What are some of the general characteristics of the DH5 alpha strain? I can not find some useful sources unfortunately.

Please tell me about some important characteristics of DH5 alpha.

What makes DH5 alpha suitable for the gene cloning?

There are two possible sources: One is the article from the Bethesda Research Laboratories (reference 1), which names a few, the other is the book "DNA cloning: A practical approach" (see reference 2)., which sits here in my bookshelf.

Taking both together, the DH5 alpha strain is derived from the DH5 strain with the introduction of a few additional features. The naming DH are the initials of Douglas Hanahan which developed the strain. The strain is easy to transform with high efficency.

The new features of DH5 alpha are the recA and the endA1 mutations:

The endA1 mutation inactivates an intracellular endonuclease that
degrades plasmid DNA.
The recA mutation eliminates homologous recombination. This reduces the chance for deletions and plasmid multimerization.

The DH5 strain also has the following features:

The hsdR17 mutation eliminates the restriction endonuclease of the
EcoKI restriction-modification system, so DNA lacking the EcoKI
methylation will not be degraded. DNA prepared from hsdR strains that
are wt for hsdM will be methylated and can be used to transform wt E.
coli K-12 strains.
Δ(lacZ)M15 is the alpha acceptor allele needed for blue-white
screening with many lacZ based vectors.

Of special interest are the references 3 and 4, which gives you all the details you want to know.

References:

Bethesda Research Laboratories. 1986. BRL pUC host: E. coli DH5α
competent cells. Focus 8(2):9. The article is on page 13 in this paper.
DNA Cloning: A Practical Approach. Glover, D. M. (ed.), 1985, Vol. 1, p. 109, IRL Press, McLean, Virginia
Choosing a Competent E.coli Strain
E. coli genotypes


Is a DNA molecule a single strand of polynucleotide or two of them linked together? Our molecular biology teacher told us that a double helix of DNA was composed of two DNA molecules linked together by hydrogen bonds. The thing is, until now, I always thought a DNA molecule was composed of two strands, those being polynucleotides, both of them being linked together. I can't find a link which is saying the same as my teacher, even if it seems technically correct to call a double helix a dimer of two DNA molecules.

I was curious to know what was the exact terminology.

Hmm, I think that the teacher is actually correct and that the previous explanation, although very nicely referring to text book diagrams, is a little misleading.

The issue here is the nature of a hydrogen bond within the DNA structure. Within a chemical context, generally a molecule is a collection of atoms primarily bonded together via covalent bonds. Hydrogen bonds, by their very nature are transient - if they weren't then the double stranded DNA wouldn't be able to opened for reading! So, a strand of DNA, from the 5' end to the 3' end is one molecule. The reverse complement strand to this is another molecule of DNA. This is important as if you were carrying out a PCR reaction (for example), you would use single, stranded DNA as primers - so this would be a molecule of DNA. Also, if we were to use hydrogen bonds as a means of defining a molecular species, then water would only be one molecule - all of those H2O molecules interact via hydrogen bonds with each other!

But what about the double helix structure? Well this is a consequence of the chemical structure of each nucleotide (and the chemical properties of those atoms), aided by the hydrogen bonding to tightly pack the atoms together - it's a form taken by the thermodynamics of the inter-molecular interactions between the two molecules of DNA.

So, a strand of DNA is a molecule. Two strands (two molecules) of DNA give us the natural, stable, helical form.


CRISPR-Cas9 knockout With CRISPR-Cas9 I have conducted a targeted knockout of a DNA region encoding a certain protein (working with leukocytes). My question is, how long does it take until this protein is not detectable any more (e.g. via surface staining + flow cytometry) after the DNA has been manipulated? Or in other terms: how often are transcription, translation etc. taking place?

To answer your question multiple parameters which one should be taken into account.

There are two main sets of parameters: gene specific and cell line specific.

Parameters related to your specific gene of interest :

Do you know the half-life of the RNA of your gene of interest? Most of the time it is not known but there are several tools and resources which can predict it based on a lot of different features such lengths and stability of 3'UTR, 5'UTR, number of exons introns, etc.
Another indication is if there are already people who have either perform a genetic perturbation (siRNA, CRISPR, etc) or a degradation assay. In this case you might be able to guess what is the relative half-life of the RNA or the protein.
Which leads us to the half-life of the protein of interest. Proteins which are soluble tends generally to have a smaller half-life than membrane proteins (not necessary true there are exceptions). For example doing a complete functional knockout of a transcription factor might be easier than a GPCR receptor. If it is a membrane protein, to which organelle does it localize? Is the organelle recycling the membrane a lot or is the cell dividing? In this case you might have chances that the viable proteins present before the genetic perturbation get diluted. In these examples, you might get ride of a soluble protein in less than 24-48 hours, whereas a very stable membrane protein might take 7-10 days.
The number of RNA copies is important as well as the number bound to ribosomes (less important) and their localization in the cell (less important)
The abundance of the protein in general.

Parameters related to your cell line of interest:

The lineage of the cell line you selected: different cell lines have different global transcription and translation rates.
The rate of division of the cell line (extremely important parameter): the faster the cell line will divide the faster  the mRNA copies which were not perturbed (wild-type) and the proteins present before the genetic perturbation will be diluted between daughter cells.
Number of copies in the cell line: if there are multiple copies of your gene of interest, you would need to make sure that each copy of the gene has been perturbed to lead to a functional KO.
Genomic stability of the cell line: some cells lines like HeLa are quite known for genomic instability where a lot of the genome can be rearranged can perturbed copies can be fix using viable copies

Last but not least, it depends technically how you do the CRISPR-Cas9 genetic perturbation: transfection of the gRNA, electroporation of the Cas9 with the gRNA, lentiviral mediated delivery etc. The time I have provided are after all the components have been delivered and are present in large amount in the nucleus.

I hope that helps!


What does the number after Vitamin B signify? Does the number after Vitamin B signify anything? For example what is the significance of 12 in Vitamin B12?

It appears to be fairly arbitrary, but they were originally numbered chronologically by discovery. However...

From Gizmodo:

  These Bs are not necessarily designated in chronological order, as B12 (Cobalamins) was discovered in 1926, B5 (Pantothenic acid) and B7 (Biotin) in 1931, B6 (Pyridoxine) in 1934, B3 (Niacin) in 1936 and B9 (Folic acid) in 1941. The missing Bs are substances originally thought to be vitamins, but later reclassified.

Wikipedia explains that certain numbered B vitamins were originally classified as other vitamin letters when discovered and only later reassigned as a B vitamin.

In conclusion, B vitamins were numbered in order as they were assigned as a B vitamin.

missing numbers are due to specific vitamins being reclassified as either different letters or as non-vitamins.


(Reference request) Formal abstract theory of evolution? EDIT: please feel free to suggest books that are the closest you can come up with to what I'm looking for, even if it doesn't exactly overlap!

I am very well acquainted with the theory of evolution as informally taught. E.g. I don’t need a book that explains the theory, or refutes popular misconceptions.

Instead, I am looking for a formal theory of evolution as a process, and I am not specifically interested in the biological aspect of evolution, but in evolution as a more generally occuring process.

How do we formally state the different assumptions of Darwinian evolution? (Random change, heritability, natural selection).
What happens if we change these different assumptions? (Non-random mutation? Maybe, selection criteria that are influenced by the mutations, rather than independent of it)
Are there quantitatively different results of evolution based on these assumptions?
Something I find very interesting: What kind of non-biological evolutionary processes can we describe formally? E.g. evolution based on some form of non-random mutation, or based on different types of heritability. What are the different implications of different formal assumptions. How do these differences apply to different evolutionary systems? (E.g. evolution of ideas, cultures, computer viruses, evolutionary algorithms).

In summary, I am looking for a book that introduces in a very abstract way the properties of evolutionary systems (does not have to be focused on biological evolution. I’m interested in the formal properties of such systems).

NOTE: I am NOT asking about a book on modelling highly specific processes that apply to specific biological systems, such as population dynamics of preditor-prey relations. I’m interested in general, abstract theoretical analysis of the notion of an evolutionary process in general.

Difficulties in your question

It is a little hard to know exactly what you're after because 1) the question is broad 2) some concepts you talk about are a bit unclear.

For example, by 'random change' I suppose you mean genetic drift but I am not sure. The term 'random mutation' is a little undefined (see this post). You list 'Random change, heritability, natural selection' as a list of assumptions (at least I think you mean those are assumptions) but those are typically not common assumptions of evolutionary models. Also, the list is not in any way intuitive, so it is unclear what you mean by it. The phrasing "selection criteria that are influenced by the mutations" is also very unclear. Of course, selection, by definition, is dependent upon the genetic variance.

From our discussion in the comments, I think you are attempting to group different fields under a single concept just because they have the same name. But it is not because they have the same name that they are governed by the same basic principles. For example, it is not because the concept of plasticity exists in both biology and physics that these concepts are in any way related and that there is a general theory of plasticity that encompass both fields.

Evolutionary genetics

That being said, you could gain from any good intro textbook to evolutionary genetics. I especially recommend Population genetics, a concise guide. You will find more such recommendation in the post Books on population or evolutionary genetics?.

Evolution of ideas, cultures, computer viruses, evolutionary algorithms

In your last question you mention 'evolution of ideas, cultures, computer viruses, evolutionary algorithms'. I think you are referring to these concepts so as to clarify that you are not so much interested in the biology of specific organisms but really into the process of evolution. I do not recommend starting reading about these concepts before having a background in evolutionary genetics. You might otherwise make the mistake to over stretch an analogy.

Note also that the field of memetics (evolution of ideas, cultures) is a young field in which very little empirical testing is possible. So, I don't think it is wise to start there if your goal is to increase your understanding of evolutionary biology.

In any case, I am not able to suggest a good book in any of these fields (Evolution of ideas, cultures, computer viruses, evolutionary algorithms).


Why does histamine cause bronchoconstriction? What purpose does histamine-caused constriction serve in lungs during allergies and such, since it's vasodilator in other parts of body. Wouldn't it be more practical to vasodilate lungs so that white blood cells can arrive and toxins can be flushed more quickly.  Thanks in advance

Basics first: Crash Course

We will be introducing:
Autonomic divisions, Histamine and Vasoactivity (or Broncho-)
Starring: Innervation of the Lower Respiratory Tract

Lower respiratory tract is mostly innervated by the parasympathetic division, it has only scarce sympathetic-receptors there.

So, why it matters?

