What is the difference between Amino acids from blood and urine? I would like to understand the difference between different tests for Amino Acids. Any blood laboratory offers amino acids tests using 3-4 methods

Blood serum
Urine Random
Urine 24 hour (all the urine samples collected in the last 24 hours)

After having tried Google and coming up empty, I have the following questions that I would like answered.

What would be the difference between testing it via each of the above methods?
What's the purpose of each of these different test methods?
Is one method better than the other? If so why?

Thank you.

Disclaimer: This question is for general knowledge purposes only. Please don't use the question or answers given as personal health advice.

Detecting protein and elevated levels of amino acids in the urine is generally a bad thing and is usually indicative of an underlying disease.

Kidneys are supposed to filter out waste products and retain metabolites that your body needs. There are many possible diseases that can cause amino acids to be detected in the urine, some as innocuous as overexertion or exposure to temperature extremes, and some as serious as Hodgkin's lymphoma, Amyloidosis, Malaria, Lupus, etc. For a more complete list see this Mayo Clinic page.

As for the blood, there are certain normal levels of amino acids found naturally in the blood. The reason for testing these levels is that certain imbalances can be indicative of different medical conditions. A doctor can use these levels to help to identify a problem that may not be noticed or may use it to diagnose a disease that you are seeking treatment for. This MedlinePlus page, has information.

Testing of Blood and Urine amino acids can and will be done in conjunction with one another in order to help narrow down the possible diagnoses that are likely.

Disclaimer: Personal medical questions and health advice are off-topic on Biology SE. We cannot safely answer questions for your specific situation and you should always consult a doctor for medical advice.

Edit to address comments

"Also, based on your answer and the Mayo Clinic link, what I understand is in a healthy individual - testing amino acids from urine might give false positives?"

I think that your concept of false positive here is incorrect. A false positive for this test would be indicating higher levels of amino acid in a sample than the sensitivity and standard error for the test would allow for.

That there is a laundry list of reasons why one might find abnormal levels of amino acids only goes to the fact that the kidneys "see" the results of several metabolic processes (normal or abnormal) and urinalysis is only a single datapoint from a spectrum of data for a clinician to begin to recognize a pattern and formulate a diagnosis.

As for greater accuracy, when comparing "Urine Random" to "Urine 24 hour" I would say that the "Urine 24 hour" test is more accurate strictly from a perspective of statistics. The larger the sample size for any test, the greater the level of confidence that the results observed are not due to random chance, error, or outliers in the data.

But this is the same concept for a political poll, marketing research analysis, or medicine; larger sample size gives you a clearer picture, but it does so at an increased cost. So the single screen is there just to look for issues, possibly based on a complaint that brought you into the doctor's office, or a way of monitoring a previously diagnosed condition and/or treatment, while the time courses are done to provide a clearer understanding of what is representative for the levels in that individual.

The single test has a number of reasons why it might be anomalous. Maybe the elevator from the underground parking garage was out of order and you had to walk up several flights of stairs to the office where they were collecting the sample, so it would show an elevated result due to exertion. Or maybe your drank a liter of water before the exam and your urine is dilute, causing a false negative. So to mitigate those anomalies, you run the time course, but usually only if there is a problem suspected because of the fact that it is an increased and unnecessary cost if all other indications are that the person is healthy or the result is easily explainable due to other data collected.

"I also understand that at times they would be used in conjunction - which seems logical. What I am trying to understand is which would give more accurate 'picture'. If one is not more accurate than the other, then what would be the difference between the 'picture' acquired from a blood test and the urine test."

Each test has its own parameters and give you an independent picture, that can be used to put together a more complete whole. Their accuracy will be based on their own sensitivities and built in standard errors and one will not be more accurate than the other because comparing free amino acids in the blood versus in the urine are two different pictures with different normal outcomes.

More samples, i.e. "Urine 24 Hours" or multiple blood draws over a time course is really the only way that you will improve on the accuracy of the individual tests, for the reasons I gave above.

They also have different baselines. Blood you expect to find free amino acids and there are ranges of normal results that you would expect to find in the blood. Here, too much or too little amino acid would be an indicator of a possible problem. For urine on the other hand, one would not expect to see elevated levels of amino acids, so here, a test that indicates elevated levels of amino acids indicates that more follow up is needed.

Think of it in terms of an analogy about astronomical observation. The electromagnetic spectrum is far broader than any one instrument can detect, so astronomers/astrophysicists use different sensors; visible light, radio waves, infrared, x-ray, etc. telescopes to detect many of these different pieces of data coming from the same object to gain a better understanding of what they are studying as a whole. Each gives slightly (or very) different views of the object, all of which contribute to a more complete picture of the object as a whole.


How can I keep HEK cells alive while expressing NMDA receptors? I am trying to express functional NMDA receptors in HEK293 line cells for single channel recording experiments.

The HEK cells are maintained in the standard way (Thomas & Smart 2005) and transfected with NR1 and NR2x subunit cDNAs and also GFP, using either lipofectamine or calcium phosphate precipitation. GFP expression suggests successful transfection, but cells exhibiting green fluorescence are uniformly swollen and dead and it's more or less impossible to obtain a successful patch. Untransfected cells seem to remain perfectly viable.

