Confusion about the construction of the rat's mental map I'm reading the article "A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology" by Y. Dabaghian, F. Mémoli, L. Frank, G. Carlsson

I try to understand the following graph:

In part a) of the graph, we are seeing a bunch of colored points. These points are in the hippocampus of the rat as opposed to the idea that these points are in the plane on which the rat is moving, and so each point is a place cell of the hippocampus that has fired at some moment in some place of the plane on which the rat is moving. Normally there is a huge number of points in this picture but we chose to put only those who fired, those who did not fire are deleted from the picture of part a). Also, each point (which means each place cell) has one color, and two place cells having the same color designate that the two place cells are considered identical and will be treated as a single place cell in the part b) of the figure.

In part b), we record the time at which each point has fired, with each point being represented by a bar on the time axis and all the bars are identical (same height, and same thickness).

In part c) the picture is in the plane on which the rat is moving as opposed to the idea that the picture of part c) is in the hippocampus of the rat. In part c) we are trying to derive the place fields from part b). Deriving the place fields means here that we are deriving the path that the rat has taken. In particular, place fields are in the plane on which the rat is moving and not in the hippocampus, and each place field in the plane is determined by seeing which place cells in the hippocampus has fired at that area of the plane.

Is my understanding correct? I'm not a specialist but I need to understand each detail of this graph because my work depends on it. My confusion comes from the fact that there are two regions here: the hippocampus of the rat and the plane on which the rat is moving and I need to be sure in which region the picture is.

You have a couple small misunderstandings that I think are making it hard to understand the figure. There is no map of the hippocampus pictured here!

1) Note: this is a schematic figure. These aren't real data, although there are real data that show this pattern. This is meant to be an easy to understand diagram that explains how place cells work.

2) Panel (a) is EXTERNAL SPACE. Essentially it's a "top down" view of a floor that the rat is running around on.

3) Panel (b) shows spike trains for three different cells: theses cells have been arbitrarily color-coded. The hash shows the times that cells 1, 2, or 3 fired spikes. There are just three cells shown in this figure: there aren't any combinations of cells considered one color or multiple cells in one color, just three cells and three colors.

4) Panel (a) is showing how researchers have connected spiking data, like in (b), to the animal's location. The procedure is this:

Start with a blank map of space.
Record from Cell 1. Every time cell 1 fires, mark a blue dot in panel (a) indicating where the animal was when Cell 1 fired.
Record from Cell 2. Every time cell 2 fires, mark a green dot in panel (a).
Record from Cell 3. Every time cell 3 fires, mark a red dot in panel (a).
(the previous steps could be done for many more than 3 cells simultaneously or in sequence; in this example they are just using 3 cells)

5) Panel (c) is in world space, just like in panel (a), and it shows a hypothesized way that the animal could be using the activity of cells 1, 2, and 3 to determine where it is in space. A researcher recording from cells 1, 2, and 3 could also use those recordings to make a guess of where the animal is. If only cell 3 fires within some window of time (an appropriate window is indicated by the outlined ovals in (b) ), and cells 1 and 2 do not, then the best guess is that the animal is in the upper left area that's shaded only red. If all three cells fire, then the best guess is that the animal is in the very center overlapped region of space.

The dashed line shows a hypothetical path the animal might take through it's environment. If the animal took this path, we'd expect to see place cells firing just like they did in panel (b): first only the blue cell, then blue+green, then all three, then red+green, and finally red only.

6) Very importantly: the animal has way way more cells encoding place than just these three. It would be really confusing to plot them all out in discriminable colors like these, but it is this more complex map with thousands of dimensions that gives the animal a good internal representation of its current location.

Hope this helps!


Asymmetric volcano plot Nearly all volcano plot I've seen tend to be roughly symmetric around the y-axis, with a fairly equal number of up- and down-regulated genes. What are the potential reasons for a volcano plot that is heavily unbalanced (i.e., many more negative fold change genes than positive)?

In my analysis, I have identified two populations of patients within a disease cohort, representing the "interferon high" and "interferon low" sub-populations. I then calculate differential expression between these groups, and visualize the results with a volcano plot (log(p-value) of differential expression vs. log(fold change)). The volcano plot is quite asymmetric, with a maximum log2 fold change of 1 on the positive end, and a minimum log2 fold change of -3 on the negative end, with many more genes significantly down-regulated in the IFN-low population.

Is it reasonable to suppose that there are lots of genes up-regulated in IFN-high, with no down-regulated genes defining this population, or is there something else going on?

I have no experience on mammalian expression analysis but I have seen these asymmetric plots quite a few times when cells were highly stressed. During one treatment they shut down protein biosynthesis and photosynthesis so downregulated genes vastly outnumbered the few genes which were involved in the adaptation response. I don't know if something similar could be happening in your samples?


Principle of 16 S rRNA technique for bacteria identification Why do we isolate DNA not RNA in 16 S rRNA technique for bacteria identification?

There are several reasons some of which are fairly obvious:

The most obvious reason is that PCR only works with DNA, because it uses DNA-dependent DNA-polymerase. One can argue that you can use an RNA-dependent RNA-polymerase, but it has several drawbacks, mainly the cost and synthesis accuracy (Lauring et al., 2013, Nature). Since RNA-polymerase itself has higher error rates than DNA-polymerase (Berg et al., Biochemestry 5th edition, 2002) RNA transcripts might already have some variation from the original gene and using a low-fidelity polymerase in PCR will only lead to exponential error accumulation, which reduces identification resolution.
RNA is less stable in aqueous solutions due to the additional -OH group at the 2' position in the ribose, hence RNA extraction and storage is more complicated and expensive in most cases.
In community studies DNA and RNA have different biological implications, hence metagenomics and metatranscriptomics are different fields.


How do white Caladiums perform enough photosynthesis to support their mass? In some white caladiums, there is less than a square inch of green space spread over the whole leaf. How do these plants perform the photosynthesis necessary to support the large leaves, the roots, the flowers, and build a corm?

There are many different kinds of plants that have independently evolved this sort of variegation (non-green areas) in the leaves. However, the mechanisms by which they effect this vary between species.

Some have little or no chlorophyll in the non-green areas, but many others have changed the architecture of their leaf cell layers in the non-green areas, creating refraction effects that make the leaves appear white, but don't significantly change their photosynthetic efficiency (Sheue et al.) In fact, Arum italicum white areas actually have higher efficiency in certain light conditions! (La Rocca et al.)

I can't find any information on which type of variegation Caladium shows. The genus Caladium is related to the Arum I mentioned above which uses the "architecture" method, but it's also related to Epipremnum, which seems to use the "no-cholorophyl" method.

Sheue et al. mention that with some species that use the architecture method, using transmitted light instead of reflected light reveals that the white spots are actually green; while in no-chlorophyll plants the spots remain white. If you have a Caladium around, you could try holding its leaf up to a bright light, and see!

So, to answer your question: if Caladium is an 'architecture-variegation' plant, its white areas perform photosynthesis at or near the efficiency of the green areas of the leaf. If it's a 'no-chlorophyll-variegation' plant, it would have reduced efficiency, but might make up for this with strategies including:

Having a larger total leaf area (La Rocca et al. and also see this question)
Only developing large white areas if there's plenty of light as they grow (Garland et al.)
Increasing the mitochondrial activity in its white areas, which could lead to other energy efficiencies (Toshoji et al.)
Using Homo sapiens to help it reproduce and provide plenty of light for it. Many of these extreme variegation patterns are found in horticulturally bred varieties!
Just using its green areas for photosynthesis, and "accepting" the fact that the white areas are not producing energy. In natural populations, you often don't find varieties as completely white as in that picture: they usually show white spots and plenty of green. This is true of Caladium species in the wild, which may use the variegation to mimic and to prevent herbivory: potential pests think the leaves are already infested, and avoid them (Soltau et al.). In other words, even if the white patches represent decreased photosynthesis efficiency, it could be a trade-off in order to achieve less herbivory.

Garland KF, Burnett SE, Stack LB, Zhang D. 2010. Minimum Daily Light Integral for Growing High-quality Coleus. HortTechnology 20: 929–933.
 La Rocca NN, Rascio NN, Pupillo PP. 2011. Variegation in Arum italicum leaves. A structural-functional study. Plant Physiol Biochem 49: 1392–1398.
 Sheue C-RC, Pao S-HS, Chien L-FL, Chesson PP, Peng C-IC. 2012. Natural foliar variegation without costs? The case of Begonia. Ann Bot 109: 1065–1074.
 Soltau U, Dötterl S, Liede-Schumann S. 2009. Leaf variegation in Caladium steudneriifolium (Araceae): a case of mimicry? Evolutionary Ecology 23: 503–512.
 Toshoji HH, Katsumata TT, Takusagawa MM, Yusa YY, Sakai AA. 2012. Effects of chloroplast dysfunction on mitochondria: white sectors in variegated leaves have higher mitochondrial DNA levels and lower dark respiration rates than green sectors. Protoplasma 249: 805–817.


How do nutrients get to the cells they need to get to? I understand the basics of digestion. I know that nutrients get absorbed by the microvilli, enter the bloodstream and travel to the liver but after all that, what is the biological mechanism that guides these nutrients to the proper receiving location?

Broadly speaking, nutrients that enter the blood from the gut, and those that are released into the blood by the liver, are available to any cells that require them. So there is no "guiding to the correct location" in the sense that you suggest.

Lipids for example are present in the various lipoproteins and can be acquired from these by all cells. Iron is bound to transferrin, and any cell with transferrin receptors can internalise the transferrin and take the iron. Glucose is available in solution in the plasma, and free fatty acids are bound to serum albumin in the blood. During starvation the liver produces ketones ("ketone bodies") which are taken up by many different tissues/cell types.


How do I name a binding antibody? “Binding antibody to”, “binding antibody against”, or “anti-[antigen] binding antibody”? I'm translating a text that describes how an immunogenicity of a drug is measured by assaying the levels of binding antibodies to the drug. Or is it "against the drug"? I'm wondering how to name these antibodies. Let's say the drug is cetuximab, and I'm writing the title of a document section:

  Assay of binding antibodies against cetuximab in serum.
  Assay of binding antibodies to cetuximab in serum.
  Assay of anti-cetuximab binding antibodies in serum.

