Question about production of CFTR protein How do organelles such as ribosomes, ER, Golgi and vesicles produce CFTR protein and mucus?

CFTR (cystic fibrosis transmembrane conductance regulator) is an integral glycoprotein of the plasma membrane, and mucous is rich in secreted glycoproteins. All proteins are made on ribosomes: CFTR will be cotranslationally inserted into the ER membrane while secretory glycoproteins are cotranslationally sent across the same membrane into the lumen of the ER. In the ER the initial glycans are added to specific amino acid residues. The folding of all proteins is carefully monitored by chaperones in the ER to avoid misfolded proteins reaching the cell surface. Various folding factors also come into play, including peptidyl proline isomerase and protein disulphide isomerase.

Proteins destined for the cell surface leave the ER in COPII-coated vesicles (CFTR will be in the vesicle membrane, secretory glycoproteins in the vesicle lumen) and are targetted to the Golgi where the glycosylation process is completed. Another round of vesicle transport gets the proteins to the cell surface - when these vesicles fuse with the inner surface of the plasma membrane the vesicle content is secreted into the surroundings, while the vesicle membrane proteins enter the plasma membrane.

The classic example of a CFTR defect, resulting in cystic fibrosis, is due to the ΔF508 mutation - the loss of a single amino acid results in misfolding, and the defective protein is held in the ER resulting in loss of CFTR function at the cell surface. Overcoming this retention is one of the targets for CFTR therapy, because if the ΔF508 protein does manage to pass through the secretory pathway to the cell surface it provides sufficient channel function to abolish cystic fibrosis symptoms.

I haven't cited any references here because this is all standard biochemistry/molecular cell biology textbook stuff, so should be easy to confirm.


Does every protein starts with Methionine amino acid During process of protein synthesis we need AUG Codon to start translation .As we know this codon codes for Methionine amino acid so can we say that every protein starts with Methionine amino acid ?

No, not every protein starts with a methionine. When the methionine is removed, it is called N-terminal methionine excision. Abstract excerpt below:

  N-terminal methionine excision (NME) is the major proteolytic pathway
  responsible for the diversity of N-terminal  amino  acids  in
  proteins.  Dedicated  NME components have been identified in all
  organisms, in all compartments  in  which  protein  synthesis  occurs:
  cytoplasm, plastids and mitochondria. Recent studies have revealed
  that NME is regulated at various levels and plays an important role in
  controlling protein turnover. NME is essential  in  Eubacteria  and
  lower  eukaryotes  and  is  the target of many natural and synthetic
  inhibitors. Such inhibitors  have  considerable  potential  for  use
  in the  treatment of various human diseases, from cancer to bacterial
  and parasitic infections.

And from a recent review focusing on the methionine aminopeptidase enzyme that cleaves the first methionine:

  Protein synthesis is initiated by methionine in eukaryotes and by
  formylmethionine in prokaryotes. N‐terminal methionine can be
  co‐translationally cleaved by the enzyme methionine aminopeptidase
  (MAP). When recombinant proteins are expressed in bacterial and
  mammalian expression systems, there is a simple universal rule that
  predicts whether the initiating methionine will be processed by MAP
  based on the size of the residue adjacent (penultimate) to the
  N‐methionine.

Mitochondria and other organelles also have different start codons. Their alternate start codons are well-characterized (AUA and AUU in humans and mainly - but not exclusively - GUG and UUG in prokaryotes).


How much of the genotype-phenotype map do we understand in HIV? From what I understand, viruses have very small genomes relative to those of standard model organisms used in biological research. For example, according to Wikipedia, "the HIV genome contains nine genes that encode fifteen viral proteins". This is several orders of magnitude below the complexity of the mouse genome for example, with over 20,000 genes encoding over 50,000 proteins.

As a bioinformatics student (from a non-biological background) working with mammalian genomes, I often find the link between genotype and phenotype quite abstract and I'm unable to fully get an intuition for concretely how genomes can encode the instructions (or recipe using Dawkins' analogy) for creating complex phenotypes.

With this in mind, I wondered whether viruses, in particular HIV, which I know has been well studied, provide the simplest models for understanding the principles of how genes can encode the complete phenotypes of a functioning biological entity. Having such a small number of genes, I assume it is feasible to follow the transcription, translation and interaction of all genes and proteins? If so, is it the case that we understand how all of the genes and proteins work in HIV? If not, what is the main barrier in our understanding?

Apologies for this poorly-defined question. I am having a hard time getting my head around how molecular/cellular biology fits in with the complex phenotypes I've been studying in developmental biology/physiology and hoped that a simpler species/biological system could help to illuminate how it all comes together! Any pointers to further resources would be much appreciated.

I'm sure HIV is well studied since as you know it has a small genome and is highly relevent to therapeutic research, but virus regulation can be complicated and not representative of what happens in normal cells. This is why model organisms exist. The yeast Saccharomyces cerevisiae has about 6,000 genes and researchers have systematically deleted nearly every gene and looked at what happens to the cell. This information is available on the saccharomyces genome database. For example if you search SNF1 (which has a human homolog) on SGD (https://www.yeastgenome.org/locus/S000002885). You can see the phenotypes associated with deletion, overexpression, as well as a summary of what it does and how it's regulated (with original references). I don't think it gets any better than that. A lot of what is known about genetics and molecular biology comes from studies in yeast so I think it is worthwhile learning about yeast genetics to get a better understanding of what goes on in cells.


Polyploidy, or why plants of different species can produce fertile offspring hybrids more frequently than animals? This site says:

  Plants hybridize much more frequently and successfully than animals do. [...] Chromosomal doubling (polyploidy) occurs more frequently in plants and facilitates the fertility of the hybrid offspring.

Outcomes of the successful hybridization of different species of plants (i.e. yelding fertile offspring) can be easily observed in agriculture - for instance, Triticum aestivum is 6n, while Triticum durum is 4n. The latter comes from the hybridization of two plants from different genera (!). So it seems to me that not only can plants hybridize more easily, but also that the evolutionary distance between the parents can be greater than in animals.

As far as I know, the preferred animal strategy to have fertile hybrids is to go partheno/androgenic (for example in Phasmida).

My question is:

Why can plants produce fertile hybrids more often than animals? What constraints are present in animals and absent in plants?

To my knowledge, polyploidization is the main mechanism by which this is achieved. If this is true, then my previous question can be rephrased as why does animal polyploidization occur more rarely?

I'm not entirely sure about my assumptions, so feel free to correct me, of course with references.

While I do not know if there is a definitive answer to this question, I suspect that at least part of the answer can be found in the fact that animals typically have much more complex and delicate mechanical interactions in their bodies than plants.

From a mechanical perspective, plants are pretty simple. They move, but generally quite slowly and via very simple mechanical principles, and the interconnection between different tissues and organs is mostly via chemical and fluid flow.  Many plants are also highly flexible in their size and also change their size by orders of magnitude even after sexually mature.

Animals, by contrast, are often ferociously complex and intricate systems of joints and complex and highly differentiated organs. They also tend to have a well-defined typical size of mature individuals, which doesn't vary all that much compared to plants.

When you have a change in ploidy, a major effect is to multiply or divid the levels of gene expression, based on the change in number of copies.  Where that interacts with the processes of morphogenesis, it will thus often have radical effects on the size or growth patterns of the effected tissues or organs.

With a more intricately connected and scale-sensitive system like an animal, it seems then unsurprising that such changes might be much more difficult to survive.


Troubleshooting for Agarose Gel Electrophoresis SI ran my 2% agarose gel on constant voltage (100 V). For a few times it worked at CV but, after a week or so the machine would automatically switch to constant current by itself. And this only happens when I try to increase the voltage to 100 V. It works fine between 50-80 V. Beyond 80 V it keeps fluctuating between CV and CC.

Is there a problem in my power supply (GENEI electrophoresis power supply) or is the TE buffer that I am using? Although I checked its pH and it's fine.

I haven't found a manual for this machine, but my guess is that you exceed the maximum current which the power supply can provide. This is something I have experienced myself for electrophoresis.

Usually power supplies then switch into the constant current mode at the maximum current they can deliver, which I think is what happens here. If the voltage you choose is lower, you do not run into this limitation, thats why it is working without problems.

So you can either run your gels at constant current, which makes them run faster but also produces more heat, which can make your gel blurry. Or you live with a slightly smaller constant voltage, have your gels run a bit slower, but probably have a bit better resolution. I have to say that I have never had any problems with the resolution, even when I ran my gels really fast.


How do ants spontaneously grow wings? On hot summer nights we get flocks of ants that have grown wings (from what I know to migrate nests).

It appears the wings are not permanent, but are grown for a temporary purpose.

From what I know these events are triggered by climatic conditions (warm evenings).

In other species, wings seem like a really big deal and are grown from birth - wheras ants seem to just grow them 'on the spur of the moment'.

My question is How do ants spontaneously grow wings? Are they a spare layer of skin that is normally discarded and only comes into action when necessary?

See the Wikipedia entry for nuptual flight.

The ants that you see most often are (wingless) female workers. The winged ants that you see are male drones whose only role is to fly with young queens for mating. The drones follow a different developmental pathway, emerge from the pupa as winged ants, and then wait in the nest until conditions are right for the big event.


Reference request: neocortex creating 11 dimensional structures I've come across several pop science articles like this one that vaguely describe a method of analyzing brain tissue involving algebraic topology and 11 dimensional structures. They all seem to cite each other. One of the researchers involved was Kathryn Hess. I've searched the web, a community college library, and the UCLA library and haven't been able to find the original paper. Does anyone know where I could learn more about their methods?

I finally found the work. It was in the sources of the sources of the article that I gave as an example.


What factors cause males to be more common than females in humans, from an evolutionary perspective? Fisher's principle states that there should be a 1:1 ratio between males and females born on average for a population.  However, if you look at birth statistics your find that boys are slightly more likely to be born then girls.   This article talks a little about how it happens

If it was truly advantageous for an even sex ratio to exist at birth I imagine we would have evolved to make that happen, by slightly favoring more female sperm or by having the processes that decides which embryos to spontaneously abort be stricter for males embryos then females.  For that matter since it's more important for males to be exceptionally healthy then it is for females, since males have to compete for a mate while females don't, you would think more strict filtering for 'bad' embryos in the case of males then females would make sense anyways.