On the basis that the toxicity might be a consequence of Ca2+ influx through open NMDARs, I've tried including a cocktail of blockers in the growth medium, including AP5, kynurenic acid and Mg2+, but the transfected cells continue to die.

Can anyone suggest anything else I should be doing to keep the cells alive? Or am I just on a hiding to nothing? Other researchers seem to have managed this (eg Medina et al 1995, Vicini et al 1998) and do not seem to be doing anything substantially different, so I'm a bit at a loss.

Try perhaps lowering the level of expression of your construct. HEK cells are notorious for expressing large quantities of your transfected insert. Do you have it under a CMV promoter? Try a milder one, such as an ubiquitin promoter or similar or, even better, a doxycyclin-inducible system (e.g., clontech's tet off) so you can manage the expression levels through the dox concentration/time of induction.


Identify this caterpillar Could anyone try to help identify this caterpillar, there are loads of them all over my garden and I've got three of them in a makeshift caterpillar house. I've had them for about a week and they've grown to about 3 or 4 centimetres in length and I am yet to see any of them form pupae. I am from London by the way.
EDIT: they don't seem to be too fussy about what they eat, I have found them on honeysuckle, rose bushes and even some nibbling on the bind weed I've pulled recently.

Actually, the animal is not a caterpillar but larva.

The species is Abia lonicerae Sawfly, discovered by Linnaeus 1758.

(Another picture)


Is diarrhoea advantageous to the microbe? Diarrhoea is a common side effect of many feco-orally transmitted bacterial infections. How does diarrhoea help the pathogen? Should it not have a selective evolutionary advantage? Do all symptoms of the disease need to have a selective advantage for the pathogen? All I can think of is that a more liquidy stool would lead to further ease in feco-oral transmission. Is this true?

Vibrio cholera for example is actively causing diarrhoea, by stimulating the CFTR channel to excrete chlorine ions, which will attract water from the gut tissue.

The answer of the function seems obvious: to promote dispersal in the environment and as such infect/find new hosts.
See also: extended phenotype (Richard Dawkins): how genes in one organism (mostly a parasite) influence the behaviour of another organism (mostly the host of the parasite) to increase the (reproductive) success of the gene/parasite.
Also: numerous (some horrifying) examples in Parasite Rex (by Carl Zimmer)


Does N1-methyl-pseudouridine occur naturally in any RNA? Pseudouridine occurs naturally in some RNAs. But what about the methylated variant of it, N1-methyl-pseudouridine? The latter is a key ingredient in both the Pfizer and Moderna Covid-19 vaccines, probably due to its relative "potency" in evading immunogenicity to exogenous mRNA itself and its ability to apparently put ribosomes in a sort of "overdrive". (It's use in mRNA therapeutics has been patented by Moderna in 2012 or so.)
Does N1-methyl-pseudouridine occur naturally, in particular, does it occur in RNA?

N1-methyl-pseudouridine occurs naturally in the tRNAs of most archaea. It replaces the ribothymidine found in the TΨC-loop of eubacterial and eukaryotic tRNAs.

Although the enzyme responsible for the conversion of uridine to pseudouridine has been known for some time, it is only relatively recently (2012) that the gene for the methylation of the pseudouridine was reported in a paper, the introduction to which provides a useful background to the topic.
Original References
Pang, H. et al. (1962) J.Biol.Chem. 257 3589-3593
Gupta, R. (1964) J.Biol.Chem. 259 9461-9471


Why is prothrombin time used to monitor warfarin and not activated partial thromboplastin time? Warfarin is said to change prothrombin time (PT) but not activated partial thromboplastin time (aPTT) (for practical purposes at least anyways, not really sure). But looking at the mechanism of action of warfarin, I dont see why that is.
Warfarin works by inhibiting vitamin K, or more specifically, vitamin K-mediated post-transnational modifications of certain clotting factors (X, IX, VII and II) which are important for the activity of said clotting factors. Warfarin affects factors in both the extrinsic and intrinsic pathway (and maybe a bit silly and irrelevant, but the same number of factors in each too; 3 by 3!). So, why is it that PT is affected by warfarin but aPPT isnt? I looked alot and couldnt really find any satisfactory answer (there werent many answers to begin with either). What I've found and have gotten from my professor are the following points:

Warfarin's effect is more pronounced on PT because factor VII (the first factor in the extrinsic pathway) has the shortest half-life and is therefore the quickest to get depleted. But in that case, warfarin usually takes a few days to be considered effective enough to stop administering patients heparin with it; wouldnt all the affected factors be depleted enough by that time to also affect aPTT?
Warfarin affects factor VII, which is the initiating factor (tissue factor aside) for the extrinsic pathway, which is why it affects PT more? Honestly I don't know how these tests work exactly so I'm not sure if this would matter. This was what my professor answered with when a student asked (or at least it's what I recall).

This article tells that warfarin can prolong aPTT too.
Now look at the image below

It is almost 5 days and some extra hours when anticoagulant effects start, during which we give heparin, also called as heparin bridge.

But in that case, warfarin usually takes a few days to be considered effective enough to stop administering patients heparin with it; wouldnt all the affected factors be depleted enough by that time to also affect aPTT?

PT is used as a standard measure not just for initiating but also for monitoring  warfarin therapy using the INR(international normalised ratio) because it gives the earliest result(as half life of factor VII is shortest) to start another treatment according to guidelines, when INR is altered beyond normal range

Warfarin affects factor VII, which is the initiating factor (tissue factor aside) for the extrinsic pathway, which is why it affects PT more?