Autonomic divisions serve as fight-or-flight and rest-and-digest mechanism for the body as to respond for sudden changes.

You are having a good picnic, your body is in a state of rest. Your body is absorbing nutrient and enjoying your day. Blood isn't needed so much on your hands, or skin, or muscle.
This is the Parasympathetic Division

Suddenly a snake appeared in front of you, you scream, you panicked, and you flight away (or fight?). Your eyes dilate (where is that snake!), your muscles work, your respiratory tract dilates, as to prepare to avoid being killed by the snake. Blood rushs in to your muscles, but shunts on your digestion part, as what every you eat doesn't matter.
This is the Sympathetic Division

What matters?

Parasympathetic division only knows how to lock down things.
Sympathetic division can lock things, open things, and so, and so, and so.

How does sympathetic division work with so many things?
It has different receptors which reacts differently on input
Imagine people when reacting to clown: NOOOO and YAYYY

Histamine serves as modulation to outputs of autonomic division, directly or indirectly

Histamine is a broad-response chemical used to respond against an infection. As different cells have different ratio of autonomic division, it can cause dilation or constriction on different places.

One thing to note that, in a nutshell, histamine serves to buffer the work of autonomic innervation. It is entirely up to the regular function of the "autonomics" there to do their business.

Vasoactivity (or Broncho-) is achieved by state of balance between innervation by the autonomic division and local signals

Local signals play a part. A balance of signal determines the effect of innervation.
For bronchi, when histamine puddles, local signal sends stronger input than global innervation. Hence, the parasympathetic takes over.

  histamine-caused constriction serve in lungs during allergies

Histamine serves as to protect the lower respiratory tract from inhaled irritants. The lower respiratory tract is innervated by parasympathetic stimulation. Parasympathetic stimulation only knows one command: constrict and strike.
When histamine buffs up the signal, it constricts.

  vasodilator in other parts of body

Indeed it is. The vasodilation effect is achieved by GPCR-mediated sympathetic innervation.
Histamine buffs a diverse response of sympathetic division, hence dilates the blood vessels.

  Wouldn't it be more practical to vasodilate lungs so that white blood cells can arrive and toxins can be flushed more quickly

In line with WYSIGYG, vasodilation is different from bronchodilation (or constriction). We have noted above that the operators are different, and they serve different functions.

As a note, white blood cells can't just come anywhere they want. Ever seen your nasal mucus being very viscous? That will happen your lung when white blood cells arrive.
White blood cells also cause fibrillation, which succumbs people when does.

It has been a reason why pneumonia and lung-infection related diseases, tend to succumb people by drowning them in "their own mucus".

Another part of sending much things down your lower respiratory part is...
How could you clean the mess up?
The upper respiratory part is the defense capable of trapping irritants by mucus and send the mucus to your stomach.
Bronchus? Not so much. More mucus will eventually drown your lungs.

I invested 50 minutes for this.


What does self-preservation stem from? Self-preservation, or preservation anyway, probably happens throughout the animal kingdom, and perhaps through the plant kingdom as well (some plants/trees, apparently, produce chemicals to repel bugs).

Where does self-preservation stem from? Is it only about a biochemical imbalance?

This is a prototypical case of evolution by natural selection. Any trait that prevents the organism from being eaten or destroyed will probably make that organism more likely to reproduce* than similar organisms that do not have that trait**. This results in self-preservation traits becoming more prevalent in the population and eventually ubiquitous.

* Or they reproduce more, or are able to provide for their offspring better, etc. Self-preservation behaviors that reduce reproductive success are not selected for and generally aren't common (unless they are a special case of some general trait that has a net reproductive benefit).

** Assuming that the trait is reproductively favorable after considering any trade-offs such as increased energy expenditure.


Dissolving cell pellet after sonication I was doing a protein prep and I made a mistake. After sonicating my cells, I was supposed to centrifuge and collect the supernatant (my protein is soluble and comes in the supernatant). I however, forgot to centrifuge and loaded the entire solution after sonication (debris and all) onto a Ni-NTA column.

Is there any way to dissolve the cell debris so that I may be able to recover the NTA beads?

Follow the instructions that came with your column for cleaning. The resin will probably be fine, but you'll need to thoroughly clean the column. My GE columns recommend washes of:

20% EtOH
30% Isopropanol
1M NaOH
1M NaCL
SDS in 0.1M Acetic Acid
Stripping buffer (EDTA)

Wash between each with several column volumes of distilled water. You may not need to do all of them. Then just recharge your column with a 100 mM Ni solution (or metal of choice)


How many polynucleotides are there in one molecule of DNA? I always thought that a molecule of DNA was made of two polynucleotides each making up one strand of the molecule... Is that right?

In general, it is right since with the term DNA you commonly refer to the double-stranded DNA. However, you need to be aware that DNA may exist in different forms.

Single-stranded DNA (ssDNA), for example, is composed of only one strand of DNA, so one chain of nucleotides or one polynucleotide molecule.

Double-stranded DNA (dsDNA) is the common form of DNA found in cells and it is composed of two polynucleotide molecules.

Triple-stranded DNA (tsDNA ?) also exist, which of course, is composed of 3 polynucleotide molecules.


What does the "Psi" in "Psi broth" stand for? When making competent cells I've been using a medium called "Psi broth", which per liter consists of 20 g tryptone, 5 g yeast extract and 5 g MgSO4. Today I got curious about why it's called "psi". Is it an acronym like SOC and LB?

Psi is the Greek letter ψ.  Psi broth is sometimes referred to as ψ-broth.

Here's an example:

  L-Broth or ψ-broth can be used instead of SOC medium, but efficiency may
  be reduced.

  L-broth： 10 g Bacto tryptone, 5 g Bacto yeast extract, 5 g NaCl, pH to
  7.5 with 1 M NaOH, bring to a final volume of 1 L, and autoclave.
  ψ b-broth： 5 g Bacto yeast extract, 20 g Bacto tryptone, 5 g
  MaSO4･7H2O, pH to 7.5 with 1M KOH, bring to a final
  volume of 1 L and autoclave.


Plant tissue culture Tissue culture means that cells are propagated and multiplied under controlled conditions. Suppose the following situations:

  a) A seed being is embedded in an Agar medium and germinated under controlled conditions.
  b) An individual cell is extracted from a parent plant and embedded in a medium, resulting in the formation of a callus (germination).

Are these both examples of tissue culture? Both situations seem to fall under my definition of tissue culture.

In situation A) there is no mention of growth, so there is no reason to assume something is cultured. If we assume that in A) a germ plant arises, it is no tissue culture but a regularly bred plant. It is no tissue culture, because a seed is typically formed after pollination, which involves the recombination of parent genes to form reproductive cells (pollen) and the fusion of these reproductive cells after pollination. Because the definition of plant tissue culture is:

  "... a form of cloning in which the plants are all genetically the same - similar to taking cuttings." (quoted from: Royal botanical gardens, NSW, australia).

it follows that seedlings are not clones of their parents.

Situation B) therefore meets the criterion of tissue culture, as new tissue grows out of a single progenitor cell.

So the answer is: they are not 2 examples of tissue culture, the difference being that A) is the result of a normal breeding and B) meets the criteria of tissue culture.


Do species which have a closer common ancestor to humans tend to be more intelligent? Q: Do species which have a closer common ancestor to humans tend to be more intelligent?

Our closest living relative, the chimpanzee, seems to be regarded as intelligent:

  Chimpanzees make tools and use them to acquire foods and for social displays; they have sophisticated hunting strategies requiring cooperation, influence and rank; they are status conscious, manipulative and capable of deception; they can learn to use symbols and understand aspects of human language including some relational syntax, concepts of number and numerical sequence; and they are capable of spontaneous planning for a future state or event.

Does this hold in general?  And, if so, how strong is the correlation?

Several issues here that make your question unanswerable:

Intelligence is not defined. How would you define it?
What kind of relationship are you exactly looking for? Comparing average intelligence between groups or trying to fit a regression with intelligence on the Y-axis and relatedness to human on the X-axis?
The general issue hidden behind methods of species comparison is "How do you define a species?"

If you want to compare average intelligence between groups, meaning that you want to compare average intelligence of a group of closely related species of human to the average intelligence of all animals? Then the answer to your question will probably be "Yes" as primates seem in average to be more intelligent than the average animal and mammals tend to be in average more intelligent than the average animal. I'd expect too that vertebrates are probably on average more intelligent than the average animal. Let's not forget that some animals have no brain (e.g. Sponge).

But now if you want to fit a regression between intelligence and relatedness to human for all animals, you will probably have some trend (a regression with a significant slope (positive correlation)), but you will have many group of points that will not fit on your line. Many birds for example may be considered as much more intelligent than humans depending on your definition. Many invertebrates such as octopuses are very intelligent, too. If you allow for a broad definition of intelligence, then you may also consider the intelligence of social insects which may be surprising. Some aquatic mammals are very intelligent although other, more seemingly stupid mammals, are closer to humans than aquatic mammals.

In short, keep in mind that intelligence is not easy to define, and depending on the definition, the answer will be different. Typically, if you use a very human-like definition of intelligence, you will probably find that intelligent species are more closely related to human. There is a correlation between intelligence and phylogeny (=tree of life), therefore yes, closely related species to humans may have some tendency to be fairly intelligent, but there are many other clades (groups of species on a phylogeny) that show some impressive intelligence, especially in insects, in mollusca, in  birds, the carnivora and the cetacea.


How can I view modENCODE data faster? I am trying to view several data tracks in the modENCODE GBrowse genomic browser. However, the site is so slow, it is practically unworkable. Is there a faster way to explore the data?

Options:

You can always download the data (as @WYSIWYG has suggested in the comment).
Transfer the data to Galaxy
Convert and export the selection of your choice.

Source: http://modencode.oicr.on.ca/fgb2/gbrowse/fly/


Any species returning to the land twice throughout their evolution? Here's a question from my son I've found interesting enough to ask here. There are plenty examples of species returning back to the water environment, like dolphins, sea lions, walruses, some snakes, crocodiles etc.

The question is - are there any evidences that in evolution of certain species there was return to the land twice, that is, they've came from sea, then evolve as land species, then, again, evolved to somewhat marine or fresh-water and, finally, turn into land species again?

UPD Chordate are the most interesting but any example, even plants, would be nice.

Woodlouse

Life emerged in the water. Ancestors of insects, spiders, myriapods and crustaceans were probably terrestrial (please correct me if that is wrong) but then, crustaceans evolved to living in the water again. Finally, woodlice went back onto land!


