Over winding vs under winding of a DNA DNA supercoiling refers to the over- or under-winding of a DNA strand.

Source : DNA supercoil

  When a relaxed DNA is subjected to bends, or openings of DNA, over winding or unwinding, its base pairs per turn changes, and the DNA is subjected to stress and strain.  In order to overcome such distortion, which has rendered the DNA unstable, the DNA twist around itself, like a circular rubber band undergoing twisting, such a twists on its own thread is called Super coiling; it is also referred to as tertiary structure.

Source : DNA Super Coiling

What they mean by over winding and under winding of a DNA ?

Imagine a covalently closed circular double-stranded DNA plasmid. In its "natural", or "relaxed" state you could spread it out, flat, on a suitable surface.

Now imagine cutting one of the strands of the DNA (i.e., cutting the sugar-phosphate backbone, the way that an endonuclease would, leaving a nick, the 5'-end of the nick has the phosphate, and the 3'-end of the nick has an -OH group), and rotating that nicked strand in a clockwise direction, several times, around the other, intact, DNA strand.  This does not involve breaking any of the basepairs, or unravelling the strands, you are just twisting it around.

Now imagine sealing that nick, by ligating the 5' phosphate to the 3' OH.  At this point the dsDNA helix is slightly "overwound", and will no long lie completely flat. It has begun to be supercoiled; these are positive supercoils.

If, alternatively, you had rotated the nicked DNA strand several turns in the counter-clockwise direction before re-sealing it then that molecule would also start to be supercoiled, but it would be "underwound" with negative supercoils (and it would also no longer lie flat on the surface).

There is an enzyme called DNA topoisomerase I that cuts, and re-seals, one of the two strands like this.  Another enzyme called DNA topoisomerase II cuts both strands before introducing supercoils.


SNP coding for association analysis I'm working on a project about detecting SNP association with a disease. As I understand, SNP is a single variation of the nucleotide that occurs for more than 1% of the population. However, I couldn't connect this idea with the dataset in hand. The rows in my dataset represent each patient and the columns contain SNP information. For example:

ID  exm355 exm615
1     T_T   A_C
2     T_T   C_C
3     A_T   C_C

I have no idea why the SNP columns contain 2 nucleotides(T_T, A_T, A_C, C_C). As the definition of SNP, I thought it should show only the variant nucleotide or am I misunderstanding anything? How could I interpret T_T or C_C and how could I know which nucleotide is the variation from the common ones in the population?

Thanks all

Each chromosome location which has been identified as being a SNP is a location at which more than one nucleotide occurs at appreciable frequencies in the general population.  This means that there are two or more bases which can occur there, so a person's test must show which bases actually occur there in that person's genome.  Since a person has both a paternal and a maternal chromosome of a chromosomal type (a pair of homologous chromosomes), the person has two instances of the SNP location and so two nucleotides to be detected and reported.  Hence your dataset has two nucleotides for each SNP location for each patient.

Just from the reported base or the SNP name you can't tell which is more frequent in the population.  If you need to know that, you must consult SNP frequency data from some other database. (The SNP names in your example, e.g. "exm355" are not familiar; usually SNPs have names like "rs1234567".)


What keeps organs suspended in the body? I'm a bit confused what prevents our organs from not collapsing into a heap or putting pressure on each other. I have a 3D anatomy app and have been studying the relationship between the organs. According to the models, the organs are remarkably complementary in geometry and compact, but this still doesn't explain what prevents gravity from distorting them or squishing them.

My Question

What keeps organs suspended in the body?

Most of the organs are attached to the abdominal wall by a fold of peritonium called mesentary.
Mesentary is a membranous tissue arising from the posterior wall of the peritoneal cavity and is responsible for keeping the organs at their designated places.Mesentary wiki


Why does scraped knee hurt more in hot water than cold water. I was asked this question by my 5year old son. I do not know how to explain to him .

2 reasons. The first (as anongoodnurse mentioned) is that cold temperatures temporarily knock out dermal surface nerves (in the winter you can verify that your face goes numb after a while outside).

The other reason is that a knee scrape produces inflammation (swelling and increased temperature). Cold water (or anything cold) counters these: stopping the inflammation temperature increase, then freezing out enzymes and proteins needed for inflammation and causing them to slow down or malfunction.


Umbrella term for agonist, antagonist, inverse antagonist, etc. For most receptors there exist different ligands that induce different responses. Depending on the response these different ligands can be classified into different groups such as agonists, antagonists, inverse antagonist, etc.

My question: is there a term that summarizes all of these different concepts?

I'm looking to express something like the following: 'addition of a methyl group to the phenyl ring changed its X from agonist to antagonist.'

activity

  "addition of a methyl group to the phenyl ring changed its activity from agonist to antagonist"


How effective are restriction enzymes in protecting bacteria? Bacteria use restriction enzymes to cut DNA of bacteriophages. Virus mutates really fast. Won't a point mutation in restriction site render the restriction enzymes of the bacteria useless ?

So how effective are restriction enzymes in protecting bacteria ?

Note that a given bacterium will probably have more than one restriction enzyme, so the viral genome probably won't ever run out of targets. Even if it did, restriction enzymes could suffer mutations that may change the specificity. When you talk about microorganisms, it's more accurate to think in populations rather than individuals, since the colony would be able to grow again if they have at least one cell. Viruses need a certain density to spread, so even if the bacteria cannot defend against, it may be able to survive simply because the virus run out of hosts before some cells can be infected. This is even easier if the bacteria have some kind of resistance form.

Moreover, restriction-modification systems aren't the only defense line against viruses. Many bacteria have a system called CRISPR-CAS that acts like an immune system, inserting RNA fragments into the bacterial chromosome and using them as "antibodies" by hybridization. In this context, you can assume that restriction-modification systems, alongside other nucleases they usually carry, act as an innate immune system, while the CRISPR-CAS would be an analog to acquired immunity.

Diagram of the CRISPR-CAS system. Source.

Furthermore, not every environment has the same viral density. Some habitats may be protected against viruses by some means, like the gut microbiota (the carbon intake goes through the stomach acid and tons of hydrolases, which is very destructive for viruses); while some others may have an incredible amount due to lack of biodiversity and high cell densities (this is the case of most extreme environments). E. coli, as a gut bacteria, would probably have enough with only restriction-modification enzymes (In fact, while it have a CRISPR system, it seems to be repressed), while many others will need more defenses.


Additive genetic variance with $n$ alleles The genetic variance of a quantitative trait (the quantitative trait in question is fitness) can be express as the sum of two components, the dominance and additive variance:

$$\sigma_D^2 + \sigma_A^2  = \sigma^2$$

, where $\sigma$ is the genetic variance, $\sigma_D^2$ is the dominance variance and $\sigma_A^2$ is the additive variance. $\sigma_D^2$  and $\sigma_A^2$ are given by

$$\sigma_D^2 = x^2(1-x)^2(2\cdot W_{12} - W_{11} - W_{22})^2$$

$$\sigma_A^2 = 2x(1-x)(xW_{11}+(1-2x)W_{12} - (1-x)W_{22})^2$$

, where $W_{11}$, $W_{12}$ and $W_{22}$ are the fitness of the three possible genotypes and $x$ and $1-x$ give the allele frequencies.

Question

The above definition makes sense for one bi-allelic locus.

How are $\sigma_D^2$, $\sigma_A^2$ and $\sigma^2$ defined for a locus that have $n$ alleles?

Here is a related question

Well, the total genetic variance is just, by the definition of the variance,
$$
\sigma^2 =\sum_{i,j} f_i f_j (w_{ij}-\bar{w})^2
$$
(using $f_i$ and $w_{ij}$ for frequency and fitness, respectively), and
$$\bar{w} = \sum_{i,j} f_i f_j w_{ij}$$ is just the average fitness.

You can calculate the additive genetic variance for different loci by simply assuming that there is no dominance effect, i.e. the alleles are independent. If it helps, think of it as a quantitative trait in a haploid organism. Thus,

$$
\sigma^2_A =\sum_{i,j} f_i f_j (w_iw_j-\bar{w}')^2 = \sum_i f_i(w_i-\bar{w}')^2.
$$
with
$$
f_i=\sum_jf_{ij};  w_i=\sum_j f_{ij}w_{ij}; \bar{w}' = \sum_i f_i w_i;
$$


Identify caterpillars and, if possible, parasitoid (Sabah, north Borneo) Someone on Twitter posted some photos yesterday of a lump of mud that, when knocked off a chair by accident, revealed a number of caterpillars:
https://twitter.com/solomilne/status/956135158381334528

I've uploaded one of the photos below. The assumption (which seems reasonable, but I suppose isn't certain) is that they were left there by a parasitoid.

Can anyone identify the caterpillars, confirm whether they are likely to have been left by a parasitoid and if so identify a likely culprit? The sample was from a forested area in Sabah, northern Borneo; I've requested a size from the person who posted the photos.

These are wasp larvae, but likely not parasitoids. They are the larvae of predatory Sphecid or Crabronid wasps, both of which build mud nests, generally provisioned with spiders or other arthropods that have been killed (and by some wasp species, dismembered) or paralyzed by the female (mother) wasp. It looks like one or two of them may be pupae (closer to eclosing--"hatching"--as adults) instead of larvae. If kept carefully they can be raised to adulthood for identification (at least by an expert familiar with the aculeate, or stinging, wasp fauna of that part of the world).


Why is chlorophyll green? Isn't there a more energetically favorable color? Chlorophyll being green means it absorbs light in the red and blue area of the spectrum. Isn't this the high and low energy light? Wouldn't plants get more energy if they absorbed light in the green area of the spectrum instead of the red one?

The reason that chlorophyll is green is because it absorbs other colors of light such as red and blue, so in a way the green light is reflected out since the pigment does not absorb it.
Because life might have been purple:

It is possible that the very first life form to process light may have been purple colored. This would mean it was reflecting red and blue light and absorbing green. In such a scenario this thing if it was the first to produce energy from light would have out competed against everything else. It would have had a population explosion and possibly covered much of the Earth or at least the oceans. Haloarchaea are an example of a simple life form that uses Retinal and Bacteriorhodopsin to produce energy though far less efficiently than photosynthesis. Had this been developed prior to photosynthesis it may have let it spread very far even though it is a less efficient energy production method. A 2% efficiency increase in a market no one has yet tapped is still a huge advantage.
In this scenario because the first thing to use light was using green light it left a niche for another form of life to exploit. That niche would have been absorbtion of the Red and Blue spectrums. Which is the same area plants absorb today. They got so good at their niche that they eventually were able to generate much more energy than the first life form did and eventually out competed for the sun. This niche has worked so well that they never developed a full system for the other spectrums.

