to prepare concentrated buffers in smaller quantities and dilute them before usage than preparing big tanks of buffer.

Worth adding that the reason for using e.g. 5x sample buffer is so that the sample can be brought to 1x without greatly increasing sample volume and thus decreasing protein concentration. In many situations you may want to load as much of your sample protein as possible in the well.

@AlanBoyd Good point. I do this often but don't think too much about it anymore :-)


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why should someone study mRNAs instead of miRNAs as a biomarker
why should someone study mRNAs instead of miRNAs as a biomarker from liquid cell-free biopsy like from exosomes? Is it wrong to do it? Does it offer you something different? Thank you in advance

What do you think? Have you looked anywhere for pros and cons? Can you add that information to your question/rationale?


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Phagocytosis and bacteria
Invading Bacteria are phagocytosed by phagocytes. Phagocytes are specialised white cells. But, if a non-phagocyte cells are infected with bacteria how those cells handle this situation? Do they succumb to the bacteria?

For cells to become infected with bacteria, some bacteria will still be present in the blood. These are still engulfed by phagocytes in the same fashion. However once engulfed the antigens on the surface of the Bacteria are placed on the surface of the phagocyte, this is known as an antigen presenting cell (APC). Specialized lymphocytes known as Th Cells bind to these antigens and then divide. These then stimulate Cytotoxic T cells which secrete a chemical known as perforin. The perforin makes holes on the membrane of 'non-phagocyte' infected cells allowing water to enter. This essentially causes the cell and the bacteria to explode, known as cell lysis.
So basically the infected cell is simply destroyed unless hydrolytic enzymes break down the Bacteria.


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Internal organs temperature
We know body surface temperature rises during fevers. Do the internal organs' temperature also rise during fevers? How do they (internal organs) maintain their temperature? Will there be a variance of temperature among them?


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Cortisol and inflammation
Cortisol is released under stressful condition. It is known to have anti-inflammatory role. In fact it is used as potent anti-inflammatory drug also.
Though stressful conditions are unwanted and unfavorable, the body's response to such conditions by releasing cortisol, seems to be beneficial only.
If so, why cortisol is considered as undesirable and dangerous?


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Renal threshold for glucose
Wikipedia in its article on 'Glycosuria' says that the renal threshold for glucose (RTG) reabsorption in the kidney is around 160-180 mg/dL. Beyond which the glucose starts to excrete in the urine. But in diabetic people blood glucose exceeds in range of 300-400 mg/dL is prevalent. How this is possible? What prevents the the excretion of excess glucose into urine?
Does it mean more glucose is reabsorbed in the nephrons above its threshold limit? Also, as the glucose is co-transported with sodium, does it mean that glucose reabsorption is tightly coupled with sodium reabsorption? Does sodium play any role in crossing the glucose threshold limit?
Or is it possible that the excess glucose (beyond RTG) is actually excreted out of blood in the kidney but the hyperglycemia is caused by the fresh gluconeogenesis of the body?
Or is it possible that both these mechanisms (RTG is exceeded as well as fresh gluconeogenesis) cause in furthering the hyperglycemia?
Is it possible to measure this state?
Thanks in advance.

Classic symptoms of untreated diabetes include excessive thirst and urination, and glycosuria. Think about the solute gradient. At some arbitrary number the level of glucose becomes saturated. The kidneys are forced to get rid of the extra glucose in urine. This increases the concentration of solutes in the urine, so where does the water go? Right? So that high blood glucose concentration translates into frequent trips to the bathroom, and frequent need to consume fluids. This can also lead to a fluid/electrolyte imbalance, which is potentially dangerous.
There's actually a limit to what can be reabsorbed, denoted the transport maximum,
but, you can only eliminate so much solute over time, so here's a figure from a Pearson physiology chapter:

Source
You've got your renal threshold around that 180 mg/dL but look at that excretion kinetic. It's known that the excretion rate increases linearly with the filtration rate above the renal threshold (ref). So say i'm an average male with 400 mg/dL plasma glucose and 50 dL of blood or 20 g of net plasma glucose. All other things held equal, it looks like it could take around 2 hours to clear that glucose on excretion alone, which doesn't typically happen. Clearance is also outlined in that Pearson chapter, and you can measure that by knowing the excretion rate, and the concentration of glucose in the urine and in the plasma.
Data shows, however, that the filtration/reabsorbtion process is maladapted in a diabetes model, and increased plasma glucose levels are maintained by an up-regulation in glucose transporters (thus an increase in the transport maximum), and an increase in the renal threshold (and thus the kidneys only begin to excrete glucose at a significantly higher level) (ref).