I googled for "binding antibodies to" and "binding antibodies against" and got only several dozen results for each of the two options. Therefore I came up with "anti-[name of the antigen] binding antibodies", but don't know how to google for it, hence my question here. Would option 3 look nice to a native speaker?

P.S. Alas, it is exactly "binding antibodies to" in my Russian text. I cannot omit the adjective "binding" before "antibodies"..

  Связывающие антитела к цетуксимабу.

I quote from the Wikipedia page on neutralizing antibodies:

  Most antibodies work by binding to an antigen, signaling to a white blood cell that this antigen has been targeted, after which the antigen is processed and consequently destroyed. The difference between neutralizing antibodies and binding antibodies is that neutralizing antibodies neutralize the biological effects of the antigen, while binding antibodies flag antigens.

My authors use the adjective "binding" to distinguish binding antibodies from neutralizing antibodies, just like in this paper, for instance: BAbs and NAbs. Another section in my document gives the results of an assay of NAbs against the same antigen.

Explanation of the difference between binding and neutralizing antibodies from the FDA:

(ADA: anti-drug antibodies)

The adjective “binding” is not used to qualify “antibody” in English scientific usage because linguistically it is thought to belong with the antigen the antibody binds.

Generally it is omitted if the prefix “anti” is used, e.g.

  anti-cetuximab antibody

(e.g. “two or more anti-hapten antibodies” here)

However if you wish to refer to the particular small portion of the antigen that is recognized (the epitope), you might write, e.g.

  tyrosine-binding antibody

(e.g. “Hapten‐binding antibodies…” here)

As far as the use of prepositions is concerned, “to” is used with binding, although it is optional. However generally with the antigen, e g.

  cetuximab binds to the antibody

(e.g. “Antigen binds to the antibody on the B-cell membrane.” here)

But

  the antibody binds cetuximab

(e.g. “An additional VNAR, Help6, which binds Hepatitis B precore protein” here.)

Completely illogical, I know, and this distinction is not universal.

However, “against” is used in relation to preparing or raising antibodies, e.g.

  We raised an antibody against cetuximab…

(See the legend to Fig 1. in this paper.)

So in general one would write:

  Assay of anti-cetuximab antibodies in serum

Addendum: Binding antibodies v. Neutralizing antibodies

The revised question makes it clear that the authors are referring to “binding antibodies” as a specific contrast to “neutralizing antibodies”. This expression was not known to me (I am not an immunologist), and, although the poster documents it, its use would appear to be limited, perhaps because the topic is or was controversial.

The question remains, how to express this idea in a clear and unambiguous manner, with the specific problem that the poster is a translator, not an editor. I would still try to avoid the use of the word “binding” in the expression. I have two suggestions:

I believe that an alternative expression would be “non-neutralizing antibody” (the paper just quoted does not hyphenate this term, but others do, and I would). If this belief is correct, one could write:

  Assay of non-neutralizing anti-cetuximab antibodies in serum

Alternatively one could use the abbreviation, “BAb”, from the paper cited by the poster, although this would have to be defined somewhere.

  Assay of anti-cetuximab BAbs in serum


How does frame-shift mutation not absolutely ruin the organism? I'm a bit curious as to how frame-shift mutation works. If you shift one amino acid towards another. How does this not affect the entire chromosome? Wouldn't this mean that the organism would be absolutely "scrambled" as it would essentially be "missing" a whole chromosome...Or having a chromosome that did all kinds of wrong things at least?

Thanks.

First of all, for a frame shift mutation to occur nucleotides (not amino acids) are either deleted or inserted into the sequence.  Read about details on this wiki page. Here's an image about frame shifts.

On panel A a new stop codon is formed  (TAG is trasncribed to UAG that is serves as stop codon during translation) thus the result is an abnormally short protein.

On panel B the codon 37 is swapped to a G thus the TA from the codon 38 is shifted left by two resulting in the new codon GTA.

On panel C exactly 3 nuleotides are deleted thus codon boundaries do not change, but a codon and the amino acid encoded by it is completely deleted.

On panel D 4 bases are deleted thus the T form codon 171 and the C from 172 are merged with the G from 170.

source: the linked wiki page.

It does not affect the choromosome in the way you describe because genes are separated and are independently transcribed (with some simplification). Every gene has its own translation  start that determines the correct frame in that gene If you think of a chormosome as a chapter of a book and the genes are paragraphs, you can see that deleting letters or words may scrable one paragraph, but the others are not affected by this because they have their own boundaries.

EDIT:
During translation the ribosome reads the mRNA in the form of triplets. When a single nucleotide is deleted then the whole sequence from that point shifts to the left by one thus the first letter of the subsequent triplet gets mixed into the frame where the mutation happened (the same goes for insertion but the sequence is shifted to the right). This causes the change in the meaning of the triplet, and can ruin stop codons that would affect the translation of the mRNA but not the transcription of the gene to mRNA.It is important to understand that transcription is a countinous process and the DNA is transcribed from base to base not in triplets, and that transcriptions stop is not encoded in the from of stop codon.


When running gels what is the difference between constant volts or constant amps? In general, you want to be consistent with running your gels either at constant volts or constant amps. However, it is very clear that during the progression of both PAGE and agarose gels, the free parameter changes due to the change in resistance of the gel.

While there are safety reasons why you run one vs. the other, I'm curious how these difference affect the migration of your gel.

I'll answer only for SDS-Page, which is the system I am most familiar with.

With a discontinuous buffer system, such as the well-known Laemmli system, resistance increases during electrophoresis, as (very mobile) chloride ions are replaced by glycinate (glycine ions).

From Ohms law:

  Voltage (V) = Current (I)  x Resistance (R)

and the definition of power (Watts):

  Watts (W) = Current (I) x Voltage (V) = I2 x R

At constant current electrophoresis will proceed at a uniform rate, however, as the resistance increases, so too will the voltage and the amount of heat generated.

In some discontinuous buffer systems, such as the Tricine/SDS system due to Schägger & von Jagow, this may be enough to crack the gel plates!

At constant voltage, the current will decrease during electrophoresis; as a result less heat will be generated than constant current electrophoresis, but the rate of migration of the sample will decrease with the decrease in current.

References

Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685. [PubMed]

Schägger, H. & von Jagow, G (1987).
Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem 166, 368-379.[PubMed]


Why might you NOT observe a tradeoff between two life-history traits? I have traditionally thought of and heard about life-history traits (e.g., size at first reproduction, number of offspring, size of offspring, survival, etc., etc.) as drawing from a finite pool of resources that an organism has, and therefore exhibiting tradeoffs. So, for instance, an organism that invests in a lot of offspring would experience a decreased probability of survival.

It has recently come to my attention that this is not always the case, and I'm not sure why. I have been directed to the work of David Houle, who wrote extensively on the topic of life-history traits, but some of his work is inaccessible to me intellectually. I was hoping that somebody had a more digestible explanation or was maybe more familiar with Houle's work.

The simple explanation is that there are three (or more) traits drawing from the pool, and you're only looking for trade-offs between two of them. The unobserved third may show the effect of a trade-off.


How many allele for one gene are found inside our cell? I know it depends on phase. So i am talking of -

1) in human (diploid organism) with cells before prophase (before replication, when 23 pair of homologous chromosomes are present ). I think answer is 2 if we not consider male XY sex chromosome because they are not homologous in which case the answer should be 1. But then i get confuse why genotype is shown like Tt (doesnt this means two alleles per chromosome).

2) in gamete cell. I think the answer should be 1.

Please tell if i'm correct.

In short. Yes.

Each diploid cell has 23 pairs of chromosomes (22 of which autosomal)

In relation to the genotype part of the question. The "Tt" refers to each allele on the chromosome and wether it is dominant or recessive. Take for instance, hair colour. On one chromosome, there would be an allele from one parent and on the other an allele from the other parent. This is why two letters are needed, to show the allele given by each parent.

You can think of dominant and recessive in terms of how powerful the copy of the gene(allele) is. An allele that is able to overpower and mask traits is called dominant, one that is not strong and cannot mask traits is called recessive. This is why you need two recessive alleles for recessive disorders, otherwise the dominant allele would cover it up.

As this is a homework question I have tried to explain this in simple terms which you should understand. Hope this helps.


To what extent is immature eggs in insects (beetles) a good approximation for maximum fecundity? To what extent is the number of immature eggs from dissected, newly emerged individuals a reasonable approximation for maximum/potential fecundity in insects (more specifically beetles)? I know that many species must feed for the eggs to become mature and viable. However, can a comparison between species on immature eggs still be used to capture the range of maximum fecundity between species or to accurately rank species from low---high fecundity?

There are a number of things to clarify here; Fecundity is the number of offspring that is produced by an individual, and this can be separated into potential fecundity (maximum reproductive capacity) and realized fecundity (number of offspring actually produced). Realized fecundity is very similar to fertility, which is defined as the number of viable offspring that are produced.

Potential fecundity can sometimes be a good proxy for future fertility, and this is especially true for species where all eggs are present after metamorphosis of the adult insect (Awmack & Leather, 2002). However, in some species the formation of eggs is a continuous process in adult individuals, and this is relatively common in beetles. Therefore, the number of immature eggs might be a poor proxy of both potential and realized fecundity in these species (Awmack & Leather, 2002), and this is more likely in relatively long-lived species that feed extensively as adults. In beetle species that do not feed as adults (often lacking functional mouthparts), immature eggs is probably a better approximation of potential fecundity.

It should also be mentioned that the quality of host plants will often affect the maturation of eggs (Sterns & Smith, 1960; Hopkins & Ekbom, 1999), and will therefore also determine to what extent the number of immature eggs is a good indication of potential fecundity. When feeding on poor quality hosts eggs may e.g. be reabsorbed by females to use for other purposes (see references in Awmack & Leather, 2002 & Hopkins & Ekbom, 1999 for further information).

The review paper by Awmack & Leather, 2002 is very comprehensive, and contains a wealth of useful references on this topic.