Because you could say that good enough is good enough:

The sun puts out a lot of energy. It is possible that there was no need to try and capture all of the spectrum or that it was actually not beneficial to do so. Often too much sun is more an issue than too little. Too much sun and heat can dry out the plant. It is possible that to gain the benefits of photosynthesis there needed to be a reduction in some energy to balance it out. Much like a black car on a hot summer day a black plant might absorb all of the spectrums but also get far too hot. Blue plus red may just be the sweet spot.

However, about your question about colour:

Wouldn't plants get more energy if they absorbed light in the green area of the spectrum instead of the red one?

Plants would probably get more energy if their leaves were black.
Sources:

https://www.quora.com/Why-did-chlorophyl-evolve-to-be-green-as-opposed-to-black-which-would-absorb-more-energy
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691134/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807594/


Lyonization vs Genetic Imprinting Lyonization is the process in which there is inactivation of an X chromosome in females. This process is implicated in mosaic forms of turner's syndrome (in this case the altered X chromosome is Lyonised, thus allowing the normal X Chromosome to express itself).

Is Lyonization considered as a form of genetic imprinting? What is the difference between the two (if no)?
Lyonization is a random process (according to the extent of my knowledge which X chromosome is inactivated is not predicatable). Is genetic imprinting also random?
Is there any known aberration of Lyonization in males? (meaning the single X Chromosome or Y Chromosome gets silenced)

I use the term "X-inactivation" instead of "lyonization". Anyway, X-inactivation is a very specific process by which an entire X chromosome (or equivalent sex chromosome) in a female mammal is completely silenced.

"Imprinting" is typically applied to single genes, wherein genes inherited from a specific parent are always epigenetically silenced. The genes are usually autosomal. Thus, we're talking about scales : entire sex chromosome composed of thousands of genes (x-inactivation) vs single genes (imprinting)

The choice for which X-chromosome is inactivated is sporadic and different in different cells within the body. It is controlled by opposing expression of different non-coding RNAs (XIST on the inactive X and TSIX on the active X).

Imprinting is very specific to the allele that is inherited from a specific parent (for example, some genes are paternally imprinted, while others can be maternally imprinted).

Males with aberrant X-inactivation will lack any expression of genes carried on their single X-chromosome, a condition that will not result in a viable fetus. However, whether there are aberrant X-inactivations in single cells or tissues of ageing adult males....perhaps likely yes, given all the other aberrant somatic mutation events that occur over the course of life.


Is Natural Selection like a Copy Editor? I am stuck on a Homework Question. It says:

  Evaluate the following statement: “Natural selection works like a copy
  editor; it works only with
  what is already present in a population.” (Note: Copy editors check
  written material before it is set into type, to correct errors in
  spelling, grammar, usage, and style.)

I thick that Natural Selection is not like a Copy editor because:

Natural Selection has no set direction, which means it does not decide on anything. A weak organism might be able to survive by luck. While a copy editor knows the mistakes and eliminates them instantly.

Can I get some help on this. Thanks!

Evolution, in the Darwinian sense, can be broadly described as the interaction of three processes: inheritance, mutation and selection.

Of those three processes, mutation is the one that produces novel innovation, by occasionally producing new alleles that did not exist in the parent population.  It is, however, a blind innovator — the novel genotypes produced by mutation are essentially random, and no more likely to be advantageous to the organisms carrying them than one would expect by change (i.e. not very likely at all).

Selection, whether natural or artificial, is what happens when the organisms carrying the diverse genomes produced by mutation end up competing for survival and reproductive opportunities against each other and against their environment.  It acts on the diversity generated and replenished by mutation, favoring those mutations that happen to confer a survival advantage.

Finally, inheritance ensures that the beneficial alleles generated by mutation and filtered by selection get passed on to successive generations, allowing them to spread in the population and to be further modified by successive mutations.  In a sense, inheritance and mutation can be seen as opposite sides of the same coin: the more faithfully genes are inherited, the less mutations there are.  Yet both are necessary for evolution; an organism that never mutates obviously could not evolve, but neither could one that mutated so much that all of its genes were totally scrambled in each generation.

Of course, this whole process is stochastic in nature — even the best adapted individual may die without offspring due to simple bad luck, just as even a maladapted individual may get lucky and prosper.  But over generations, there is nonetheless a statistical tendency for individuals carrying certain alleles, or combinations of them, to be more fecund than others, and those will be the alleles that will eventually come to dominate the population (assuming they're not it turn displaced by even more successful mutants).

Thus, I would personally say that, of these three components of evolution, (natural) selection indeed "works only with what is already present in a population."  However, it's not really like a copy editor, since it does not seek to "correct errors" in the genome; it's more akin to a slush reader, who just sorts the incoming texts into ones to keep and ones to throw away.


Can I execute/model a genome? Hi I am wondering if we can execute a genome on the sub-cellular level by running it on the computer. What I mean is using the genome as data to examine by having the cells reproduce and see what happens as they grow.

A simple genome can be modeled, however imperfectly, on a computer, where some have taken experimental genomics data and built simulations from it.
For instance, from the paper A Whole-Cell Computational Model Predicts Phenotype from Genotype:

Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally different cellular processes and experimental measurements. Our whole-cell model accounts for all annotated gene functions and was validated against a broad range of data. The model provides insights into many previously unobserved cellular behaviors, including in vivo rates of protein-DNA association and an inverse relationship between the durations of DNA replication initiation and replication. In addition, experimental analysis directed by model predictions identified previously undetected kinetic parameters and biological functions. We conclude that comprehensive whole-cell models can be used to facilitate biological discovery...
We have developed a comprehensive whole-cell model that accounts for all of the annotated gene functions identified in M. genitalium and explains a variety of emergent behaviors in terms of molecular interactions. Our model accurately recapitulates a broad set of experimental data, provides insight into several biological processes for which experimental assessment is not readily feasible, and enables the rapid identification of gene functions as well as specific cellular parameters.

(cite)
Also:

Given the vast behavioral repertoire and biological complexity of even the simplest organisms, accurately predicting phenotypes in novel environments and unveiling their biological organization is a challenging endeavor. Here, we present an integrative modeling methodology that unifies under a common framework the various biological processes and their interactions across multiple layers. We trained this methodology on an extensive normalized compendium for the gram-negative bacterium Escherichia coli, which incorporates gene expression data for genetic and environmental perturbations, transcriptional regulation, signal transduction, and metabolic pathways, as well as growth measurements. Comparison with measured growth and high-throughput data demonstrates the enhanced ability of the integrative model to predict phenotypic outcomes in various environmental and genetic conditions, even in cases where their underlying functions are under-represented in the training set. This work paves the way toward integrative techniques that extract knowledge from a variety of biological data to achieve more than the sum of their parts in the context of prediction, analysis, and redesign of biological systems.

(cite)
Gentle advice: Avoid answers from cartoonists, whose domain of knowledge does not include biology.


Is there a genomic code for nucleosome positioning? What does a genomic code for nucleosome positioning in eukaryotes actually mean? By the code is it right to think that specific DNA sequences favour nucleosomes and others don't? I see that there for and against arguments on this topic. What is the current view on this topic?

The genome is the complete set of DNA in an organism, including genes and non-gene sequences of base pairs (bp).1 Each codon of three base pairs in a DNA sequence specifies one of twenty different amino acids. There are four available bases in DNA; Adenine (A), Thymine (T), Guanine (G), and Cytosine (C).  Four letters taken three at a time (where order matters and repetition of a letter is permitted) gives 64 possible codes. There are only 20 amino acids necessary in most life on earth, so only 20 codes are needed from the 64 possible. One codon is also used as a start codon (start translation) and three codons are used as stop codons (stop translation). So there are 41 extra codons available. As it turns out, for most of the 20 amino acids several different codons can specify the same amino acid, but each codon only specifies a single, unique amino acid, so there is no ambiguity. The code is therefore said to be redundant or degenerate. This degeneracy allows the same protein (composed of amino acids) to be coded with different base pair sequences, which is important if one base pair sequence is better than another in its mechanical properties of bending DNA around a histone octamer to form a nucleosome.

If the DNA molecules in a typical human cell were lined up head to tail, they would form a string about 2 meters long. The diameter of a cell nucleus is only 5 μm (0.000005 meter), so the DNA really must be packaged or organized to fit. The packing solution eukaryotes developed is to coil DNA around histone proteins to form beadlike units called nucleosomes (packing the DNA also has implications for gene expression, but we will ignore that here).

Each nucleosome constains a 147 bp (base pair) stretch of DNA, which is sharply bent and tightly wrapped in a 1 and 3/4 turn (a left-handed superhelical turn to be exact) around the histone protein octamer. There are many of these nucleosome beads on each strand of DNA. Human chromosome 19, for example, has 58.6 million base pairs, so that makes for a lot of 147 base pair beads, even with streches of unwrapped linker DNA between the beads--about 75 – 90% of the base pairs end up wrapped in nucleosomes.

The bending of the DNA around the histone is made easier or more difficult depending on the geometrical and mechanical properties of the specific two base pairs or dinucleotides at the bend. This is not a trivial mechanical property: Some sequences may have a more than 1000 fold capacity to bend around the histone octamer compared with other sequences; we will say these sequences have an affinity for nucleosome positioning since they make it easy for the DNA to wrap. Conversely, some sequences are very "stiff" and are much more difficult to bend, e.g. poly dA:dT sequences. On average, high affinity sequences have more AA, TT and TA steps at positions where the minor groove faces inward towards the histone octamer, i.e., when more bendable di-nucleotides like AT and TA occur on the face of the helical repeat where it can directly interact with the histones (the helical repeat is about every 10 bp; see below).

What do we mean by "grooves?" Remember that DNA is a double stranded helix (as if you were twisting a flexible ladder) coiling two chains of sugar-phosphate "backbones" around the outside of the helix with the nitrogenous base pairs that connect the strands (with hydrogen bonds between base pairs) pointing toward the center of the helix (if you were twisting a flexible ladder into a helix the rungs would be the connected base pairs beween the two backbones). If you held up a screw you would see the threads as "grooves" in this similar helical structure. The backbones of the two strands are closer together on one side ("minor groove") of the double helix than the other ("major groove"). In undeformed β-DNA, the complementary base pairs of the "rungs" rise about 0.34 nm and twist ~36 degrees around the center axis of the "ladder" from each base pair rung to the next. A "helical repeat" will therefore occur every 10 bp's (10 x 36 = 360 degrees) as the helix completes a full turn around its axis. Don't confuse this helix with the wrapping of the DNA around a histone core; the DNA is a double stranded helix and that is in turn wound around the histone in a nucleosome.