Why do humans not have a powerful sense of smell? It seems like a useful ability to be able to detect many different things about, say, another organism. A lot of mammals have this ability. Why not humans? Did we evolve it out or never develop it?

Humans' poor sense of smell is a myth, borne of 19th century speculation rather than actual data. This is described in an excellent recent paper in Science , "Poor human olfaction is a 19th-century myth" by John P. McGann. Quoting from a recent blog post of mine,

  The myth dates to the work of the pioneering and hugely influential
  anatomist and anthropologist Paul Broca, who concluded that the
  relatively small olfactory bulbs in humans and other primates enabled
  the occupancy of this space by facilities of intelligence and even
  free will: “…it is no longer the sense of smell that guides the
  animal: it’s intelligence enlightened by all the senses… This is the
  cause of the atrophy of the olfactory apparatus of primates." This
  presumed “atrophy” and poor sense of smell however, were not based on
  any actual data on primates’ sense of smell! The myth propagated and
  expanded in the 20th century, becoming dogma. Back in the 19th, even
  Freud weighed in, noting that the lack of a strong sense of smell
  contributed, in humans compared to other animals, to sexual repression
  and mental disorders.

Humans, when trained, smell quite well, and can for example follow scent trails through grassy fields. Interestingly, the number of olfactory neurons is very similar in humans and other mammals (plotted in the aforementioned post).


Is this adaption of the Gillespie algorithm using Michaelis constants justifiable? I would like to run a discrete simulation of a biological system as it can be done, e.g., using the Gillespie algorithm. However, the Gillespie algorithm requires you to know the reaction rate constants of each involved reaction whereas I only know the Michaelis constant $K_M$ and the maximum rate $V_{max}$ of each reaction.

Since the Gillespie algorithm only uses the reaction rate constants to calculate the reaction rate $v$ (which, again, is used to determine the probability of a given reaction), I wonder wheter it is justifiable to simply replace this calculation of $v = k * [S]$ by $v = \frac{V_{max}\cdot[S]}{K_M + [S]}$ for each reaction $S \rightarrow P$ and, apart from that, use the Gillespie algorithm as is? If not, is there any better way to run a discrete simulation of the system with the given parameters?

Note: I've already asked in a different question whether it is possible to get (an estimation of) the reaction rates knowing only the parameters $K_M$ and $V_{max}$. I hope my both questions are sufficiently distinct to justify two different posts.

The stochastic simulation algorithm by Gillespie makes the assumption that reaction propensity (probability) in an infinitesimally small interval of time is same as the macroscopic reaction rate. (For details, you can see my answer in Chemistry.SE).

You can model and simulate every step of enzyme catalysis or you can also use the Michaelis-Menten model. In any case, you can extend the same approximations to the stochastic model.

This is also applicable to other Michaelis-Menten like (or Hill) functions of the form $$\frac{x^n}{k^n+x^n} \qquad \text{or}\qquad \frac{k^n}{k^n+x^n}$$.

There are many papers that have done this. Note that the non-linear nature of these functions results in deviation of the stochastic behaviour from the deterministic behaviour. Read about stochastic focussing. Modelling each step exactly (binding, unbinding and catalysis) may result in different behaviour depending on your parameters. Whether you should use Michaelis-Menten function to describe reaction rate totally depends on how reasonable your approximation is.


What are the longterm effects of pancreatitis? As the title asks, what are the longterm effects of pancreatitis?  Having one event, is the person more susceptible to have a recurrence, or are they at higher risk of other conditions such as diabetes?

Pancreatitis may cause a condition called ''systemic inflammatory response syndrome'', a immune system reaction affecting the whole body.

Also, more frequently, pancreatitis is linked with steatorrhea, which means oily fat, and it may cause malnutrition and weight loss, due to restriction of secretions containing digestive enzymes. Longer term inflammations of pancreas may cause fibrosis (scar tissue) in the organ, therefore restricting the endocrine functions including insulin secretion, so acquired diabetes is another risk.

Obstruction of the bile duct and jaundice, leading to possible liver damage is another complication of pancreatitis.


What is a "fairy smile"? From Hrdy and Burkart (2020):

At birth, both chimpanzee and human newborns seek out eyes, are capable of mutual gazing, and caught just right, may imitate someone else’s outstretched tongue or other facial expressions. Both species exhibit reflexive ‘fairy smiles’, soon to be replaced by more open-eyed ‘social smiles’ in response to someone else.

From Sarah Hrdy (email):

A “fairy smile” is a reflexive smile that spontaneously and briefly flickers  across the face of a newborn baby.  Some years ago, Tetsoro Matsuzawa discovered that these occur even before birth, en utero in chimpanzees! (Long story, but Tetsoro was using laser probe with a camera on a highly habituated pregnant chimpanzee female, accustomed to working with him to learn this). So of course do humans en utero.  After birth, one may see a reflexive “smile” flicker across the face of a baby even while sleeping —no outside stimulus or engagement with another person needed, tho may occur in response to a sound. "Fairy smiles" are different from “social smiles” that emerge later, and occur in response to someone else speaking to or smiling at them, etc.

I grew up in the southern part of the U.S. and people around me used the term,  but now that you ask, am curious to know where this term to describe “reflexive, non-social smiles” in newborn babies comes from.


What is this raptor on a building in California? So I took this picture of a bird that was sitting just outside my workplace a few weeks ago:

At first I searched the internet for raptors in California and found the Cooper's hawk. It looked so much like this bird so I thought that must be it and left it at that. However I just recently came across this bird and also this recent hawk identification question and they both look very similar to my bird as well. So I realized I don't know what to look for when trying to identify this bird.

Does anyone know what this raptor could be?

If it helps, the specific location was the city of Tustin in Orange County, California (Southern California). It is about 10 miles from the coast.

It is a Red-shouldered Hawk (Buteo lineatus).

  Its breeding range spans eastern North America and along the coast of California and northern to northeastern-central Mexico.

Identifying features:

Presence of dark wings with white spots.
Presence of dark-brownish head, orangish-brown chest.


Does the word "polymorphism" refer to the gene, the phenotype, or both? In genetics, does the word "polymorphism" properly refer to genes, to phenotypes, or both? For example, if there are two alleles that lead to differences in the structure of the D2 neuroreceptor, would I talk about "a polymorphism in the gene for the D2 neuroreceptor" or "a polymorphism in the D2 neuroreceptor"? I've seen both uses in the literature, but it's not my primary field, so I don't have a feel for whether one is more widely accepted.

Bonus question: is there a preference regarding "polymorphism of," "polymorphism in," and "polymorphism on"?

The term "polymorphism" itself is more generally defined as "the quality or state of existing in or assuming different forms" (Merriam-Webster dictionary). So I guess semantically, it would be correct to say that there is polymorphism in a gene that can occur in different allelic variants, or polymorphism in phenotype because of variant traits (such as sexual dimorphism).

However, when biologists today speak of polymorphisms, often they refer to variations at the level of individual nucleotides (single nucleotide polymorphisms or SNPs; some people use the terms polymorphism and SNP interchangeably). These SNPs have become popular for genotyping and for correlation with a variety of diseases or other observable phenotypes.

And regarding the bonus question, I think "polymorphism in" is the most correct usage--it's definitely the most widely used. For example, you could say "there is a polymorphism in nucleotide 257 of..." or simply "there is polymorphism in nucleotide 257 of..." or even "nucleotide 257 of ... exhibits polymorphism".


Gene expression: which allele is considered? For human beings, we have two copies of each gene inherited from the parents. The question is, when referring to gene expression, which copy (or allele) is considered?

Genome assemblies usually feature a haploid set of genes, unless particular effort is applied to assemble separately the homeologs. With that said, the gene copy you have in the assembly is usually one of the two, and usually the one you had more genomic reads for.

In terms of gene expression, if you measure it by RNASeq you will get reads from both and both of the read pools will map on the same gene. The ones that come directly from it will map with no mismatches (ideally) and the ones that come from the homeolog chromosome will map with a few mismatches (probably).

The expression of the "gene" will therefore be the expression of both genes, summed together. If we consider it as the same gene, though, it doesn't really make a difference if you sum them up or count them twice separately; unless we are talking about specific homeolog silencing like the Xist mechanism, in which it is important to remember that one copy of the two is off.


Why doesn't the human skin grow back exactly how it was before being damaged? Very simple: Why (and how) is regenerated skin different from original ?

As we know we lose skin cells that becomes the dust in out homes and it always grows back to full thickness right ? So when I have a cut, I imagined it to heal provisionally with whatever possible and then after some time to replace itself with the normal skin that is coded in my chromosomes. So why doesn't it do that ? Scars remain and the color is always different from the neighbor parts.

Update:

Why we get scars?
What about skin transplants ?
Why doesn't skin actually grow/replace itself?

Update 2:

(I've been thinking) Skin has lots of different layers, right ? So when an area is damaged does it regenerate all layers or just one for being simple and efficient (in "hope" the subject will take precautions not to damage this part of body again, so that regenerating everything back to 100% would be overkill) ?
I'm not a scientist, I have only the basics from school, so I'll probably not understand most of the technical terms
also I'm more interested about an explanation that goes towards the "survival of the fittest" rule, and not so much about the biochemical reactions in our bodies (because it was just some random mutation that turned out to be the better choice for us → why?)

Human skin is made up of three layers [1]:

Epidermis; it contains no blood vessels; it has 5 cellular layers (starting from surface):

stratum corneum
stratum lucidum
stratum granulosum
stratum spinosum
stratum germinativum

Dermis; it is separated from the above by the basal membrane; made up of connective tissue (with blood vessels and nerve endings)
Hypodermis - it is not even considered part of the skin

"Gray940". Licensed under Public domain via Wikimedia Commons.

  Why (and how) is regenerated skin different from original ?

Why? Skin is a very important organ. It protects from pathogens, it maintains body temperature, it keeps body water [1], etc. How? That depends on what causes the regeneration. I've emphasized two terms in the above list.