Thus I'm inclined to think that the increased number of males to females is not random evolutionary fluke, but adaptive.  I'm wondering what would cause there to be a benefit for males to be slightly more common then females.

I know males are more likely to die in childhood, due to risk taking activities to impress the females, so could it be that the increase in males is due to the expectation that more males will die before reaching sexual maturity?  I'm not certain I buy this logic, it doesn't seem you should favor a sex any more because it's likely to take higher risks.

I know that strong/healthy mates would prefer males and weak ones prefer females, since strong males would out compete weak males for mates it's good to have strong males that can achieve multiple mates and weak females since their guaranteed to have at least one mate.  Is it possible that our increased nutrition and health of recent generations simply results in more males because our bodies judge each of us as 'healthy' compared to the standard that existed for 99% of our evolution, ie, evolution hasn't caught up with technology when judging health to decide which sex to favor?

Is there some more obvious explanation for why favoring males slightly would be adaptive in humans?

Edit: I want to stress again, I'm not asking how the bias happens.  The article I linked clearly explains what causes males to occur more in terms of pregnancy.  I'm asking why the bias happens.  This could be evolved away in the past if it was disadvantageous,  Whatever mechanisms cause there to be a bias this bias is presumably adaptive for it not to be evolved away.  Both the possible duplicate and the current answer only address what causes the bias to happen today, not why it would be evolutionarily adaptive to have.

Nice question! The answer is in your linked article. I quote:

  When you put this all together, it turns out more males are born because more female fetuses are lost during pregnancy.


Do blind birds bob their head when they walk? Birds try to keep their heads still for short periods of time between steps to improve their ability to see. You can find amusing videos of chickens used as small video camera stabilizers. But does this happen to blind birds? Is it something all birds do regardless of their ability to see?

The forward thrusting movement so peculiar of pigeons and other fowl (Fig. 1) while walking is thought to be related to shifting the visual field. The less visible backward motion of the head is thought to be related to fixating the field of view (Dunlap & Mowler (1931).

According to the meticulous observational study by Dunlap & Mowler (1931), blindfolded pigeons stop making head movements altogether while walking. They stop their forward thrusting motion, the backward motion as well as more random scanning head movements. Hence, the authors conclude that the forward and backward jerking movements are related to vision, and not to hold their balance or whatsoever.

Fig. 1. Snapshots of a pigeon walking. The head thrusts forward in the middle frame. source: Dunlap & Mowler (1931)

Reference
- Dunlap & Mowler, J Comparative Psychol (1931); 11(1): 99-113


Can there be medium height(neither tall nor short) pea plants in Mendel's experiment? Can there be medium height(neither tall nor short) pea plants in Mendel's experiment?

All textbooks I have read seem to imply that pea plants have to be either tall or short, nothing in between.

Medium height (like in people) and other traits that seem like a mixture of two extremes are often a result of incomplete dominance. For example, a red and white flower are bred to produce an offspring with pink petals.

Mendelian genetics does not include incomplete dominance (which is classified as, surprisingly, non-Mendelian genetics).

Basically, Mendel got very lucky with his choice of plant. Pea plant height is strictly dominant, meaning one dominant allele results in tall plants, regardless of the identity of the second inherited allele. This is a consequence of the genetic makeup of pea plants. Had he tried a similar experiment with snapdragon flower color, he would be very confused.

(See https://www.ndsu.edu/pubweb/~mcclean/plsc431/mendel/mendel2.htm for snapdragon incomplete dominance example.)


Why does HPV Infect Squamous Epithelial Cells and Not Others? I've seen this question about HPV and the reference therein. The link states "Human papillomavirus (HPV) is a DNA virus that presents tropism for epithelial cells, causing infections of the skin and mucous membranes. Replication of HPV occurs in the nuclei of squamous cells and its life cycle is directly related to the differentiation program of the host cell. "

Why does HPV infect squamous epithelial cells and not others, what are the major differences? And why can't that difference be used to provide medication?

The answer usually lies in whether the cell of interest expresses the correct receptor.

Check this:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820467/

This excerpt from that review explains why:

"Although both the α6β4 and α6β1 heterodimer were capable of binding VLPs in vitro, only the former was supposed to function as a HPV receptor, which was concluded from the results that the α6 subunit associated preferentially with the β4 in epithelial cells [12], and the α6β4 complex was expressed exclusively in the basal cellular layer of the stratified squamous epithelium [13], which was presumably the only site of productive PV infection"


What are the max angles of human eyeball rotation? How much can our eyeballs rotate towards the nose, away from it, towards the top and bottom?

There shall be slight differences due to physiology. Nevertheless, the average vertical ascending angle is 25 degrees and descending angle, 30 degrees.
Within the x-y plane of which we assume to be coplanar with the central line of vision, the maximal angle of rotation is 35 degrees in the left and right directions respectively.

I attempted to construct an image which depicts these angles - simply a Cartesian diagram.
You can find further clarification of details from this link by Nelson & Associates

Finally, it is important to note that although the eye may be capable of these rotations, the eye may not be able focus on all objects in this field acutely, namely, focusing light on the fovea.

Happy muscular experiments.


Do animals feel emotions, or display empathy? Since we can't know much of what's going on inside an animal's brain, can there still be a consensus among zoologists on whether animals feel emotions, display empathy, care, etc.? Or is it disputed?
To clarify what I said since commenters asked for clarifications: Of course I don't mean SENSES (touch/vision/taste...) and also I do NOT include humans.

A suggested definition of emotion:

  An emotion is a feeling such as happiness, love, fear, anger, or
  hatred...the part of a person's character that consists of their
  feelings, as opposed to their thoughts. (Collins Dictionary)

An example of emotion:

  No one doubts that dogs know when they are in trouble,” writes de
  Waal, “but whether they actually feel guilty is a point of debate.”
  According to a study by Alexandra Horowitz, the canine guilty
  look—“lowered gaze, ears pressed back, slumped body, averted head,
  tail rapidly beating between the legs—is . . . not about what they
  have done but about how their owner reacts. If the owner scolds them,
  they act extremely guilty. If the owner doesn’t, everything is fine
  and dandy.” (Greater Good Magazine, University of California, Berkeley)

Empathy:

  Empathy is the ability to share another person's feelings and emotions
  as if they were your own. (Collins Dictionary)

Example of empathy:

  Macaques refused to pull a chain that delivered food to themselves if
  doing so also caused a companion to receive an electric shock.[48][49]
  This inhibition of hurting another conspecific was more pronounced
  between familiar than unfamiliar macaques, a finding similar to that
  of empathy in humans. (Wikipedia: Emotions in animals)

The answer to the question "Do scientists agree whether animals feel emotions, or display empathy?" is No. However, there are some animals that certainly do not have emotions or empathy (for example animals that have no substantial nervous system, like sponges), and some animals that certainly do have emotions. The only disagreement is in the middle and where to draw the boundaries. In reality, drawing such boundaries is probably not all that productive, coming down to semantic rather than biological argument.

As a citation for the disagreement, see the two answers and the comments here already.

The difficulty in assessing a statement like this is largely one of operational definition: you need to define what an emotion is, and depending on that definition you will get entirely different answers. You will also get different answers depending on your philosophical approach to questions like these and what the essence of experience is. I would also point out that emotion and empathy are vastly different levels of cognitive ability according to typical definitions of the two.

However, I will say that there are a lot of recent findings of higher cognitive abilities in non-human animals than previously thought. Rodents have long been used as generic models of mammalian nervous systems, including emotional processes. Mirror neurons in non-human primates respond to the behaviors and movements of conspecifics, which is an important aspect of both social learning and potentially empathy. Self-recognition is an important aspect of theory of mind, and has been observed in several species of different types. Mourning behaviors have been observed in various animals in response to death of conspecifics. There can be some disagreement of the interpretation of these findings, but I'll include some references here so readers can do some of their own research and find if they are convinced.

Note that these works study particular animal abilities in particular contexts, rather than making blanket judgments about "all animals" or anything like that. This is typically how science works, incrementally based on the results of individual experiments.

References

Gallese, V., & Goldman, A. (1998). Mirror neurons and the simulation theory of mind-reading. Trends in cognitive sciences, 2(12), 493-501.

Lane, R. D., & Nadel, L. (Eds.). (1999). Cognitive neuroscience of emotion. Oxford University Press.

Mulcahy, N. J., & Call, J. (2006). Apes save tools for future use. Science, 312(5776), 1038-1040.

Plotnik, J. M., De Waal, F. B., & Reiss, D. (2006). Self-recognition in an Asian elephant. Proceedings of the National Academy of Sciences, 103(45), 17053-17057.

Prior, H., Schwarz, A., & Güntürkün, O. (2008). Mirror-induced behavior in the magpie (Pica pica): evidence of self-recognition. PLoS biology, 6(8), e202.

Rajala, A. Z., Reininger, K. R., Lancaster, K. M., & Populin, L. C. (2010). Rhesus monkeys (Macaca mulatta) do recognize themselves in the mirror: implications for the evolution of self-recognition. PloS one, 5(9), e12865.

Roth, G., & Dicke, U. (2005). Evolution of the brain and intelligence. Trends in cognitive sciences, 9(5), 250-257.


How to check if a population density obeys replicator dynamics Say we have a probability vector or population density $p = (p_1,...,p_n)$ with $p_i \geq 0$ and $\sum_i p_i =1$. Also assume we know the functions $g=(g_1,...,g_n)$ such that:

$$p_i(t+1) = g_i(p(t))$$

where $t$ is a discrete time index. Is there a way to check whether $g$ implements a discrete time replicator equation? I.e. whether there is a function $f=(f_1,...,f_n)$, called the fitness landscape, such that:

$$p_i(t+1)= \frac{f_i(p(t))}{\langle f \rangle_{p(t)}} p_i(t).$$

where $\langle f \rangle_{p(t)}:=\sum_j p_j(t) f_j(p(t))$ is the average fitness of the population density.
Pluggin in $g_i(p(t))$ gives an equation that we could try to solve for $f$ but I don't know how:

$$g_i(p(t)) = \frac{f_i(p(t))}{\langle f \rangle_{p(t)}} p_i(t)$$

or equivalently:

$$\frac{g_i(p(t))}{p_i(t)} = \frac{f_i(p(t))}{\langle f \rangle_{p(t)}}.$$

We can of course also drop the time dependency and write:

$$\frac{g_i(p)}{p_i} = \frac{f_i(p)}{\langle f \rangle_{p}}.$$

Is there a (in the best case necessary and sufficient) criterion that has to be satisfied for this equation to have a solution?
I am also grateful for tips how to tackle this problem in a principled way, including numerically.