But do nucleosomes in actual living organisms ("in vivo") actually tend to position themselves on sequences of DNA that wrap more easily around the histone core of the nucleosome, i.e., do nucleosomes in vivo actually show an affinity for specific DNA sequences?  If they do, then that could be considered to be a "genomic code  for nucleosome positioning." There are other factors (e.g., remodelling complexes which can move nucleosome positions) and related questions, e.g., do stiff sequences like poly dA:dT inhibit the formation of nucleosomes (and are nucleosome inhibitory sequences more common in DNA sequences like transcription start sites that should be exposed to facilitate interaction with trans proteins), but we will just consider simply the basic question.

By analogy, suppose I had a printer that could only print strips of paper a sentence high (vertical height of the strip sufficient to contain a 10 pitch character, say 0.1 inch high) but of arbitrary length. Imagine the printer is fed with a spool of this strip paper, like an old time printing calculator (or ATM receipt printer). If I printed this answer text page, out would come English sentences (at least I intend this to be recognizable English) on a long, thin strip. This sounds rather like a phylactery (tefillin) printer, now that I think of it, but that is a topic for comparative religion. If there are 66 lines of 7 inch long sentences on my page, then that is 38 feet of 0.1 inch paper strip to carry around for every page of text. I might find it more convenient to wind up portions of that long strip on little wooden dowels (like empty sewing thread spools for example) and then unwind them only when I wanted to read my article again (which I can never do enough). If DNA is kind of like this analogy (it is far more complex actually), then the spools are "histones" and when wrapped with paper strip become "nucleosomes." Does it makes sense that the letters I chose to construct the words in the sentences of my article were chosen to some extent based on some hypothetical capacity for some sequences of alphabetic characters to bend and coil around a spool (say some sequences had less cumulative stiff ink drying on the paper strip)? That gives you one angle on the controversy involving the idea of nucleosome positioning by genomic code. However, consider that, as in the case with degenerate DNA codons, I can choose different sequences of characters, i.e., words, to mean the same thing, so possibly I could still choose my words for meaning, but select synonyms that hypothetically bend easier, making it easier on average to coil my sentence strip up on spools.

A recent study, Multiplexing Genetic and Nucleosome Positioning Codes: A Computational Approach, demonstrated that the local minima (the easy bending sequences) of a real gene could be repositioned (in computer simulation), that is, the nucleosome moved to another place in a real DNA gene sequence, by substituting equivalent base pairs (remember that a single amino acid can typically be defined by several different codons) to preserve the same protein encoding (a protein being a specific sequence of amino acids). This suggests that nucleosomes can at least theoretically be positioned anywhere on top of a gene, multiplexing the genetic information with the mechanical information as it were.

But do real genomes show any evidence of multiplexing genetic and mechanical information as described above? Experimentally mapped nucleosomes on top of genes do show strong signals in the probability for occurrence of mechanically favorable dinucleotides, but that does not prove the case (since shifting nucleosomes on random sequences may also demonstrate similar signals). The researchers in the study just cited then reasoned that if multiplexing is actually occuring, that is, if actual genomes have to balance the energy benefit of placing nucleosomes on DNA sequences where it is easier to bend the DNA into a coil around the histone, then it must be easier (and a more frequent occurrence therefore) to do that in non-coding sequences of DNA where only the "mechanical preference of the amino acids" need be considered (and not the necessity to maintain a specific sequence of amino acids to encode a particular protein).

Accordingly, they looked at the probability distribution for the amino acid threonine codons along nucleosomes on top of coding and non-coding regions of the S. cerevisiae and S. pombe genomes (high resolution nucleosome maps exist for both organisms). Both spectra showed a peak at the 10 bp (remember our earlier discussion of helical repeat), indicating that the codons for threonine display an overall rotational preference with respect to DNA bending within nucleosomes, but the non-coding peak was significantly higher for both organisms. When the 10 bp periodicity was plotted for all 20 amino acids for coding vs non-coding regions in both organisms the majority of points exhibited higher amplitude outside of genes, i.e., in non-coding regions where only the position preferences were a factor.

These findings (that the local minima, the easy bending sequences, of a real gene could be repositioned using degeneracy; that strong signals in the probability for occurrence of mechanically favorable dinucleotides are found in real genomes; and that the amplitude of 10 bp periodicity is higher in non-coding regions of actual genomes) at least suggest the possibility that nucleosome positions are the product of a mechanical evolution of DNA molecules, i.e., that there is a genomic code for nucleosome positioning in eukaryotes.


Why is maintaining a circadian rhythm important? What are the real consequences of never maintaining a circadian rhythm?
How is circadian rhythm important for health and function? Where did it arise in evolution?

In theory, having a circadian rhythm should help anticipating daily environmental changes (light, temperature etc.) so that the metabolic performance is maximized.

In practice, mice chronically exposed to environmental light-dark cycles with a period length dramatically shorter or longer than that of their circadian clock are prone to become obese. Moreover, animals kept under short cycles die earlier than mice kept under normal or extended cycles. So, chronic circadian disturbance by a shortened light-dark cycle increases mortality (at least in mice). In humans, shift workers are likely the population that is more susceptible to circadian cycle derangements.

Ref: Park et al., Neurobiol Aging. 2011


What is meant by 'topologically continuous' in the context of cell compartmentalisation? I am reading the textbook 'Molecular Biology of the Cell', and I am reading the chapter about the compartmentalisation of cells. I have come across the following statement:

The nucleus and the cytosol, which communicate with each other through
nuclear pore complexes and are topologically continuous (although
functionally distinct).

With regards to the above statement, what is meant by 'topologically continuous'? Any insights are appreciated.

What "topologically continuous" appears to mean in this context is that materials can flow between them.
So far as I am aware, this is not a well-defined mathematical term, which is part of what makes this confusing. In topology, some spaces are continuous and others are not, but the meaning of "continuous" in topology is rather more general than the authors usage here.


How far can parrots fly without needing to land? This is for a story I'm writing.  I can't find any information on how far various parrot species can travel without needing to land-- the closest I could find is this page saying that a macaw flies up to 15 miles looking for food.  Intuitively I would think that larger birds, like macaws and African greys, would be able to fly farther than smaller ones due to having stronger wings, but the nonstop-flight record-holder is about the size of a robin so I guess that's not necessarily true.

Can anyone tell me how far various parrots can fly in a stretch, or at least the farthest that any parrot species can fly?

Birds of flight were the original inspiration for the design of a machine that could fly and carry a person aloft, hence it's not surprising that the aerodynamics of avian flight and aircraft have much in common. Specifically, they both consume mass as the source of energy to maintain flight; jet fuel or gasoline in the case of airplanes, and stored body fat in birds, and they both have wings that provide aerodynamic lift as the air moves over them during flight. In addition, both share another characteristic of flight, the ability to glide, to continue flight without providing any of their own energy to maintain that flight. This energy is provided by the atmosphere itself in the form of rising air currents caused by a difference in temperature of a local 'pocket' of air; a pocket of air that is warmer than the surrounding air will rise because it has lower density, the Archimedes Principle in action. A similar process occurs when a parcel of moist air is surrounded by dry air at the same temperature as the moist air hence less dense than dry air. The third source of rising air is due to the local topography; the air on the windward side of a ridge or mountain is forced upward and is frequently used by birds as a source of lift.

Any discussion of gliding flight will unavoidably involve some aspects of atmospheric physics (a.k.a., weather), it's no different here. As stated above, a parcel of moist air surrounded by dry(er) air at the same temperature will rise. As long as that temperature is above the saturation temperature (the dew point) for that parcel of air, the water will remain in vapor form. We all know that as we go higher in the atmosphere the temperature drops; it's cooler at the top of a mountain than at its base. Therefore, as our parcel of moist air rises its temperature will drop, and eventually that temperature is the same as the dew point in that parcel leading to the condensation of that moisture, i.e., a cloud forms. As a surface of constant temperature in the atmosphere is nearly a level surface, we see clouds in the sky whose bases are all at the same level, the level where this condensation begins. Now, for a little of thermodynamics; when we boil water by adding heat (that is energy) to it, we are turning liquid water into a vapor (steam). Here's the thing, when we cool that steam down to the dew point it will condense back into liquid water, and in doing so, we get the heat (that was put in to make it boil) back again! That recovered heat shows up as an increase in temperature of the air that just gave up the water vapor. This increase in temperature causes that air to continue to rise, now due to a temperature difference with the surrounding air rather than a water vapor pressure difference; the cloud continues to grow upwards. This is the source of the cumulonimbus clouds we see in the sky that may eventually form thunderstorms. This discussion hi-lights a key fact about weather that relates directly to our discussion about gliding flight; if there are no updrafts, there are no clouds. That's correct, for a cloud to form, there must be updrafts containing moist air. No clouds indicates no updrafts. If there are no updrafts, there is no gliding flight. However, we note that really dry air is very hard to find; there still might be thermals around, but not likely, and those not very strong. The take away from this discussion is this: if we want to include increases in maximum range resulting from gliding flight, we need to be able to predict the weather (which hasn't happened yet, and I say this as one who has spent years as an undergraduate and graduate student active in atmospheric research.). Hence, long distance gliding flight will not be addressed any further here.

We begin our analysis of powered flight by considering a specific airplane, say a Boeing 787 passenger jet. To find its maximum range, the aircraft would be completely fueled up, take off and fly a level, constant speed flight path, as any accelerations (by changing altitude or going faster) would waist fuel. When the fuel tank goes dry, you have reached the maximum range of powered flight (assuming no head or tail winds of course).

From an analytic point of view, the fuel carried by the 787 is the source of energy, $E_s$, that powers its engines. These engines produce the thrust force, $\mathbf{T} = T\mathbf{\hat{T}}$ directed horizontally, parallel to the 787's longitudinal axis and to the flight path, that counteracts the effect of the atmospheric drag force, $\mathbf{D} = D\mathbf{\hat{D}}$ that opposes the 787's motion along its flight path. Under steady flight conditions (constant speed and altitude), the net horizontal forces on the 787 is zero so that $\mathbf{T} + \mathbf{D} = \mathbf{0}$, or $\mathbf{D}=-\mathbf{T}$. Taking the magnitude of both sides of this expression we find that $D=T$ so that $\mathbf{\hat{D}}=-\mathbf{\hat{T}}$. We find that the thrust generated by the engines has the same magnitude as, but directed opposite to the atmospheric drag.