Stratum corneum represents the "skin cells that becomes the dust in our homes and it always grows back to full thickness". It is lost during a physiological process called desquamation [2]. The cells that are lost are non living corneocytes. Their only purpose is to from a protection barrier [3].
Basement membrane holds the germinativum layer of the epidermis. Injuries that do not affect it are repaired by complete regeneration of all destroyed layers. However, if the injury destroys membrane continuity, the germinative cells on the edges will fail to "reconnect" with each other, thus the layers derived from them will follow the same rule. A process of fibrosis is triggered. The result of  extensive fibrosis is a scar, containing collagen secreted by the granulation tissue with dermal origins. Yet, the germinative layer tends to join back together [6], but probably the excess collagen production, without the limiting basement membrane, bulges into the epidermis and limits germinative layer extension. That's why keeping the edges of the tissue close to each other reduces excessive fibrosis and allows germinative layer regeneration, thus resulting in none to small, barely visible scars.

How deep should an injury be in order not to affect basement membrane? No more than 0.06 to 0.08 mm [5].

  What about skin transplants ?

Skin grafts contain at least a part of dermis [4], which will allow granulation tissue formation thus permitting revascularisation and making the graft stick. Otherwise it would fall off and/or be lost by necrosis.

References:

Wikipedia contributors, "Skin," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Skin&oldid=619454074 (accessed August 4, 2014).
Wikipedia contributors, "Desquamation," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Desquamation&oldid=614028888 (accessed August 4, 2014).
Wikipedia contributors, "Stratum corneum," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Stratum_corneum&oldid=615247326 (accessed August 4, 2014).
Wikipedia contributors, "Skin grafting," Wikipedia, The Free Encyclopedia, http://en.wikipedia.org/w/index.php?title=Skin_grafting&oldid=603324006 (accessed August 4, 2014).
Sandby-Møller J, Poulsen T, Wulf HC. Epidermal thickness at different body sites: relationship to age, gender, pigmentation, blood content, skin type and smoking habits. Acta Derm. Venereol. 2003;83(6):410-3. doi: 10.1080/00015550310015419. PubMed PMID: 14690333.
Dawn A. Tamarkin, Ph.D. Repair of skin. 2011 STCC Foundation Press. Available from http://faculty.stcc.edu/AandP/AP/AP1pages/Units1to4/skin/repairof.htm (accessed 04.08.2014)


Why is the number of cells virtually a constant? Going back to highschool, I learnt about mitosis: in order to renew their cells, eucaryots' cells divide themselves into two copies.
But my course didn't cover what moderate the replication. By moderation, I mean something that prevent the number of cells to grow forever.
So here is my question:
What phenomena are responsible for the moderation of cell replications?
I did some research on my own on both the internet and SE, but couldn't find anything (maybe because I don't know the correct keywords)

You have to understand this is a very, very, very, very broad question. Decades of research in multiple disciplines allow us to answer this question in a million directions. However, I would start by looking up information about the cell cycle and its checkpoints. Here of course I would point you - for starters - to this page:
Khan Academy's page on cell cycle checkpoints
For further reading, you can consult the college-level chapter on Cell communication and cell cycle regulation. Here the most relevant section would be Regulation of cell cycle, it's a great introductory read, well researched and well presented didactically.
A short tl;dr
In short, cells have checkpoints at different stages of their life cycle - both before and after they divide. You can imagine that, for instance, a nutrient starved cell incapable of copying its DNA prior to division, will arrest its progress through the cell cycle at the checkpoint before S (DNA synthesis) phase. And under the right conditions, it will resume its progress and get ready for division. This example is only one of many checkpoints that exist, and varying types of cells may have varying checkpoint requirements.


What exactly happens to hydrogen atoms in step 4 of citric acid cycle? It seems that there are four hydrogen atoms in alpha-ketoglutarate and one in HS-CoA (not counting the ones in CoA), five in total. Two of them go to NADH and H+, so there should be three atoms in succynyl-CoA instead of four. What am I missing here?
picture taken from Molecular Biology of the Cell, 6th ed., by Alberts et al.

Short answer:

There should have been an additional $\text{H}^+$ on the left-hand side.

Long answer:

You have rightly observed that the left side of the equation is deficient in one hydrogen atom. Let me draw your attention to another issue: the charges on both sides are different too. The left side has one negative charge too many. This gives us a clue: possibly there is a missing $\text{H}^+$ on the left.

This reaction is actually the sum of three reactions catalysed by a multi-enzyme complex. If you add the balanced equations for the reactions of $\alpha$-ketoglutarate dehydrogenase, dihydrolipoyl transsuccinylase and dihydrolipoyl dehydrogenase, you will see that there is indeed an additional $\text{H}^+$ on the left-hand side, which is omitted in your textbook.

But that is the case with most biochemistry/molecular biology texts. Biologists are very bad at balancing their equations, especially when it comes to $\text{H}^+$ and $\text{H}_2 \text{O}$. They balance out only the major reactants and products. The rest is often, er, left as an exercise to the reader.


Is eye colour of Drosophila a polygenic trait or an X-linked trait? I have seen examples of various eye colours in Drosophila and they have been described both as "X-linked" and "polygenic". I thought these were mutually exclusive. Is Drosophila eye colour polygenic or X-linked?

Polygenic and X-linked are not mutually exclusive; a trait can be polygenic, X-linked, neither, or both.

Polygenic traits are those affected by many genes. According to Conner and Hartl, "Traits that are affected by many gene loci are often called polygenic traits." For example, childhood intelligence is affected by many genes throughout the genome. Monogenic traits are relatively rare, but are linked to some diseases, and occur when a single gene affects the trait; most traits are affected by multiple genes.

X-linked traits are affected by genes (only) situated on the X. If a trait is monogenic, it is very easy to describe it as being, or not being, X-linked. If the gene is on the X, it is X-linked. If it is on the Y, it is Y-linked. If it is in the autosomes, it is autosomally linked. If all of the genes affecting a trait are found on the X then that trait is X-linked. A gene on the X is X-linked, but I would only call a trait X-linked if all genes were on the X. If there was a mix of X-linked and autosomal genetic variation I would describe the trait as having some X-linked genes.

For polygenic traits it is less likely that the genes would be all X-linked, so it is less likely that the trait is X-linked. Imagine a trait affected by 10 genes, and those 10 genes are randomly spread across the genome. It is unlikely that all 10 would be on the X. However, if some were on the X, then we could describe the trait as having X-linked variation. Many highly polygenic traits will have some X-linked variation.

Having more genes affecting the trait further increases the probability that some genes will be on the sex chromosomes. For example, lifespan is expected to be a highly polygenic trait, and genetic variation in lifepsan can be attributed to the Y chromosome in Drosophila melanogaster, despite the Y carrying just a tiny fraction of the genes.

Many eye colour traits in Drosophila can be attributed to single genes, and White in the image below is X-linked. However, one can also produce a white-eyed fly using multiple genes; in this paper one of the lines used has white eyes as a result of combining genes (T(2;3) rdgC st pp bwD) which are on the autosomes.


Why can Toll-like receptors be found either inside and outside the cell? Innate immune cells may present Toll-like receptors either inside (TLR3 and TLR9, for instance) or outside (TLR4 and TLR5, for instance) the cell, but is there any beneficial reason for this? If so, what is it?

TLRs are used to identify features that are typical of pathogens. Different TLRs tend to identify different features, so that a wide range of pathogens can be identified. Some of these pathogens may be extracellular (such as some kinds of bacteria that are recognized by TLR4, which is extracellular) and some are intracellular, like viruses (some of which may be identified by TLR7, which is intracellular).

The fact that innate immune cells have these is a little bit of a red herring, because they aren't limited to innate immune cells -- they're widespread among many cell types, and are effective at protecting the specific cell, not just activating innate immune cells.


Is the 6th rib attached to 7th rib, and 7th rib to 8th? I'm just confused between a lot of pics that draw the thoracic cage in their way. what are these white things that I've shown?

or why the 7th rib is attached to the 8th?

Those are just a part of the costal cartilage, which is only found at the anterior ends of the ribs, providing medial extension. This connects the ribs to the sternum and is made of hyaline cartilage. Here is a clearer diagram of the cartilage part:

Ribs 8–12 are called false ribs (vertebrochondral ribs- attached to vertebra and cartilage). The costal cartilages from these ribs do not attach directly to the sternum, but are all attached to the cartilage of the 7th rib. For ribs 8–10, the costal cartilages are attached to the cartilage of the next higher rib. So, in a way, you are right in saying that the 8th and 7th ribs are attached.
The 6th and 7th ribs, though, are not attached. There are just cartelagenous bridges present in between them. The first seven are called vertebrosternal ribs. (attached to vertebra and sternum)

Sources:

https://opentextbc.ca/anatomyandphysiology/chapter/7-4-the-thoracic-cage/

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

https://www.pulsus.com/scholarly-articles/cartilaginous-bridges-between-the-adjacent-costal-cartilages--a-case-report.html


Protein food eating tendency As I understand human love fatty food as they taste good because it has more energy which was good when we were primitive and food was scarce and unreliable,
Is there same urge for protein food too? it doesn't give much energy.

Proteins are actually pretty calorific but indeed much less than fat. From wiki > food Energy

However, we crave for proteins for other reasons. We digest proteins to get their building blocks, the amino acids. With these amino acids we can rebuilt our own proteins. Proteins are at the very center of our metabolic activity. From wikipedia > protein

  Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, and transporting molecules from one location to another.

Many of our DNA sequence are called protein-coding-sequence (often just called gene although definition of what a gene is vary quite a bit). Those sequences are transcribed into mRNA and then translated into protein in order to have some effect on our body. A protein could be an enzyme for example.

For more information on the role of proteins in living organisms, have a look at an intro course to Biology such as for example those of Khan Academy. Khan Academy > macromolecules > protein and Khan Academy > Central Dogma.


Resources of all known biochemical pathways? I am looking for a encyclopedia or biochemical pathway atlas of all known or reported pathways. I am very much interested in network and systems biology. Also the references can be open databases, books or whatever. I came to know about a site called wikipathways , but it is not opening for me.

You can find biochemical pathways on KEGG pathway for example.

  KEGG PATHWAY is a collection of manually drawn pathway maps representing our knowledge on the molecular interaction and reaction networks for:
  1. Metabolism
      Global/overview   Carbohydrate   Energy   Lipid   Nucleotide   Amino acid   Other amino   Glycan
      Cofactor/vitamin   Terpenoid/PK   Other secondary metabolite   Xenobiotics   Chemical structure
  2. Genetic Information Processing
  3. Environmental Information Processing
  4. Cellular Processes
  5. Organismal Systems
  6. Human Diseases
  and also on the structure relationships (KEGG drug structure maps) in:
  7. Drug Development

To illustrate the information you can find there, here is a screenshot:

If you click on kegg atlas, you get an atlas with all metabolic pathways. You can zoom in to great detail en click for further links.