For discrete time replicator dynamics, fitness is defined only up to a multiplicative factor. I.e. if you pick some number $k$ then $(f_1, ..., f_n)$ defines the same fitness function as $\hat{f} = (f_1/k, ..., f_n/k)$. In particular, this mean for any $p$ you can always pick a $k$ such that $\langle \hat{f} \rangle_p$ = 1.

So using your final equation, just let $\hat{f}_i(p) = g_i(p)/p_i$.

Note that the resulting landscape $\hat{f}$ will be a relative fitness landscape and not an absolute fitness landscape. But there is no way to recover an absolute fitness landscape from the data you have. You would need information on how the population size, not just frequencies evolved for that.

As a final note: if you're trying to match this to experimental data, the discrete time approach might not always be necessary. In that case, you can try the method that I describe in this post or depending on your experimental system, you might be able to just do the game assay as we defined in this paper.


How lion can carry the cub without harming it? We can see in the picture that lion is carrying its cub by the scruff of its neck without causing harm to it.

The skin of the felines has geneticaly evolved in such a way that the parent can do this.

Its strong and stretchy in the neck area.

Moreover, the cub enters into an obedient state.


What kind of succulent is this? I have this succulent at home and was wondering about the following questions:

What kind of succulent is this?
What will the leaf grow into?
Will there appear more leafs or just a single one?

Your plant looks like this one: https://es.wikipedia.org/wiki/Euphorbia_heteropoda. It could be this species or a close relative. I found it in the "Monadenium" section of http://succulent-plant.com/families/euphorbiaceae.html, so the exact species likely belongs to this (former ?) genus.

It seems difficult to find it on other versions of Wikipedia, which makes me think that Euphorbia heteropoda might not be its valid scientific name.

The leaf will likely fall, leaving a scar as can be seen on the older parts of the plant.

From the photos illustrating the Wikipedia article, it seems it can have more than one leaf at a same time.


Why don't we develop immunity against common cold? We all suffer from common cold, and that, frequently. Why have we not developed immunity against it till now? By immunity I mean immunity as a species.

Long lasting immunity is obtained by means of the adaptive immune system, and mainly involves the development of antibodies that identify specific parts (epitopes) of the pathogen's proteins. Common cold is typically caused by a type of virus called rhinovirus. Viruses have very high mutation rates, which alter the sequence of the virus proteins, modifying their antigenic properties. This consequently alters the ability of antibodies to recognize a particular antigen.

In other words, we do develop long lasting immunity against the virus that causes us a cold today, but the virus that causes us a cold a few months later is somewhat different, and the adaptive immune system has to start from scratch.


How do I interpret this graph regarding introduced genes and virus-infected cells? This graph appeared in a practice test for the MCAT. I am trying to interpret it, but it confuses me a bit. On the x-axis we have some introduced genes, and on the y-axis we have % of cells infected. What I don't get is what the top part represents. How do the "Culture cell genotypes" relate to the rest of the graph. I would also like to know what -/- and +/+ mean. By the way, information in the passage lists CatB and CatL as mammalian proteases, and their inhibitors reduce the infectivity of viruses with the EGP glycoprotein (found in Ebola virus).

Here are some questions based on the graph:

Based on the passage, does optimal VSV-EGP infection in vitro require CatB, CatL, or both?

Based on the passage, is CatL expression sufficient for VSV-EGP infection of the mouse cell lines presented in Figure 1?

Plus and minus describe what is happening in a specific locus in the genome. When a + sign is shown, the locus contains the natural, fully working gene (wild type). When a - is shown, it means that by natural mutation or lab manipulation, cells lack that natural gene, or make a negligible amount of it, or make a broken variant etc.

These cells are diplod, meaning they have two homologous chromosomes. If +/+ is shown, both chromosomes carry, in that locus, a working gene. If -/- is shown, both copies are not working. If a cell is CatL -/-, both its natural copies of CatL are missing or defective, and the cell is unable to make the corresponding protein. The manipulation through which a naturally occurring +/+ is turned into a defective -/- is called a knock out.

The top part of your chart shows what is happening in the nucleus, on the chromosomes, at the actual places where normal cells store their CatL genes. You don't give much detail, but the bottom of the chart appears to show some manipulation away from the normal locus. There are ways to introduce more copies, to stick them into the nucleus, or even in chromosomes etc, but the main point about introducing DNA is that often it will not work as well as the natural thing.

Optimal infection means something close to the first column, about 25%. By skimming through the chart we are definitely seeing good infection in column 3. Also by comparison with the low levels, we could call acceptable the infection in column 8. The other columns are all clear failures to infect.

The second column is the simplest to interpret: knock out CatB alone, and the infection is gone. Thus, CatB is required for infection. The third column reinforces the same point: restore CatB and infection is back to normal.

The sixth column shows cells where CatL and CatB were knocked out, but then CatB was reintroduced. We know from column 3 that knocking out and restoring CatB should keep infectivity, but in column 6 infection is gone. The only difference between columns 3 and 6 is the knockout of CatL, and its consequence is lack of infection. Thus, CatL is also required for infection. You may say both CatL and CatB are required.

The other columns are control conditions which show that the experiment was well designed and yielded expected results, rather than gibberish. For example, column 5 show that if you knock out both, infection is gone. It would have been very concerning if it weren't gone. Etc.

Your second question is really one of logic: is CatL sufficient? We established that CatB is required, and so there is little CatL could do to supplant its absence. Therefore, logically, CatL should not be sufficient.

But we have a better proof, from the experiments. In column 4, those cells have their natural (endogenous) CatL, topped by some more CatL. But they are still not infected, beause they lack CatB. So CatL, even in larger-than-life amounts, cannot compensate the absence of CatB. CatL is not sufficient.


Why does our voice change when we get affected by cold or cough? Why does our voice change when we get affected by cold or cough? I observed the voice change thing in so many people including me.

The important point is that your voice is influenced by airflow, and your vocal cords. When we're sick, and it depends on what it is, a number of factors change the sound of your voice by influencing the two of these, either: By changing airflow due to respiratory tract swelling or fluid buildup, or by damage/swelling/alterations to the vocal cords. In a couple  of examples: A weak airflow might produce a higher pitch or weaker voice, or perhaps swollen vocal cords produce that hoarseness associated with decreased frequency of vibration.


Just how dangerous is ethidium bromide? A common precaution for preparing EtBr-agarose gels is to add EtBr only after the gel solution has cooled somewhat, because EtBr is a dangerous mutagen. Supposedly, adding it to a hot liquid allows EtBr vapors to get into the air and everyone's lungs, where it can act as a carcinogen.

In addition to this are commonly seen special procedures for handling EtBr vials and gels (fresh nitrile gloves, avoid contaminating other work areas, special waste disposal rules).

However, there's also some saying that EtBr isn't all that mutagenic and all this care is over the top.

What's the reality? Just how dangerous is EtBr, especially in amounts used at a typical biological lab? How long does the danger persist? Are even trace amounts hazardous (for instance, touching a "clean" pipette without changing gloves after working with EtBr)?

I usually find the treatment of Ethidium bromide in the lab widely exaggerates the true dangers of this chemical.
It is not really toxic (the LD50 is 1.5 g/kg bodyweight, as a comparision NaCl has a LD50 of 3 g/kg). It has also only been shown to exhibit mutagenic potential to bacteria after it had been treated with liver extracts. This means that some of the metabolized products of EtBr in the liver are mutagenic, but EtBr itself not. See reference 1 for details here. It is also not classified as a cancerogenic substance by the regulation bodies (for example see the National Toxicology Program of the US on Ethidium bromide).

As already mentioned, it is used to cure Trypanosoma infections in cattle (reference 2). Here up to 1 mg/kg bodyweight are given, with no signs of toxic or other adverse effects. The typical concentration used in the lab to prepare gels is 1 μg/ml. It works as a drug by interfering with the mitochondrial DNA (changing it to the Z-form, which is not available for replication). See reference 3 for details. Ethidium bromide also acts as a Topoisomerase I inhibitor as other chemotherapeutic drugs. See reference 4 for more details.

Additionally, EtBr is negatively charged and cannot enter cells or the nucleus, since cannot pass the membranes. I would wear gloves and also apply the usual safety rules when working with gloves (do not touch anything you don't need to touch, especially things like door knobs, keyboards or phones as you might spread contamination) dispose your gloves when not needed anymore and you should be fine.

References:

Detection of carcinogens as mutagens in the Salmonella/microsome
test: assay of 300 chemicals.
Comparison of isometamidium chloride and homidium bromide as
prophylactic drugs for trypanosomiasis in cattle at Nguruman, Kenya.
A low dose of ethidium bromide leads to an increase of total
mitochondrial DNA while higher concentrations induce the mtDNA 4997
deletion in a human neuronal cell line.
The geometry of DNA supercoils modulates the DNA cleavage activity
of human topoisomerase I


Cicada Killer Behavior I've had a giant wasp hanging around outside my window the past few days, so I've resolved to learn more about it. I believe it is a male Cicada Killer, because it displays the following behavior:

During the day, it is extremely localized in a region less than a square meter.
It lands or hovers in the same grassy area all day, and occasionally chases off other wasps that come near it.

First question: Am I correct that this is a male? The females should be off burrowing or catching Cicadas, right? He is quite large (2 inches?), but I don't have a female for comparison in terms of morphology.

Second question: Where does this guy go at night? He leaves before sunset (~5 pm) and shows up again in the morning (~10 am).

Third: If he's around, I should be able to find some female burrows in the area as well, right? Where should I look for these for confirmation?

The question is admittedly a little vague since I am just trying to confirm I understand the behavior I am observing, but I've tried to isolate the specific questions I want answered.