Under the same flight conditions, we find a similar relationship for the vertical components of force acting on the 787, its weight, $\mathbf{F}_w = F_w\mathbf{\hat{F}}_w$ is balanced by the lift $\mathbf{L} = L\mathbf{\hat{L}}$ generated by the wings so that $F_w = m_p g = L$ and $\mathbf{\hat{L}}=-\mathbf{\hat{F}}_w$ where $m_p$ is the instantaneous mass (= takeoff mass of the plane, $m_{p_0}$, less the mass of fuel expended so far generating thrust) of the 787 and $g=9.8\, \text{m/s}^2$ is the standard gravitational acceleration on the surface of the Earth. We note here, that under these flight conditions, both $\mathbf{L}$ and $\mathbf{F}_w$ are perpendicular to $\mathbf{T}$ and $\mathbf{D}$.

If the thrust is removed so that $\mathbf{T}=\mathbf{0}$, then the drag force will no longer be opposed and will slow the plane down, reducing the speed of air flowing over the wing, which in turn will cause the wing to generate less lift, thus initiating the plane's descent (its weight is greater than the lift produced by the wings). If the plane is then 'nosed down' by an angle $\alpha$ from the horizontal, the projection of the plane's weight vector, $\mathbf{F}_w$ onto the plane's longitudinal axis will no longer be zero, but will instead be $\mathbf{F}_w\sin\alpha$ directed forward opposing the drag force. If $\alpha$ is chosen so that the sum of this projection and the drag vector is zero, then the plane will descend at a constant rate and the magnitude of the drag is given by $D = F_w\sin\alpha$. The projection of the weight vector onto the axis perpendicular to the plane's longitudinal axis, $\mathbf{F}_w\cos\alpha$, is balanced by the equal magnitude but oppositely directed lift vector, whose magnitude now becomes $L = F_w\cos\alpha$. If we form the ratio $D/L$ we find
\begin{equation}
\frac{D}{L} = \frac{F_w\sin\alpha}{F_w\cos\alpha} = \tan{\alpha} \tag{1}\label{1}
\end{equation}
The inverse of this ratio, $L_D = L/D = (\tan\alpha)^{-1}$, is known in aerodynamics as the lift to drag ratio while the angle $\alpha$ is called the glide slope angle. These two  parameters are important in the overall characterization of the aerodynamics of an air-frame. Once this ratio is known, it can be used to estimate the drag in level flight. But in level flight, the lift is equal in magnitude to the plane's weight, $L=F_w=m_p g$. Substituting this expression into Eq.~$\eqref{1}$ and solving for the drag
\begin{equation}
D = L\tan\alpha = F_w\tan\alpha = m_p g\tan\alpha  \tag{2}\label{2}
\end{equation}

We have reached the point in our analyses that we need to address the mass/energy budget for the plane's flight. It will be useful to separate the mass of the plane into its empty (no fuel) mass, $m_{p_e}$, and the mass of available fuel, $m_f$, with the initial, takeoff mass of fuel given by $m_{f_0}$. With these quantities defined, the initial takeoff mass of the plane is given by $m_{p_0} = m_{p_e} + m_{f_0}$ while the instantaneous mass is given by $m_p = m_{p_e} + m_f$. During flight, the mass of the fuel available, $m_f$, varies such that $m_{f_0} \ge m_f \ge 0$ while the mass of the plane, $m_p$, varies as $m_{p_0} \ge m_p \ge m_{p_e}$.

There are two additional constants required to determine the net effective energy available to do work against the drag force when consuming the (differential) quantity $\delta m_f$ of fuel while flying the (differential) distance $\delta \mathbf{r}$. The first of these, $\kappa$, determines the total (differential) energy, $\delta E$, available from the combustion of the quantity $\delta m_f$ of fuel
\begin{equation}
\delta E = \kappa \delta m_f   \tag{3}\label{3}
\end{equation}
For an American airplane such as the 787, $\kappa$ will have units something like BTU per pound of fuel expended.
The second, $\eta$, specifies the efficiency of converting the available energy into actual work, $\delta W$, generating thrust that counteracts the drag
\begin{equation}
\delta W = \eta \delta E = \eta \kappa \delta m_f = - \mathbf{T}\cdot\delta\mathbf{r} = - m_p g\tan\alpha \delta r \tag{4}\label{4}
\end{equation}
where $\delta\mathbf{r} = \delta r \mathbf{\hat{T}}$ is a differential displacement vector along the flight path during constant velocity, horizontal motion and the minus sign accounts for the fact that the plane's energy stores are consumed as that energy is used to counteract drag (a fundamentally dissipative process).

Letting the $\delta$'s become derivatives, dividing through by $m_p$ and using $m_p = m_{p_e} + m_f$ and replacing the integrated variables by primed quantities, , Eq.~$\eqref{4}$ can be rewritten in the integral form
\begin{equation}
\eta \kappa \int_{m_{f_0}}^{m_f} \frac{dm'}{m_{p_0} + m'}
= - g\tan\alpha \int_0^r dr'   \tag{5}\label{5}
\end{equation}
with the limits of integration evaluated at takeoff and the current downrange position a distance $r$ from takeoff.

Performing the integrations indicated in Eq.~$\eqref{5}$ and simplifying, we have the result
\begin{equation}
m_p = m_{p_0} e^{-\frac{g\tan\alpha}{\kappa\eta}r}   \tag{6}\label{6}
\end{equation}
We find that the mass of the plane, $m_p$, is an exponentially decreasing function of the distance flown, $r$. Letting $r=r_m$ be the maximum range of plane where all fuel has been expended (when $m_f=0$ so that $m_p = m_{p_e}$), Eq.~$\eqref{6}$ becomes
\begin{equation}
m_{p_e} = m_{p_0} e^{-\frac{g\tan\alpha}{\kappa\eta}r_m}   \tag{7}\label{7}
\end{equation}
We note the similarity of this expression to that of the Tsiolkovsky rocket equation.

Eq.~$\eqref{7}$ can be solved for the maximum range $r_m$
\begin{equation}
r_m = \frac{\kappa\eta}{g\tan\alpha}\ln\left(\frac{m_{p_0}}{m_{p_e}}\right)
   \tag{8}\label{8}
\end{equation}
an amazingly simple result, all things considered! This result remains valid for any aerodynamic system that obtains its lift via forward motion through the air provided by a propulsion system that consumes mass to produce thrust. It could be applied to a Cessna 172, or even a nitro powered radio controlled (RC) model of a 172. It could not be applied to an electrically (battery) powered model of the 172 because there is no mass loss from a battery, or to any type of glider (no thrust or mass loss). And it can, however, be applied to any bird of flight, including our parrot!

For the parrot, the energy source is the fat stored in its body. This mass is consumed through metabolic processes that convert it into $\text{CO}_2$ and water vapor that is expelled during respiration, and as sweat and urine as the parrot flies (the parrot's "exhaust" as it were!). The energy content of body fat ($\kappa$ as defined in Eq.~$\eqref{3}$) is 9 (food) Calories per gram. One food Calorie is equal to one kilocalorie which is in turn equal to 4184 Joules in SI units, see the Wikipedia article Food energy.

The efficiency of converting stored energy in the human body into mechanical work has been estimated to be $18\%$ -- $26\%$ (see Wikipedia page Muscle). One would expect similar numbers for other warm blooded vertebrates, so that, to one significant figure, we take $\eta = 20\% = 0.2$ (a dimensionless quantity).

There seems to be a very broad range for the percent of body mass that is fat. Some migratory birds have up to $70\%$ (see Obese super athletes: fat-fueled migration in birds and bats, however the parrot is not generally considered a migratory bird. The web page Comparison of flight mileage for various wild parrot species states a migration distance of 320 km for Thick-billed Parrots for example. Hence the $70\%$ number is likely far too large. At the other extreme, ground beef is considered lean if it contains $10\%$ fat, but more generally it is closer to $20\%$. We will select a value somewhat below the median of these extremes, say $35\%$.

A typical mass for a parrot is another difficult number to ascertain, as there is a very large difference in body mass for the various members of the parrot family. For example, the web page Average Bird Weights of Common Parrot Species gives data for 52 parrot species with links to four other species, each with several entries. These vary from 10 grams for the Zebra finch to 1530 grams for the Green-winged Macaw covering a mass range of over two orders of magnitude! Upshot: there is no such thing as a "typical" parrot! We will choose the Thick-billed Parrot as we have some long distance data to compare our result to. The Wikipedia page Thick-billed parrot gives its mass range as 315-370 grams, we shall use 370 grams so that $m_{p_0} = 0.37 \, \text{kg}$, $35\%$ of which is to be considered fuel so that $m_{f_0} = 0.16 \, \text{kg}$ leaving the parrot's 'empty mass' at $m_{p_e} = 0.24 \, \text{kg}$.

We have one remaining parameter to estimate, that being the glide slope angle, $\alpha$, used to find the lift to drag ratio above. Consider the order of magnitude estimates of $\alpha = 10^0 = 1\, \text{radian} \approx 60^o$, $\alpha = 10^{-1} = 0.1\, \text{radian} \approx 6^o$ or $\alpha = 10^{-2} = 0.01\, \text{radian} \approx 0.6^o$. Clearly $60^o$ is far too steep and $0.6^o$ is much too shallow, leaving $6^o$ as the only acceptable order of magnitude choice, hence we set $\alpha=10^{-1}$ radian, a number valid for most birds of flight.

Repeating Eq.~$\eqref{8}$ above,
$$
r_m = \frac{\kappa\eta}{g\tan\alpha}\ln\left(\frac{m_{p_0}}{m_{p_e}}\right)
$$
and substituting the parrot's values from above (including unit conversion factors)

$$
r_m= \frac{\left[\left(\frac{4184\,\text{J}}{\text{gm}}\right)
\left(\frac{1000\,\text{gm}}{\text{kg}}\right)
\left(\frac{\text{kg m}^2}{\text{J s}^2}\right)
\right] \left(0.2\right)}
{\left(\frac{9.8\,\text{m}}{\text{s}^2}\right)
\left(\tan\left(0.1\right)\right)}
\ln\left(\frac{0.37\,\text{kg}}{0.24\,\text{kg}}\right)
\approx 370 \text{ km }
$$

we find the answer to the question, "How Far Can a Parrot Fly [under power] in a Single Day?" to be

$$
\boxed{r_m\approx 370\, \text{km}}
$$

a number which is in close agreement with the (limited) data available which gave an actual (vs maximum) daily migration range of 320 km.