If you click on glycolysis or oxidative phosphorylation for example, you will get linked to the following page (see picture). In these detailed schemes of the metabolic pathway, each intermediate can be clicked on, leading to a more detailed page.


What is this ? Found under my bed Found under my bed. Looked and there was nothing else like it or eggs of any kind.

At a glance it looks like a flattened perfectly ordinary dead woodlouse to me.


Can PolyA tails be within Expressed Sequence Tags? Can polyA tails occur within (rather than at the end) of a sequenced tag? Consider, for example the following two sequences from NCBI:
DY008075

>gi|119423037|gb|DY008075.1|DY008075 19ACACYS_UP_022_A11_29OCT2004_095 Brassica napus 19ACACYS Brassica napus cDNA 5', mRNA sequence
TGGTACGGTCAGATGCTTGCTAAAGGAGAAATAAATAGAGACATGGGTGATAGTATAAGCGGAAAGGGAA
TGATTCAGGGTGTTTCTGCAGTGGGAGCGTTTTACCAACTGCTTAGTCAGTCCAGCCTAAGTATATTGCA
TTCTGAAGAGAAGAAACCTGTGGCTCCGGTTGAATCATGTCCTATTTTGAAAACACTCTACAAGATACTC
ATCACAAGAGAACAATCAACACAAGCGATTCTGCAAGCATTAAGGGATGAAACACTGAATGACCCAAGAG
ACAGGATTGAGATTGCACAGAGCCATGCATTCTACAGGCCTTCCCTTCTAGATCAGCCTTGATTAGTCTG
TCATGGCTCATAATCCGAACTTCTAAGATCTTACTTGTGCAAACTGCAGATTCTGCTATGTTAAACATCA
TGTCTTAAAATTGATTGTTGTTCAGCCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACATGTC

or EE485195

>gi|126492146|gb|EE485195.1|EE485195 DHBN8DCT_UP_012_C05_25FEB2005_043 BRASSICA NAPUS SEEDS BNDH8DCT Brassica napus cDNA 5', mRNA sequence
GTTACAGCTGGTTGAGAACAGTGACAATTCCCGGTTGAGCAAAGAAATTGCAGACAAGAGCCACCAACTA
AGGCAAATGAGAGGAGAGGAACTTCAAGGACTTAACATAGAAGAGCTGCAACAGCTGGAAAAGGCCCTTG
AAGCTGGTTTGACGCGCGTGATTGAAACAAAGAGTGAGAAGATTATGAGTGAGATCAGTGACCTTCAAAG
AAAGGGAATGAAATTGATGGATGAGAACAAGCGGCTAAGGCAGCATGGAACACAACTAACAGAAGAGAAC
GAGCGACTAGGCAAGCAAATATATAATAATATGCATGAAAGATACGGTGGTGTTGAGTCGGAGAAGACCG
CCGTGTACGAGGAAGGGCAGTCGTCAGAGTCCATTACTAACGCCGGAAACTCCACCGGCGCTCCTGTTGA
CTCCGAGAGCTCCGATACCTCTCTTAGGCTCGGCTTACCGTATGGCGGTTAGAGATGGAACCATACAAAG
AAGTTCATGGAGTGAGGAGATGCTCTGTAGTAACAAGTGGCAATGTAGTAATTTCTCTTGTTTGATGTAA
GTTTTTGTCTGAGGAAGAGGTTTTCCTTTTATGTTCTCTTTGATATTATTATCTTTCTTCACTGCAAAAA
AAAAAAAAAAAAAAAAAAAAAAAACATGTC

It seems to me that both the polyA sequences at the end are some sort of tail rather than actual coding for poly lysines. If we BLAST either of the sequences, the polyA part doesn't align with any reliable nucleotide or protein (i.e., with the NCBI non-redundant databases). I can give more examples and show their best alignments to nr-Sequences but it will make the question too long.

Cross posted to SeqAnswers.

The CATGTC sequence at the end of the poly A tail is an artefact of the method used in constructing the original cDNA library.

According to https://www.ncbi.nlm.nih.gov/nucest/EE485195.1 this EST comes from a library constructed in the Clontech vector pDNR-LIB

The Clontech SMART cDNA cloning system manuals are linked to from here
and the general manual descibes the use of a primer for 1st strand synthesis:

  CDS III/3' PCR Primer  5'-ATTCTAGAGGCCGAGGCGGCCGACATG-d(T)30N-1N-3'

  (N = A, G, C, or T; N-1 = A, G, or C)

If you look carefully at the primer you will see that the oligo dT portion, designed to anneal to the poly-A tail of the mRNA is preceded by the sequence GACATG and a SfiI site that is used in some clever cloning strategy that I don't fully understand. What is clear however is that the use of this primer will put CATGTC immediately after the poly A in the cDNA:

           .....SfiI....
5'-ATTCTAGAGGCCGAGGCGGCCGACATGTTTTTTTTTTTTTTTTTTT...
   TAAGATCTCCGGCTCCGCCGGCTGTACAAAAAAAAAAAAAAAAAAA...5'

>>> turning bottom strand around -  5' ...AAAAAAACATGTC


Are there any drawbacks to having a fixed-Köhler microscope? I am considering to buy the Zeiss Primo star microscope. There are two variants: one with so called "Full Köhler" illumination and one with "Fixed-Köhler" illumination. Are there any drawbacks to having it fixed? When I would not want to have Köhler illumination?

IMHO: there's hardly any reason why you should't use Köhler illumination. It's the method of choice to achieve bright and even illumination, in the entire FOV, permitting max. resolution. In a well designed system.
Köhler has only one drawback: often it turns out to be impossible to achieve even illumination at low power in the entire FOV. Usually, but not aways, the manufacturer has made provisions to achieve propper illumination at low power at the condenser level.
Allow me to add that I'm not a fan of the Primostar stand, which is a microscope build on order for Zeiss, probably by Meji.
Compared to the older Black, grey and white Zeiss Standard stands, it's a toy...


How does the DNA cross through bacterial cell wall during electroporation? There exists a lot of literature on electroporation of Gram-positive and negative bacteria. Most of it gives an explanation that electroporation works by creating transient pores in cell membranes of bacteria for the DNA to pass through.
Both types of bacteria have a cell wall as well (differing in thickness). How does the DNA pass through the cell wall that it encounters on the way?

The bacterial cell wall is quite porous, and is not considered a permeability barrier for most small molecules. It mainly functions as structural support and to resist turgor pressures.
The average pore size of relaxed peptidoglycans were measured to have a radius in a range of about 2.0 to 2.5 nm, regardless of thickness (i.e. Gram + and Gram - bacteria have similar pore sizes), but when stretched under turgor pressures, peptiglycan is permeable to globular proteins of 50 kDa or more, while hyperosmitic shock of bacterial cells can trigger the release of proteins up to 100 kDa in size (Vollmer et al., 2008). That equates to ~6.5 to 8.5 nm in diameter by one method of estimation.
A single strand of DNA double helix is around 2 nm in diameter, so it stands to reason that even a circularized plasmid could potentially pass through pores just a little more than 4 nm wide.
Reference:
Vollmer, W., Blanot, D., & De Pedro, M. A. (2008). Peptidoglycan structure and architecture. FEMS microbiology reviews, 32(2), 149-167.


Sense and anti sense strand Why the sense strand is only involved in transcription though the antisense strand just has the compliment strand of the sense strand?

The short answer is the transcription machinery will only bind on the correct orientation.  The binding of proteins and such to the promoter DNA strand is determined by the sequence of the DNA, the sequence is not correct on the anti-sense strand for a given gene.


How does Natural Selection shape Genetic Variation? Background

Importance of the additive genetic variance

As stated here, the fundamental theorem of Natural Selection (NS) by Fisher says:

  The rate of increase in the mean fitness of any organism at any time ascribable to NS acting through changes in gene frequencies is exactly equal to its genetic variance in fitness at that time.

NS reduces the additive genetic variance

On the other hand, NS reduces additive genetic variance (discussion about the origin of this knowledge can be found here). The genetic variance of a population for multiple traits is best described by the G-matrix (here is a post on the subject).

What is a G-matrix

A G-matrix is a matrix where additive genetic variance of trait $i$ can be found at position $m_{ii}$. In other words, the diagonal contains the additive genetic variance for all traits. The other positions $m_{ij}$, where $i≠j$ contains the additive genetic covariance between the traits $i$ and $j$.

Question

How can one model how the G-matrix changes over time because of selection (assuming no mutation)?

First of all, here is a program which simulates the evolution of the G-matrix over multiple generations, it's a few years old (they seem to have stopped developing it) and I've only played with it briefly. This could solve how to model the evolution of the G-matrix.

Fisher's fundamental theorem is a great place to start off with the theory of this:

  The rate of increase in fitness of any organism at any time is equal to its genetic variance in fitness at that time.

What this means (as I am sure you realise but I will put in so the answer can help others too) is that evolution by selection depends not only on the strength and form of selection, but the genetic variation underlying the selected trait. This is captured in the breeders equation $\Delta \bar z = G \beta$  where $\Delta \bar z$ is the response (in a multivariate space), $G$ is a matrix of the genetic variance within traits covariance between traits (different traits, the same traits in either sex, or the same traits in multiple environments) and $\beta$ is the vector of selection gradients on all of those contexts. It seems reasonable to expect that given enough time selection will erode variation because standing genetic variance is a finite resource and selection removes polymorphism while not adding any new variants (that's for mutation & migration).

This paper discusses the effects of both selection and drift on the G-matrix, they also deal with some modelling to support their results. More specific to simulation, this article by Arnold et al (a number of the big players in the G-matrix circle). It reviews "empirical, analytical, and simulation studies of the G-matrix with a focus on its stability and evolution." It would be a really good read for you on this subject.

This paragraph captures the essence of your question:

  Focusing on a longer time scale, we find that the G-matrix evolves in expected ways to the AL [adaptive landscape] and the pattern of mutation. In the absence of correlational selection (rω = 0) and mutational correlation (rμ = 0), the average G-ellipse is nearly circular, although the ellipse fluctuates wildly about this average (first row in Fig. 6). At the opposite extreme, when the leading eigenvectors of the AL and the M-matrix [mutation matrix] are both inclined at an angel of 45°, the leading eigenvector of G is pitched at the same angle (last row in Fig. 6). Between these two extremes, G tends to evolve to a shape and orientation that represents an intermediate compromise between the AL and M. In other words, the simulation results confirm our intuition and theoretical expectations (Lande 1980b) that G should evolve toward alignment with the AL and M.