Well I might not have any sources to answer that, but I can try to deduce answer by some logical arguments. In intrinsic pathway there is multiplication of factors, for eg. Factor XII activate factor XI and factor XI activate factor IX but by this time more and more factor XI are getting activated thus causing more interaction with whatever factor IX is left in blood(factor IX is less here due to warfarin) so no relative profound anticoagulant effect of warfarin is present. But in case of extrinsic pathway factor VII is the intiating factor and is already less due to warfarin, and there is no such factors multiplying before that to cause their maximum interaction and therefore activation of factor VII so relatively more profound anticoagulant effect is present.


Autosomal Recessive Trait when skipping one generation I learned recently that given a pedigree it is possible to tell whether a disease is autosomal recessive by observing if the trait skips a generation. If the disease does skip a generation, then the disease is autosomal recessive. But the converse is false. That is a disease that is autosomal recessive does not necessarily mean the disease skips a generation.

Does someone know of a proof of this fact?

What you are saying is very similar to the statement that:

  Absence of evidence is not evidence of absence

Suppose you have an autosomic gene A, which has a mutant allele a, causing an illness (or any other phenotype, for that matters). The particular nature of a makes its associated phenotype recessive.

You have three possibilities:

AA -> no illness
Aa (or aA) -> carrier, with no illness
aa -> ill

Now, let's take an aa individual (ill) and cross it with a sane AA individual:

aa x AA

All of the individuals of the first generation (F1) will be carriers (Aa) because the father will always give a and the mother always A.

Now if we breed them together

aA x aA

both parents have 1/2 probability of giving a and 1/2 of giving A. We will then have a proportion of:

1/4 aa
1/2 Aa (1/4 A from mother and a from father, 1/4 vice-versa)
1/4 AA

But this is just down to statistics. You have only 1/4 chances of seeing the trait reappearing, so you are much less likely to see it if they have 1 offspring then if they have 20.
Moreover, you have Aa offsprings in the progeny... this means that these could pass the mutant allele to the third or fourth generation.

Another important thing is that all we said is true if the first cross is

aa * AA

If it was

aa * aa

or

aa * Aa

The trait will (surely in the first case, and with 1/2 chance in the second) appear directly in the first generation.


Which cells release inflammatory mediators? Wikipedia says

  Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens.

then it mentions

  The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells, and mastocytes. These cells present receptors contained on the surface or within the cell, named pattern recognition receptors (PRRs), which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRRs recognizes a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation.

From this we can clearly deduce that the inflammatory mediators are released by Pattern recongintion receptor producing cells. But while studing this topic from different sources some, books on nursing and Pharmacy. They keep repeating that inflammatory mediators are released by injured cells.

What is correct?

There are several kinds of inflammatory mediators. You can broadly classify them as cytokines (including interferons) and chemokines.

Cells which sense antigens (or pathogen associated molecular patterns) do secrete cytokines, as you said but infected cells also secrete some cytokines like interferons- α and β. Infected/injured cells also secrete chemokines that attract leukocytes to the site of infection/injury (Saiman and Freidman, 2012).


DNA-DNA cross-linking with formaldehyde? The 3C (chromosome conformation capture) technology for studying chromatin 3D organization starts by a cross-linking step using formaldehyde to find segments of DNA interacting. In my understanding the cross-linking happens only between the DNA and proteins forming a DNA-protein-DNA complex. The "only" is from a DNA stand-point as of course protein-protein cross-links will also occur.

Can formaldehyde cross-link two double stranded DNA molecules? Is the 3C approach also capturing direct DNA-DNA interactions?

I looked at the literature, especially Dekker et al. description of the method, but couldn't find this information. Thanks.

The fact that there is no inter-strand cross-linking between different double strands might be just because the cross-linker cannot bridge the distance between amines of different bases on different double strands.

The formaldehyde based linking of nucleobases has been described by Chaw et al. (1980) where formaldehyde bridged a gap of app. 3 angstroms (2x 1.3 A for N-C bond).

Even if you take the most condensed form of DNA as in nucleosomes (see X-ray model of nucleosome with bound DNA) you still have at least 20 angstroms between the bases of different double strands.
At the same time there are only 3 angstroms between the nucleobases of the same double strand, agreeing well with the length of a methyl-bridge.


Could a horse-sized duck fly? The more general question would be whether or not one can scale an animal to some other size and preserve its properties. The method of scaling is by volume, scaling all dimensions by the same factor. The mass is scaled so that the mass/body ratio is constant.

Some factors I thought about:

How does muscle strength scale with muscle size?
Could the joints support the new mass?
If ducks rely on aerodynamics/wind to fly, how does the size change influence those factors?

The largest flying bird ever was probably Argentavis, which weighed about 70 kg, far smaller than a horse but still pretty impressive:

A duck scaled even to 70 kg wouldn't be able to fly since it wouldn't have the same relative wingspan.  A 1 kg duck has a wingspan less than 100 cm; volume (and weight) increase as the cube of dimensions, so a 70 kg duck would have maybe a 4-meter wingspan, whereas Argentavis was nearly double that (around 7 m).