It's interesting to note that this maximum range for powered flight can be viewed as the minimum range when gliding flight is included. Under ideal weather conditions, the actual maximum range could be extended considerably if the parrot were to capitalize on any available thermals it encountered during its flight.


Have webs woven by LSD-intoxicated spiders ever been studied for their efficiency in fly catching? I ask, because I have a different interpretation of the experiments performed on web-weaving spiders. The famous Robert Pirsig maintains that LSD is somehow helpful to web-weaving spiders, because it makes their web more straight. Pirsig seems to imply, as I remember, that the spider is somehow more attentive to its web while on LSD.

However, I maintain that it isn't the case and that it is actually the reverse.  The spider is much less attentive, for it needs chaos in its web to catch the fly!

Short answer
A low dose of LSD has been shown to lead to larger, more regular webs. This obsessive perfection of the web comes with an increased effort and likely an increased required building time. Whether LSD-affected webs are more effective or not has not been assessed as far as I am aware. Personally I think that, if anything, larger webs are more efficient for their purpose, regardless of their enhanced regularity.

Background
I traced down the experiments with d-lysergic acid dietheylamide (LSD-25) and web-building spiders to the experiments of [Peter Witt]*1 performed in the 1950's and 60's.

The original article of Witt (1951), dealing with the effects of LSD on the web building behavior of spiders (Zygiellax nohta) is not accessible to me. He reiterates on the data in a review (Witt, 1971). In this review he discusses the effect of a low dose of LSD on web building (Fig. 1).

Fig. 1. Web of an untreated spider (Araneus diadematus) (left) and a web of a spider (Zygiellax nohta) treated with a low dose of LSD-25. Source: Witt, 1971

Witt concludes that low dosages of LSD increase the regularity of the webs. Spiders which had received less than 0.05 pg LSD-25 built larger webs, with fewer oversized angles and significantly more regular central angles. The spiral was unusually regularly spaced. He did not investigate the effectiveness of these webs (Witt, 1971). However, I reckon that because of the larger size they may be more effective.

Witt notes that the normal web is far from a perfect geometric structure and that one can think of a web as a compromise between regularity, which serves to cover a wide area with a trap of a certain mesh size, and a quick construction. For example, Araneus diadematus makes a new web every morning before sunrise. It requires quite some labor producing and the webs are, arguably, structures of precision and beauty (Fig. 1). The webs take between 20 and 30 minutes to build. (Witt, 1971).

The balance between regularity and quick construction of the web is what may be distorted after relatively low doses of LSD (Witt, 1971). The spider seems to put too much and almost compulsory effort in making the perfect web, and likely without too much benefit in efficiency (The Guardian, 1971). But again, the author has not addressed this hypothesis directly.

Note that higher dosages of LSD (>0.05 pg) result in smaller and more irregular webs. The Guardian (1971) reproduced some figures on this (Fig. 2), showing an example of a grossly distorted and inefficient web.

Fig. 2. Web before and after a high dose of LSD. Source: The Guardian (1971)

References
- Witt, Experientia (1951); 7(8): 310-1
- Witt, Behav Sci (1971); 16(1): 98-113

Note
*Robert Pirsig is an American writer and philosopher who has not devoted his time to spiders as far as I know.


Why is methanol poisonous? What should we do when someone is diagnosed with the methanol poisoning What harm does methanol cause on our body, such as the harm to some proteins? What first-aid measures should we take?

Methanol is highly toxic in humans. As little as 10 ml of pure methanol can destroy the optic nerve and cause permanent blindness,  while 30 ml dose is fatal (Vale et al, 2007). However, its toxic effects take hours to come up after ingestion,  and antidotes are often helpful in preventing permanent damage.

Methanol exerts its toxic effects by two main methods:

Much similar to ethanol, methanol is also a CNS depressant since it enhances the activity of inhibitory neurotransmitter GABA and also interferes with excitatory neurotransmitters.
When ingested, methanol is converted in liver first to methanal by alcohol dehydrogenase, and then to methanoic acid (or formic acid) by aldehyde dehydrogenase (Schep et al, 2009). Under cellular pH,  formic acid exists as formate. Formate interferes with the mitochondrial enzyme cytochrome c oxidase, causing cellular hypoxia and metabolic acidosis (Liesivuori et al, 1991).

To prevent methanol toxicity, two kinds of antidotes are used:

Bicarbonate can alter the metabolic acidosis and potentially reverses the visual deficits.
Ethanol and fomepizole are also used as antidotes to methanol. Since the affinity of liver enzymes alcohol dehydrogenase and aldehyde dehydrogenase is about 10-20 times more for ethanol than methanol, ethanol can thus prevent (or at least delay) metabolism of methanol to formate. During this time, methanol can be removed from the body by kidneys or through dialysis. Fomepizole is also metabolized by the same enzymes, but ethanol is generally preferred due to high cost and low availability of fomepizole (Medscape). Thus, intravenous injections of ethanol can (under some circumstances)  serve as a first-aid measure (although consulting a physician is always the best option).

References:

Vale A (2007). "Methanol". Medicine. 35 (12): 633–4. doi:10.1016/j.mpmed.2007.09.014.
Schep LJ, Slaughter RJ, Vale JA, Beasley DM (2009). "A seaman with blindness and confusion". BMJ. 339: b3929. doi:10.1136/bmj.b3929.
Liesivuori J, Savolainen H (September 1991). "Methanol and formic acid toxicity: biochemical mechanisms". Pharmacol. Toxicol. 69 (3): 157–63. doi:10.1111/j.1600-0773.1991.tb01290.x
Methanol Toxicity Treatment & Management: Medscape


Are there any drugs that target the lipid envelope of viruses? Many drugs go after the unique viral enzymes but do any target their lipids? Viral membranes are of course similar to the host membrane but might have a different composition and do have a different curvature and protein composition. Is anybody aware of research or even existing drugs that attempt to hit the lipid envelope of viruses to limit them?

There are evolved molecules that target the lipid membrane, for example. A subgroup of those pore-forming toxins are cholesterol-dependent, so they might target a membrane high in cholesterol over one low in it. I'm trying to think out of the box here whether properties of the viral lipid membrane could be exploited in a similar way.

The lipids in the viral envelope come from chunks of the host cell membrane. Therefore, something targeting those lipids is unlikely to be virus-specific, and not suitable for use in a living animal.

Out in the environment where the virus is found in surfaces and such, sure, one can target the lipid envelope using soaps/detergents and such, but you wouldn't want to take those internally.


What's the cause of the scars on these cherries? These cherries have some scars. Are they coming from a disease? Is it correct to call them "Cherry scabs"?

Here's the photo:  -

Are they coming from a disease?

No, this appears to be a combination of rain damage and pests. If a disease were present, much more of the cherry would suffer, there would be signs of rotting, and, the damage wouldn't solely be so superficial, as is the case in your posted images.

Consider the next few images which demonstrate the effects that various diseases have on a cherry, and notice how much more detrimental [and different] the impact.

Bitter Rot (Colletrotrichum gloeosporioides & C. acutatum)

Brown Rot (Monolinia fructicola)

Alternaria Rot (Alternaria sp.)

There are other [equally common] diseases of cherry trees (Prunus sp.), including cherry spot leaf, black knot, silver leaf, and PNRSV, however, in pretty much all of these cases too, there's no modification to the cherry fruit (excluding extreme circumstances, as is the case with spot leaf, I believe).

Instead, as mentioned, one major cause of the damage is rain. Just before harvest, when the cherry is at it's greatest [and possibly maximum] volume, rain that's absorbed through the surface of the cherry causes the cherry to further enlarge, which ultimately splits the cuticle (skin). The result is the following:

For more information on cherry splitting/cracking:

Fruit Splitting (Cracking) – What causes it and can we do anything about it?
Fruit Split In Cherries: Learn Why Cherry Fruits Split Open
A Review of Cherry Fruit Cracking
Story: Stone fruit and the summerfruit industry
Cherry Weather Worries

Given the irregularities of scarring on some of the cherries, I also suggest that insects and/or birds scratched/ate away at them. Consider the following images that illustrate the kind of damage that birds & wasps cause when feeding on cherries, and notice the similarities to those in your images.

bird damage

wasp damage

This, in combination with the rain, is most likely what caused damage to your cherries.

  Is it correct to call them "Cherry scabs"?

I just call it scarring, and I believe many other people do too. I'm not sure if there's a specific term for fruit damage that's then been "scabbed" over. If someone knows of a term for this, please provide in a comment and I will supplement my response with it. Thank you.

While continuing to research this topic, specifically when attempting to find alternative reasons that could explain this kind of damage, I did ran across this article which talks about wind damage, and provides an image that slightly resembles the markings on your cherries. I'm still heavily convinced though that your cherries suffered their damage from rain & pests.


How to search for a DNA sequence in a genome on ENA (European Nucleotide Archive)? I have to do a search for small DNA sequences in the genome of an organism in ENA. I have the accession number and project id. However, I can't download the whole genome because of the download size and would prefer to do it online if possible. I have a rough idea of the part of the genome I wish to scan in, don't know if that's relevant.

While it is much better/easier to download and do the exact search on your own, it is possible to do something similar, online. You can use NCBI-BLAST and increase the word length and mismatch/gap penalty. It also allows restricting the subject space; you can even align two sequences. The BLAST on ENA does not have much flexibility (subject restriction/word length). Perhaps you can look for a duplicate sequence on NCBI.

If this genome is available on UCSC genome browser then you can use BLAT too. However, it only accepts sequences larger than 19nt.


Why is polyploidy lethal for some organisms while for others is not? Polyploidy is the multiplication of number of chromosomal sets from 2n to 3n (triploidy), 4n (tetraploidy) and so on. It is quite common in plants, for example many crops like wheat or Brassica forms. It seems to be rarer in animals but still it is present among some amphibian species like Xenopus.

As I know in mammals polyploidy is lethal (I don't mean tissue - limited polyploidy). I understand that triploidy is harmful due to stronger influence of maternal or paternal epigenetic traits that cause abnormal development of placenta, but why there is no tetraploid mammals?