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Could humans choose to establish fibre digesting colonies in our guts?
Humans don't digest fibre, and nor do any animals, but some creatures have micro-organisms (bacteria, I'm guessing) in their gut which digest fibre for them.  My question is, could humans take some sort of pill and establish our own fibre-digesting colonies in our intestines?  Has this been tried?  Supposing it could be done, would you suppose it would have any negative effects on our health?  (i.e.. would those whose gut digested fibre for them be stuck on a low-fibre diet?).
Purpose of question: just wondering.  It would be cool to be able to eat bark.

Go ahead and eat it - not taking nutrients from something doesn't mean you can't eat it :P

Related: https://biology.stackexchange.com/q/59205/24354

Probably not without some substantial evolution to change our physiology, depending on what you are wanting.  If you just want to digest fibre, that might be done, but if you wanted to see nutritional value out of it, its not clear that's going to be worth it..
Soluable fibre is currently used by the human body, so you are probably be asking about insoluble fibre.
It might be possible to do a little of this experimentation - I'm not recommending this - but there would be several likely issues depending on your goals in such a project, which could vary.

the human gut microenvironment probably will not accommodate the bacteria you need and they might not grow in significant quantity.
the human gut is not physiologically arranged for digesting such fibre - ungulates generally have four stomach chambers that they can use to store some of the hard for the longer time it takes to break the fibre down.
the nutritional value of plant fibre is low XKCD has some numbers on this and a cow can eat 10kg of plant matter a day and in doing so they don't tend to move that much.  Humans have to eat a greater volume of vegetables to get the calories they need.  Is getting that last 2-5% or so of the energy from digesting fibre worth the trouble? Eat one more apple or a handful of grain.

Lastly, there would likely be some impact on human health - if you succeed then you would be modifying fibre's role in human diet as it stands - which is to help keep the intestines cleaned out.

Just to add something to the answer from @shigeta - even assuming that you did manage to establish a gut microbiome that was capable of metabolising fibre, this wouldn't be a source of glucose: in ruminants the gut bacteria ferment the sugars released from the cellulose, releasing short chain fatty acids (a.k.a. volatile fatty acids,  e.g. propionic acid).
These compounds are used to fuel gluconeogenesis in the liver of the animal: in  a lactating cow this can amount to kilograms of glucose synthesised per day. Although you wouldn't be aiming to eat that much fibre, the release of these VFAs into your bloodstream might still cause some metabolic problems.


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What the difference between an inverted and everted retina?
I'm looking specifically for examples and comparisons, because the definitions of inverted and everted are remarkably similar; e.g. from Dictionary.com/Reference.com:

everted
  verb (used with object)
  to turn outward or inside out.

http://dictionary.reference.com/browse/everted
vs. (esp. #5)

inverted
  verb (used with object)
  1. to turn upside down.
  2. to reverse in position, order, direction, or relationship.
  3. to turn or change to the opposite or contrary, as in nature, bearing, or effect: to invert a process.
  4. to turn inward or back upon itself.
  5. to turn inside out.

http://dictionary.reference.com/browse/inverted
I'm curious because of this:

Structurally, the cephalopod eye differs from the vertebrate eye.
  Cephalopods do not have a cornea, and the retina is everted so that
  the distal end of photoreceptive cells lies directly behind the lens
  and points toward incoming light. As a result, photoreceptor cells
  connect to the optic nerve behind the retina (Packard 1972).

From: Evolution: Education and Outreach
October 2008, Volume 1, Issue 4, pp 439-447
http://link.springer.com/article/10.1007%2Fs12052-008-0084-1
http://link.springer.com/article/10.1007%2Fs12052-008-0084-1/fulltext.html
via
https://en.wikipedia.org/wiki/Cephalopod#cite_note-Serb2008-12

If you have the rep please tag this with cephalopod; the tag doesn't exist and I don't have enough rep to create it. Thanks.

Based on your title and description, all that means is that in vertebrates the retina is inverted in a sense that light sensing cells sit at the back of the retina meaning light has to pass through layers of neurons and capillaries before reaching light sensing cells, whereas cephalopod has the photoreceptors at the front side of the retina, with processing neurons and capillaries behind them hence retina is everted i.e. inside out. See this page (http://en.wikipedia.org/wiki/Retina) under "In other animals" section.
Hope this helps!

Oh, of course.  After re-reading this, it's actually very clear.  Also very interesting in the diagram was concerning the optical cavity vs. the cornea & lens; really "opens" the possibilities for "getting something in your eye"!


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Human female chest model or data representation?
I am looking for professionally used representation of female chest (I know how it sounds ;). Generally - a model comprehensive enough to effectively represent human chest, with focus on breasts.
The data it needs to represent are at least: width, height, depth, distance between cardinal points, so on. I do know there's a questionnaire for patients willing to undergo an implant operation - I'm looking around for something similiar. Optimally the model would be directed towards computer represenation.
With that in mind, I've checked some computer implementations:

SOFA (seems promising, but somewhat generic),
MakeHuman (nice
customization, but again, pretty general).