The largest flying animal we know of was probably Quetzalcoatlus, or perhaps one of the other Azhdarchid pterosaurs, which were definitely horse-sized depending how you measure:

These pterosaurs were comfortably over 250 kg, which puts them into small-horse range, so something that is "horse-sized" could definitely fly.  However, these are very differently shaped and scaled from ducks, as you can see.

One important difference is probably that pterosaurs launched from the ground using their wing muscles -- quadrapedal launching -- whereas birds use their legs; heavier leg muscles needed to launch a big bird are wasted weight in flight, while heavier wing muscles needed to launch a big pterosaur remained functional in flight. That re-emphasizes that big things are not just scaled-up small things, but need to reshape their bodies to cope with their size; the square-cube law is just part of it.


Will a dog develop similar feelings with a robot as like human? I think we are connected to the world by Biochemistry first and then physical and verbal interactions. If a robot feeds a dog regularly, pampers it and cuddles it regularly, would it develop the same feeling to the dog as it would have developed with a human?
A sci-fi robot like Ultron from Avenger movie.

Assuming you mean a robot "designed to be human" (that means human-like behavior patterns, human-comparable intelligence, being self-aware and able to learn), then from the dog's perspective, the only significant difference is the differing smell.

There is no scientific evidence for mystical or metaphysical "connections to the world".

From the dog's perspective, the defining factors are:

Owner's behavior (petting, feeding, walking, training, rewards for good behavior or learning tricks). In this case, the robot is no different from the human.

Owner's speech (voiceprint). There's evidence that dogs understand human speech to some extent (https://www.independent.co.uk/news/science/dogs-can-understand-human-speech-scientists-say-a7216481.html). Given how adaptable organic brains are, I assume a dog would be able to adapt to even a synthetic (digitally altered) voiceprint over time or one that spoke in a conspicuously robotic manner (for example: "Temperature alert. Please fetch an external cooling fan./Your assistance above your designated specifications continues to be noted." instead of "It's getting hot in here. Grab a soda from the fridge over there?/Good dog!"

Owner's scent. The only real difference from a dog's perspective. A robot would lack the distinctive scent cues from a human, except if the robot was designed to produce those as well. Even if those aren't present, a dog should be able to adapt to a robotic owner's distinctive smell (plastic with motor oil and a hint of ozone).


Which kind of electrical brain activity is associated with consciousness and why? According to this article The ethical brain

At the end of the week 5 into the 6 (42-43 days) the first electrical brain activity occurs in a pre-born developing human.

And according to the same article

  This activity, however, is not coherent activity of the kind that
  underlies human consciousness, or even the coherent activity seen in a
  shrimp's nervous system

My question is, which kind of electrical brain activity is associated with consciouness and why?

Gamma band oscillations (GBO) (Wikipedia) (NCBI)  are 30-90 Hz electrical waves generated by the brain and are thought to possibly be associated with cognition and consciousness (Panagiotaropoulos, 2012). Some evidence for this putative relationship can be seen with experiments such as pre-pulse inhibition (PPI), which can describe how our sensations are interpreted by the brain. Also, PPI may be aberrant in Schizophrenic patients (who have altered cognition). Changes to PPI are associated with aberrant GBO, which could imply an association between GBO and an individual's interpretation of stimuli, their cognition and by extension consciousness.

But of course, the counter-argument is that the intrinsic activity of the brain isn't changed, merely how the brain processes stimuli. However, all forms of measuring cognition that I've studied involve investigating responses to external stimuli, so as far as I know, this is a universal problem. Furthermore, there's a lot we still don't know about consciousness and no model or measurement is perfect. This article gives quite a nice overview on neural correlates of consciousness.


Which hormones/factors affect Calcium absorption in the small intestine and its regulation? I think the question is very broad and cannot find precise mechanisms.
I am not sure about the precise mechanisms of the regulation.

I think they are at least Vitamin D, diffusion and specific calcium channels: calbindins.
More specifically, calbindin-D9K and the basolateral calcium pump transport calcium from cell interior to extracellular space.

The calcium gradient should also be free, -2-6 mmol/l, in the lumen to allow diffusional calcium absorption from the interstitial space.
Similarly, free calcium concentration in the extracellular fluid of the lamina propria.

I think that the most important mechanism for this absorption is the electrochemical gradient of sodium across the epithelial cell boundary of the lumen, similarly as for carbohydrates.
To keep the extracellular space free from calcium, the NA/K-ATPase i.e. sodium pump has to work.

I did not find any hormones that affect the intestinal calcium absorption.
Which factors affect calcium absorption and its regulation?

Parathyroid hormone increases intestinal calcium absorption by increasing production of vitamin D, which in turn uses calbindin. It also enhances calcium reabsorption from the kidney and the release of calcium from bone.


What bacteria results in a Gram +ve cocci and catalase +ve? What test comes next? Results so far.
We are trying to determine unknown microorganisms in intro to microbiology course. I first did gram stain and they were all cocci morphology, purple color and clumped together  (actually I'm not so sure if clumped is right word, but they definitely were not in chains and I didn't see any isolated coccus, so if that's qualifies as clumped then they were clumped.
So I have a gram+ here.
Next I did catalase test and got bubbles on slide; I put thick chunk of the unknown on slide and dropped 2-3 drops of ${H}_{2}{O}_2$; instant bubbling.
Next test.
So now I will test for coagulase but I'm uncertain what a positive or negative result will tell me about he organism and whether this is the terminal test (for ID-ing organism I mean)
My notes say that positive for coagulase indicates S. aureus.
But does that mean that it is unnecessary to do the Mannitol test at that point then? Or is Mannitol used as a confirmation test?
Further, if unknown tests negative for coagulase, my notes say that if its also novobiocin sensitive (pos) then it is S. epidermidis.
But my same question then is, is it necessary to still do the mannitol test?