EDIT: Finally got some pictures, only these two came out.

Yes, it's a male.

http://bugmugs.org/wordpress/wp-content/uploads/2012/08/cicada_killer_pair_00052.jpg

Source: http://bugmugs.org/2012/08/cicada-killer-pair/

Update:

Wasps are in general very territorial. Even a paper bag can scare them as they take it as enemy hive. More on this: Do fake wasp nests actually fool wasps?

  Where does this guy go at night?

Wasps are known to be lazy(less active) at night. Probably they go to the nearby mud nest.

  If he's around, I should be able to find some female burrows in the area as well, right?

yes, there are chances of finding a female burrow near by, as they rarely fly away farther than the nest. Otherwise, there main food(cicada) is very heavy for them to carry to the nest.

follow this if you want to find it's borrow: http://www.wikihow.com/Get-Rid-of-Ground-Digger-Wasps-(Cicada-Killers)-from-Your-Lawn


C.elegans and antioxidants How would you test the effect of antioxidants on C.elegans lifespan?
Is this done through feeding E.coli with antioxidants and then C.elegans with E.coli, or is there another method?

base on a article they do the test of nano-Pt, kind of SOD, and they do the experiment in several steps, first choose C. elegans strains and growth conditions, meanwhile prepare the nano-pt. then, do the lifespan assay. thired is Oxidative stress resistance. the last step is Fluorescence microscopy. in the mictoscopy they do several steps, include Measurement of lipofuscin accumulation, Detection of ROS, Measurement of SOD/catalase activit, Thermotolerance and Effects of dietary restriction


Are there any known consequences of the right-handedness of the DNA double helix? In this article it is suggested (without evidence) that the right-handedness of DNA may be the cause that "kick[s] off asymmetry in the early embryo [of snails]".

On the one hand we know that symmetry breaking in an organism's development happens at multiple levels, from molecular to larger structural levels (see this). On the other hand we also know that right-handed DNA double helix does have many notably distinct properties from their left-handed cousins (see this). Are there any visible macroscopic asymmetries in some organisms that are known to be ultimately traceable back to DNA's handedness? More generally, what could be some consequences of the right-handedness of DNA double helix?

The short answer is no, there currently aren't any visible macroscopic asymmetries in some organisms traceable to DNA's handedness.

The long answer is still no, but I want to clarify that this "no" is more of a "not really". This is because there can be potentially drastic consequences when left-handed DNA is present in a cell in addition to the traditional right-handed DNA.

Let me explain. First, left-handed DNA is officially called Z-DNA. Right-handed DNA, which is the normal DNA configuration, is named B-DNA. There's a third type of DNA, which is also right-handed, that is called A-DNA. A-DNA is essentially super-coiled B-DNA.

Z-DNA isn't that unusual, and it is regularly found in human cells in addition to B-DNA. One study, done in yeast, found that Z-DNA can act as a nucleosome boundary element. Another study, by Kwon and Rich, found that the consequences of Z-DNA weren't as benign. The vaccinia virus requires Z-DNA to bind to a key protein that has anti-apoptosis activity. When Z-DNA does this, apoptosis is effectively blocked.

Furthermore, Z-DNA has been found in patients suffering with Alzheimer's Disease. Suram, et al., found that the hippocampus of severely affected AD patients used Z-DNA instead of B-DNA. This change in the DNA coil has potentially drastic consequences with regards to gene expression.

Finally, the presence of Z-DNA antibodies were found in patients that suffered from Systemic Lupus Erythematosus (SLE). Lafer, et al., describes how non-SLE patients do not have these antibodies, which suggests that Z-DNA is involved in the clinical manifestation of SLE.

So, with those thoughts in mind, yes, there can be visible asymmetries traceable to DNA handedness. In fact, some tumors depend on genes that have Z-DNA domains (one study by Alan Herbert found that it was about 40% of tumors on their panel). While this isn't really what I think you're asking, it's technically true as tumors do qualify as visible asymmetrical phenotypes traceable to DNA handedness. Diseases associated with Z-DNA could also technically qualify as since they're diagnosable, they're visible in that manner.

Regardless, there is currently no proof that the handedness of our DNA actually causes any real macroscopic phenotypic effect in the developmental stages of life. The reason why left-right asymmetry happens in organisms is due to asymmetric gene expression, not the direction of the DNA coil. This review by Michael Levin talks explicitly about how the left-right borders are established in embryonic development, and there is nothing regarding the direction of DNA's double helix.

Nonetheless, DNA handedness is still a rapidly developing field. I anticipate that more research on these subjects will quickly become available. But as of now, no. Snails shells are not right-handed because of the right-handedness of their DNA.


Why is AIDS not a congenital disease? AIDS can easily pass from mother to the newborn, then why do we not consider it to be a congenital disease (or syndrome)

A congenital disorder or disease is a disorder that is present at birth.  This term can be applied to many conditions, including some that are infections.  More typically, the term is used for developmental birth defects such as spina bifida and cleft palate.

Although HIV/AIDS can be congenital (since a mother has about a 25% chance of passing it to her newborn), most cases of HIV/AIDS are not transmitted by pregnancy and birth, but rather by sexual contact between adults.  Hence it is inappropriate to call AIDS congenital since most cases do not occur in newborns.  This can be contrasted with, for instance, spina bifida and cleft palate, which essentially only occur in newborns and so can reasonably be called congenital disorders or diseases.

A specific case of HIV/AIDS, one which has occurred in a newborn, can be called congenital HIV/AIDS, but HIV/AIDS cannot, in general, be called congenital.


Relationship between the ambiguity (wobble) at codon position 3 in elongation and codon position 1 in initiation In prokaryotes the usual observed start codon frequency is AUG > GUG > UUG.

An explanation for this is that

  AUG is the most common initiator codon because it forms the most stable interaction with the CAU anticodon in fMet-tRNA

But does this have anything to do with the more general wobble rules?

  Codon-anticodon pairing takes place according
  to the wobble rules (Crick 1966). During translation,
  base-pairing occurs in the usual way (A with U, and
  G with C) between the first and second nucleotides
  and the second and third anticodon nucleotides. The
  wobble rules state that in the pairing between the
  third codon nucleotide and the first anticodon nucleotide,
  there is a certain amount of play, or "wobble."
  This enables G in first anticodon positions to
  pair with U or C in codons, U with A or G, and I
  (inosine) with U, C, or A. In first anticodon positions,
  C pairs only with G, and A (very rare) only
  with U. These rules are fundamental to all discussions
  of codon capture. Table 1 shows anticodons
  in the universal genetic code as predicted by the
  wobble rules (Crick 1966).

I'm confused because that seems the exact opposite of what happens in the start codons' case, i.e. the "play" is in the first (not third) codon nucleotide in the start codon case. And the table in this last paper only gives CAU Met as the only pairing for CAU, so no wobble.

Am I interpreting this correctly and there's no "Crick" wobble in the AUG > GUG > UUG start codon, but rather another wobble-like mechanism that explains the start codons' first nucleotide wobble-like behavior?

Summary

The difference in the nature of codon–anticodon ambiguity seen between bacterial initiation and elongation lies not only in the position of the codon at which it occurs (5′ v 3′, respectively), but in the partial or absolute nature of the interactions (only some AUG and GUG etc. codons initiate and insert fMet, whereas all AUU and AUC codons will recognize the Phe-tRNA with anticodon, 3′-UAG-5′. It can be accounted for by the quite different molecular interactions occurring at the ribosomal P-site (for initiation) and the A-site (for elongation) and the importance of the base-pairing between the Shine & Dalgarno (RBS) region of the mRNA for initiation.

Wobble in context

Wobble was the term applied by Crick in 1966 to the non-standard base-pairing between the 3′ position of mRNA codons and the 5′ position of anticodons of certain tRNAs. To avoid violating the genetic code Crick assumed strict base pairing at the first two codon positions and asked the question “If one sRNA [old term for tRNA] codes both XYU and XYC [because of experimental evidence that this might be the case for Phe codons], how is it done?”. And then, given the many ways bases might be paired added the constraint “How many base pairs are there in which glycosidic bonds occur in a position close to the standard one?”.

On the basis of geometry Crick predicted that anticodon 5′-U might be able to pair with a codon 3′-G (in addition to the standard A), and anticodon 5′-G with codon 3′-U (in addition to the standard C). He — unwisely in my opinion — referred to these predictions (and his prediction for inosine, I) as ‘rules’. The predictions are summarized below, together with the actual pattern that has since emerged.

It should be noted that although the two predictions involving G=U base pairs would appear reciprocal, that involving an anticodon 5′-U does not occur except in mitochondria, were it is incorrect in that the interactions are not restricted to Crick’s ‘rules’.

The subsequent elucidation of the structure of phe-tRNA by Quigley and Rich in 1976 suggested why the wobble occurred at the 5′ position of the anticodon. This position (G34 in my modification of their figure, below) lacks the base-stacking that would be expected to constrain the interactions at the other two positions of the anticodon, and which was aided by a modified base (yW37) 3′ to the anticodon.

As the amino acid, methionine, has only a single codon (AUG) in the genetic code, one would expect it to have a tRNA that does not allow wobble at the 5′-codon position. This turns out to be the case:

  Both the tRNAmet for elongation and initiation have
  the anticodon 3′-UAC-5′.

In summary: 5′-codon wobble allows mRNA to be decoded accurately by fewer than the 61 amino acid codons, and one can speculate that its emergence involved evolution of both the structures of tRNAs and the ribosomal A-site.

Initiation and decoding ambiguity

In bacteria (eubacteria) there are two main differences in codon recognition during translation from that in elongation.

There is a single specific tRNA species involved which, uniquely, can interact with initiation factors and be bound to the P-site of the ribosome.
Interaction is required between the 16S rRNA of the 30S ribosomal subunit and a polypurine sequence 5′ of the initiation codon (the Shine & Dalgarno sequence or ribosome-binding site) in addition to the codon–anticodon interaction.