I do not know whether this question is in scope of this site. If it's too specific, then consider the simplified: what are the methods used to describe female chests OR what would be a good source of information about these methods?

@leonardo, for exactly that - to export it to DICOM for radiotherapists.


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How to incorporate size data with shape in stereographic morphometrics?
This may be an extremely simple point that I am missing, but how are you supposed to know the exact size of a structure being analyzed in three dimensions? When doing two dimensional morphometrics, you simply have a scale bar with your image. I know that microCT and some other methods may do this automatically, but some are now using free software like 123D Catch from Autodesk to create mesh models. In this case, are you strictly restricted to shape independent of size? If not, how do you add in a 3D scale bar, so to speak?

A cube of known dimensions in your field of view would suffice.

But can I then set the scale in these programs just as I would using a 2D ruler? How does the actual calibration occur with the object in view? None of the programs I've looked at using (tps, landmark, R, etc...) seem to have a way to do this.


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Retrieve the associated annotation from Uniprot
I have a dataset that I extracted using Cytoscape and STRINGAPI
Hoz can I retreive the annotation of that network from uniprot  as it has more than 1k proteins . and doing it manually is not possible

Do you want anything specific from the annotation?

not really but it should contain the name the associated id , function maybe ...

You can upload your list of accession numbers to the batch retrieval service for the UniProt Konwledgebase, http://www.uniprot.org/uploadlists
A video tutorial for this service is available at https://www.youtube.com/watch?v=kLdgjqWoMZc
Once you have retrieved your proteins, you can click on "Columns" to customize your output and add columns, e.g. for function annotation. See also http://www.uniprot.org/help/customize or http://insideuniprot.blogspot.ch/2015_03_01_archive.html
Results can then be downloaded in tab-separated format.
If you have any additional questions, please don't hesitate to contact the UniProt helpdesk.


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Cytoscape export network
I'm using Cytoscape to visualise a ppi network having 2000 proteins ... I m trying to export it but the supported format are only cytoscype formats not a usable ones
and for the table format the network is separatted , I don't find it explorable .
How to I export that network in format convertable to csv . or csv so that I can use it in a tool supporting only csv  file format format

The SIF network format produces an edgelist. If you have attributes attached to nodes or edges then you'll need to export in xgmml, graphml or xml and then parse from there.


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Biogrid interaction protein network
I need a ppi network for cancer or Alzheimer .
I'm using BioGrid , In the search field I can specify the gene id only ,
I want to know how can I make an interaction network for one of the disease ? the only condition is the network ought to be huge , 3k 2k proteins .
I had used IntAct , String but none seem to give me what I'm looking for
If not could anyone give me a direct download link of such network


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Stringdb using R Bioconductor package
I need to retreive a large dataset from String-db.
I 'm newbie in R so even with the documentation , I could not get the dataset fron String
How do I do to retreive a network from String 2k to 3k proteins
what are the functions  to use for such matter  ?

I think this question belongs to [SO]

String uses REST API, although the link to the help page for that results in a blank page instead (contact the authors!). In general, I would use the API. Alternatively, just download the database locally, they have a quite neat collection ready to be downloaded

If I donwload it locally  , I can retreive 200k proteins ? and download the network I need right ?

Correct. Check the download page, they have different "packets" download the one you are interested in.

Okay I'm downloading the first packet in the interaction data section  for homosapien. What I don't get is that how am I going to use it ?  how would I know the proteins or the specific network for cacaner ?

It has 11353057 interaction , I have no Idea how to get only cancer network ?

You need to have list of protein you are interested in. There is no shuch a thing like a "cancer network" you may find different databases online, like the COSMIC, that lists genes found to be linked with cancer. You can start there. But this goes beyond your question.

Now I have alist of proteins of interest how do I proceed ? Is there any tool I can use to gget the 200k I need

If don't know how to start then please take time to study and try out. This forum is not meant to ask other people to do your job. One thing is if you have a particular question,  but you are asking to solve a rather complex bio information problem without knowing the basics. Now you have a database and a list of proteins of interest. Write down what is that you want to know about them and use the database to answer your questions. If you don't know how to do that than step back and start studying how to query a database with R.

Well thank you for clarifications, Actually I did and I used R to retreive neighbors , which got me 5827 mapping identifier, with 3916 interaction. yet I need more like 200k  mapping identifier to work with . and I have no clue how to proceed as the resources are so limited down there

Try ask on https://www.biostars.org It's specific for bioinformatics.