At this point you have staph, you can use this flow chart (from here) to figure out what staph exactly.

If the test comes back as coagulase positive be very careful as Staph aureus is pathogenic.


What does γ mean before a gene name? I am reading the following paper and I have come across the following statement:

It has been demonstrated that the phosphorylation of histone
H2AX-Ser139 to form γH2AX.

I am not sure what the γ before the gene name H2AX means. Is γ used to indicate that H2AX is phosphorylated? Any insights are appreciated.

Yes, in this context $\gamma$ indicates phosphorylation. See e.g. "The phosphorylated form of H2AX is called $\gamma$-H2AX [18, 19]." from here, and references therein.
I am unsure of the exact basis of this, but I believe that it is because the gamma phosphate group of a nucleotide triphosphate is the one that is generally used by kinases to phosphorylate other functional groups. SEE UPDATE for derivation.
Other notations such as the $p$ prefix are more readable to me, but the usage appears to be cultural and somewhat field-specific.
Update
In response to @MattDMO comment, I read further and found that the terminology derives from this paper. They don't directly explain the terminology, but in context it's pretty clear:

At the maximum, approximately 1% of the H2AX becomes $\gamma$-phosphorylated per Gy of ionizing radiation.

In mammals, the serine in this motif is residue 139, the site of γ-phosphorylation.

When mammalian cell cultures are exposed to ionizing radiation and the acid-soluble nuclear proteins are analyzed on two-dimensional AUT-AUC gels, novel components that will be referred to as $\gamma$ (Fig. 1, A and B) are found in the H2A region of these gels.

It appears that the name probably derives from an observation that was just "whatever in this 2-D gel is $\gamma$-P32 labeled when we induce DSBs when $\gamma$-P32 ATP is present."
@MattDMO also points out that the irradiation that induces the gamma component in this context is gamma radiation. So it's all a bit of a muddle, it could also be that.


What marine animals exhibit deep hibernation/aestivation? Do marine animals exhibit deep hibernation/aestivation as land-based creatures do?

If not, Why?

Fish are ectothermic, and so, by definition, cannot hibernate because they cannot actively down-regulate their body temperature or their metabolic rate. However, they can experience decreased metabolic rates associated with colder environments and/or low oxygen availability (hypoxia) and can experience dormancy. For example, epaulette sharks have been known to stay dormant for long periods without oxygen (reference) Turtles in freshwater lakes have been known to hibernate by burying themselves in mud (reference). The mechanism through which turtles can experience several months of hypoxia or anoxia is explained in this paper. The Antarctic fish (Notothenia coriiceps) has been found to be able to activate and deactivate their metabolic processes independent of body temperature and hence enter a state of dormancy similar to hibernation through metabolic suppression (reference).


CD4+ as Monocytes cell surface receptors Today in class,  our teacher was discussing about the pathogenecity of the HIV virus.

He said that the binding between HIV virus and macrophages is done by the interaction between the GP120 of the virus and CD4 receptors,chemokine receptors(CCR-5 and CXCR-4) and fusin receptor present on Macrophages.

My doubt is
I think CD4 receptors are present on T-helper cells only. Are they present on Macrophages too? Do i have a wrong notion about CD4 receptors?
If not, then are there some other receptors responsible for the transfer of viral particles inside monocytes and dendritic cells?

Any extra information is appreciated.

Macrophages and monocytic cells can express CD4, CD8 or even co-express them. The CD4 and CD8 molecules interact with MHC complexes on neighboring cells, and as you can imagine elicit varying effect in a cell type-dependent manner.

Plainly enough, Zhen et al. demonstrated that monocytic CD4 ligation to MHC-II molecules on other cells, such as activated endothelium, induced an expression pattern conducive to macrophage differentiation (1). Gibbings et al. also demonstrated that CD8 associates with FcyR on the monocyte's surface similar to CD8/TCR associations, and stimulates the secretion of cytokines (2).

I'll try to find a model source, but CD8a on dendritic cells can associate with MHC-II molecules on T cells like HLA-DR and aid in cross-priming the T cells.

Now what CD4 does on functional, differentiated macrophages is less clear to me, and I need to review the literature on that a bit more. It could just be expression imprinted because they're monocyte-derived cells, or it could also elicit an effect like CD8/FcryR above. I do not know.

There are more cases, so these serve as selected examples.


Can a trait be too successful? Wouldn't overwhelmingly successful traits limit variability, which is one of the requirements of NS? Can a trait be too successful?  Wouldn't an overwhelmingly successful trait soon limit the gene pool, and if so, how would the process of natural selection react to that?  If an individual is born with a trait that allows it to reproduce unimpeded, and it passes that trait on to its offspring, wouldn't the variability be quickly reduced in the population?  And if so, then would NS limit the trait so that it isn't overwhelming?
And thanks to everyone who contributed here, you have been very helpful and I am very grateful.