Great question, and one about which there has historically been a lot of speculation, and there is currently a lot of misinformation. I will first address the two answers given by other users, which are both incorrect but have been historically suggested by scientists. Then I will try to explain the current understanding (which is not simple or complete). My answer is derived directly from the literature, and in particular from Mable (2004), which in turn is part of the 2004 special issue of the Biological Journal of the Linnean Society tackling the subject.

The 'sex' answer...

In 1925 HJ Muller addressed this question in a famous paper, "Why polyploidy is rarer in animals than in plants" (Muller, 1925). Muller briefly described the phenomenon that polyploidy was frequently observed in plants, but rarely in animals. The explanation, he said, was simple (and is approximate to that described in Matthew Piziak's answer):

  animals usually have two sexes which are differentiated by means of a process involving the diploid mechanism of segregation and combination whereas plants-at least the higher plants-are usually hermaphroditic.

Muller then elaborated with three explanations of the mechanism:

He assumed that triploidy was usually the intermediate step in chromosome duplication. This would cause problems, because if most animals' sex was determined by the ratios of chromosomes (as in Drosophila), triploidy would lead to sterility.
In the rare cases when a tetraploid was accidentally created, it would have to breed with diploids, and this would result in a (presumably sterile) triploid.
If, by chance, two tetraploids were to arise and mate, they would be at a disadvantage because, he said, they would be randomly allocated sex chromosomes and this would lead to a higher proportion of non-viable offspring, and thus the polyploid line would be outcompeted by the diploid.

Unfortunately, whilst the first two points are valid facts about polyploids, the third point is incorrect. A major flaw with Muller's explanation is that it only applies to animals with chromosomal ratio-based sex determination, which we have since discovered is actually relatively few animals. In 1925 there was comparatively little systematic study of life, so we really didn't know what proportion of plant or animal taxa showed polyploidy. Muller's answer doesn't explain why most animals, e.g. those with Y-dominant sex determination, exhibit relatively little polyploidy. Another line of evidence disproving Muller's answer is that, in fact, polyploidy is very common among dioecious plants (those with separate male and female plants; e.g. Westergaard, 1958), while Muller's theory predicts that prevalence in this group should be as low as in animals.

The 'complexity' answer...

Another answer with some historical clout is the one given by Daniel Standage in his answer, and has been given by various scientists over the years (e.g. Stebbins, 1950). This answer states that animals are more complex than plants, so complex that their molecular machinery is much more finely balanced and is disturbed by having multiple genome copies.

This answer has been soundly rejected (e.g. by Orr, 1990) on the basis of two key facts. Firstly, whilst polyploidy is unusual in animals, it does occur. Various animals with hermaphroditic or parthenogenetic modes of reproduction frequently show polyploidy. There are also examples of Mammalian polyploidy (e.g. Gallardo et al., 2004). In addition, polyploidy can be artificially induced in a wide range of animal species, with no deleterious effects (in fact it often causes something akin to hybrid vigour; Jackson, 1976).

It's also worth noting here that since the 1960s Susumo Ohno (e.g. Ohno et al. 1968; Ohno 1970; Ohno 1999) has been proposing that vertebrate evolution involved multiple whole-genome duplication events (in addition to smaller duplications). There is now significant evidence to support this idea, reviewed in Furlong & Holland (2004). If true, it further highlights that animals being more complex (itself a large, and in my view false, assumption) does not preclude polyploidy.

The modern synthesis...

And so to the present day. As reviewed in Mable (2004), it is now thought that:

Polyploidy is an important evolutionary mechanism which was and is probably responsible for a great deal of biological diversity.
Polyploidy arises easily in both animals and plants, but reproductive strategies might prevent it from propagating in certain circumstances, rather than any reduction in fitness resulting from the genome duplication.
Polyploidy may be more prevalent in animals than previously expected, and the imbalance in data arises from the fact that cytogenetics (i.e. chromosome counting) of large populations of wild specimens is a very common practise in botany, and very uncommon in zoology.

In addition, there are now several new suspected factors involved in ploidy which are currently being investigated:

Polyploidy is more common in species from high latitudes (temperate climates) and high altitudes (Soltis & Soltis, 1999). Polyploidy frequently occurs by the production of unreduced gametes (through meiotic non-disjunction), and it has been shown that unreduced gametes are produced with higher frequency in response to environmental fluctuations. This predicts that polyploidy should be more likely to occur in the first place in fluctuating environments (which are more common at higher latitudes and altitudes).
Triploid individuals, the most likely initial result of a genome duplication event, in animals and plants often die before reaching sexual maturity, or have low fertility. However, if triploid individuals do reproduce, there is a chance of even-ploid (fertile) individuals resulting. This probability is increased if the species produces large numbers of both male and female gametes, or has some mechanism of bypassing the triploid individual stage. This may largely explain why many species with 'alternative' sexual modes (apomictic, automictic, unisexual, or gynogenetic) show polyploidy, as they can keep replicating tetraploids, thus increasing the chance that eventually a sexual encounter with another tetraploid will create a new polyploid line. In this way, non-sexual species may be a crucial evolutionary intermediate in generating sexual polyploid species. Species with external fertilisation are more likely to establish polyploid lines - a greater proportion of gametes are involved in fertilisation events and therefore two tetraploid gametes are more likely to meet.
Finally, polyploidy is more likely to occur in species with assortative mixing. That is, when a tetraploid gamete is formed, if the genome duplication somehow affects the individual so as to make it more likely that it will be fertilised by another tetraploid, then it is more likely that a polyploid line will be established. Thus it may be partly down to evolutionary chance as to how easily a species' reproductive traits are affected. For example in plants, tetraploids often have larger flowers or other organs, and thus are preferentially attractive to pollinators. In frogs, genome duplication leads to changes in the vocal apparatus which can lead to immediate reproductive isolation of polyploids.

References

Furlong, R.F. & Holland, P.W.H. (2004) Polyploidy in vertebrate ancestry: Ohno and beyond. Biological Journal of the Linnean Society. 82 (4), 425–430.
Gallardo, M.H., Kausel, G., Jiménez, A., Bacquet, C., González, C., Figueroa, J., Köhler, N. & Ojeda, R. (2004) Whole-genome duplications in South American desert rodents (Octodontidae). Biological Journal of the Linnean Society. 82 (4), 443–451.
Jackson, R.C. (1976) Evolution and Systematic Significance of Polyploidy. Annual Review of Ecology and Systematics. 7209–234.
Mable, B.K. (2004) ‘Why polyploidy is rarer in animals than in plants’: myths and mechanisms. Biological Journal of the Linnean Society. 82 (4), 453–466.
Muller, H.J. (1925) Why Polyploidy is Rarer in Animals Than in Plants. The American Naturalist. 59 (663), 346–353.
Ohno, S. (1970) Evolution by gene duplication.
Ohno, S. (1999) Gene duplication and the uniqueness of vertebrate genomes circa 1970–1999. Seminars in Cell & Developmental Biology. 10 (5), 517–522.
Ohno, S., Wolf, U. & Atkin, N.B. (1968) EVOLUTION FROM FISH TO MAMMALS BY GENE DUPLICATION. Hereditas. 59 (1), 169–187.
Orr, H.A. (1990) ‘Why Polyploidy is Rarer in Animals Than in Plants’ Revisited. The American Naturalist. 136 (6), 759–770.
Soltis, D.E. & Soltis, P.S. (1999) Polyploidy: recurrent formation and genome evolution. Trends in Ecology & Evolution. 14 (9), 348–352.
Stebbins, C.L. (1950) Variation and evolution in plants.
Westergaard, M. (1958) The Mechanism of Sex Determination in Dioecious Flowering Plants. In: Advances in Genetics. Academic Press. pp. 217–281.

(I'll come back and add links to the references later)


Is there a dominant gene for right-handedness? Has there been any definitive research about handedness being genetic? Also, why is right-handedness clearly dominant in humans? I'm interested in evolutionary theories, as well as any molecular explanation (if known).

There is a lot of information at OMIM  - too much to summarize here - regarding the genetics of handedness and links to which hemisphere of the brain dominates (in an individual), to schizophrenia (slight association with non-right-handedness), and to hair whorl patterns on the scalp. References are provided at the above link. Basically, hand skill appears to be a complex multifactorial phenotype with a heterogeneous background.


What Species of Duck/Waterfowl is this I snapped a picture of this beaut in Irvine, CA, but I do not believe it is in the list given in "Ducks at a Distance: A Waterfowl Identification Guide" by Bob Hines (http://www.gutenberg.org/ebooks/18884). What species of duck is this? I believe it has the shape of a duck, but the colors are unfamiliar to me.

I think this is an Egyptian Goose (Alopochen aegyptiacus), see the image (First from the Wikipedia article, the second from here, interestingly taken in Irvine):

You can see the distinctive spot around the eye and also the colored feathers on the back. Also, this bird is too big to be a duck.


Does animal fat and meat contributes differently to our body? Is animal fat harmful to our body or is it harmful if the amount eaten exceeds a certain amount?
I have heard fat is more concentrated than protein. If I am correct then we can get more energy from fat. Then why is fat not desirable?
Our ancestors used all the parts from their hunt, even the fat. How did it work for them?
Would eating fat be beneficial for an athlete? (May be for different purposes: power, endurance or building muscle)

Have you read the Wikipedia article on Fat?  It has literally all of the answers you are seeking.  However...

1: Every single thing is bad for you if you get too much of it.  Animal fat, sugar, water, you can over-do it on anything.  Fat can be bad for you but it is definitely required.  In particular, "Vitamins A, D, E, and K are fat-soluble, meaning they can only be digested, absorbed, and transported in conjunction with fats. Fats are also sources of essential fatty acids, an important dietary requirement."  Fat does a host of other things, as mentioned in the article.

2: Fat is indeed a concentrated store of energy, but there's more to life than just energy.  Protein, like other nutrients, are required for life.  Protein happens to be particularly important, providing the structure for all our cells, is required for muscle growth, and provides amino acids, which are needed to make other proteins in your body.  Proteins are used as hormones, cellular messengers, immune receptors, so on and so forth.  You couldn't live without protein.  Energy, while concentrated in fat, could come from elsewhere.

3: It worked just the same for them as for us.  I will add, however, that our ancestors did not necessarily use every part from every animal, and these days, we actually use every part of many animals, just not always for food.