To adopt an extreme position, the situation in initiation may almost be thought of as one in which the fMet-tRNA is bound at the P-site of the small ribosomal subunit waiting for mRNA to bind, in contrast to elongator Met-tRNA binding to an A-site with the elongation codon AUG. The energy provided by the Shine–Dalgarno interactions may thus be enough to allow initiation if one of the initiation codon bases is incorrect. This raises at least two questions:

What advantage would allowing such ambiguous recognition have?
Why is the ambiguity in the first codon position and how does it operate in molecular terms?

I have no answer to the first question. Perhaps it has none, but is tolerated because it has no disadvantages either. The second question is the crux of the poster’s concerns.

First, ambiguity at the 3′-position of the codon would not be expected on grounds of structure or precedent: the table above shows anticodon 5′-C only base-pairs with codon 3′-G.

Second, the anticodon loop of initiator tRNAmet differs from that of elongator tRNAmet in having an internal-facing rather than an external-facing disposition (Woo et al., 1980). Furthermore it lacks a modified base 3′ to the anticodon.

Third, the interactions between initiator and elongator tRNAs with the rRNA at the A- and P-sites, respectively are quite different (Berk et al. 2006), conceivably allowing more flexibility at the 3′-anticodon position.

Despite the fact that the predicted anticodon-U/codon-G wobble never occurs at the A-site, it is reasonable to suppose that structural differences allow it at the P-site, explaining the second bacterial initiation codon, GUG. As regards UUG, U=U base-pairs were considered by Crick but regarded as “rather close together”. Presumably in certain contexts this is not too energetically unfavourable to be prevented.

Finally…

The poster asked:

  Am I interpreting this correctly and there's no "Crick" wobble in the AUG > GUG > UUG start codon, but rather another wobble-like mechanism that explains the start codons' first nucleotide wobble-like behavior?

To which I would reply that:

  There is not and cannot be any wobble at the 3′-position of either initiation or elongation AUG codons of bacteria because it would involve non-standard base-pairing of the anticodon C. To the extent that the ambiguity at the 5′-position of the alternative initiation codons used (GUG>UUG) follows a pattern consistent with the most likely non-standard base-pairing predicted by Crick, it would seem to involve base-pairing achieved by movement (wobble) of the 3′-anticodon residue U of initiator fMet-tRNA.


How did the "serendipitous rediscovery" of Sulfasalazine as an antirheumatic agent after 30 years happen? This excellent answer describes the history of the ~50 year old drug Sulfasalazine, and it's worthwhile to take a moment and read through the answer now.
Roughly speaking the drug is an antibiotic molecule linked to a molecule of aspirin, developed at a time when rheumatoid arthritis inflammation was assumed to be caused by an infection. Ironically the drug is now widely used as a treatment for RA, but its mechanism of action does not seem to be related to the way that it was originally designed to work.
Sulfasalazine is on the World Health Organization's Model List of Essential Medicines. See section 17.3, Anti-inflammatory medicines.
Within one of the block quotes in that answer from a publication by the Department of Medicine at Princeton can be found:

[...] Early therapeutic results were encouraging, but the drug was discarded as an antirheumatic agent for 30 years, until its serendipitous rediscovery (emphasis added).

Pubmed shows this to be Pinals R.S., J Rheumatol Suppl. 1988 Sep;16:1-4., PMID: 2903922, but I can't find access to the Journal of Rheumatology Supplements that far back in time.
Can somebody track this down and relate the "serendipitous rediscovery" story here? Or perhaps find a link to another author's version of the story I can read? What was the serendipitous biological evidence that led to rediscovery of Sulfasalazine as a disease-modifying anti-rheumatic drug? (DMARD, see also arthritis.org)

Your question led me to:

Pinals, RS (1988) Sulfasalazine in the Rheumatic Disease. Seminars in Arthritis and Rheumatism 17:246-259. I reproduce the introduction to this paper below:

  Most physicians are familiar with sulfasalazine (SSZ) as an agent commonly used to treat inflammatory bowel disease for more than 40 years. In 1978, McConkey et al reported preliminary studies suggesting that this sulfonamide might be effective in rheumatoid arthritis (RA).1 The use of SSZ arose from earlier open and controlled trials with a sulfone, dapsone, which had demonstrable efficacy in RA, but the benefits were accompanied by relatively frequent, often unacceptable adverse effects.2 Dapsone was effective in dermatitis herpetiformis, presumably because of immunosuppressive activity. Another therapeutic agent for this skin disorder was sulfapyridine (SP), a drug with a poor record of gastric tolerance. Therefore, McConkey et al elected to try SSZ, a compound that released sulfapyridine in the bowel after passage through the stomach. Ironically, McConkey was initially unaware that SSZ had been synthesized specifically to treat RA in the late 1930s. In 1980, McConkey et al reported their open experience with SSZ in 74 patients treated for up to 1 year.3 The improvement in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and clinical score (a global evaluation) was similar to that achieved with the disease-modifying antirheumatic drugs (DMARDs), and appeared somewhat sooner, often within 2 months. Moreover, although adverse effects were frequent, they were seldom of sufficient severity to discontinue treatment. This encouraging report led to several controlled trials in the United Kingdom and elsewhere, all confirming the efficacy of this interesting agent. The first study in the United States has been reported4 and, although SSZ has not been approved by the Food and Drug Administration for use in RA, many rheumatologists have used it as an alternative DMARD because of its availability and long record of safety and efficacy in inflammatory bowel disease.

What I have gleaned from this and a couple of papers cited there is that B McConkey, working at a hospital in Birmingham in the UK became interested in developing methods of clinical assessment of rheumatoid arthritis (RA) in the 1960s and this led eventually to the discovery that the drug dapsone is effective as a treatment but with an unacceptable level of adverse side effects. Then, to quote McConkey:

  We had studied dapsone partly because of its effect in leprosy and dermatitis herpetiformis; its mode of action in those diseases may be through its immunosuppressant properties. Another drug used in dermatitis herpetiformis is sulphapyridine;it did not attract us as a contender but it is a constituent of salicyl-azo-sulphapyridine (sulphasalazine), a compound originally formulated for RA and latterly found to have immunosuppressant properties.

  McConkey et al (1980) Sulphasalazine in rheumatoid arthritis. British Medical Journal 1: 442-444

  (This is ref 3 in the Pinals introduction.)

So clearly there was a strand of chemical logic in the rediscovery of the drug; the only serendipitous aspect was that McConkey did not at first know that sulfasalazine was originally designed as a treatment for RA.


Chromosome position mismatch for SNPs in dna tests TL;DR: why is the position reported by DNA testing companies for an SNP on a particular chromosome different than the one in dbSNP/SNPedia databases?

I'm analyzing the raw DNA exports for the same person from 2 different companies.

There is, as expected, a small number of discrepancies on the genotype reported.

Strangely, there is also a (smaller) number of discrepancies on the chromosome and position reported for the same SNP (about 0.02% of the rs-ids that are common to both exports).

Trying to find out who is right, I looked at SNPedia and dbSNP. To my surprise, while SNPedia and dbSNP (logically) agree on the positions, they never seem to match the positions reported in the raw DNA exports.

While the two companies that I used agree on the position in the vast majority of SNPs, they are apparently always different from dbSNP. In 75% of the 101 differences between the two companies, the position number only differs by 1.

I'm surprised by this and I feel that I'm missing some underlying piece of information.

What can explain these differences?

Does the "position" in the DNA exports from 23andme and MyHeritage represent some other biological property than the position reported by dbSNP/SNPedia? Or is there a conversion formula? Or is the information from the exports unreliable?

Most or all consumer DNA companies doing autosomal SNP tests deliver their raw data (at least by default) based on human reference genome build 37 (GRCh37).  This is effectively the standard for this arena because it is compatible with existing files and other companies, allowing matching and other processing.  dbSNP and SNPedia have changed to use the next major genome update, build 38 (GRCh38).  The major genome builds can be expected to have different position numbers for most all comparable places in the genomes, including of course all SNPs which are defined in both builds (most of them).

So the differences in positions shown in your raw data files and dbSNP/SNPedia are due to this difference in the reference builds they are based on.  I don't know a way of getting build 37 positions on SNPedia, but on dpSNP one way of seeing the build 37 position is to scroll down to "Genomic regions, transcripts, and products", "Choose placement" of GRCh37, and then hover over the blue highlighted SNP name, which will show a drop-down list with the (build 37) position, among other things.


Why are restriction enzymes not frozen? We all know restriction enzymes are proteins, but we never freeze them. They are instead provided in high glycerol containing solutions by companies and stored at -20C. Is there a reason why this is so?

It's just so much more convenient to have the enzymes ready without having to thaw them. The main reason you freeze enzymes is to keep them active, if you figure out a buffer that keeps them unfrozen without compromising activity, that is a huge increase in convenience.

Not having to thaw the enzymes before use saves a lot of time, if you can manage to keep the enzymes active in those non-freezing conditions that is a clear advantage.

Glycerol also stabilizes proteins in solution, and multiple freeze and thaw cycles can negatively affect enzyme activity for some enzymes.


Importance of fate maps I did some normal google.book search and found the two importance of fate maps-

1. They helped establish the idea that communication between different parts of an embryo leads to the formation of new cell types and have thus helped discover different signalling pathways.

  2. They enable us to interpret experiments in which cells of the embryo are exposed to conditions that may alter their developmental fate.

I really don't know where to look for the experiments that support these merits of fate maps. So is my question,what are some experiments that support these merits?

A good place to begin is with the experiments of Hans Speymann and Hilde Mangold, done in the 1920s. They transplanted a piece of the dorsal lip in a newt gastrual to the ventral side of another newt gastrula with different pigmentation. Because of this transplant, a "secondary" embryo formed, on what would have been the belly, in addition to the standard embryo expected. (Some picture show this to be rather like a second head.) Use of differently pigmented embryos allowed the researchers to note that the transplanted dorsal lip material developed into a second notochord. But the interesting facet is the newly developing notochord induced the development of a new neural tube in the adjacent cells which were otherwise destined to become "belly stuff".

My appologies for not finding a great reference with diagrams, my source is the 7th edition of Biology, Campbell and Reece. Here's a very thorough reference, with diagrams, if you're up for it.
https://app.shoreline.edu/kwennstrom/spemannmangold.pdf
This work contributed to a Noble Prize for Speymann. The bottom line here is that tissues receive information from adjacent tissues that influence their developmental fate.
Later experiments showed that the inducing agent was chemical in nature


What were the mammal ancestors like 65 million years ago? What we know about our mammal ancestors that were alive (and survived) at the extinction event 65 million years ago?