How do infants get their very first gut bacteria? First of all, I'm a complete layman in Biology. Recently I read "The evidence for evolution" by Richard Dawkins. Pondering about this matter, I wondered about the origin of human gut bacteria (could be more generalized to mammal gut bacteria).

Generally, I see two possibilities:

These bacteria are

acquired later on through the environment (probably after birth) or
they are produced by the organism itself

The former option seems to me a little bit too vulnerable to be true (different food, different bacteria due to geographical location, etc.)

The latter option seems baffling to me. Bacteria are, as far as I know, independent lifeforms. Is it possible, that our DNA contains the information for other lifeforms as well?

Well, the former is exclusively the answer. Humans (or other mammals, or any species in general) cannot give birth to new species (of bacteria, here); they have to be acquired from the environment at all costs. However, the environment does vary, leading to variance in gut microbiome, as will be discussed later.
First of all, gut microbiome is only a part of the total microbiome of humans (Sherwood et al, 2013). Now, usually, gut bacteria are acquired by a person within one to two years of birth (Sommer et al, 2013), while the gut of a fetus is considered as sterile. However, microbial colonization in a fetus is possible (Matamoros et al, 2013). For example, species of Lactobacillus and Bifidobacterium were found in biopsies of placenta in one study (Mueller et al, 2017).
During birth and rapidly thereafter, bacteria from the mother and the surrounding environment colonize the infant's gut. Infants born by caesarean section may also be exposed to their mothers' microflora, but the initial exposure is most likely to be from the surrounding environment such as the air, other infants, and the nursing staff, which serve as vectors for transfer. During the first year of life, the composition of the gut flora is generally simple and it changes a great deal with time and is not the same across individuals (Sommer et al, 2013).
Now lets talk about variation in gut microbiome among individuals. The gut microbiome of an individual may vary depend mainly due to:

Age:  the diversity of microbiota composition of fecal samples is significantly higher in adults than in children, although interpersonal differences are higher in children than in adults. Much of the maturation of microbiota into an adult-like configuration happens during the three first years of life.
As the microbiome composition changes, so does the composition of bacterial proteins produced in the gut. In adult microbiomes, a high prevalence of enzymes involved in fermentation, methanogenesis and the metabolism of arginine, glutamate, aspartate and lysine have been found. In contrast, in infant microbiomes the dominant enzymes are involved in cysteine metabolism and fermentation pathways (Yatsunenko et al, 2012).

Diet: Gut microflora is mainly composed of Prevotella, Bacteroides, and Ruminococcus. There is an association between the concentration of each microbial community and diet. Prevotella is related to carbohydrates and simple sugars, while Bacteroides is associated with proteins, amino acids, and saturated fats. Specialist microbes that break down mucin, survive on their host's carbohydrate excretions. One enterotype will dominate depending on the diet. Altering the diet will result in a corresponding change in the numbers of species (Wu et al, 2011).

Geography: In simple terms, gut microbiome composition depends on the geographic origin of populations. For example, the US population has a high representation of enzymes encoding the degradation of glutamine and enzymes involved in vitamin and lipoic acid biosynthesis; whereas Malawi and Amerindian populations have a high representation of enzymes encoding glutamate synthase and they also have an overrepresentation of $\alpha$-amylase in their microbiomes. As the US population has a diet richer in fats than Amerindian or Malawian populations which have a corn-rich diet, the diet is probably a main determinant of gut bacterial composition (Yatsunenko et al, 2012).
Further studies have indicated a large difference in the composition of microbiota between European and rural African children. The fecal bacteria of children from Florence were compared to that of children from the small rural village of Boulpon in Burkina Faso. The diet of a typical child living in this village is largely lacking in fats and animal proteins and rich in polysaccharides and plant proteins. The fecal bacteria of European children was dominated by Firmicutes and showed a marked reduction in biodiversity, while the fecal bacteria of the Boulpon children was dominated by Bacteroidetes. The increased biodiversity and different composition of gut flora in African populations may aid in the digestion of normally indigestible plant polysaccharides and also may result in a reduced incidence of non-infectious colonic diseases (de Filippo et al, 2010).

Also, as @com.prehens.ible says in comments, there are various other modes through which an infant may acquire bacteria to give rise to their gut microbiome. For more information, you can also read the Wikipedia page on Gut Flora.
References:

Sherwood, Linda; Willey, Joanne; Woolverton, Christopher (2013). Prescott's Microbiology (9th ed.). New York: McGraw Hill. pp. 713–721. ISBN 9780073402406.

Sommer F, Bäckhed F (2013). "The gut microbiota—masters of host development and physiology". Nat Rev Microbiol. 11 (4): 227–38. PMID 23435359.

Matamoros S; et al. (2013). "Development of intestinal microbiota in infants and its impact on health.". Trends Microbiol. 21 (4): 167–73. PMID 23332725. doi:10.1016/j.tim.2012.12.001.

Mueller, Noel T.; Bakacs, Elizabeth; Combellick, Joan; Grigoryan, Zoya; Dominguez-Bello, Maria G. (2017-04-08). "The infant microbiome development: mom matters". Trends in molecular medicine. 21 (2): 109–117. ISSN 1471-4914. PMC 4464665 . PMID 25578246. doi:10.1016/j.molmed.2014.12.002.

Yatsunenko, T.; Rey, F. E.; Manary, M. J.; Trehan, I.; Dominguez-Bello, M. G.; Contreras, M.; Magris, M.; Hidalgo, G.; Baldassano, R. N.; Anokhin, A. P.; Heath, A. C.; Warner, B.; Reeder, J.; Kuczynski, J.; Caporaso, J. G.; Lozupone, C. A.; Lauber, C.; Clemente, J. C.; Knights, D.; Knight, R.; Gordon, J. I. (2012). "Human gut microbiome viewed across age and geography". Nature. 486 (7402): 222–227. Bibcode:2012Natur.486..222Y. PMC 3376388 . PMID 22699611. doi:10.1038/nature11053.

Wu, G. D.; Chen, J.; Hoffmann, C.; Bittinger, K.; Chen, Y.-Y.; Keilbaugh, S. A.; Bewtra, M.; Knights, D.; Walters, W. A.; Knight, R.; Sinha, R.; Gilroy, E.; Gupta, K.; Baldassano, R.; Nessel, L.; Li, H.; Bushman, F. D.; Lewis, J. D. (2011). "Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes". Science. 334 (6052): 105–8. Bibcode:2011Sci...334..105W. PMC 3368382 . PMID 21885731. doi:10.1126/science.1208344.

De Filippo, C.; Cavalieri, D.; Di Paola, M.; Ramazzotti, M.; Poullet, J. B.; Massart, S.; Collini, S.; Pieraccini, G.; Lionetti, P. (2010). "Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa". Proc. Natl. Acad. Sci. U.S.A. 107 (33): 14691–14696. Bibcode:2010PNAS..10714691D. PMC 2930426 . PMID 20679230. doi:10.1073/pnas.1005963107.


How does population stability evolve? The number of individuals constituting a population is called population size.  Over time population size does not remain constant, it fluctuates to different extent over generations because of several internal and external factors.  Populations with violent fluctuation in population size are called unstable and are more prone to extinction as they hit lower population sizes frequently.  And once a population in extinct, it is gone for ever.  Thus it would be interesting to investigate how population stability evolves.

I guess you meant the population size stability.

It is considered that the biosystems will increase their capacity of adaptation when evolving in very fluctuating environments. I believe the population stability is embedded in the adaptability of individuals.

There is a measurement about it, evolvability, when the environment changes, the faster the population adapted to the new environment, the higher evolvability it has. This means that if the population has higher evolvability then the population may be more stable to environmental variation.

Even so, there might be plenty of underlying mechanisms to enable a certain population stability. I recently read a paper about two mechanism: phenotypic switching and sensing machinery, which are common in bacteria and fungi. Please refer to Edo Kussell and Stanislas Leibler's science paper (2005).

As the organism increase its complexity, biosystems invented many more tools to make the individual survival from disasters. Such as human's intelligence. Well it would be an endless issue.


Reason for variation in the site of onset of edema What is the reason for the observed clinical difference in the earliest site of onset of edema in cases of different etiologies?

For example, in Congestive Heart Failure, it appears initially as pedal edema (edema of the dependent portions, in general) but in nephrotic syndrome (or other kidney causes) appears first as periorbital edema?

In both these cases, since the onset of edema is distal to the organ of the original pathology, it must be a systemic hematological effect caused secondary to the pathology that causes this specific pattern (as opposed to a localized portal hypertension in liver disorders initially appearing as ascites). Although all of these may progress to anasarca, what determines the specific pattern observed?

We should first recall how plasma (intravascular) fluids moves to the extravascular space. It can be approximated by Starling equation. Briefly:

  The rate at which fluid is filtered across vascular endothelium (transendothelial filtration) is determined by the sum of two outward forces: capillary pressure ($P_c$) and interstitial protein osmotic pressure ($\pi _{i}$), and two absorptive forces: plasma protein osmotic pressure ($\pi _{p}$) and interstitial pressure ($P_i$).

See more: Starling equation

Primary edema localisation depends on the underlying pathophysiological mechanism that disturb the balance between aforementioned forces pushing fluid outside the vessels. Whether the Starling forces are alerted globally or locally, how long the edema develops etc.

Example from Harisson's Principles of Internal Medicine (I recommend the whole section regarding the edema):

  Edema due to an increase in capillary pressure may result from an elevation of venous pressure caused by obstruction to venous and/ or lymphatic drainage. An increase in capillary pressure may be generalized, as occurs in heart failure, or it may be localized to one extremity when venous pressure is elevated due to unilateral thrombophlebitis.

In Congestive Heart Failure edema usually appears in places, where intravascular hydrostatic pressure is the highest. When the individual walks it is typically seen as ankle swelling, when the individual lies down, it is lumbar region edema.
While there is a decrease in osmotic pressure (like in nephrotic syndrome), the fluid moves toward extracellular tissues of relatively "loose"  structure (so for example periorbital region).

What is important, in some medical condition (eg. renal failure) different mechanisms may coexists and change the clinical picture.