4: Sure?  Energy is good, but protein is probably better.  "Athlete" is a vague term, as strength-training and endurance activities are very different from each other.  Protein is probably better for strength, carbohydrates are probably better for endurance.  But you can ask over at https://fitness.stackexchange.com/.


Open database of medical images Does anyone know of an open repository of medical images (e.g., CT scans) organized by disease category? I'm working on some computer vision software that requires a large set of controls from which to learn.

Open-access medical images:

MedPix (by keyword, organic system, pathology and diagnosis A-Z)
Radiopaedia (by keyword)
PEIR Radiology (by keyword, organ or anatomic region)
Ultrasound Cases (by keyword and organic system)
Open Access Biomedical Image Search Engine (Openi) (by keyword)
Wikimedia Commons (by keyword)
Google image search (using the filter "creative commons," "public domain" or "open access")
Google image search (using filters: black/white, noncommercial, photo)

More:

Gray's Anatomy
Dermatology Atlas


How can a homozygous mutation, considered pathogenic, occur on a gene such as HFE without the disease developing? What happens when you have a homozygous mutation on a gene (eg. a swapped base), that is considered pathogenic, but without developing the disease?

It it were a heterozygous mutation I would get it, because we still have at least one healthy/wild-type copy of the gene, so at most the disease will just manifest in a more mild form, but with a homozygous I have no idea how is it possible to NOT develop the disease.

Also, what happens when heterozygous mutations develop the disease? In these cases why does the healthy version of the gene goes "quiet"?

One example is HH caused by HFE gene mutation (mostly C282Y and H63D), and not everyone develops the disease, doesn't matter if they are heterozygous or homozygous.

What happens when you have a homozygous mutation on a gene (eg. a swapped base), that is considered pathogenic, but without developing the disease?

It may be an example of incomplete penetrance of variable expressivity. Simply, you are probably dealing with a complex trait in which either more than one gene is involved, or there is interaction between genetics and envronmental factors.

  Also, what happens when heterozygous mutations develop the disease? In these cases why does the healthy version of the gene goes "quiet"?

I assume you are still talking about a putatively recessive disease. One possible explanation is haploinsufficiency, i.e. the WT allele alone doesn't produce enough transcript and the heterozygous individuals has "problems"

  One example is HH caused by HFE gene mutation (mostly C282Y and H63D), and not everyone develops the disease, doesn't matter if they are heterozygous or homozygous.

And indeed HH is an excellent example of complex disease, in which genetics is involved, but the inheritance is not purely Mendelian.


When is a person declared to be dead? From what I can tell, it is not well defined, but at least in the US it has to do with cessation of cardiopulmonary functionality. Any reliable sources that give a definition of when a human being is considered to be no longer living?

Although there exist some differing opinions mostly to do with brain function, the best answer is definitely the heartbeat. Here's why:

In some ways the human body really does operate like a machine. The process of delivering oxygenated blood is THE foremost example of a time-critical activity that must occur constantly in order to maintain life. That process stops when either breathing or pumping of the heart ceases, and since the circulation of the blood is more immediately critical than breathing it makes sense to place more weight on that criterion.

Some medical conditions can lead to a person being essentially "Brain-dead" before they are biologically dead, but these situations are almost always extreme outliers to the general discussion of alive vs dead. Furthermore, the arguments surrounding that state too often and too easily cross over into philosophical/metaphysical commentary.

The only serious wrinkle to the argument above is hypothermia. This wrinkle is encapsulated quite nicely in the old medics' axiom "You're not dead until you're warm and dead." And it is well documented that hypothermic patients can sometimes be revived after long periods of time - in excess of a half hour - using special techniques and equipment (to prevent frostbite).

Bottom line: Has the subject's heart been pumping any blood (including during CPR chest compressions) in the last 10 minutes? Is the subject hypothermic with a core temperature below 95 degrees Fahrenheit? Answers of "No." and "No." mean that the subject is no longer living.


What is this marmot-like animal (Tigray, Ethiopia)? I was searching what are the animals I frequently saw in the north of Ethiopia. I took some bad quality pictures.

For me it looked like a large squirrel, local people called it a rat, and on the internet I find rock hyraxes are quite frequent in the region, but they appear not to have a long tail like the animals I saw, and they don't have the white lateral line

This looks like some sort of ground squirrel. Especially in the second picture, the posture is  very characteristic of squirrels in general. The tail also looks very squirrel-like to my eyes. My best guess, without better pictures, is the Striped Ground Squirrel (Xerus erythropus).

See the images at:
http://www.flickriver.com/photos/8834404@N02/2902284598/
http://www.flickriver.com/photos/kpzaremba/5094580855/


At which temperature is the Tick-Borne Encephalitis Virus destroyed? At which temperature is the Tick-Borne Encephalitis Virus destroyed? If there is no data specifically for TBEV, is there any data for typical temperatures at which other Flaviviruses / Flaviviridae / other similar viruses are destroyed? (Or if there's nothing specific at all, then viruses in general?)

A very basic model of virus inactivation is exponential decay.

You can describe exponential decay with the $N(t) = N_0e^{-\lambda t}$ equation, of if you want to use half-time, then with the $N(t) = N_02^{-t/t_{1/2}}$, where $N$ is the value which reduces by time, $t$ is the time, $\lambda$ is the exponential decay constant and $t_{1/2}$ is the half-life (the time required to reduce the actual value to its half).

Exponential decay looks like this on diagrams:

Figure 1 - exponential decay

Figure 2 - exponential decay on log scale is linear

In the case of your TBEV virus, the $N_0$ will be the initial virus titer, the $N(t)$ will be the virus titer by a specific time, the $t$ will be the time and the $t_{1/2}$ will be the half-life, which depends on many things; TBEV strain, temperature, dry/moist heat, pH, etc...

Now real life logarithmic diagrams of TBEV thermal inactivation are linear only by the first 30 mins or so (the inactivation is exponential during that period) as you can see on Figure 3.

Figure 3 - virus inactivation at 60°C
2004 - West Nile virus: recent experience with the model virus approach.
where $TCID_50$ is the tissue culture infective dose

By virus inactivation most of the articles like to use log 10 reduction factors. For example $3 lg$ or $3 log 10$ means in this context, that lowering the initial value to $10^3 = 1000$ fold.

According to this article most of the checked TBEV strains has an inactivation index (the reduction factor difference between two temperatures) around 1.7lg between 50°C and 37°C for 15 mins. So you need 15 mins at 50°C to reduce them at least $10^{1.7}=50$ fold. The reduction factor by this study was around 4lg by 37°C for 15mins (so the virus count reduces certainly not just because the heat, but other environmental factors).

  Thermoresistance (Т50) of TBEV strains was tested by Ovchinnikova et
  al. method [17] using 24-hour cell culture grown in 96-hole plates at
  the presence of СО2. The thermoresistance was determined by
  inactivation index – difference in lg of titers of virus samples
  heated at 50°С during 15 minutes or unheated (4°С). In case of titers
  difference equal or less than 2.0 lg the strain was characterized as
  Т50+, from 2.1 to 3.0 lg – as medium, equal or more than 3.1 lg – as
  Т50-.

  The values of lgTCD50/ml at 37ºС varied from 3.5 to 8.26. According to
  the thermoresistanse feature all tested strains were divided into
  three group: thermostable (Т50+) - nine strains; thermolabile (Т50-) –
  one strain; strains with medium thermoresistance – three strains. It
  should be noted that all strains isolated from I. persulcatus ticks
  collected in Krasnochikoiskiy district of Transbaikalia were
  thermostable.

2013 - Genetic and Biological Properties of Original TBEV Strains Group Circulating in Eastern Siberia

According to another study TBEV required 6 hours of moist heat at 60°C for inactivation of 6.6 lg.

  Vapor heating of a FVII concentrate in another study (which used
  lyophilization, followed by adding water to achieve homogenous
  moistening, then heating at 60°C for 10 hours, followed by heating at
  80°C for one hour in an airtight container under nitrogen gas
  atmosphere) was evaluated for its ability to inactivate HAV, HIV-1,
  TBEV, PRV, and MVM. HAV was readily inactivated within one hour at
  60°C (5.9 log 10 ). TBEV required six hours of this treatment for
  inactivation of 6.6 log 10 , and three hours were required to
  inactivate
  6.2 log 10 of HIV-1 and 6.9 log 10 of PRV.

2002 - Part 3a, Plasma and Plasma Products - Heat and Solvent/Detergent Treatments

According to this study TBEV is considered not heat resistant, so if you are worried for example about raw milk pasteurization, then I think boiling the milk for a few minutes is enough.

  Due to the lipid envelope, TBEV is readily inactivated by heat
  treatment, detergents and organic solvents. Even though a viremic
  phase is common during a TBEV infection in several animal species,
  foodborne infection via contaminated meat or organs is unlikely due to
  the fast virus inactivation at elevated temperatures.

2011 - Scientific Opinion on an update on the present knowledge on the
occurrence and control of foodborne viruses


Is Sinus node conduction necessary for heart beating? Assume a patient with previous cardial infaction which SA node not possible to activate action potential anymore.
However, SA trying to beat unsuccessfully repeatedly waisting energy.
Therefore, I thought in this discussion about the possibility to stop Sinus node from trying to start action potential; which was deleted but the article about the SSS (sick SA) and remodelling is about its goal. The proposed treatment (laser ablation) of AF/AFL can backfire and cause SN (Sick Node) through remodeling. Assume there is no bypass of impulses through SA node.

Can the heart still beat through AV node and bundle? Yes.
Do you have any evidence that [heart] can "beat" properly on just the AVN? Yes, see article. Short-term mechanisms where electrical/metabolic remodeling. Long-term mechanisms where irregular rhythms and complete heart block can occur because of anatomical remodeling.

I want to know if these pacemakers are in series or parallel.
If they are in series, then laser operation can be dangerous to the SA node.
The series connection is however the idea which I get from many schematic drawings:

The SA node is not necessary for contraction of the heart.

The reason that this works is exactly what you mentioned: schematics.

They are in sequence, but within that sequence, there are multiple autonomous signal generators in the heart, where spontaneous depolarization occurs to initiate contraction: the SA node, the AV node, and the purkinje fibers.

The SA node fires the most rapidly, 60-90 times per minute - which is the average normal heartrate, because in most people the signal for contraction arises from the SA.

The AV node fires at 46-60 times per minute.  If it receives the signal from the SA node then it depolarizes in sequence like the normal sequence we learn.  But if there is no SA node signal received, the AV node will depolarize on its own.