Yes, in neutral theory of evolution this is called fixation - when all the alleles (for a given locus) become identical. Note that it may happen, even if the gene does not have a striong selective advantage - due to the random effects.
If you are looking for the basic background in population genetics, Gellespie's book is a good starting point.


Dark veil when getting up too fast I was asking myself this weird question.

When you get up or stand up too fast, sometimes, you see something like a dark veil, and you aren't able to see anything distinctly for 2 or 3 seconds, then it come back to normal.

Do you know what causes this weird phenomenon (biologically speaking), or am i the only weird person feeling this sometimes?

It's caused by a sudden shift in the pressure needed to circulate blood to your brain which your body fails to respond to sufficiently quickly. This results in a sudden loss of blood pressure termed Orthostatic Hypotension which, in term, results in a transitory reduction in the blood supply necessary for brain function. You experience a momentary loss of vision for the same reason that you would if someone strangles you.


Telomere shortening during replication It is widely know that each cell cycle during DNA replication some fraction of the telomeres is lost, and this phenomenon is called the end replication problem. Well this is due to the fact that the DNA polymerase only adds nucleotides in 5´--> 3´ direction, thus the synthesis of one of the two DNA strands will need some RNA primers for its polymerization (and DNA polymerase will replicate DNA in a "jumping" pattern). Then, in the very end of the synthesis of this strand (called lagging strand) one last fraction will not be copied from the template as even if the last primer is set in the very end of the chromosome, once this RNA is degraded a void space is going o remain invisible for DNA polymerase.

Well this is all well known, but my question is whether during each DNA replication it is ONLY the telomere of the chromatid whose origin was in the lagging strand  which will be shortened? (Thus chromosome shortening is happening in a truly asymmetrical and stochastic pattern)

In replication, both the chromosomal halves (which are simultaneously threaded through the replication complex) have a lagging and a leading strand. A part of the segment will be replicated as leading and a part as lagging.


Range of feasible coefficients in an unlimited growth model If you are given an unlimited growth model in the form:

$\frac {dP(t)}{dt} = k P(t)$

Obviously the population growth would never be unlimited, but let's presume for the moment that we are introducing a species into an environment where there is the possibility for unlimited growth, at least on for a given time -- i.e. invasive species.

$k$ is some rate of growth of the population at time $t$, denoted by $P(t)$

What are some feasible values of $k$? In other words, if a number is way above or way below $k$, where would I know that the research I am reading is preposterously off-base?

I am sure it is different for different types of animals, including mammals, birds, bacteria, etc.

A solid limit: k must be greater than zero. Unless you're talking about some cannibalistic species or something that isn't suited to the model at all.

As long as the species is productive in the new environment: k is greater than 1. The population is probably growing or again you probably won't be using an exponential growth model.

As mentioned before you would need to know the species for more information. But if you look at generation times and litter sizes:

Some bacterial generation times (from here) range from 10 to
2000 minutes (33 hours). So that is $k=2$ per generation time. Per
day you're looking at a lower bound of 2 per day and an upper bound
of $k=2^{14}=10^{43}$ per day.
Mice are something like 12 week generation time and a litter of 10
giving something like $k=10^{10}$ per year.
Elephants are one young every 25 years. So $k=16$ per century or so.

Of course this is all based on gross assumptions. But you're looking for guidelines for a unrealistic model so hopefully they'll do.


What do you see if you look at your own retina with the same eye? (optical feedback) When you record a video while pointing the viewfinder towards the screen showing a live preview you create optical feedback: video example. An anoalogous effect occurs when you turn your microphone towards the speaker.

Once you look at your own retina with the same eye, does our brain create a similar effect as recorded in the video? Or could it be something different all together?

Obviously the best way to find out is to 'just go ahead' and see for myself, but it seems as if I don't have the proper conditions to test this at home: The pupil gets too small in the mirror and thus the retina is plain dark. Such an experiment would require eye drops to force widen the pupil and allow for more light onto the retina.

You would see your retina and that's all. There would have no "mise-en-abyme".

In order to experience this feedback loop you describe, you need to see something which includes the total picture of what you see. For example: You might see a woman holding a frame of the totality of what you see.

When you look at your retina, you can't see something which includes the total picture of what you see, you just see your retina! It would probably work if the retina was a mirror (or any output device)

This question might not really a good fit for Biology.SE. You might have a chance to make a good fit by asking a question on the mechanistic nature of the process called mise-en-abyme on Phylosophy.SE. And ask wether one can live this same process with any of their sense (perception). You can ask whether the Larsen effect (audio feedback) is a similar process to the one we experience when looking at this picture and in what terms they are similar and in what terms they differ. If you ask such question, I welcome you to add the link on this post (except if the post get closed)!


Multiple start and stop codons in mRNA and pre-mRNA I have a main question that will lead to further questions depending upon the answer.

In the process of transcription, will there be multiple start and stop codons in one sequence of pre-mRNA?  If there is, do they remain in the mRNA after splicing?  If they do, does that mean one mRNA has the coding sequence for the synthesis of multiple different proteins?

One last question: assuming a single mRNA has the sequence for synthesis of a single protein, is the stop codon always the final sequence before the poly-A tail?

Thanks in advance for your help and sorry for the mini rabbit hole.