Why is human vision restricted to 400-700 nm? Across the electromagnetic spectrum, 400-700 nm is a narrow spectrum of frequencies and focused in the region of short wavelengths. For example, radio waves cover a large range of frequencies unexploited by the visual system. So what biological reason is there that evolved us to use such a small frequency bandwidth for vision?

Short answer
The visible spectrum has the highest energy in sunlight at the earth's surface, explaining the gross location of the visible spectrum in life on earth. The specific frequency range varies across species and can be explained by species-specific survival strategies.

Background
When you look at the solar light spectrum at the earth's surface the visible spectrum has the highest intensity (fig. 1).

Solar irradiation. Source: University of California.

So it makes sense to use the range of frequencies that is represented most in sunlight as a starting point.

Then the question becomes, why do humans utilize approximately 400 to 700 nm, and not infrared or UV? That can be explained because we do not need it. Our range has been hypothesized to be related to foraging behaviors and our visual system is particularly sensitive in the frequency range of the coloring of (ripe) fruits, which is thought to have been of great benefit to our hominid ancestors (Osorio & Vorobyev, 1996).

Why then do animals extend their vision into UV? Many fish, amphibian, reptilian, avian, and some mammalian species use UV vision. Many birds can identify UV-reflected nectar and berries, and UV-reflecting plumages in birds, and scales in fishes are used for recognition (Shi & Yokoyama, 2003). Moreover, some arthropod species are know to use UV vision to reduce light-reflection distortions under water, such as in the mantis shrimp that features 12 photoreceptor types (as opposed to four in humans) (Thoen et al., 2014).

Why then do animals extend their dynamic range into the infrared? A notable beneficial effect of perceiving infrared is the detection of body heat. The generation of heat is accompanied by the generation of infrared light. The detection of this emitted light is highly useful for nocturnal predators, like the rattle snake (Hartline & Newman, 1982).

References
- Hartline & Newman, Sci Am (1982); 246(3): 116-27
- Osorio & Vorobyev, Proc Roc Soc B (1996); 263(1370)
- Shi & Yokoyama, PNAS (2003); 100(142003): 8308-13
- Thoen et al., Science (2014); 343(6169): 411-3

Further Reading
1. Is our color vision calibrated to sky, vegetation, and blood?
2. Is there a physical reason for colors to be located in a very narrow band of the EM spectrum?


How is sweetness measured? Some time ago, I read in a newspaper--though I can't recall the details--a list of (mostly artificial) sweeteners and a list comparing how many times sweeter each was than sugar. How is relative sweetness quantified? Is there a standard method?

Response of the gustatory receptor neurons can be measured using standard electrophysiological techniques, under different conditions(exposure to substances). For example see this article.

However, it is difficult to say if a person feels sweetness or not or how the substance produces complex taste perceptions in some people.


Growing bacterial culture on gelatin I'm very new to experimental biology and don't know much about it. So, i was looking to grow some bacteria in petri dishes and looked up how to do it. Unfortunately, I'm finding it difficult to get my hands on the 'agar-agar' required to make the culture medium. So, is it possible to use any other alternative which would give the same results? Like for example regular gelatin?

My school lab teachers have also shown little to no interest in helping me with my project, so I'm on my own here. Any tips would be greatly appreciated!

You can use Gelatin - actually this was used by microbiologists before agar came in use. That gelatin is more or less completely abandoned in this field tells quite a story, right?

Gelatin has the main disadvantage that it cannot be autoclaved together with the medium to sterilize it. Using it would need some experience and probably advanced techniques to which you have no access.
But there are some good news as well: Agar is also used as a geling agent when making food, and when you cannot find it in your local supermarket, Amazon can deliver it. You don't need much, around 15 gram/litre.


What is the smallest oligocelluar organism? What is the smallest oligocelluar organism?

How many cells does it have?

EDIT

The question is motivated by this comment@Philosophy.SE

EDIT as recommended in comments

I'm looking for an example of an organism made of very few (the fewer, the better) sister cells (obtained by mitosis or aggregation) that are morphologically and functionally different. I would accept examples of species that exist in different "conformation" (unicellular and multicellular).

The classic example, though I am sure there are others that are smaller, is the slime mold Dictyostelium discoideum:

It can have up to 100,000 cells and exists as both single cells and as a multicellular organism (emphasis mine):

  Dictyostelium amoebae grow as separate, independent cells but interact to form multicellular structures when challenged by adverse conditions such as starvation. Up to 100,000 cells signal each other by releasing the chemoattractant cAMP and aggregate together by chemotaxis to form a mound that is surrounded by an extracellular matrix. This mechanism for generating a multicellular organism differs radically from the early steps of metazoan embryogenesis. However, subsequent processes depend on cell-cell communication in both Dictyostelium and metazoans. Many of the underlying molecular and cellular processes appear to have arisen in primitive precursor cells and to have remained fundamentally unchanged throughout evolution. Basic processes of development such as differential cell sorting, pattern formation, stimulus-induced gene expression, and cell-type regulation are common to Dictyostelium and metazoans.


How do enhancers induce transcription? DNA response elements are DNA sequences that are could be found upstream, downstream of genes that regulate gene expression at the transcriptional level.

One type -Enhancers- bind specific transcription factors called activators, this binding leads to the bending of DNA, bringing the otherwise distal enhancer near the promoter region of the gene, leading to induced transcription.

My question is:

  How and by what mechanism do enhancers induce and increase transcription rates? i.e how does the interaction between the activators and the transcription complex, increase transcription rates?

The activators are proteins that bind to specific DNA sequences in the enhancer region. These activators also bind to the RNA polymerase and other associated members of the transcription complex, which makes it more likely for an RNA polymerase to hang around the promoter sequence of the region it enhances.

This in turn increases the chance of the gene being transcribed.

It's basically a little magnet that sucks in the RNA polymerase and then nudges it towards the promoter.


Estimation of tissue-partition coefficients and clearance for liposomic nanoparticles I am working on developing a PBPK model for liposomic nanoparticles used to deliver drugs to fells in the bloodstream. However, I do not have any in vivo data or in vitro data. Given only chemical and physical properties like pKa or the octanol-water partition coefficient, how can a get a relatively accurate estimate of the tissue:blood partition coefficient, as well as the renal & metabolic clearance?

Regarding the tissue partition coefficient, Li et al. said:  "By using such a parameter, it is assumed that there is the same transfer kinetics of nanoparticles from blood into tissues as from tissues back into blood circulation, and an equilibrium of concentrations between blood and tissue exists. These assumptions may not be appropriate for nanoparticles."

Physiologically Based Pharmacokinetic Modeling of Nanoparticles
Mingguang Li, Khuloud T. Al-Jamal, Kostas Kostarelos, and Joshua Reineke
ACS Nano 2010 4 (11), 6303-6317
DOI: 10.1021/nn1018818

However if you are set on using a tissue:blood partition coefficient (Kp), Yun and Edginton have done a review of 6 in silico methods for determining Kp for small molecules.  You may be able to extrapolate to nanoparticles.

Yun, Y.E., Cotton, C.A. & Edginton, A.N. J Pharmacokinet Pharmacodyn (2014) 41: 1. doi:10.1007/s10928-013-9342-0

Finally, if you are looking for data to help determine a partition coefficient, there is an excellent review of liposomal doxorubicin pharmacokinetic data in animals and humans here.

Gabizon, A., Shmeeda, H. & Barenholz, Y. Clin Pharmacokinet (2003) 42: 419. doi:10.2165/00003088-200342050-00002


How does transcription end? In rho-dependent termination in prokaryotes, how does RNA polymerase “know” that it has reached the end of a gene and that it has to stop so that the rho-factor can bind mRNA’s rut site? Is there a termination sequence on the template DNA that “signals” the end of a gene?

And consequently, how does the rho-factor “know” when to bind to mRNA?... how does rho-factor recognize that the RNA polymerase has stopped so it can start its ATPase activity to dissociate the transcription complex from DNA and release the mRNA?

Termination  of  the synthesis of  the RNA molecule in bacteria is also signaled by  a sequence in the template  strand of the DNA molecule.
This sequence of nucleotide in the template strand is the RNA polymerase pause site. When the RNAP continues its transcription it reaches this site and pauses it's transcription activity over here. The longevity of this pause can also be affected by various factors like high $Mg^{2+}$ ions in some cases.

Meanwhile, rho factor which after binding to rut-site, continues it's translocation along the mRNA (supposing mRNA is synthesized here) in 5'-3' direction using its ATPase activity. The rho factor utilises this opportunity when RNAP has paused it's transcription activity at the RNAP pause site to reach this ternary transcription elongation complex. When it had reached this complex it starts it's ATP dependent helicase activity which separates the RNA-DNA hybrid helix, causing the release of the mRNA.


Biology view on trait variability In reading the annotated Origin... I have come to the following note by Costa on p. 168:

  Again, modern biologists would disagree with Darwin's idea that especially well-developed traits vary to a greater degree than expected simply because they have been varying and undergoing selection in the past (as evidence by their considerable development)...

I am not sure I understand what the problem with Darwin's view is. From reading his work I understood that he, Darwin, is simply saying that traits that have been more recently acted on by natural selection would vary more than those that have been acted in the past and over a longer period of time (given that conditions remain relatively the same - I assume).

What is the modern view of biologists on this?

P.S. The excerpt to which this side note refers, follows:

  In these remarks we have referred to special parts or organs being still variable, because they have recently varied and thus come to differ; but we have also seen in the second Chapter that the same principle applies to the whole individual; for in a district where many species of any genus are found - that is, where there has been much former variation and differentiation, or where the manufactory of new specific forms has been actively at work - there, on an average, we now find most varieties or incipient species.