Many of them looked like little rodents. However, several distinct mammalian lineages were already present, including Monotremes, marsupials and placental mammals. Throughout the whole Mesozoic era, mammals were already quite diversified! Also, even though most of the mammals that survived the K/T boundary were rather small, there were already some larger mammals around in the Cretaceous.
Here is a nice picture of a symmetrodont:

See a nice page on early mammals.


Growth rate oscillation in the a population of non-interacting bacteria I have come across this theoretical paper claiming that if you start a batch culture from a single E. coli cell, the exponential growth rate of the population defined as $$k = \frac1N \frac{dN}{dt}$$
could oscillate for as long as 30 to 40 generations. In this equation, $N$ is the number of cells, and $\frac{dN}{dt}$ is the rate of change of the number of cells with time.

My question is:

  Have these oscillations been ever observed? This seems like a very simple experiment. Looking for references.

Edit: As mentioned in the paper, the "oscillations are hidden to the optical density measurements which provide a proxy for the total mass of the population" and not the number of cells.

The theoretical article concerns growth rates of single cells. There are many studies that model cell cycle as a non-linear oscillator (see Tyson and Novák, 2015).

However, growth rate measurements in microbiology are usually done on cell populations consisting several cells. You generally do not observe any oscillation because:

Cells are not synchronized
There can be variations in growth rate of different cells because of noise
The measurement time points are much larger than the period of oscillation

Some of these reasons are already mentioned in the paper you linked (Jafarpour, 2019).

I do see some ups and downs in the growth rate in my own data; E. coli growing in LB in a 96 well plate.

X-axis is the time in seconds; measurement was made every 15minutes. Y-axis denotes difference in OD between two consecutive measurements. The different colors are biological replicates. However, I cannot say that this is the kind of oscillation that Jafarpour talks about. It appears more like stochastic fluctuations in growth rate or measurement errors (they are also not damping by the end of growth).


Why would a mammalian vector plasmid require an antibacterial resistance gene? I have been trying to understand the composition of plasmids used in recombinant DNA cloning, such as this: https://www.genecopoeia.com/wp-content/uploads/2020/02/pReceiver-M35-051818.pdf
and I am wondering what purpose the ampicillin resistance gene has when transfected into a mammalian cell host (as it says it is for).
I understand that ampicillin resistance is used for selection in bacterial cells so that only transformed bacteria are grown as well as ampicillin being needed to prevent bacterial contamination among a mammalian cell culture, but I don't see why mammalian cells require a resistance gene to an antibiotic.

Thanks

I think the assumption you are making is that the ampicillin resistance gene would save a purpose in the mammalian cells.
It does not.

As you said, it is only use during the cloning process to select the bacteria to replicate and produce more of it.

There is a resistance gene on the vector you posted which affect mammalian cells: neomycin. In this case, once transfected into mammalian cells, you could select only the cells with the plasmid by adding neomycin the cell culture medium.

Note: neomycin selection can take some time (4-5 days) and higher dose than for example puromycin. Hope this helps!


Identify hematophagous insect There's a small insect that seems to enjoy residing near trees and takes blood meals. The pain is sharp, comparable to being stung by a wasp.

I'm located in Serbia, Eastern Europe, bordering Hungary and Romania. It's currently August, warm and very moist from the grass being regularly sprinkled.

This is an "aphid lion", a larva of a lacewing (family Chrysopidae). They eat aphids and other small animals, not blood, but are capable of biting humans. Here is a text about that (seems reasonable even with the silly title). It also says that "When a lacewing larva bites a human, it’s likely that any persistent itch or redness is due to the saliva injected at the site of the bite" so that would explain your pain.


Need help in codon optimization I want to chemically synthesize a GFP gene for expressing in rice.I am using the IDT Codon Optimization program and found that not all the codons are 100% optimized. Some of them are the 2nd or 3rd in frequency of usage. Also, the stop codon in the gene optimized is the least used in rice. I don't think all the codons can be the ones that are the most used in rice as there is need of translational pauses to get optimal protein expression. But how do I decide which codons are to be used in what positions to get maximum efficiency. Do I just use the automatic codon optimized gene given by IDT or further optimize it manually?

So should the stop codon used be the one which is the most frequently used in rice for proper mRNA termination?

Please help me as I am new to this and want tips and suggestions for getting optimized codons in this gene.

Generally the codon optimization is the most frequent tRNA found in your species of interest. However, your codon must not result in something that disrupts standard molecular biology practices. For instance, if your codon places a restriction site in a unique cloning vector, then the algorithm will just look for the next best codon which does not cause unwanted addition or elimination of a cloning site. Places like IDT will also weigh the cost of the codon vs. the ease of manufacturing in their algorithm (see here.)

What you describe as translational pausing that is 'needed' by the organism to optimize proper gene expression is a consequence and not a necessity of infrequent codons (to my full understanding). See here. That means you don't want to add this translational pausing in optimized gene expression. It is a simply an evolutionary byproduct.

Edit -

To answer your question more bluntly, I can tell you with some experience to trust the codon optimization algorithms from biotech companies like IDT. I find they work very well. Rice is a common enough organism :)


Reverse tomography to create 3D scalpel Isn't it possible to reverse tomography methods to create means to deliver heat or radiation precisely in 3D? This would be "3D scalpel" i.e. device which would be able to eradicate tumor cells precisely in otherwise unreachable areas?

The principle of targeting cancers with high intensity radiation is already in use. For example:

http://www.mayoclinic.org/tests-procedures/gamma-knife-radiosurgery/basics/definition/prc-20014760


What are the most efficient heat exchange sites on the human body? Where on the body would be the best place to achieve the greatest cooling effect with a "cooling undergarment"?  Concentrated over the kidneys, groin, inside the wrists, back of the neck?

From personal experience, the best places to put a cooler (at maximum metabolic load) are across the back and over the neck and head.

Good candidate areas for a heat sink or exchanger:

Any region where large volume per unit time of blood travels close to the skin. Some dinosaurs are thought to have cycled blood through spiny fins on their back to cool down (obviously this works for non-dinosaurs too, and even better if the blood vessels in the fin are pressurized (see Are there any known examples of animals with air-conditioner type cooling? ).

Regions where a lot of metabolic activity takes place, including muscles in active use and "brown fat" (see https://www.webmd.com/diet/features/the-truth-about-fat)


How are smell and taste in fish differentiated? The senses of taste and smell in different fish classes are described as two distinct senses; smell is mediated by the nasal openings, and taste by epithelial taste buds.

They are both forms of chemoreception and therefore it is not clear to me what intrinsically defines them as two distinct senses. The more so because reception of chemical substances is mediated by water.

What defines them as different senses? Is it only the difference of receptors that defines them as two distinct senses, or are there other reasons to differentiate them?

Short answer
One way to distinguish between the olfactory and gustatory system in fish is by their  anatomical differences. For example, olfactory receptors are clustered in the nasal region, while gustatory receptors are scattered in the head region and beyond. In turn, olfactory information is sent via a single cranial nerve to the brain, while the gustatory system includes three cranial nerves.

Background
The olfactory and gustatory system both receive their inputs through chemoreceptor cells. The chemoreceptor proteins in both systems are G-protein coupled receptor systems. However, the olfactory and gustatory systems are anatomically separated.

The olfactory end organ is in fish comparable to that in humans, namely sensory epithelia situated in nostrils. The olfactory receptor cells form axons that are grouped into the olfactory nerve (cranial nerve I). The nerve innervates the olfactory bulb, where its axons synapse onto mitral cells. Mitral cell axons group into the olfactory tract that projects to the telencephalon in the brain.

Schematic of olfactory system of a fish (not all structures shown). Source: Global Warming Australia.

The gustatory end organs are less well anatomically localized. The taste buds can be found in various structures including gills, barbels, fins, oral cavity and pharynx, dependent on the species. Unlike the olfactory system, gustatory information is transmitted to the brain via three separate cranial nerves: facial (cranial nerve VII), glossopharyngeal (cranial nerve IX) and vagal nerve (cranial nerve x). Normally, the facial nerve innervates taste buds on the extraoral surface, the glossopharyngeal on the anterior part of the oral cavity, and the vagal nerve on the pharynx. The facial and vagal nerves respectively terminate in the facial and vagal lobes in the medulla. The glossopharyngeal nerve terminates in a dorsal medullary region between the facial and vagal lobes.

Reference
- Hara, Rev Fish Biol Fisheries (1994); 4: 1-35


Are there any solitary species of ant or termite? The social insects consist of the ants, the bees, and the termites, which live in colonies rather than living solitary.

But I've heard that there are some species of bee which are solitary and don't live in colonies.

Are there also any species anywhere of either ants or termites which are solitary?

I do not know of any solitary ants, but there are species that form very small colonies.

One such species is Jerdon's Jumping Ant (Harpegnathos saltator). They usually live in colonies smaller than 100 individuals and workers may reproduce, so the colony can survive after the queen's death.


What are the limiting factors for gene length and number of exons? I recently downloaded gene annotations for Homo sapiens from Ensembl for some bioinformatic analysis. The vast majority of the gene annotations have 20 exons or less, although there are some that have as many as 250. I know enough about gene annotation to take these predictions with a grain of salt, but it got me thinking...what are the biologically relevant factors that might limit the length, exon number, etc of a gene? Is there any real possibility for a gene to have 50 exons? 100 exons? 250 exons? From a biological standpoint, where is the line drawn and why?

This question drops firmly into the lap of molecular evolution and the constraints that are placed upon genes by the forces of mutation, selection, drift and recombination.

There are numerous situations, particularly gene duplication, that can result in a gene that is free from the selective constraints of it's parent, many of which will accumulate so many deleterious mutations as a result of stochastic processes that they will become non-functional e.g. psuedogenes. Some can be altered and rearranged, accumulating exons and introns, and if they infer a fitness benefit on the organism, may be moved to fixation within a population.