Simulation studies of the G-matrix:

Bürger R, Wagner GP, Stettinger J. How much heritable variation can be maintained in finite populations by mutation-selection balance. Evolution. 1989;43:1748–1766.
Multivariate mutation-selection balance with constrained pleiotropic effects.
Wagner GP
Genetics. 1989 May; 122(1):223-34.
On the distribution of the mean and variance of a quantitative trait under mutation-selection-drift balance.
Bürger R, Lande R
Genetics. 1994 Nov; 138(3):901-12.
Predicting long-term response to selection.
Reeve JP
Genet Res. 2000 Feb; 75(1):83-94.

The last article there by Reeve is probably the best paper for your question because it describes in some detail the simulation model they use and how it is all set up. Briefly they simulate a population of 4000 diploid individuals with three genetically correlated traits with separate but identical sexes, random mating, and discrete generations. 20000 generations are simulated to allow mutation-selection-drift equilibrium (almost like a burn-in time on an MCMC chain). They then shift the optimum for one trait by 10 standard deviations and simulate 1500 generations in five replicates. There are 100 unlinked loci underlying the traits, with 50 loci affecting each trait (randomly assigned) meaning there is likely some degree of genetic correlation though it is not perfectly correlated (for some reading on genetic correlations and the evolution of differences you can read Bonduriansky & Rowe 2005, Poissant et al 2010, and Griffin et al 2013). The model then assigns phenotypic values to individuals, and fitness is derived. Figure two shows how the mean, skew, and kurtosis of the variance distributions changed for those 1500 generations.

Addition

Roff 2012:

  "While the mean trait values change under selection, so also will the
  G matrix, its orientation tending to shift in the direction of
  selection. ... Genetic drift may also play a role in changing the G
  matrix, but in this case the change will be random though on average
  producing a proportional change in the constituent variances and
  covariances."


How does the counter-current multiplier work in the nephrons? Why is the counter-current multiplier called like that? What is flowing in the opposite direction to the glomerular filtrate for it to be called "counter-current"?

Can you please explain the counter-current multiplier mechanism in the loop of Henle in the nephron, including details about the ascending limb, descending limb and the collecting duct?

I have searched it everywhere and I cannot find a satisfactory explanation that I can fully understand.

Countercurrent multiplication

What is flowing in the opposite direction to the glomerular filtrate for it to be called "counter-current"?

The filtrate is moving in the opposite direction of the filtrate. It's a loop. Filtrate moves in two directions relative to the nephron, down (from the cortex toward the papilla/through the medulla) and up (from the medulla to the cortex). We'll start with up, because that's where the active transport occurs

Up: as filtrate moves up the ascending limb, $Na^+$, $K^+$ and $Cl^-$ are actively pumped out of the filtrate and into the surrounding ECF. This limb, the ascending limb, is impermeable to water, so water doesn't follow the active transport of solutes and the fluid becomes more concentrated in the ECF than in the tubule lumen. So on the way up, the filtrate becomes more dilute.

Down: the descending limb is permeable to water and to ions along with it, so as filtrate moves down the descending limb, the osmolarity of the filtrate equilibrates with the concentrated ECF. This equilibration between descending limb filtrate and the ECF, makes the filtrate more concentrated, so on the way down, the filtrate becomes more concentrated.

By itself, the active transport of solutes out of the filtrate and into the ECF on the way up the ascending limb, (with dilution again by the water on the way down the descending limb) would seem to make only a small difference, but consider what happens as the filtrate continues to flow, while the ECF doesn't.
Consider this diagram from Constanzo Physiology, Chapter 6:

First, the active transport of solutes out of the ascending limb brings the ascending limb filtrate from 300 mOsm to 200, while the ECF becomes concentrated. The descending limb and ECF equilibrate, and you're left with an ECF and descending limb osmolarity that has gone from 300 mOsm to 400. This gives you the state represented in frame (1). The increase in ECF and descending limb filtrate osmolarity that is caused by active transport of solutes from the ascending limb is called the single effect.
When fluid moves, 300 mOsm filtrate flows in from the glomerulus, replacing the 400 mOsm filtrate at the beginning of the descending limb (which equilibrates with the ECF), but 400 mOsm filtrate from the end of the descending limb flows around the hairpin and continues along the ascending limb, giving you the state represented in frame (2). This new state is the result of the flow of fluid.
Now the single effect operates on this new state. At each point along the ascending limb, active transport of solutes dilutes the filtrate in the ascending limb and concentrates the ECF, which equilibrates with the filtrate in the descending limb, giving you the state represented in frame (3). Here you can start to see an up/down gradient establish. Continue these steps, and you can see how a substantial gradient can form.
Countercurrent exchange
After being presented with countercurrent multiplication, students will often ask how it is that solutes and water equilibrate horizontally in this diagram (i.e., between the descending limb and the ECF), but not vertically. This is a different question, and is where you start to need yet another compartment, the blood in the vasa recta. This mechanism is called countercurrent exchange, but is the answer to another question (how come the corticomedullary gradient doesn't dissipate?).
Original paper
In addition to physiology texts (e.g., Costanzo Chapter 6), you can read one of the most important original papers supporting this mechanism. Originally published in 1959, it was reprinted here in 1997 and available for download. See if you can follow the connection between the data and this mechanism.


If Tumors have lots of mutations in them how is it the immune system can't detect them? If a cancerous tumor has a lot of mutations in them why can't the immune system detect them? If a person has cancer could this somehow alter the person's immune system so it doesn't function effectively to detect greatly mutated cells? Does the fact that a tumor is 'made' of 'mutated' non-foreign human cells help it to be undetectable?

This is a good question and it gets to the most basic foundations of immunology. Your immune system is made to be flexible - able to adapt to almost any challenge. However, with so much flexibility comes the potential to generate immune cells that react against the 'self'. So, at the other extreme, the immune system needs to be limited.

In order to meet these two (potentially conflicting) goals, immune (at least lymphocytes) cells have a two-step development pathway. In the first step, the body randomizes its immune receptor specificity. In the second step, it ensures that these receptors are not auto-reactive.

Doing so means that immune cells are aware of their environment at the time that they are 'born.' Take a look at this review from the Fuentes-Panana lab to read about how tumors actively cultivate the immune system of their host in order to maintain a more favorable environment.


Is sigma factor a transcription factor? After I googled 'sigma TF' I stumbled upon two papers(only).
From a paper:

Sigma factors (sigmas) are bacterial transcription factors that bind core RNA polymerase (RNAP) and direct transcription initiation at cognate promoter sites.

and another paper had the title -

Specific binding of the transcription factor sigma-54 to promoter DNA.

However this contradicts with my book- Principle of Genetics Snustard and Simmons:

Unlike their prokaryotic counterparts, eukaryotic RNAPs cannot initiate transcription by themselves .... require the assistance of protein transcription factors to start synthesis.

Is it a TF?
Note: From what TFs are, sigma factor seems to be a TF to me.

Prokaryotic sigma factors confer specific promoter recognition to RNAP via Sigma subunit σ1.1, which acts as a DNA 'mimic' - occupying the downstream DNA binding site. This interaction is displaced only when the promoter region is bound, hence conferring the specificity.
Note that Sigma factor on its own cannot bind DNA, as σ1.1 binds σ4 in the unbound form, preventing binding to any sequence.
Source: Section 2. Structural Organisation of σ70 and Other Group 1 σ Factors in this paper

This is in contrast to eukaryotic transcription factors, which can bind to the DNA on their own - indeed the assembly of the general transcriptional machinery in eukaryotes (read: In Yeast) is stepwise and involves first the binding of TFIID to the DNA, then TFIIA, then TFIIB, before finally the Polymerase is incorporated into the growing complex. Source: Molecular Biology of the Gene - James D. Watson, p.g.449-454

In prokaryotes, the sigma factor needs to be bound to the core enzyme (forming the holoenzyme) in order for this promoter specificity to be achieved. Your book 'Principle of Genetics - Snustard and Simmons' is referring to the core RNAP, not the holoenzyme with the Sigma factor bound.

This is why sigma factors are often not included under the umbrella term of 'transcription factor' - they achieve the same functionality as eukaryotic TFs, but are fundamentally different in terms of their binding to the polymerase.

Often authors note that eukaryotes need TFs whereas prokaryotes don't because the point they want to convey is that eukaryotes use huge multiprotein complexes bound to the Polymerase, whereas prokaryotes just use the RNAP holoenzyme, giving Sigma factors a somewhat 'special' place among the transcription factors.


The human brain in numbers I: neurons Even though knowing the number of neurons in a functional unit or with the same function is not of main importance, it may be interesting to know their orders of magnitude, especially in the human brain. For example:

|------------------|------------------|
| cerebellum       | 100,000,000,000  |
| cortex           |  20,000,000,000  |
| telencephalon    |  10,000,000,000  |
| brainstem        |   1,000,000,000  |
| sensory neurons  |                  |
|          haptic  |     500,000,000  |
|          visual  |     100,000,000  |
|        auditory  |           2,000  |
| limbic system    |                  |
|         amygdala |      10,000,000  |
|------------------|------------------|

Surely, for many parts of brain you will find a reference where the number of its neurons is estimated (e.g. for the amygdala) - when you search hard enough. I also found The Human Brain in Numbers where some numbers are given. But I am looking for a reference where many of these numbers are given in a systematic way, ideally in a table like the one above. Is there any?

First of all, let me clear out that these numbers are calculated, not observed (obviously, nobody has counted the number of neurons in any part of brain). So, take these with a grain of salt.

I was unable to find any report that collects and displays all numbers together (Bio Numbers too didn't yield significant information). So I will compile here all the numbers I have found so far (and keep adding as I find more):

|----------------------|------------------|------------------------|
|PART OF BRAIN         |NUMBER OF NEURONS |               REFERENCE|
|----------------------|------------------|------------------------|
|The human brain       | over 120 billion |  Herculano-Houzel, 2009|
|Telencephalon         |  12-15 billion   |           Shariff, 1953|
|Cerebellum            |   101 billion    |    Anderson et al, 1992|
|Cerebral cortex       |  21-26 billion   |      Pelvig et al, 2008|
|Amygdaloid complex    |    12 million    |    Schumann et al, 2005|
|Hippocampus (CA1)     |  11-24 million   |        West et al, 1990|
|Brainstem             |   < 1 billion    |  Herculano-Houzel, 2009|
|Visual cortex         |   140 million    |       Leuba et al, 1994|
|Auditory cortex       |    1 billion     |University of Washington|
|Corpus callosum       |   200 million    |          Healthline.com|
|Spinal cord           |    1 billion     |University of Washington|
|Cortical minicolumn   |      80-120      |               Wikipedia|
|Cortical hypercolumn  |   5,000-10,000   |               Wikipedia|
|----------------------|------------------|------------------------|

I will continue adding more numbers as I find them. Again, nobody will claim these numbers to be exact, these are just estimates from calculations. Even different sources show different numbers. For example, the Washington University page puts the number of neurons in visual cortex to 528 million. Thus, don't expect these numbers to be anywhere near exact.