The variance of a trait's allele frequency can follow different trends over time depending on several factors such as whether one or several of the alleles are consistently selected for or the population dynamics. For example Disruptive Selection will tend to increase the allele variance. On the other hand Directional selection, or Stabilizing selection will tend to decrease variance by driving the allele frequency to one side of the distribution (in the first case) or by "cutting down" its sides in the second case. It is true that stabilizing and directional selection processes are more common especially under relatively stable environments. Therefore for the majority of cases, during the first phase of selection for a trait variance will most commonly decrease . This, however, is not a rule.
There are additional, rare, but from an evolutionary point of view extremely important cases where allele frequency variance can see a sudden "ballooning". Consider for example the case of selection processes after mass extinction events. Then, because of the sudden availability of previously occupied niches, genetic drift due to small population sizes as well as changed conditions the previously stabilized traits will start...well...drifting. The same is true for almost any circumstances that will destabilize equilibrium and lead to speciation.


Why do left and right eyes can require different power of lenses? Both the eyes almost see the same things throughout our life. It is not like we use one eye more than other that it should become weaker. What causes requirement for different power of lenses for both eyes? Shouldn’t they be same?

Because we have two hands, two feet, two ears, etc., we are tempted to think that we are perfectly symmetrical.  But if you compare the details of your two hands, for example, you will find that the blood vessels are in somewhat different positions, the lines in your palms are different, and the fingerprints of corresponding fingers are different.  The same is true of your eyes: they differ from each other.  These kinds of differences are due to the fact that genetic instructions relating to symmetry during embryo development are not exact; they are approximate.

Probably if you measure the size of the biceps on each arm, or the size of the forearm muscles, you'll find that they are slightly different.  This is partially due to the fact that you use one arm and hand differently from the other: you are right-handed or left-handed.  Similarly, people tend to be left-eyed or right-eyed, using the two eyes differently.  And, people tend to sleep more on one side than the other.  These are differences that emerge due to experiences and habits.

Those factors make it unlikely that the two eyes will ever be identical, and make it likely that eventually they will need different eyeglass prescriptions.


Why is it advised that infants are fed mother's milk? I have heard that mother's milk is preferred over other baby foods, because it contains immunoglobulins (secretory IgA), and other essential nutrients.

But why is mother's milk so special? Any mammalian milk, such as the widely available cow's milk, should presumably have a similar composition as human milk? What makes mother's milk in specific so healthy?

Could the mere act of breastfeeding, in itself, lend to some beneficial outcome?

The phrase "Breast is best" is a hotly debated one (source: The Guardian and personal communications with many folks). The reason why we don't want to feed infants cow's milk is, however, anything but debated, because

Cow's milk does not provide enough:

Vitamin E
Iron
Essential fatty acids

And because it contains too much:

Protein
Sodium
Potassium (source: NIH's MedLine)
Further, mother's milk is generally free of pathogens, cow's milk may not be (source: Australian Unity). However note that, unfortunately, HIV can hitchhike within the maternal white blood cells to the infant (Quintanilla, 1996)

There are many benefits to mother and infant of breast milk. These benefits are, however, typically compared to the benefits over formula. No study will compare the benefits of mother's milk over cow's milk, simply because infants should never be fed cow's milk.

The benefits of breast milk for the infant are the following:

Breast milk a nearly perfect mix of vitamins, protein, and fat, all provided in an easily digestible form, as compared to formula;
Breastfeeding lowers baby's risk of having asthma or allergies;
Plus, babies who are breastfed exclusively for the first 6 months, without any formula, have fewer ear infections, respiratory illnesses, and bouts of diarrhea. They also have fewer hospitalizations and trips to the doctor (source: WebMD).
Breast milk contains a variety of growth factors, including EGF, BDNF and GDNF that may promote vascularization and neural development (Ballard & Morrow, 2014).

There are a host of immunoprotective factors present in breast milk. These proteins offer protection against diarrhoea, food allergies and infections. The immunoprotective components of human milk include, but are not limited to:

Lactoferrin : binds to iron, thus rendering it unavailable to viruses, fungi and bacteria, which is an effective means of inhibiting their growth (Ballard & Morrow, 2014);
Lysozymes: destroy viruses and bacteria by disrupting their integrity (source: NIH's MedLine);
Secretory IgA: immunoglobulins that destroy viruses and bacteria. Secretory IgA is believed to survive the harsh conditions of the intestines, especially in infants and is therefore active in the intestines of the baby. IgA can bind to pathological viruses and block their receptors necessary to invade the epithelial cells lining the intestinal wall. It also clumps bacteria together through cross-linking, which may affect their dispersion. Bacterial cell membranes, like shown in Salmonella, may be disrupted by IgA binding (Mantis et al., 2011). As mentioned by anongoodnurse in the comments; because mother and baby share the same habitat and hence encounter the same pathogens, the antibodies produced by the mother will be more beneficial to the baby than any other mammal on earth;
Human milk contains a variety of chemokines and cytokines that can cross the intestinal barrier, where they communicate with baby's cells to influence immune activity. Many cytokines and chemokines have multiple functions, and milk-borne cytokines may be grouped broadly into those that enhance inflammation or defend against infection, and those that reduce inflammation (Ballard & Morrow, 2014);
Bifidus factor: promotes the growth of beneficial bacteria in the gut and limits the growth of disease-causing bacteria (source: NIH's MedLine).
A variety of immune cells, including macrophages, T cells, stem cells, and lymphocytes. In early lactation, the breastfed infant may consume as many as 1010 maternal leukocytes per day. They can differentiate into dendritic cells that stimulate infant T-cell activity (Ballard & Morrow, 2014).
Breast milk changes in composition according to the infant's needs, something cow's milk can never accomplish; The first fluid produced by mothers after delivery is colostrum, which is distinct in volume, appearance and composition. Colostrum is produced in low quantities in the first few days postpartum and is rich in immunologic components such as secretory IgA, lactoferrin, leukocytes, as well as developmental factors such as epidermal growth factor. It contains relatively low concentrations of lactose, indicating its primary functions to be immunologic and trophic rather than nutritional. Levels of sodium, chloride and magnesium are higher and levels of potassium and calcium are lower in colostrum than later milk (Ballard & Morrow, 2014).

For more complete reviews on the immunochemistry of breast milk, please refer to Ballard & Morrow (2014) and Mantis et al. (2011)

The mother also benefits:

Breastfeeding burns extra calories, so it can help mothers to lose pregnancy weight faster;
Breast feeding releases the hormone oxytocin, which helps the uterus return to its pre-pregnancy size and may reduce uterine bleeding after birth;
Breastfeeding lowers the risk of breast and ovarian cancer. It may lower the risk of osteoporosis;
Breastfeeding has been linked to higher IQ scores in later childhood in some studies (source: WebMD);
During lactation, menstruation ceases, offering a form of contraception;
Mothers who breastfeed are less likely to develop breast cancer later in life;
Breastfeeding is more economical than formula feeding;
Hormones released during breast-feeding create feelings of warmth and calm in the mother (source: NIH's MedLine).

In terms of bonding:

Skin-to-skin contact during breastfeeding, and eye contact all help a baby bond with the mother and feel secure.
Oxytocin release is known to promote the bonding with bubba. A newly born person can cause dramatic changes in the life of mommie (and daddy!), and a steady release of oxytocin promotes the bonding and love of mommie for the bubba (source: WebMD).

References
- Ballard & Morrow, Pediatr Clin North Am (2013); 60(1): 49–74
- Mantis et al., Mucosal Immunology (2011) 4: 03–611
- Quintanilla, Nurs Times, (1996); 92(31): 35-7


How can a disease be transmissible animal-to-human but not human-to-human? I have heard some debate about whether or not the Wuhan virus can be transmitted human-to-human, but this doesn't make sense to me.  Why wouldn't it be able to?  Are there diseases that can only be transmitted from animals, not humans?

I have heard some debate about whether or not the Wuhan virus can be transmitted human-to-human, but this doesn't make sense to me. Why wouldn't it be able to?

A virus has to be able to physically get out of one person and then into another in order to infect them.  If it can't do that, it can't spread between people.  Just because you can get a virus by (for example) eating an infected animal doesn't mean you'll be able to spread it to other people, at least without them eating you.

  Are there diseases that can only be transmitted from animals, not humans?

Yes, and this is very common.  Rabies for instance can be transmitted from hundreds or maybe even thousands of animals to humans, but is virtually incapable of moving between people because it infects the nervous system which severely limits the ability of the virus to get into another host.


What is the most primitive organism that can die of aging? I know that simple organisms containing of just few cells have no mechanism of dying because of aging. I guess, they typically die due to being out of food or due to becoming someone else's food.

Leaving aside the numerous theories of what can be the origin of such phenomenon as aging, I'm asking a simple question: what is the most primitive organism known so far which has the feature of aging and (as a consequence) dying, even if the environment is perfect?

The adjective primitive is undefined, at least when comparing extant species. We have all gone through almost 4 billions years of evolution.

I would suspect you would consider a bacteria quite primitive though, so note that bacteria appears to age (see Do bacteria die of old age?).


Can vaccines move from person to person? Can someone who has been given a vaccine "infect" another person with the virus used in that vaccine? For example, let's say Bill is vaccinated against tuberculosis. If Frank is exposed to Bill, is there a chance he could "catch" the tuberculosis vaccine, and become immune?

Most immunizations are not transmissible. A few are. To be transmissible, an immunization would have to be a live attenuated vaccine (i.e., a vaccine that can reproduce in the host, but doesn't cause disease), AND have the necessary reproduction rate and virulence factors that would allow for person to person transmission. There are many live attenuated vaccines in use today, but only one that is transmissible, Oral Poliovirus Vaccine, or OPV. OPV is currently not in use in the US, but is used in the developing world, and can circulate in communities. Some would argue that this is a good thing, as it further disseminates immune protection to the population, but it is a little problematic, because it is not without risk, including reversion to a virulent type that can cause Vaccine associated Paralytic Poliomyelitis.

On editing your question, I'm reminded that your example was of TB. I would note that BCG, the vaccination against Tuberculosis, may be a particular case, and I'm not as familiar with it except as a complicating factor in interpreting the results of a TB test in U.S. immigrants. BCG is a live attenuated strain of Mycobacterium bovis, can (rarely) produce disseminated disease itself, and the mycobacterium itself can be isolated in the blood of individuals some time after vaccination. There is also a possible report of vertical transmission of the mycobacterium (from mother to child), but these results use novel methods, and I'm unfamiliar with this group's work. Whether this would lead to immunity of the child is definitely an open question. BCG even when administered in the standard way (as in intradermal inoculation) isn't particularly good at producing immunity, though it is good at preventing meningitis and miliary TB in young children. I'm not aware of any documented case of horizontal person-to-person transmission, but wouldn't declare it impossible.