The last "generator" are the perkinje fibers.  If there is no signal from previous nodes, they will spontaneously depolarize.  However, they depolarize VERY slowly, at a rate usually under 40 bpm.  This severe bradycardia is potentially life-threatening, but allows the heart to keep some circulation going if there is a sudden complete AV node block - but prompt treatment is critical.

Regarding the lack of necessity of the SA node:

In fact, in some cases of supraventricular tachycardia (for example IST, see here) that are not responsive to conservative treatment, they will actually ablate (surgically destroy) the SA node in order to slow the heartrate down because a persistently extremely high heart rate can be dangerous.

Good question!


What is meant by "alien" probe in a microarray? In my lab we did a microarray to analyze differential gene expression in S. cerevisiae treated with UV irradiation. We are now analyzing the results and one of the up-regulated genes is labeled "Alien4_60." I believe this is some kind of control, but I am having trouble understanding what it is.

I would think that a probe labeled "alien" in a microarray would be some kind of negative control. The probe-list (excel file) says "Control stringency: 60% identity to oligo Alien4" as the description for this probe. What does this mean?

..As you can imagine, searches for "Alien4" only brings up sci-fi movies!

p.s. perhaps someone with enough rep could tag this question with more meaningful tags.

It's a probe to detect external 'Alien' RNA standard, a synthetic mRNA commercialized by Stratagene/Agilent.

  The Alien RNA transcript is a ~500-nt, polyadenylated RNA molecule that
  is synthesized by in vitro transcription. The Alien RNA transcript is
  nonhomologous to all known nucleic acid sequences currently in public
  databases, as determined by BLAST comparisons against NIH sequence
  databases. https://www.chem.agilent.com/Library/usermanuals/Public/300602.pdf

As any other external standard, you spike in the same amount of Alien RNA standard in your different reactions and then using the Alien probe you can normalize for extraction efficiencies etc. It works not only for microarrays, but also for qPCR, RNA-seq etc.

If you didn't spike in any of it, I expect your probes giving very low signal that's probably why you thought about negative controls.


Determining limiting nutrients from a graph The question was
Which of the following statements is supported by these data?
A. Phosphorus was the first limiting nutrient followed by nitrogen.
B. Nitrogen was the first limiting nutrient followed by phosphorus.
C. Phosphorus was limiting but nitrogen was not limiting.
D. Nitrogen was limiting but phosphorus was not limiting.
E. Neither nitrogen nor phosphorus was limiting.

The answer was B: Nitrogen is the first limiting nutrient followed by phosphorus, but I do not know why. I thought it would be only phosphorus as the Nitrogen values are always greater than the control values.

The control graph shows the baseline against which we can compare the other graphs. It is the graph without any changes, and hence is the graph in which one of the nutrient is limiting.

In the graph for +P, there is no rise in biomass and the graph resembles the control. This shows that Phosphorous is not the first(initial) limiting nutrient, as its addition did not affect the biomass production.

The +N graph shows a significant rise in biomass, indicating that N was indeed the initial limiting nutrient. On its addition, the biomass production increased.

The +N and +P graph shows a higher biomass than +N and the control. This indicates, that while  N was established to be the first(initial) limiting reagent, addition of Phosphorous also significantly improves the biomass yield, and hence P must also have become a limiting nutrient once N was added and its limiting effect removed. That is the reason why +N+P graph is higher than just +N graph. If phosphorous would not have been limiting even on addition of N, then the +N+P graph would have resembled +N graph.


When should endocytosis inhibitors be used in cell binding assays? I'm beginning to do some cell-binding assays and I would like for my proteins to not be endocytosed by my mammalian cells. Typical suggestions are for the cells to be kept on ice and that the binding experiment also occurs when the cells are chilled.

However, to be sure it has been suggested that I use endocytosis inhbitors. So my questions are, when are the endocytosis inhibitors necessary? How would I know that endocytosis inhibitors are necessary? Which ones would I actually use?

I recognize that there are both clathrin and non-clathrin mechanisms of internalization. Which mechanism would be more useful to study for an antibody-receptor interaction?

As with so many things, it depends. Also, I'm a bit unclear when you say antibody-receptor interaction, do you mean that you have an antibody that's specific for a receptor, or that you're studying Fc receptors binding to antibodies? (for the following, I assume the former)

For most cell types and most cell surface molecules, simple antibody binding isn't going to induce endocytosis, and keeping the cells on ice is sufficient to prevent most background endocytosis (i'd do the assays in a cold room as well so that even when you take tubes out of the ice bucket they stay cold).

On the other hand, if you're using highly phagocytic cells (like macrophages), and/or you're triggering a receptor through cross-linking or some other mechanism, you might get some endocytosis that affects your results.

The mechanism (clathrin vs non) can also vary, again depending on what's being bound.

You should do some optimization - ie: do the same assay on a set of samples, with or without  inhibition and see if your antibody binding is affected. But be aware that a lot of drugs for inhibiting endocytosis can do other stuff too, so watch out for artifacts. Maybe read this: http://www.ncbi.nlm.nih.gov/pubmed/18369934


Why do you retch when you see something disgusting? Why do you retch when you see something disgusting?

I imagine it is some sort of evolutionary response, although I can't see the connection between receiving a signal that unhealthy conditions are in the current environment and wanting to empty the contents of one's stomach, which likely were eaten elsewhere. The response I would have expected to have developed would have been one of fleeing, rather than vomiting.

As a subquestion, why does the same reaction sometimes occur when imagining something disgusting, even if it is not real?

(I know "disgusting" is subjective; I'm referring to things humans may want to not be around for health reasons, e.g. rotting flesh, infestations of traditionally disease-carrying insects, etc.)

Physiologically speaking, your body is reacting to something you have known associations learning. An extreme form of this phenomenon is seen in drug addiction.  After chronic use of a substance there are certain cues a person associates with the drug effects. Whether that be a certain group of people, a sound, a place, or an object the stimulant is eventually associated with the drug effect. After a certain amount of time a physiological reaction occurs with just the introduction to the stimulant without the drug. Often, if an addict receives a stimulation without a drug they are, at first, excited, calm, or feeling whatever the drug effects caused. But then, if no drug is received, the withdrawal effects come into play and makes the addict feel worse and crave the drug more intensely.

Anyway, so when you see something you associate with being gross or awful, your bodies physical reaction is essentially prepping you for the event.The biological and cellular effects of associative learning are regulated in the central nervous system (brain). The main theory is that the initial effect of the stimulus is regulated by dopaminergic channels, and the learning and associations are regulated by serotonergic channels. However, it is more like a complex network of synaptic channels at work in various parts of the brain. The regions known to be apart of associative learning are the emotional cortex of the brain are the amygdala, prefrontal cortex, and hippocampus.

For gastrointestinal upset the stimulus is most likely associated with an event that caused GI upset previously. For example, let's say you went out to a party and had too much to drink. You throw up everything you've eaten that day and you just generally feel awful and 'sick to your stomach.' Now, every time you see, smell, or taste that brand or flavor of alcohol you consumed, you immediately gag because your body is remembering the previous event and associates that stimulus with the vomiting and sick feeling. Does that make sense? Let me know if you would like more clarification.

Sources:

Drug Addiction Drug Habituation - Profiles in Science
Control of cocaine-seeking behavior by drug-associated stimuli in rats: Effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens
Neural and psychological mechanisms underlying appetitive learning: links to drug addiction
Physcopharmacology by: Meyer and Quenzer (ISBN 978-0-87893-510-9) (best source)


Why are some protein sequences known but their 3D structure isn't? Why are there some proteins that have a known amino acid sequence, but their 3D structure is not known? Wouldn't finding the former in a lab lead to the discovery of the latter? Please correct me if I have misunderstood something.

Protein sequencing is a nicely constrained problem: you have a one-dimensional sequence of amino acid members, which come from a limited set of options (made a bit more complicated by post-translational modifications, but not much more so). Because it's one-dimensional, it's a problem you can easily solve by chopping up a protein into little bits, using mass differences between amino acids to understand their constituents, and determining the order from that distribution. If a DNA (or mRNA) sequence is known, it becomes even easier - you can skip the protein sequencing process and get the amino acid sequence directly from the nucleic acid sequence and the genetic code.
By comparison, protein folding is an absolute nightmare to solve for. Chemical bonds between amino acids are not rigid, they can bend and twist in all directions. The conformation of those bonds also depends not just on adjacent amino acids (as in a 1-D problem) but potentially on any other amino acid in the sequence (not to mention external influences..).
In a large molecule like a protein there is a massive massive degrees of freedom problem. From Wikipedia, describing Levinthal's paradox, bold mine:

In 1969, Cyrus Levinthal noted that, because of the very large number of degrees of freedom in an unfolded polypeptide chain, the molecule has an astronomical number of possible conformations. An estimate of 3300 or 10143 was made in one of his papers[1] (often incorrectly cited as the 1968 paper[2]). For example, a polypeptide of 100 residues will have 99 peptide bonds, and therefore 198 different phi and psi bond angles. If each of these bond angles can be in one of three stable conformations, the protein may misfold into a maximum of 3198 different conformations (including any possible folding redundancy). Therefore, if a protein were to attain its correctly folded configuration by sequentially sampling all the possible conformations, it would require a time longer than the age of the universe to arrive at its correct native conformation.

Now, of course that's not the actual process that proteins use to fold (they don't iterate through all possible combinations, they settle through an energy landscape where only certain intermediate conformations are realized), and we can use that in computational models to solve protein structures more quickly than the age of the universe, but it's still quite a slow process. Projects like Folding@home have aimed to distribute the computational load among unused processing power in devices around the world, including idle gaming consoles and personal computers, but there are many many protein structures to solve.
It's possible to get a general picture of protein shape using imaging techniques like X-ray crystallography or cryo-EM, and for some purposes these techniques give a lot of information, but these techniques are also by no means simple and can be prone to errors.


How does the enzyme Dicer function in the RISC complex? I know that the RISC (RNA-induced silencing complex) is one of the primary complexes involved in gene regulation through RNAi.  What I want to know is, what role exactly does Dicer play in this complex?

Dicer is an endo-ribonuclease belonging to the RNAse-III class. Dicer is not a part of the RISC. It however helps in the formation of RISC by cleaving dsRNA or the stem of hairpin RNA on two ends which liberates a small dsRNA product. Then one of the strands is loaded into the RISC.

There are several reviews on this topic and there is a video as well which you can find on youtube.