Whether or not there are multiple start and stop codons depends on what you mean by "start codon" and "stop codon".

The start codon has the sequence "AUG", and the stop codon has the sequence "UAG", "UAA", or "UGA". Both the pre-mRNA and the mature-mRNA can, and usually do, contain multiple instances of all of these sequences. However, only one "AUG" instance serves as the translational start site, and only one instance of the stop codon sequence serves as the translational stop site.

The translational start site is usually the first (5' most) AUG. However, for reasons that are still not entirely understood, in about 5% of genes the first AUG is skipped, and translation starts at one of the other AUG sequences.

The translational stop site is always the first stop codon to occur in-frame with the translational start site in the mature mRNA.

The stop codon is usually not (I'm tempted to say never) the final sequence before the poly-A-tail. The coding sequence (the RNA region that codes for the protein) occurs in the middle. There is a 5' untranslated region (UTR) before the protein coding region, and a 3' UTR after the protein coding region. The UTR sequences vary among genes and can have different functions depending on the sequence.


What is the role of lamellar bodies in lung cells? Lamellar bodies have been found to be secreted in lung cells many of their associated proteins have been identified. What is the current consensus or research on the function that these lamellar bodies play in lung?

(Sourced answers, please)

Well, The paper published in Nature 2003:

Despite two decades of progress in understanding the role of LGs and
their contents in epidermal barrier function, almost nothing is known
about the mechanisms responsible for the assembly of these unique
organelles.source: http://www.nature.com/jid/journal/v120/n4/full/5601763a.html

Since then the word "Lamellar Granule" appeared only 5 more times in journals:

1: Sando GN, Zhu H, Weis JM, Richman JT, Wertz PW, Madison KC.
Caveolin expression and localization in human keratinocytes suggest a
role in lamellar granule biogenesis. J Invest Dermatol. 2003
Apr;120(4):531-41. PubMed PMID:
12648214.
2: Akiyama M. The roles of ABCA12 in epidermal lipid barrier formation
and keratinocyte differentiation. Biochim Biophys Acta. 2014
Mar;1841(3):435-40. doi:
10.1016/j.bbalip.2013.08.009. Epub 2013 Aug 15. Review. PubMed PMID: 23954554.
3: Sakai K, Akiyama M, Sugiyama-Nakagiri Y, McMillan JR, Sawamura D,
Shimizu H. Localization of ABCA12 from Golgi apparatus to lamellar
granules in human upper epidermal keratinocytes. Exp Dermatol. 2007
Nov;16(11):920-6. PubMed PMID:
17927575.
4: Lee WS, Oh TH, Chun SH, Jeon SY, Lee EY, Lee S, Park WS, Hwang S.
Integral lipid in human hair follicle. J Investig Dermatol Symp Proc.
2005 Dec;10(3):234-7. PubMed PMID: 16382672.
5: Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T, Mein CA,
Dopping-Hepenstal PJ, Dale BA, Tadini G, Fleckman P, Stephens KG,
Sybert VP, Mallory SB, North BV, Witt DR, Sprecher E, Taylor AE,
Ilchyshyn A, Kennedy CT, Goodyear H, Moss C, Paige D, Harper JI, Young
BD, Leigh IM, Eady RA, O'Toole EA.  Mutations in ABCA12 underlie the
severe congenital skin disease harlequin ichthyosis. Am J Hum Genet.
2005 May;76(5):794-803. Epub 2005 Mar 8. PubMed PMID: 15756637; PubMed
Central PMCID: PMC1199369.
6: Ishida-Yamamoto A, Deraison C, Bonnart C, Bitoun E, Robinson R,
O'Brien TJ, Wakamatsu K, Ohtsubo S, Takahashi H, Hashimoto Y,
Dopping-Hepenstal PJ, McGrath JA, Iizuka H, Richard G, Hovnanian A.
LEKTI is localized in lamellar granules, separated from KLK5 and KLK7,
and is secreted in the extracellular spaces of the  superficial
stratum granulosum. J Invest Dermatol. 2005 Feb;124(2):360-6. PubMed
PMID: 15675955.

According to the last mentioned paper[6]:

LG(Lameller granule) constitute a specialized secretory system within the epidermis.

LG are seen as isolated oval-shaped granules in post-embedding methods, whereas they appear as parts of beaded tubular structures in cryo-ultramicrotomy

Result highlights the biological significance of LG in regulation of protease activities.

LEKTI labels were aggregated and not evenly distributed throughout the LG system, indicating the heterogeneous nature of the LG  (Ishida-Yamamoto et al, 2004).

Biologically active fragments derived from LEKTI are released extracellularly (Bitoun et al, 2003).

LEKTI labels were seen in the extracellular spaces in the superficial granular layers and the first cornified layer with release from the apical side of upper granular cells. Aggregates of LEKTI immunolabels were also closely associated with the TGN46-positive trans-Golgi network .

Double labeling with antibodies to glucosylceramide, a well-known LG molecule, showed that each occupies a distinct domain of beaded tubular structure

The ultrastructural localization of LEKTI was compared with that of KLK7. As reported previously (Sondell et al, 1995; Ishida-Yamamoto et al, 2004), KLK7 was localized in the LG system but was not co-localized with LEKTI within keratinocytes.