References:

Herculano-Houzel, 2009
Shariff, 1953
Anderson et al, 1992
Pelvig et al, 2008
Schumann et al, 2005
West et al, 1990
Leuba et al 1994
University of Washington
Healthline.com
Wikipedia Cortical minicolumn
Wikipedia Cortical hypercolumn


How can Southern blotting be used to establish gene copy number? I am reading a paper on a certain marine microorganism that can eat alkanes and therefore might be useful for cleaning up oil spills, etc. This sentence struck me as odd (although I am sure that the answer is pretty simple):

  Using the same probe, Southern blotting analysis showed that there was only one copy of alkB1 in the B-5 chromosome.

I realized that I don't know how Southern blotting can tell you about copy number. Can someone help me on this?

This method is commonly practiced. Atleast I see the people working with zebrafish transgenics using it.

When you shear the genomic DNA or do a restriction digestion, you are likely to get fragments of different sizes.
It is highly probable that the two (or more) locations harboring a copy of the DNA element are a part of fragments with different sizes. So on the blot you'll get two bands.

But as I said this test relies on probability that the two fragments are dissimilar in length. Therefore, southern blot should not be considered as an absolute test to determine copy number. Inverse PCR, FISH, etc can be used to determine copy number.


How correlated is the chirality of different molecules? In astrobiology, a proposed way of testing whether life found on another world is alien or originates from Earth is to determine the chirality of its molecules. This is of course only useful when the biochemistry is similar enough that one may suspect contamination.
But this test has a weakness. While different chirality can confirm alien origin, similar chirality does not exclude alien origin.
To mend this, a plausible idea is to cross check the chirality of a wide range of compounds. A false positive suggesting Earth origin would then have an exponentially smaller chance to match every single compound tested.
...or so I hope.
The issue is that I fear various chiral compounds do not have statistically independent default chirality. For instance, common biochemical pathways may produce one compound from another, leading the chirality of the first molecule to directly determine the chirality of the second.
I'm looking for a high level perspective: Does the chirality of a single compound more or less determine the chirality of all other compounds in an entire biochemistry, or are there a great number of compounds that have an arbitrary default chirality compared to others?

Hypothetically if an alien species were found , and if they contained similar biochemical polymers (DNA with A,T,C,G , Protein with 20 Amino acids etc) then we MAY be able to conclude that they share an origin with us. (Just similar chirality does not necessitates the theory of same origin)

Does the chirality of a single compound more or less determine the chirality of all other compounds in an entire biochemistry?

Yes. As Chiral molecules are almost always produced/purified from chiral medium (containing other chiral molecules and/or chiral physical attributes e.g. polarized light).
Therefore (Assuming that the reaction is enantioselective and you want pure chemical with a specific stereochemistry) the configuration of the chiral center of a new molecule does depend on the reagent chirality. Still this relation is not constant and differs from one reaction to another. For instance textbook SN2 reaction leads to inversion of configuration while Williamson ether synthesis reaction maintains the chirality.
A non-racemic mixture of a chiral compound is resulted from previous non-racemic mixture and so on. therefore the stereochemistry of the first non-racemic mixture determined the S/R , L/R ,(-/+) chirality of the entire life per se whose identity may never be fully understood.


Is summation linear in a passive membrane? I am not too sure what it means for summation to be linear? I am running a simulation and as I decrease time for the second EPSP the amplitude decreases. Does summation being linear mean that there is a direct negative linear relationship between delay of onset and amplitude? I also noticed there is no change when I double or triple my conductance value.

I am just not too sure what the relationship is telling me.

For a membrane to satisfy the conditions for linear summation implies that when two EPSPs of amplitude $A$ and $B$ are summed at the integration zone, the resulting output signal will be of amplitude $A+B$. Since the signal dissipates due to time and length constants, increasing the delay between the two inputs means that the later input will be dissipated so $A+B$ will be smaller than it would have if the delay was shorter. Under this scenario, inputs $A$ and $B$ are still summed linearly. However, if the delay is shorter than the time constants or the inputs are delivered closer in space than the length constant, then you may get non-linear summation since the output signal at the integration zone will be larger than $A+B$.

Have a look here for more information (especially Figure 7):
Silver RA. Neuronal arithmetic. Nature reviews Neuroscience. 2010;11(7):474-489. doi:10.1038/nrn2864.


Why does shaving dehydrate the skin? Is there an hormonal effect involved? I want to understand why the face becomes dry after shaving and if shaving affects hormones? I've heard that after shaving, hair grows back faster, why? Shaving damages hair follicles and they become inflamed. One could get an infection JUST by shaving because tissue is ripped from the hair follicles. So maybe the increase in hair growth can be attributed to the natural blood rush that brings nutrients to the damaged follicles when they are inflamed after shaving....

First of all 'Testosterone' hormone controls the growth of hair on our body and also oil secretion. Depending up on the nature of a person's body, this hormone controls the growth of the hair.

Why shaving facial hair leaves the skin dry ?

First let me explain the reason behind the oiliness of the skin. Sebum is produced by the sebaceous glands and is a complex made up of cholesterol, free fatty acids, glycerides, squalene, and wax esters. Sebum and sweat, along with the epidermal lipids discussed earlier, make up the oil on the surface of the skin. Some people will have more oily skin and some have less which depends on the nature of body.

While shaving the sharp razor cuts the hair and also damages the skin and hair follicles. The level of damage to skin also depends whether you are shaving downwards or upwards. Because upward shaving usually causes more damage to skin and hair follicle. Complete detail of damage to hair follicle can be found in this article: Science of shaving.

Shaving also removes skin lipids and water content creates pores which exposes the skin. If the surrounding atmosphere is dry then skin loses water. Or if the surrounding is moist or humid then water content will be balanced. That is the reason why we use artificial face moisturizer for immediate remedy to avoid infection and balance the wetness of face. So it takes a while for the skin to get back to normal state if nothing is done after shaving which sometime leads to acne or rashes due to infection.

Another reason for dry face is use of hot water which removes skin oil instantaneously. So lukewarm water or cold water will further reduce the dryness of the skin. (Use of shaving cream with high alkaline content will obviously result in dry skin. This holds for soaps also.)

Complete details can be found in the first link provided and Drying skin after shave.


Effect of a doubling of the start codon in a gene I am learning about frameshift mutations. Frameshifts can occur due to a nucleotide deletion. Suppose that due to a frameshift, because of a deletion somewhere upstream from the original start codon, two additional start codons are generated, just before the stop codon in the new reading frame. What would happen in terms of translation?

AUG-GCC-AUA-AUG--------UAA
Start       Start then stop

There is a basic misconception in the question you have asked, which @biogirl has explained. There is only one start Codon in any mRNA and it defines the open reading frame.

All other AUGs in the open reading frame are simply codons that encode for the Amino Acid Methionine and have no function in the start of translation. There are factors other than AUG that determine the start of translation.

So a frame shift that gives you an additional AUG only means that you will have a different Amino Acid encoded for in the resulting polypeptide. A frame shift will generally completely alter the protein product of the gene. If however the frameshift does disrupt the start codon, then it is unlikely that you will have any translation what-so-ever, as the other elements necessary for determining the start of translation will likely not be present in other areas of the coding sequence. In prokaryotes, you need a Shine-Delgarno sequence to initiate translation, and in Eukaryotes, though all of the factors for translation start are not well understood many genes carry a Kozak sequence that indicates to the ribosome the start of the open reading frame.

The more important codons to look for are introductions of stop codons. These three codons, UAA, UAG, and UGA do not have tRNAs with complementary anticodons (for the most part, as tRNA genes can also sustain mutations that change their anticodon) and therefore all result in the termination of translation if the shifted frame results in the ribosome reading one of the three stop codons in frame.


Can the mutation rate vary for individuals of the same species, growing in similar environments? Suppose we consider several populations who originally inherited their genome from the same ancestor, and that we put for a few thousands generations in similar environments.
Could the mutation rate vary between the different populations or within the same population, but between different time points?

Yes.

between individuals: https://academic.oup.com/mbe/article/34/2/419/2528250
between individuals: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617969/
hypermutation (transient): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1087688/


When in the cell cycle is the number of chromosomes normally reduced? Page 96 of the Study Guide for Campbell Biology, 11th Edition has the following question:

  A reduction in the number of chromosomes per cell occurs

  a. During meiosis I

  b. During meiosis II

  c. During mitosis

  d. During the S phase of interphase

Page 451 states that the answer is a.

I thought that the number of chromosomes at the end of meiosis I per cell equals the number of chromosomes in the parent cell (although sister chromatids remain attached), whereas the number of chromosomes at the end of meiosis II per cell equals half the number of chromosomes of the parent cell. If so, isn't the answer b?

It is the other way around. Meiosis I (or reductional division) splits chromosome pairs so each cell gets half of the chromosomes of the parent. Meiosis II (or equational division) splits double-chromatid chromosomes (making two single-chromatid chromosomes), so cells retain the number of chromosomes, like in mitosis.

If more clarification needed:

before the S phase: 23 pairs of chromosomes, 46 single-chromatid
chromosomes
before the meiosis I: 23 pairs of chromosomes, 46
double-chromatid chromosomes
before the meiosis II: 23
double-chromatid chromosomes without their homologous other
after the
meiosis II: 23 single-chromatid chromosomes without their homologous
other
after fertilization = before the S phase

(I'm talking about humans here.)


How to safely conserve my current DNA methylation marks? I read the Wikipedia article on DNA methylation

Let's say I want to extract and then stock my current DNA methylation marks somewhere so that I can use it safely 20 years in the future for a medical procedure that doesn't exist yet.

What method should I use?