What would be the membrane's form if phospholipid tail lengths vary? I was trying to visualize and draw the situation if the membrane lipid chain length varies.
I assume so many possible conditions if in a membrane some taller or shorter components mixed:
Such as:

etc.
But which one of this is correct? or all / some from them could be applicable?

Some the scenarios depicted are not energetically favorable and will lead to very unstable membranes if at all.

In the presence of many short-chain lipids, where the difference in chain lengths is very drastic, it will become more favorable for the membrane to reorientate some of the short-chain lipids such that the hydrophobic gaps/pores in your cartoons convert into hydrophilic ones with the head groups forming the pore walls (see fig. below).

If the difference in chain length between the two lipids is not much, the bilayer will adjust its thickness to minimize the hydrophobic mismatch. In such cases, the bilayer will be thinner in some regions. The possibility of interdigitated bilayers is also very much there and will depend on the choice of lipids in question. Interdigitated lipid membranes have been reported before and you can look it up.


Is there any evidence for secondarily poikilothermic vertebrate? Is it possible that an endothermic physiology can evolve into an ectothermic (poikilothermic) physiology? I have a non-scientific gut feeling that it is irreversible. Whales and dolphins are evolved from land mammals, and they've remained warm blooded. While it doesn't give them any obvious advantage in the water, apparently they've compensated with massive amounts of body fat instead of devolving. If the ocean offers opportunity for mammals, then why haven't fish evolved to be warm blooded directly?

What do you mean by cold-blooded?

There's an issue with what you mean when saying "cold blooded". The correct words you may want to use are homeotherm, poikilothermic, ectotherm, and endotherm. In short…

Source of heat

endo = inside
exo = outside

Variance in warmth

Poikilo = varies
homeo = does not vary

Any combination of these two axes exist. For example: If the temperature in the environment never varies you can be homeotherm without needing to be endotherm. A fun example also are the large dinosaurs that are thought to be homeotherms because their metabolism produce some heat and they are so large that they remain warm thanks to this heat source. However, they were probably not able to regulate actively their temperature. Therefore, I would tend to qualify dinosaurs as homeo-exo-therm but I wouldn't be surprised if someone prefers to call large dinosaur home-endo-therm individuals. Hope that makes sense to you.

Note that the terminology might be a bit more complicated in reality as the diversity of mechanisms of body temperature regulation is important.

What did you mean in your question when talking about "cold blooded" species?

Transition from endothermy to ectotherm

Thanks to @tchrist. naked mole rat is ectotherm while its ancestors where endotherm.


Do axonal conduction delays have a function? I'm reading about mathematical models of biological neural networks, which can be grouped into two categories:

The model accounts for the fact that a signal takes time to travel from the excitatory to excited neuron
The signal is modeled as if it travels instantaneously between neurons

I'm trying to understand whether a signal delay is introduced for the purpose of realistically modelling a neural network, or whether it has other functional roles in the model. So by function I mean a role in the information-processing capacity of the network that extends mere physical limitations of axon signaling. I'm referring specifically to their function in biological neural networks

Here are three distinct cases that I expect the answer should fall under, to further illustrate what I mean by function:

They don't, signal delays are a mere physical necessity of biological neural networks, irrelevant for the information-processing aspect of their operation. The differences between delay durations are primarily due to the fact that low reaction times are metabolically expensive and spatially-inefficient and are thus reserved for specialized purposes such as reflexes, instead of having a wider functional role as a parameter.
They do, signal delays are fundamentally required for neural networks to process spatio-temporal patterns. However, the differences between the durations of delays are unnecessary to explain any fundamental internal property and are still due to external factors.
They do, and the differing durations themselves are operational parameters, i.e. the function of a sub-network can only be fully understood if the ratios of the delays in signal transfers are taken into account.

Your point #1 is correct, signal propagation is not instantaneous in real physical world. But for some models it is "good enough" to approximate action potential to go through axon in an instance.

There is also biological role of signal propagation timing. One example, is classic Hebbian learning model. Based on "fire together - wire together" idea, connected neurons that become active relatively close in time, will increase synaptic connectivity, illustrated here:


Why are monotremes so rare? There are currently only five species of monotremes remaining, and all of them are found in Australia. Additionally, I read a science article claiming that competition from marsupials essentially forced monotremes into the water, where marsupials couldn't follow without drowning their young.

Why are monotremes so rare? Are the traits that define a monotreme (such as egg-laying) inherently less competitive, or is their relative scarcity more of a quirk of fate?

When you stop to think about it there is one big reason live birth has an advantage. Lets assume with habe organism A and organism B, A and B both have offspring of exactly the same size and needing the exact same amount of resources (nutrients, etc.) A lays and egg and B gives live birth. A needs to have all of the nutrients its offspring  will need all together at once because once it forms hte egg it cant add anything while organism B does not need it all, they can keep eating and supplying the nutrients over an extended period of time, as they gain it, so they need less "on hand" as it were. A and B may be putting the same amount of resources into their offspring but A does it all at once but B can spread it out over a long period of time meaning it does not need to build up huge reserves before breeding. As an added benefit if times are bad B can dump the offspring and try again later, saving all that would be wasted material for itself, so it can survive famine and drought better.


What do we call these containers used in biotechnology? I'm translating an autoclave instruction from Russian, and it says that these containers (ванночки) (see the black circle on the below photo) are to be sterilized in the autoclave. I'm not sure what they are called in English-language biotech texts.

The Russian text uses the vague term "ванночки", literally "little bathtubs". Maybe just "containers"?

That would be a Reagent Reservoir, or just a Reservoir. These tall and narrow ones are specifically designed for use with a robot, but there are also shorter and wider ones for manual pipettes:

120 mL Reagent Reservoirs


Doing a medical study on yourself? What research guidelines is a person legally mandated to follow if they want to do medical experimentation on themselves?

There is a large amount of variation in the types of medical experiments so I wanted to ask people focusing on the change in practice as a function of the type of medical experimentation you do in the biological sciences (e.g., drugs, blood samples, tissue regeneration, testing medical equipment), including invasive and non-invasive studies. This question seemed almost equally suited to academia and biology SE, but given the focus on different types of biological experiments I felt this might be the more suitable site.

I am most interested on research practices in the United States, and anything touching FDA regulations would be great.

One of the cornerstones of research ethics worldwide is the Nuremberg code, which was formulated shortly after the Second World War and set off by the cruelties performed by the Nazi Doctors. The Declaration of Helsinki, which is currently widely used as the guiding principle of research ethics, was directly inspired by the Nuremberg code.

Interestingly, article 5 in the Nuremberg code reads, and I quote:

  No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.

Basically what this tells you is that when you are a physician, you are not only ethically allowed to experiment on yourself, even when you can reasonably expect death may follow, you are even allowed to put others at that risk(!) Admittedly, it does not specifically talk about non-physicians. Nonetheless, with regard to your question, this Nuremberg article implies that self-experimentation is allowed, regardless the risks.

Annas (2010), rightfully argues that, even where risks are minimal, prior ethics committee review of research should always be sought, if only to confirm the reasonableness of the risk assessment and regardless whether investigators are subjects.

The problem then becomes whether self-experimentation (an experiment done by the investigator on himself or herself only) must be reviewed and approved by an ethics committee before it is conducted. Here Annas (2010) concludes that:

  [...] When an investigator proposes to experiment only on him or herself, that activity is not properly categorized as research at all, but as self indulgence (or, some may say, self abuse). Trivial interventions masquerading as research studies are primarily a source of amusement.

Although I do not necessarily share the concluding accusations against self-experimentation, I do share her view that self-experimentation should not be regarded as proper scientific research, and therefore should not be subject to ethical review.

Reference
Annas, BMJ (2010); 341: c7103


Are there any DNA base sequences that are fully conserved between the genomes of all humans? That is, they don't differ throughout the entire population. I understand of course that we can't DNA sequence every human, so by "fully" I mean there's an incredibly small probability of there being a mutation retained in a living individual.

Also by the genome I'm referring to the consensus of all the cells composing in the individual.

I guess my question is really, where are the crucially important sections of DNA that are simply unmodifiable without being incompatible with life?

In 2004 Bejerano et al. identified "481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes". These were found to be mostly in/around genes related to RNA processing, which is perhaps unsurprising given that it is such a primitive/inherent biological process.

Bejerano's paper has been cited over 500 times on Scopus, with numerous papers reporting variants in such regions that cause diseases such as colorectal adenocarcinomas.

So few conserved regions exist because there is plenty of redundancy in the genome; many genes functionally overlap with others, and many genetic variants are 'silent' - they have no effect on the phenotype. Having this variability is advantageous in Darwinian terms because this increases the evolvability of the species.

There are many regions of very high homology between individuals (protein-coding regions are highly conserved even between species), but there will still be natural variation; each mutations effect will be dependent on the rest of the genome. Genes work together to produce a working organism - they do not each code for a little 'bit', and therefore a change in one portion of the DNA may be 'balanced' by a change elsewhere.

It is only in 'ultra-conserved' sequences that mutations are presumably incompatible with life because the process is so finely-tuned and indispensable.


What do proton pump inhibitors do? I know that sodium azide and 2,4-DNPH inhibit proton pumps. The azide is called an inhibitor and 2,4-DNP is called uncoupler. I want to know what's the difference between the mechanisms of action of sodium azide and 2,4-DNPH in proton pumps. Why is one called an inhibitor and the other an uncoupler?

There's a decent presentation here that basically goes over what you're asking.

As an inhibitor, azides are similar to cyanide in that they inhibit complex IV by binding cytochrome oxidase, resulting in a sort of chemical asphyxiation.

Uncouplers are a little harder to wrap your head around. They embed in the membrane space, and we know that ETC and proton pumping depends on the established proton gradient across a membrane. Uncouplers uncouple the proton gradient from the electron transport chain, allowing protons to diffuse across the membrane, effectively negating the proton gradient.