Evolution is a population genetics process, and there are many variables which can effect the outcome, not least the difference in populations size. The genomes of larger populations (such as those of bacteria) appear to have much smaller genomes, and of course no (at least not spliceosomal) introns, perhaps as a result of increased fitness due to the decreased generation time of an organism with a more slender genome. It would be a good idea to read The Origins of Genome Architecture by Michael Lynch, as I think he answers your questions, better than I can.

Many of the genes you retrieve from EnsEMBL will of course have experimental evidence to support them. The genes that are predicted in the pipeline can be looked upon with less confidence, but you can of course look at the alignments with closely related species to see if you think the introns/exons are indeed viable. An example of a gene with 79 exons is the Dystrophin (DMD) gene, the longest annotated gene at 2,217,347bp (see Roberts et al, 1993 and Nishio et al, 1994).


How could cyanobacteria survive the anaerobic conditions of ancient earth? I was reading about cyanobacteria and came to know that they are the first organisms that filled the atmosphere with oxygen around 2.3 billion years ago but then I realized that they themselves are aerobic and I couldn't understand how an aerobic organism would be able to survive the oxygen poor atmosphere in the first place to make enough oxygen that filled the whole atmosphere and caused almost all anaerobic organisms go extinct

The first cyanobacteria were probably anaerobic, and this matter seems to be a hot topic of contemporary research. A recently published studya that performed a phylogenetic analysis of various Cyanobacteria genomes states:

  The most parsimonious inference from these data is that the last
  common ancestor of the Cyanobacteria did not use oxygen and that the
  three classes [of Cyanobacteria] acquired aerobic respiration independently after their
  divergence. The absence of aerobic respiration in ancestral
  Cyanobacteria suggests that abiotic oxygen sources on early Earth were
  insufficient to allow for its evolution until after the appearance of
  oxygen produced by photosynthesis.

Reference

a Soo, Rochelle M., et al. "On the origins of oxygenic photosynthesis and aerobic respiration in Cyanobacteria." Science 355.6332 (2017): 1436-1440 (http://web.gps.caltech.edu/~wfischer/pubs/Sooetal2017.pdf)


Bacteria trapped in crystal inclusions found 'alive' after 50,000 years - what were they eating all that time? The phys.org article Biologists find weird cave life that may be 50,000 years old describes the announcement by NASA Astrobiology Institute director Penelope Boston at the 2017 AAAS meeting$^{(1)}$ of micro-organisms found in small inclusions within crystals of hydrated [Calcium Sulphate][] (Gypsum) that had grown while underwater in a cave in Naica, Mexico. It is estimated that some of these organisms have been isolated within inclusions for as long as 50,000 years, and yet can grow and reproduce when carefully extracted and provided with fresh chemosynthetic nutrients.

(BBC Radio interview with Penelope Boston)

This particular discovery has just been formally announced so there is no peer-reviewed material to read yet, but it's possible someone here in Biology SE attended the meeting or has read further about the announcement.

50,000 years is a long time (for a bacteria, not a crystal), and if I understand correctly the energy source for these organisms is chemosynthesis. Put simply, wouldn't they have eventually used up all their food and died? I'm thinking the crystal is a good electrical insulator and the cave was dark, so there couldn't be external energy sources to replenish the oxidation state of the iron or sulphur or whatever they were eating.

The elevated temperature and ubiquitous radiation would have presented a relentless, potential source for DNA damage mechanisms, and repair would require a constant supply of energy. So I'm guessing there had to be some minimal source of energy to keep them viable, if not actually 'alive' for 50,000 years.

Is this thinking roughly correct? If so, what might that source of energy have been?

Below: Giant gypsum crystals in a cave in Naica, Mexico, from here. Note the person for scale at lower right.

(1) Currently 2017 AAAS meeting links are all re-directing to the 2018 meeting, so I can't find a link to the particular talk or session.

The question is interesting, but I must say it is too early to say anything. But let me tell you what I can.

Dormancy, first of all, is a state in which all metabolic activities of an organism temporarily stop or slow down, and when saying all, I literally mean it. Dormancy can be considered, in layman's terms, as molecular level of hibernation. Any organism, in dormant state, does perform all kinds of activities, but in super slow motion. Again, we don't know anything about those microbes, so I can just tell the currently known mechanisms by which those microbes could have survived. Gypsum i.e. $CaSO_4.2H_2O$ contains sulfate ($SO_4^{2-}$), so those microbes (let me call them X from now) must be sulfur metabolizing ones to survive. Now, known mechanisms of sulfur metabolism include:

sulfur oxidation
sulfate reduction
sulfite reduction

which are summarized as:

source

Now, with sulfate already available from gypsum (considering dissociation) as:

$CaSO_4.2H_2O \rightarrow Ca^{2+} + SO_4^{2-} + 2\hspace{1mm}H_2O$

The reactions it can perform are sulfate reduction and sulfite reduction. Some of the mechanisms are:

source

In the presence of $CO_2$, glucose can also be formed as:

$12\hspace{1mm}H_2S + 6\hspace{1mm}CO_2\hspace{1mm}\rightarrow\hspace{1mm}C_6H_{12}O_6 + 6\hspace{1mm}H_2O + 12\hspace{1mm}S$

The required $CO_2$ might come from respiration. During dormancy, this process is highly slowed down, so that X may have survived such a long time by just this process.

Again, this is just the known mechanism, X may have evolved other, possibly even more efficient, mechanism. The above example was just to suggest how X could have survived in gypsum crystals for as long as 50K years. We don't know anything about X yet. From the article you cite:

  If confirmed, the find is yet another example of how microbes can survive in extremely punishing conditions on Earth.

meaning we don't even know yet whether they are really viable or not.

  The life forms—40 different strains of microbes and even some viruses—are so weird that their nearest relatives are still 10 percent different genetically. That makes their closest relative still pretty far away, about as far away as humans are from mushrooms, Boston said.

Now, viruses ain't alive. And 90% similarity means a lot of difference, which means they almost certainly have different mechanisms for survival. At last, I would again remind that it is too early to say anything unless some scientific studies are performed and published.

P.S. talking about energy source, even the heat and radiation from environment could be used as a source of energy. Obviously, harnessing energy directly from external heat is pretty difficult, but when one finds fungi using radiation for growth, then you never know!


Maximum RPM in zero-g before losing consciousness, spinning head-over-heels There are more than a few scenes in Gravity that I find dubious. Specifically the ones where people are revolving very quickly, either about their own center of gravity or at the end of a rather long pole. I'd guess we'd need to know how long the pole was, but I'm more concerned with a person themselves, just flipping around out there (and I suppose we'd need their height, or does that cancel out?). How fast can they spin until it's night-night? Is it reasonable to assume they should've passed-out in at least one of those scenes?

I think people can easily endure head-over-heel revolutions in space such as seen in Gravity. I am no mathematician (let alone physicist, both of whom could answer this more accurately) but here is my reasoning (faulty though it may be).

You are assuming that someone would pass out from lack of blood supply to the brain.  Given we have absolutely no problems normally at 1 g (the force of gravity on earth), the average non-couch-potato person can tolerate forces of up to 20 G for less than 10 seconds, to 10 G for 1 minute, and 6 G for 10 minutes before passing out.

But g is very dependent on (as you stated) distance from center. It's also very dependent on revolutions per minute.

$$g=\frac{R\left(\frac{\pi\times rpm}{30}\right)^2}{9.81}$$
or
$$R=\frac{9.81 g}{\left(\pi\times rpm\over30 \right)^2}$$

g = Decimal fraction of Earth gravity
R = Radius from center of rotation in meters
π = 3.14159
rpm = revolutions per minute

The average North American male is 1.75m tall. That means the distance of the top of the head and bottom of the feet (if stretched out at full length) from center is under a meter (.875m). At 60 rpm's (that's pretty fast), solving for the above, g = 3.52.

g = [.875({3.14159x60}/30)^2]/9.81 = 3.521 (so just over 3.5G)

Gravity at the top of the head and the bottom of the feet would be 3.5G, while the gravity at the center would be zero G. The heart can easily compensate for that for a while. An astronaut, trained for increased Gs, can do well for longer.

Much worse than too little blood to the head is too much, which is what I would be worried about. Eventually, slightly less than half the blood volume would end up below the waist with the feet feeling the most pressure, and the rest above, with the brain being engorged with blood, which can cause hemorrhage (not taking into account here precise fluid physics). I'm not sure how this would play out in space over longer periods of time, but survival would be the norm for the scenes we see in Gravity.

An Air Force physician named John Stapp was the first to determine just what humans could take in the way of G forces. On his final run, firing nine solid-fuel rockets, his "sled" accelerated to 632 miles per hour in five seconds, slamming him into two tons of wind pressure, then came to a stop in just over one second. A witness said it was "absolutely inconceivable anybody could go that fast, then just stop, and survive." But Stapp did—in fact, he went on to live another 45 years, dying quietly at home in 1999 at the age of 89—and he experienced a record-breaking 46.2 G's. For an instant, his 168-pound body had weighed over 7,700 pounds.  Stapp's efforts put him on the cover of Time, and he was called "The Fastest Man on Earth." More importantly, his work led to greatly improved safety in both planes and cars, and he gave us a much-improved understanding of human tolerance to G forces.

All About G Forces


Zinc finger nuclease specificity If I want to make sure that a ZFN cuts at only a certain position in a genome, how many subunits would I need to ensure this?

If the human genome is roughly 3 billion base pairs, we need a sequence that is 16 base pairs because 4^16 exceeds 3 billion (if my thoughts are correct). But then I don't quite understand how the subunits of the ZFN come into this.

The human diploid genome is ~6.5 billion bp, so you need to find the length of a sequence that has a probability of occurring only once (assuming the sequence is completely random):

$4^n=6.5\cdot10^9$

$n\cdot log(4)=log(6.5)+9$

$n=\frac{log(6.5)+9}{log(4)}$

$n\approx16.30$

According to this article, each finger of a ZFN recognizes 3 bp, which means you'd need $\frac{18}{3}=6$ fingers to probabilistically recognize a unique site. Interestingly, the article also says:

  The requirement for dimerization is a great advantage for this reason: because a monomer is not active, cleavage does not occur at single binding sites. The cleavage reagent is assembled only at the target if the fingers have adequate specificity, and the combined requirement for binding two proteins brings the overall specificity into a very useful range; e.g., two three-finger proteins specify the location of 18 bp, which is sufficient, in principle, to pick out a single target, even in a complex genome.