To record the current methylation state of your DNA, you can use bisulfite sequencing. Basically, you take half of your DNA sample and treat with bisulfite, which deaminates cytosines (C->U) , so they read as T instead of C. Methylated cytosines are protected, so they still read as C. You run two sequencing reactions, one with bisulfite-treated and the other with untreated DNA, so you can tell where the true Cs are in the genome. See the below diagram:

Wikimedia commons

Note that if you're thinking of doing this from a longevity point of view, that there are hugely different methylation patterns in different cell types; I'm not sure which cell type you'd want to pick. Also, methylation is not the only covalent modification of DNA that exists, there's also hydroxymethylation, and I'd bet there are more that we haven't discovered yet. There certainly are in bacteria and phage (glucosyl-hydroxymethylcytosine, for one). The hard thing about saving things for the future is that we really don't understand the full picture of what's happening now epigenetically, and as such, we don't have assays to detect things we don't know about.


Sickle-cell trait : Why is only one type of beta chain found in any one hemoglobin molecule? I was reading a textbook (iGenetics, 3rd edition page 71), and came across the following passage:

  Homozygous bS bS people make Hb-S, the defective hemoglobin, with two
  normal a chains specified by wild-type a-globin genes and two
  abnormal b chains specified by the mutant b-globin bS allele: these
  people have sickle-cell anemia. Heterozygous bA bS people make both
  Hb-A and Hb-S and have sickle-cell trait. Because only one type of b
  chain is found in any one hemoglobin molecule, only two types of
  hemoglobin molecules are possible—one with two normal b chains, the
  other with two mutant b chains.

(Emphasis mine)

My question is: Why is only one type of beta chain found in any one hemoglobin molecule? Or is this statement simply false?

I did search biology SE for similar questions, and found this one, but it is phrased poorly and the only answer does not address my question.

For one specific hemoglobin molecule, yes it's just one type of beta chain.  In the case of a heterozygote, this hemoglobin molecule could be expressing from the bS gene OR the normal beta gene.  Let's call it a 50/50 chance for each hemoglobin to be expressing bS.  Because RBCs have a ton of hemoglobin in them, this 50/50 or so expression of bS wouldn't be enough to cause RBC sickling and disease, and it also helps explain the heterozygote advantage vs malaria.


How to parse SCOP parseable files PDB residue identifiers? I am trying to parse the SCOP parseable files, specifically dir.des.scop.txt ver 1.75. But, I have been facing problems with the PDB residue identifiers in the file. This is a tab limited file and the PDB residue and chain identifier is the 6th column which. An example of this identifier is A:1-28,A:77-837 for domain d1kk8a2.  Hence forward I'll represent that as domain_id (pdb_id chain&range). This particular example is straightforward, which means the domain d1kk8a2 consists of residues 1-28 and 77-837 of chain A of the corresponding PDB entry 1kk8. But some of them are unintuitive and like d3ckra1 (3ckr A:-2-385), what does the negative entry for the start mean? And this example d2p83b1 (2p83 B:61P-385), there is a P in the range (61P-385).

If you go to pdb website and search for the corresponding entries, then go to the sequence tab, you will see the alignment of the PDB chain and the corresponding SCOP domains. The ranges shown there correspond to the entries in SCOP, but it is difficult to make sense of it. Can someone please explain or provide some pointers. Thank you.

PDB residues are described by the residue number and an insertion code. Residue numbers can be any number, including negative values. In 3CKR the first residue has nr. -6, followed by -5, etc. This might indicate that there are additional residues at the beginning of the sequence, relative to other PDB entries. In 2P83, the first residue has the number 61P. Take a look at https://lists.sdsc.edu/pipermail/pdb-l/2004-March/001513.html for an explanation why PDB residue numbers have insertion codes.


Do decibels matter if the sound is outside human hearing? I bought a dog training device that emits sound at 25K hertz and 130 dB. Can this damage anyone’s hearing since they can’t hear it?  Also is it possible for an infant to hear in the 25K hertz range?  Thanks

Your dog training device produces what is called ultrasonic noise. Children can hear in the 25 kHz range, though they may not develop that ability until they are school aged.

This review has a good overview of the literature around ultrasonic noise. They draw the conclusion that it's hard to isolate the effect of a particular frequency or frequencies exactly, but there is some inconclusive evidence that noise at the frequency and dB of your dog training device could cause hearing damage and have other negative effects. In several countries, you're above the admissible range, but this is for longer term exposure.


identification of purposeful (engineered) genetic changes vs. random mutations Okay, first - I'm not a proponent of intelligent design. I do not think it's a valid scientific theory (it has no mechanism of change/design). Second, I could be wildly off on what I think I know, in which case, my apologies for the question.

My question is, I know that scientists manipulate the genes of organisms (both animals and crops we use as food). I think this could be considered legitimate intelligent design (right? I'm talking as opposed to looking at an organism and saying that this couldn't have evolved naturally, therefore it was intelligently designed).

So, mankind has modified organisms - outside of knowing we did this, can we tell they were intelligently created? If so, how? Can we tell when a genome has been altered?

Also, if I'm totally off base, please correct me.

One should be able to tell this from comparison of the sequence with that of the original organism in GenBank etc. The differences in an engineered organism will generally be extensive and of such a kind that a specialist in the field will be able to identify their origin and deduce that they did not arise naturally.

However there is no general and guaranteed method. If I were to engineer a single base change, there would be no way to distinguish that from a natural mutation. The only thing is that if the mutation were beneficial then it would probably have occurred naturally and I wouldn’t have needed to engineer it.


Can we determine a person's age by dating methods or other means? There are many sports restricted to players of a certain age (e.g. 16 and under, 18 and under, etc.) What if a person is older and fakes his birth certificate to say that he is younger? Is there any way to expose this person?

Can we determine such a person's age by radiocarbon dating methods or other means?

No, one can't confirm age by carbon dating. That doesn't mean we can't make a decent guess by other methods.

There is an interesting case of a 33 year old Texas woman who enrolled in 10th grade in Texas. She said she had no transcripts because she had been homeschooled. She looked like a teenager and acted like a one too. She even fooled her new 23 year old boyfriend. So it happens. It also happened in the Little Leagues World Series, if I remember correctly. A twenty-something guy passed himself off as a 14 year old. He was a star (for a while).

In children and adolescents, the combination of a dental exam, dental films and bone X-rays can narrow a one's biological age well. Once the bones are done growing in length, that avenue is closed.

After that, someone might have to provide a tooth. Chemical analysis of tooth dentin, such as aspartic acid racemization, has shown reproducible and fairly precise results.

Global levels of carbon-14 (14C) have been carefully recorded over time. In one 2010 study, forty-four teeth from 41 individuals (one per individual) were analyzed
using aspartic acid racemization analysis of tooth crown dentin or radiocarbon analysis of enamel. Teeth from individuals with dates of birth ranging from 1936 through 1994 (aged 13–70 years) were analyzed, and where the date of birth was known, yielded a 14C-based date of birth estimation accuracy of 1.3 years (S.D. = 0.9 years). In one case, a date of birth was determined to be 1948.4. In another, it was determined to be 1988.

  [T]en of these were split and subjected to both radiocarbon and racemization analysis. Combined analysis showed that the two methods correlated well (R2 = 0.66, p < 0.05). Radiocarbon analysis showed an excellent precision with an overall absolute error of 1.0 ± 0.6 years. Aspartic acid racemization also showed a good precision with an overall absolute error of 5.4 ± 4.2 years. Whereas radiocarbon analysis gives an estimated year of birth, racemization analysis indicates the chronological age of the individual at the time of (tooth extraction).

During the course of aging, l-forms of amino acids are transformed by racemization to the d-forms.

  [T]he extent of racemization of amino acids may be used to estimate the age of various tissues. Of all stable amino acids, aspartic acid has one of the fastest racemization rates and is therefore the amino acid most commonly used for age estimation....[T]eeth are the tissue of choice for age estimation analysis.

Both methods have strengths and limitations.

  The radiocarbon birth dating method can tell the birth date of the person regardless of the time of (extraction). However, the time window for this analysis is limited to subjects born after the early 1940s because the calculations are based on the measurement of bomb pulse-derived 14C.

Clearly this wouldn't be of too much use in people trying to pass themselves off as teens.

Some studies of aspartic acid racemization report accuracies of age ±3 years. The radiocarbon and racemization can further narrow it down.

Why did Charity Johnson pretend to be a teenager for 20 years?
Age Estimation in Forensic Sciences APPLICATION OF COMBINED ASPARTIC ACID RACEMIZATION AND RADIOCARBON ANALYSIS
Strategy for the estimation of chronological age using the aspartic acid racemization method with special reference to coefficient of correlation between D/L ratios and ages


What is this spider? I took the following picture of this spider in northern Switzerland (alt: ~700m) with macro flash (then it is not so big: probably around 2-3 cm, including the legs)

This spider made its web on the house and it goes out only during night.

In this region we have many Araneus diadematus, but this one looks totally different.

Is it the same family or another? Does anybody have a clue for the real name?

UPDATE: I saw it this afternoon (gave a fly to the web to make it go out), the body is probably around 7-8 mm wide and 9-11 mm long). And now I am sure the colors are more or less right.

I'd guess it's Nuctenea umbratica, or otherwise similar in appearance and coloration pattern, but less frequent Nuctenea silvicultrix.

At least Nuctenea umbratica was recorded in Switzerland.


Differences among competent cells? What are the differences among the following competent cells DH5 alpha, Nove blue, and BL21? Why some of them are for cloning and others are for protein expression?

Any references where I could find the answer?

There are a lot of differences, you can check the companies that sell competent cells for guides on how to choose (NEB, Sigma Aldrich). But there are only a few things that matter for the really common uses of competent cells.

The most important part of selecting your cells is choosing cells suitable for protein expression or for plasmid preparation.

The cells meant for plasmid prep carry certain mutations like endA that inactivate nucleases that would otherwise degrade DNA. Typical choices here would be DH5$\alpha$ or XL1-Blue.

Cells meant for protein expression have some proteases mutated, and can often use different promotors like T7. A typical example are BL21 cells, and BL21(DE3) which can use the T7 promotor.


What is this angiosperm from Morocco? What is this species of angiosperm? It's got succulent stems and leaves that do not produce latex. Photographed in spring.

It is a species of Carpobrotus, probably Carpobrotus edulis. However, after looking online, several of the Carpobrotus species look very similar. It is an invasive species in the Mediterranean region. See the Wikipedia link.

https://en.wikipedia.org/wiki/Carpobrotus#Species