Phronima sedentaria anatomy I would like to know how many appendages the arthropod Phronima sedentaria has, and how they are arranged. It's not hard to find picture references, but Phronima's transparency makes it difficult to tell from live photos, while what drawn diagrams and text descriptions I've been able to find diverge wildly.

From what I've been able to determine, it has a bulbous head which may or may not have antennae, near to which are two to four pairs of limbs. There is a small gap, then a much longer pair of limbs ending in claws, followed potentially by a second longer pair, and then two to four shorter pairs of limbs. The tail is lined by three pairs of swimmerets, possibly tipped with paddles or bristles.

The best possible answer for this would be a picture like this one, with the assurance that it does indeed represent Phronima sedentaria accurately, though I would be happy with a confirmation of appendage count. Additionally, while I would prefer information about Phronima sedentaria specifically, I can make do with such information about any member of the genus so long as it is specific.

After finding some higher-quality images/videos with some views of the creature from the front, I can say that the image I linked is mostly accurate, if lacking in detail. There does appear to be a set of antennae, though they are significantly shorter than the legs, the front two pairs of legs are shorter than the others and end in small claws, and are positioned more 'underneath' than 'to the side of' the body relative to the other legs. The reason for the confusion seems to have been a combination of the different position of the front four legs, some pictures of other Phronima species misnamed as sedentaria, and that the antennae appear to be able to fold in close to the head, making them nearly invisible.


What is the criticality of the ribosome binding site relative to the start codon in prokaryotic translation? In prokaryotic translation, how critical for efficient translation is the location of the ribosome binding site, relative to the start codon?

Ideally, it is supposed to be -7b away from the start. How about if it is -9 bases away or even more? Will this have an observable effect on translation?

I found an oldish paper on this topic (from 1994).  Here's a summary:

Determination of the optimal aligned spacing between the Shine-Dalgarno sequence and the translation initiation codon of Escherichia coli mRNAs. by Chen, Bjerknes, Kumar, & Jay. Nucleic Acids Research. (1994)

Experiment

The authors constructed a series of synthetic RBS regions that varied the length separating a synthetic 5-nt Shine-Dalgarno sequence from the start codon.  The regions varied in size between 2 to 17 nt.  They assayed the activity of a downstream enzyme, chloramphenicol acetyltransferase.

Conclusion

The authors concluded that the optimal spacing between a consensus 5-nt Shine-Dalgarno sequence (5'-GAGGT-3') and the start site was 5 nt. Note: this synthetic SD was made of the last 5 nt of a 9 nt SD consensus sequence.  They also tested a synthetic SD made from the first 5 nt (5'-TAAGG-3')of the consensus SD.  In this case they found the optimal distance was 9 nt.

So the optimal distance depends on where your desired SD aligns with the consensus SD sequence, which optimally is 5 nt from the start.  Read on for more details.

Details

the RBS is considered to be large, extending 20bp on either side of a core Shine-Dalgarno (SD) sequence.  These days, I often hear of the RBS spoken of in sizes that are equivalent to the SD.  So in the parlance of the paper, you question is rephrased as "how does distance of the SD from the start codon effect translation?"
the canonical SD sequence referenced in the paper is 5'-UAAGGAGGU-3'.  It is 9 nucleotides long.  Distances between the SD and the start codon are defined as the number of nucleotides separate the 3' Uracil of the SD from the Adenine of the start AUG.
Example: the distance is 5 nt in the following mRNA

       5'.....UAAGGAGGUnnnnnAUG......3'

if the SD is not a complete 9 nt long, the distance is between the position of where the canonical Uracil would occur.  In the following example, the distance is still calculated as 5 nt:

       5'.....UAAGGAnnnnnnnnAUG......3'

the average distance between the SD sequence and the start codon varies considerably and on average is 7 nt. Other investigators have found "optimal" spacing (circa 1994) ranged from 5 to 13 nt.
the SD site complements with region on the 16s rRNA. The start codon complements to the anticodon of fMet-tRNA loaded into the ribosomal P-site.  So there are two distinct sites on the ribosome that contact the mRNA during translation initiation.

Also good to read

Designing Genes for Successful Protein Expression by Welch et al. Methods in Enzymology, Vol 498. (2011) (pdf)
Automated design of synthetic ribosome binding sites to control protein expression by Salis, Mirsky & Voigt. Nature Biotechnology. (2009). (pdf)

Note

I enjoyed researching this question because I found my own knowledge to be lacking solid empirical details. I do not have any direct experience besides this little lit review with this topic.


What is the difference between endomysium and sarcolemma They both are lining of muscles so how can we differentiate these two? Please answer in simple terms.

Just to illustrate Gerardo's answer, this picture is provided. The endomysium as you see is a layer of connective tissue which surrounds the individual muscle fibres (cells) (in between one muscle cell and the next) but each muscle cell in particular is lined or covered by a plasma membrane called the sarcolemma.


Comprehensive database of cell types Wondering if there is a comprehensive list/database of cell types, similar to this wiki list of cell types in the human body. It lists probably 100+ different types, but this is just for a human. If we include all animals, and plants, and bacteria, and single celled organisms, etc. then the list would probably get larger.

Wondering if any such aggregation exists, either just as a collection of lists or as a database of cell types. Doing a search returns CELLPEDIA, but the last results are from 2011, so it looks like it never came to be. I also saw MorphoBase, but it didn't look like it was there either. But something like that would be good, otherwise just a list. Basically like a cell taxonomy.

A currently active cell database is SHOGoiN, which says it is a significant extension of the world-first human cell database, CELLPEDIA.  It focuses on human cells but also has information on mouse, sea urchin, and C. elegans.

The site says:

  The database consists of several modules that store cell lineage maps, transcriptome, methylome, cell conversions, cell type markers, and cell images with morphology data curated from public as well as contracted resources, based on sophisticated cell taxonomy.


Chest muscle and female breast size Do female chest size have anything to do with muscle?

I know many female athlete and their average breast size is much bigger than normal female that does not tend to play sports. Do this have any relation to chest muscle?? If so can you explain how it does.

Thanks in advance

The female breast is composed primarily of fat and connective tissue plus lobules and ducts for milk production and delivery.  The pectoralis muscles form a thin layer beneath the breast, as seen in the figure in the link. An athletic female can enlarge the size of the pectoralis muscle and the laterals muscles, just as male athletes can enlarge their "pecs" and "lats".

Exercise burns fat so athletic women often experience reduction in breast size. Of course, other factors such as diet and genetics also influence the effects of exercise on fat burning.

So, athletic females with enlarged lateralis muscles and pectoralis muscles may have a larger overall bust size but the cup size of their breasts might actually be reduced.


What are the roles of guanidine-HCl and ethanol in binding of DNA to silica? I'm trying to understand how exactly the binding to silica gel (in kits) step works and I cannot find any papers which provide an explanation of the physics or chemistry; especially on the way that Guanidine-HCl works.

So lets get them from the beginning.

First of all, we adjust DNA binding conditions by adding a buffer which includes
Guanidine-HCl and ethanol and then we centrifuge our sample. I knew that Guanidine-HCl destroys the tertiary structure of proteins but somewhere I read that also it helps the DNA to bind to a silica column. I searched to find the way that it works but I couldn't find a paper. Also what is the role of ethanol in this step? Is it just to remove proteins and polysaccharides from the sample?

Guanidine HCL is a chaotropic salt.  Chaotropic salts are critical for cell lysis and binding to the silica resin. Specifically, Chaotropes have two important roles in nucleic acid extraction

Destabilize hydrogen bonds, van der Waals forces and hydrophobic interactions.

Leading to destabilization of proteins (including nucleases).

  Macromolecular structure and function is dependent on the net effect of these forces (see protein folding), therefore it follows that an increase in chaotropic solutes in a biological system will denature macromolecules, reduce enzymatic activity and induce stress on a cell (i.e., a cell will have to synthesize stress protectants). Tertiary protein folding is dependent on hydrophobic forces from amino acids throughout the sequence of the protein. Chaotropic solutes decrease the net hydrophobic effect of hydrophobic regions because of a disordering of water molecules adjacent to the protein. This solubilises the hydrophobic region in the solution, thereby denaturing the protein. This is also directly applicable to the hydrophobic region in lipid bilayers; if a critical concentration of a chaotropic solute is reached (in the hydrophobic region of the bilayer) then membrane integrity will be compromised, and the cell will lyse. [Source]

Disrupt the association of nucleic acids with water.

Thereby providing optimal conditions for their transfer to silica.

  Salts can have chaotropic properties by shielding charges and preventing the stabilization of salt bridges. Hydrogen bonding is stronger in non-polar media, so salts, which increase the chemical polarity of the solvent, can also destabilize hydrogen bonding. Mechanistically this is because there are insufficient water molecules to effectively solvate the ions. This can result in ion-dipole interactions between the salts and hydrogen bonding species which are more favorable than normal hydrogen bonds. [Source]

Ethanol, like Guanidine HCL, is a  chaotopic agent.  Ethanol is added for 2 reasons:

Enhance and influence the binding of nucleic acids to the silica.

Interfere with non-covalent intramolecular forces as outlined above.
Reduce association of nucleic acids with water. From Melzak et al. (1996):

  Decreaing the water activity in solution through addition of either a chaotropic salt or an alcohol changes the helical structureof B-DNA either continuously to C-DNA or through a sharp  cooperative transition to A-DNA (28). Either transition is  accompanied by a decrease in solvent-accessible surface  area.

The correct concentration allows for washing of the salts from the membrane. [Source].

Citations

Melzak et al. (1996) Driving forces for DNA adsorption to silica in perchlorate solutions. J. Colloid Interface Sci. 181: 635 - 644.


Definition of Cis-eqtl I have simple question, do cis-eQTLs use the SNPs that are within 1 Mb from the gene's TSS on the same chromosome ?

Kind of.