Can the dendrites of sensory neurons be a meter long? The typical textbook structure of neurons is a cell with a short dendritic tree and a long axon. The dendrites receive information and send it to the axon via the cell body (soma). The axon is a long structure designed to send the information to distant parts.

A neuron. source: ASU School of Life Sciences

In sensory neurons of skin receptors, however, the dendrites are considered to receive information about the outside world, i.e., the dendrites are the receptive parts of sensory neurons. They generate action potentials that are sent to the soma. But I've been told that the soma of sensory neurons are located in the dorsal root ganglion of the spinal chord?

Does this mean that the dendrites of sensory neurons are exceptionally long? Suppose I feel a prick in my finger, do the pain receptors really have dendrites a meter long all the way to the dorsal root?

Short answer
Axons can be over a meter long, but dendrites are never that long. Distance in the body is covered by axons. The dendritic part of skin receptors is generally considered to be the receptor part and the receptor part only. The elongated structure leading to the soma, as well as the axonal part to the spinal cord are generally considered to be one and the same axon, the soma being attached to the axon in this case.

Background
The sensory receptors in the skin have their cell bodies located in the dorsal root ganglia situated adjacent of the spinal cord (Bourinet et al., 2014). In the case of pain receptors it is shown in Fig. 1. The same basic structure holds for the touch receptors in the skin.

Fig. 1. Signaling of pain receptors in the skin. source: Bourinet et al. (2014)

The cell bodies are located in the dorsal root ganglia of the spinal cord. Action potentials are sent from the dendritic region in the skin to the cell body in the ganglion. From there on it is transmitted to spinal interneurons in the spinal cord and up to the brain.

The nomenclature of these sensory neurons is generally as follows: in the cell body the axon splits in two. The afferent part that transmits the pulses from the skin to the cell body and the part that transmits the signal from the soma away from the cell body to the spinal cord are both considered as a part of the axon. The dendritic region is generally considered to be the nerve ending (Fig. 2C). So the axons of peripheral sensory neurons, as well as motor neurons for that matter, can indeed be over a meter long (Lodish et al., 2000).

Fig. 2. Types of neurons. Arrows indicate the direction of conduction of action potentials in axons. (A) Multipolar interneurons. The dendrites receive signals at synapses with several hundred other neurons, and there is a single long branching axon. (B) A motor neuron innervating a muscle cell. Typically, motor neurons have a single long axon extending from the cell body to the effector cell. (C) A sensory neuron in which the axon branches just after it leaves the cell body. The peripheral branch carries the nerve impulse from the receptor cell to the cell body, which is located in the dorsal root ganglion near the spinal cord; the central branch carries the impulse from the cell body to the spinal cord or brain. Both branches are structurally and functionally axons, except at their terminal portions, even though the peripheral branch conducts impulses toward, rather than away from, the cell body. source: Lodish et al. (2000)

References
- Bourinet et al., Physiol Rev (2014); 94(1): 81-140
- Lodish et al., Molecular Cell Biology, 4th ed. New York: Freeman (2000)


How did scientists discover HIV? Imagining that we're now in 1983 (when HIV was discovered), there were no modern machines at that time to sequence massive genome extracted from blood. There was a strange disease and no one know what caused it, it's a virus or a bacteria or something else... So how did scientists find out HIV at that time?

-- Update: I just think that they extracted RNA from blood of those patients who have the same symptoms and using electrophoresis to find out if there was a large ARN fragment exists to indicate that they was infected by a virus, is that true?

HIV was identified as an infectious disease through classical epidemiology, and the virus was identified through classical virology.
I won't get into the epidemiology, but briefly it went pretty much as you'd expect -- a cluster of symptoms were identified, patient characteristics were analyzed, the contagious nature of the symptoms were recognized, all through standard approaches of patient tracking and so on.
As for the virus identification, that was long before modern molecular techniques were available.  It was even before PCR was commercially available!  So the techniques that were used were those of classical microbiology.
It seemed most likely that the agent was a virus rather than a bacterium (though every possible angle was covered), and just about every virologist tried looking for their favorite agent, but retroviruses also seemed like logical candidates and several groups tried isolating infectious agents from the blood of AIDS patients.
The two groups who were most successful were those of Luc Montagnier and Robert Gallo.  There turned out to be a lot of politics and personalities involved and I won't get into that.  Here are some comments from Montagnier summarizing the story:

There were only a few patients with this disease in France, but Gallo's idea that a retrovirus was the cause had already crossed the Atlantic. His idea was disseminated by a small group of clinicians and immunologists led by Jacques Leibowitch and Willy Rozenbaum. At the end of 1982, Françoise Brun-Vezinet, a former student of mine and a member of this group, proposed that we collaborate to discover if a retrovirus was the cause of this disease, now called AIDS.
We were ready to start because my laboratory was equipped to hunt for lymphotropic retroviruses in human T cell cultures.  ... On 3 January 1983, Françoise Brun-Vezinet obtained a lymph node biopsy from one of Rozenbaum's patients, ... I minced the lymph node, dissociated the fragments into single cells, and cultured the T lymphocytes with interleukin-2 and antiserum to human interferon. Fifteen days later, Françoise Sinoussi (by then Barré-Sinoussi) found the first traces of RT in the supernatant of the lymphocyte culture, indicating the presence of a retrovirus.  ... A few months later, I received a blood sample from a young hemophiliac (LOI) with full-blown AIDS, and blood and lymph node samples from a young gay man (LAI) with advanced Kaposi's sarcoma. The LAI virus could be isolated from the patient's blood cells and grew very quickly in the patient's cultured T lymphocytes, killing them as well as killing T lymphocytes from blood donors.
New evidence that this strange retrovirus was the cause of AIDS came from our team in the fall of 1983 and the winter of 1984 (7). We observed a high frequency of antibodies against the virus in lymphadenopathy patients, and noted the favored tropism of this virus for CD4+ T lymphocytes. Our results were still controversial, however, and we had difficulty in obtaining the funding needed to better characterize the virus and to develop a blood test. The tide only turned in France when Robert Gallo and his group in the United States made a similar discovery. In the spring of 1984, Gallo published more convincing evidence that HIV causes AIDS ...

--A History of HIV Discovery
Gallo's approach was similar -- focused on isolating replicating virus, more than performing the molecular biology that's become standard in the meantime.


What kind of red/green/black, spiny caterpillar is this? It's red and lime green with black on its back and a few white spots as well. Found in Tulsa, Oklahoma (USA).

Looks like a greenish variant of Hemileuca maia – the Buck Moth, which according to here does occur in Oklahoma. This source also suggests that touching the caterpillar (or its relatives) is a bad idea...

 Source: statebystategardening


Why do some people become more aggressive when tired? Why do some people become more aggressive when they are tired? I've been thinking about this question for a few days and my 'hypothesis' is that the neural activity in the prefrontal cortex lessens as the brain prioritises the other more primitive parts of the brain. Is it also so that the amygdala becomes more active when tired for some reason?

I've tried to search for answers on Google but can't find any satisfying ones. Optimally, I'd like to see brain scans and have them explained, but maybe that's asking for too much.

From Poor sleep as a potential causal factor in aggression and violence

  In most people poor sleep will not evoke actual physical aggression, but certain individuals, such as forensic psychiatric
  patients, may be particularly vulnerable to the emotional
  dysregulating effects of sleep disturbances

  The relation between sleep problems and aggression may be mediated by the negative effect of sleep loss on prefrontal cortical functioning. This most likely contributes to loss of control over emotions, including loss of the regulation of aggressive impulses to context-appropriate behavior.

  Other potential contributing mechanisms connecting sleep problems to aggression and violence are most likely found within the central serotonergic and the hypothalamic-pituitary-adrenal-axis. Individual variation within these neurobiological systems may be responsible for amplified aggressive responses induced by sleep loss in certain individuals.


Why can't I read everything in my field of view? When I look at a piece of text, I can see all the text on the paper, no matter where I look, because my field of view covers it all. However, if I stare at a specific word, I cannot read the text a few lines above the position I am staring at, even though I can clearly see there is text there. I don't think it has anything to do with the text being out of focus, since I observe this phenomenon no matter what distance the paper is from me. What are the specific causes of this?

The field of view is determined by the light-receptive parts of the eye: the retinae (Kolb, 2012). The fovea is the region with the highest resolution. It is located in the central part of the retina and covers only about 2 degrees of the field of view (Lauweryns, 2012). The total field of view is roughly 180o (Fig. 1).

Fig. 1. Schematic of the human field of view showing the foveal region. Source: Medical Dictionary.

The reason for the regional differences in retinal resolution (referred to as visual acuity) is that the cone photoreceptors are densely packed in the foveal region, while rod photoreceptors predominate the retina outside the fovea region (Fig. 2) (Kolb, 2012).

Fig. 2. Distribution of rods and cones. Source: Webvision.

The cones sense color and are specialized to work under well-lighted (photopic) conditions. In contrast, rods are hardwired to converge onto a single optic fiber to collect responses for dim lighting (scotopic, or night vision). Because many rods (tens of rods) connect to a single optic nerve fiber, the spatial acuity is dramatically reduced (Fig. 3). Hence, you can read with only a few degrees of your vision. While reading, your eyes continuously scan the page for the next word to center it onto the foveal region.

Fig. 3. Many rods converge onto a single ganglion cell, while one cone synapses onto a single ganglion cell. Source: Slideshare.

This is the big handicap that people with age-related macular degeneration face. The macula (that includes the foveal region, see Fig. 1) degenerates and the cones are lost. Hence, they loose their high-acuity region and cannot read anymore without using magnifiers or other low vision aids.

References
- Kolb, Webvision - The Organization of the Retina and Visual System (2012)
- Lauweryns, Brain and the Gaze: On the Active Boundaries of Vision (2012)


I'm trying to figure out what the name of this flower is This is a flower that grows in my backyard. I really want to know the name so I can read about it and possibly get more.

That is a rose. At least we have such flowers around my flat and we called them roses for 18 years. See: Rosa Gallica