What you describe is a cis-eQTL, but the exact distance (1Mb in each direction, 1Mb total, ...) and the definition of the location of the gene (TSS, transcript borders, ...) depend on whoever calculates a cis-eQTLs and are not universal.
The 'cis' part just means the SNP is somehow near the gene, there is no defined limit on the distance.


How small does a nanobot have to be to "swim through the brain" and access any neuron it wants to? I read on this question What is in the space between neurons in a brain? that there is actually not much empty space in a brain. But my question is slightly different. Is there a visual demonstration I can see of approximately how "packed full of cells" the brain actually is?

Obviously there wouldn't be a fixed answer as it is likely a continuum where the bigger you get the harder it is to swim through without being blocked by all the neurons/synapses. But what is a good ballpark size to be to swim through with relative ease?

Is there a visual demonstration I can see of approximately
how "packed full of cells" the brain actually is?

Yes. You can inject tracers in the CSF (Cerebrospinal fluid) or in the ventricles and monitor them. In this study, the authors have injected a fluorescent tracer in the CSF and used a direct imaging.

  We used in vivo two-photon imaging to compare CSF influx into the
  cortex of awake, anesthetized, and sleeping mice. The fluorescent
  tracers were infused into the subarachnoid CSF via a cannula implanted
  in the cisterna magna for real-time assessment of CSF tracer movement.

You can also inject a radiolabeled tracer. The tracer should be a molecule that is not taken up by the cells. You can then visualize the space using Positron Emission Tomography (PET).

 But what is a good ballpark size to be to swim through with relative ease?

You may find this interesting: the abovementioned study shows that the "space" expands during sleep and CSF percolates deeper into the brain. This allows clearing of toxic metabolites. Having said that, some interior regions would be difficult to reach. Apart from neurons, there are several glia which occupy the space. I am not entirely sure about this but in interior regions there would be very less of extracellular space (I am just guessing it would be less than ~1µm. See the black regions in the figure below). Extracellular space is 20% of total brain tissue but it is not constant throughout. For more details refer to this book.


Why would diffusion be faster across a non-specialised tissue? The standard protocol for a person experiencing chest pains is to chew a 300mg aspirin tablet, the argument being that chewing rather than swallowing the tablet results in the aspirin entering the blood stream faster.

From a biological standpoint, why is this the case?  Given that the stomach and GI tract are specialised tissues to allow for maximum diffusion, why would it be faster to pass aspirin across the gums (bucaal administration?) tongue and cheeks which are not specialised for this purpose?

It is not just a special case for aspirin either, as HypostopTM/GlucogelTM (acute treatment for hypoglycaemic shock, essentially concentrated sugar) is applied directly to the gums or cheek with a similar argument that in critical situations it is faster.

The only suggestion I could find was  very vague from the "Merck Manual":

  The stomach has a relatively large epithelial surface, but its thick mucous layer and short transit time limit absorption
  Which I assume could mean that it is the reduced absorption rate in the stomach that makes the oral membranes faster, yet it also says that the delay in the stomach is brief.

I'd be really interested to know the biology behind this!

There are several issues here:

1) Any mucous membrane is a specialized tissue for absorption.

Mucous membranes are indeed not so good for passive diffusion, that makes them absolutely perfect tools for active absorption of certain substances, almost independently from the membrane type. To provide some examples: many drugs like cocaine are inhaled and absorbed in nasal cavities, whereas the rectum is also known and favorite delivery way for medicines.

Generally the absorption force of the mucous membrane is dependent upon how well it is vasculated, for after going through the basal membrane the substance directly enters the blood flow and quickly travels away, thus the concentration gradient on both sides of the basal membrane -- the main barrier in mucosa -- remains relatively high.

See  Bhat P. 1995. The limiting role of mucus in drug absorption: Drug permeation through mucus solution for an experimental model for this statement.

2) Mouth mucosa can absorb many substances.

There is a special term called "oral absorption" to describe the rapid drug absorption into blood flow from the mouth cavity. The mucous membrane is not specialized here, but small molecules are able to permeate here through all barriers.

3) Advantages of oral absorption.

There are some:

The mucous membrane in the mouth cavity is very highly vascularized. The whole mouth can be seen as a bundle of skeletal muscles and every muscle requires a lot of energy and oxygen, therefore they have one of the highest vascularity rates, having much less distance between single capillaries.
Blood flow is higher in the mouth cavity walls than in other inner organs. This is mostly because muscle contractions (during chewing) lead to increased propulsion of blood through capillaries and small vessels here.
Any substance that enters blood flow here bypasses the hepatic-portal system. This means that the substance does not have to wait until it is filtered by our liver, it is immediately distributed through the whole body.
There are special reflexes from oral mucosa to inner organs. Even not so important in case of aspirin, this is very important for some placebo drugs like methyl valerate (known as "Validol" in many countries) used a lot for treating angina pectoris whose only action is to activate the cold receptors in mouth and thereby leading to reflectory dilating of cardiac vessels.

This is why many drugs, like for example loperamid, are administered only as sub-lingual tablets. And this also explains why in emergency medicine many remedies are injected directly into the tongue.


Biological validation of computationally determined gene-gene interaction How can a computationally determined three-way gene interaction be biologically validated? What kind of assays or tests must be performed using cell/tissue-based and/or mouse models to prove that the three genes may indeed have a joint effect?

Let's say, it is easier to identify and validate gene interactions that involve transcription factors like FOXM1. Consider a three-way gene interaction in Breast cancer - FOXM1-BUB1-CHEK1 - that can be tested for direct interactions via western blot and reporter assays. But such interactions may or may not be interesting - given the fact that transcription factors may be affecting expression levels of other genes. Most computational studies are focussed on identifying gene interactions based on coexpression or co-occurrence. There is literature on computationally identifying AND/OR relationships between interacting genes. I don't have a specific example to provide but, for argument sake, if we did suspect that three genes are interacting in an AND like manner, how do we biologically validate this finding? I'd also appreciate if you may have comments on the usefulness of such findings, particularly, with regard to designing more efficacious combination therapies against a disease".

Thanks

Hang in there, this answer will grow over time.

Just off the top of my head, I think we could write a small book (or a very long review article) to cover both the depth and the breadth of your question(s).

First, we need to define, and/or clarify, some terms.  The term interaction probably means different things to different authors at different times.  In fact, one author may use this term to mean different things at different times.  So I would like to propose that we make some distinctions.  For example, I would make a distinction between a genetic interaction between two genes (which is typically detected in one of the model organisms, using a genetic test between two loss-of-function alleles) versus a protein-protein interaction (sometimes called a PPI) between the two proteins encoded by those same two genes.  PPIs have been detected classically by co-sedimentation in a sucrose density gradient, or co-immunoprecipitation (co-IP), or by affinity chromatography.  More recently PPIs have been detected by mass spectrometry (MS) (sometimes coupled with affinity chromatography).  PPIs have been inferred by using proxy assays, such as the yeast two hybrid (Y2H) assay.

PPIs can also be detected by surface plasmon resonance (SPR) assays, and there may well be others.

So, when you say gene-gene interactions, what precisely do you mean?


Are resonances the reason receptors work? From Visual phototransduction - Wikipedia:

  When struck by a photon, 11-cis retinal undergoes photoisomerization to all-trans retinal which changes the conformation of the opsin GPCR leading to signal transduction cascades which causes closure of cyclic GMP-gated cation channel, and hyperpolarization of the photoreceptor cell.

From the physics point of view, does this mean the proteins in the eye are combinations of oscillators, each of them in charge for a specific wavelength, so that if one oscillator resonates with the photon, the signal is produced? In general, does all receptors work this way? Note that physical oscillators should have exponential or sinusoid functions. See this Photography question: How to capture a swinging pendulum?

Photoreceptors themselves dont act as oscilators, a single receptor is either 'on' or 'off' - it does not respond differently to different wavelenghts. Humans have Trichromatic vision, which means that we have 3 different kinds of photo-receptors that respond differently to light of a given wavelength at a given intensity. By combining multiple signals from these 3 different receptor types the brain can translate this to different colors (its actually kind of similar to how RGB color works).

Therefore I would say that even photo-receptors don't work like oscilators, only their specific ligands switch between the 11-cis & trans state, but this is more of a statistical and physico-chemical process (which does involve resonance between the energy of the photons and the electrons in the cis bond)


What is the name of this fly? I've seen the following insect in Austria at the border to Bavaria (high resolution). It was quite small. I would guess not longer than 1cm:

Could somebody identify it?

Could somebody identify it?

Sure, I'd be glad to help you with that!

The fly in question is indeed a member of the Empididae family, and of the genus Empis. I couldn't quite decide on the species, but it's either Tessellata or Opaca (with me leaning more towards Tessellata). This fly (genus) is commonly referred to as a "Dance Fly".

Empis Tessellata

Empis Opaca


How to write a palindrome sequence as-wish (create, theoretically) ? (self-answered) There are specific examples from nature,  of palindromic sequences.

But without memorizing them, is there any way to randomly write or create or derive a palindromic sequence for a theoretical discussion?

by the way, Genetic palindromes are not an exact ditto of verbal-palindrome.

I once developed a method, but it is so-basic and simple that I'm pretty sure it is already discovered. Here I "shared my knowledge, Q&A-style"

Step-1

Write a small sequence randomly.

    5'... A T G C C

Step 2

Write the sequence in opposite-direction, on the next line. It will end at just at the next-place of last place of previous sequence, i.e.

         -------->

   5'... A T G C C

                        C C G T A ...5' .

                    <-------------

Step-3

Fill-in-the blanks following base-pair rule, and the sequence is now ready.

5'... A T G$\:$ C C$\:$ | G G C A T ...3'

3'... T A C G G | C C G T$\:$ A ...5'

Addendum (courtesy: user@Another'HomoSapien')

The previous method was similar way we usually read a verbal palindrome (though unlike a verbal palindrome, any reflection-symmetry was Not present ). But  there is a rotational-symmetry (2-fold), (rotational symmetry means it contains parts which are superposable on rotation).

So we could create a palindromic sequence using rotation also.

Or could rotate pre-filled up sequence (if exactly follow the user's instructions)

The brown dot indicates the axis of rotational-symmetry of the written-sequence, vertical to the plane of paper.