This finding suggests that LEKTI is expressed and released earlier than its target proteases, which is consistent with a role in preventing premature proteolysis of extracellular matrix proteins or cell surface adhesion molecules, and in controlling the timing of desquamation.

Source: [6]. http://www.nature.com/jid/journal/v124/n2/fig_tab/5602696f4.html

(source: nature.com)

Caption: Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is
transported through the lamellar granule (LG) system. Post-embedding
immunoelectron microscopy using Lowicryl HM20 resin (A, D) and a
cryo-ultramicrotomy method (B, C, E). (A, B) LEKTI signals (black
arrows) are detected in the LG using polyclonal antibodies against
D8–D11 in (A) and D1–D6 in (B). Note that LG are seen as isolated
granules in the post-embedding method (A), but appear as beaded
tubular structures in the cryo-ultramicrotomy (B). Lamellar internal
structures are seen in both methods (white arrows). (C) LEKTI is
secreted from the apical side of upper granular cells (arrows). d,
desmosomes. Polyclonal antibody to D8–D11 and desmoglein 1 monoclonal
antibody were used and were labeled with 5 and 10 nm immunogold,
respectively. (D) LEKTI antibody to D8–D11 labels are closely
associated with those of the TGN46-positive trans-Golgi network. (E)
LEKTI (monoclonal antibody, 5 nm gold labels) and glucosylceramides
(GlcCer, 10 nm gold labels) are localized within the same continuous
beaded tubular structure of the LG system.


Do potassium channel blockers affect the resting membrane potential? I am reading about scorpion venoms and toxins for my bio class and they appear to have a variety of potassium channel blockers. My professor asked "What effect would this have on a neuron?" and naturally two things came to mind

Potassium channels are necessary for repolarization
Potassium channels participate in controlling the concentration gradient of the cell.

I have found evidence in articles supporting the first claim, but I don't know much about the second.

Do potassium channel blockers affect the resting membrane potential?  Would they significantly alter the concentration gradient?

Potassium channels participate in controlling the concentration gradient of the cell.

I would rephrase this to "Sodium/potassium pumps establish the concentration gradients of sodium and potassium across the cell membrane." Potassium channels do not.

  I have found evidence in articles supporting the first claim, but I
  don't know much about the second.

Right; because the channels don't set up concentration gradients.

  Do potassium channel blockers affect the resting membrane potential?

If they block the resting state "leak" potassium channels, you bet. The resting membrane potential is largely set by the electrical conductance through those channels. Blocking them would greatly depolarize the cell compared to typical resting membrane potential values. But there are many different potassium channels. You may be thinking of blocking the delayed rectifier potassium channel, which shouldn't do much at all to change the resting membrane potential.

  Would they significantly alter the concentration gradient?

Probably not, since though the cell would be losing less potassium through this conductance, what matters more to the concentration gradient of potassium are the sodium/potassium pumps.


How can I purify RNA after gel electrophoresis to remove residual acrylamide? I sometimes use denaturing gel electrophoresis on a preparative scale to purify RNA produced by in vitro transcription. The major issue with this is that the sample after extraction from the gel still contains significant amounts of acrylamide, or acrylamide oligomers/polymers.

Exchanging the buffer using Vivaspins doesn't reliably remove it, precipitating the RNA also only reduces the amount, but can't remove the acrylamide entirely.

In some cases the acrylamide doesn't interfere much with the later experiments, but there are some experiments that won't work with acrylamide in the sample.

What are the options to purify the RNA after gel electrophoresis that would reliable eliminate acrylamide from the sample? Preferably they should be simple and fast, not something like a full FPLC/HPLC run.

If you don't want acrylamide in your preparation, don't use it, as you will always have some carry-over in the solution. And you will not get rid of it completely, as it at least partly co-precipitated with the nucleic acids (it's used as a co-precipitation agent for this purpose).

I think the best solution is to use chromatography, either size-exclusion or charged resins. See these two papers for more information:

Large-scale preparation and purification of polyacrylamide-free RNA
oligonucleotides
Rapid, non-denaturing RNA purification using weak anion-exchange fast
performance liquid chromatography


How can paleontologists identify morphologically different fossils as members of the same species? I recently saw a documentary about Tyrannosaurus rex, which detailed the growth stages of the dinosaur. Apparently, it underwent a huge growth spurt at around 14 years of age, growing into the massive predator so well known in the popular imagination. From what else I've read, this much seems uncontroversial.

However, it made another claim which is that pre-teen Tyrannosaurs had a radically different morphology from adults. The skull was smaller, the legs much longer and the two-fingered forearms far larger in proportion to the rest of the body.

Given that there is some limited evidence for the animal living and hunting in social groups, the program speculated animals of different ages may have filled different hunting roles. The faster, more agile teens driving prey toward the massive, slower adults which then tackled the actual killing. Lions in Africa hunt in packs in this way, but whether Tyrannosaurs did remains speculative.

Anyway, on seeing the body plan of the young Tyrannosaur, I immediately wondered at how any palaeontologist could identify it as the same species as the adult. And lo, the documentary went on to say that, for some years, it was presumed to be a different species.

So the question is: given the radically different body shapes of these two forms and the limited evidence one can glean from the fossil record, how were scientists able to conclusively identify that young and adult tyrannosaurs were, in fact, members of the same species?

Radically different body shapes and sizes represent overall phenotype. Overall phenotype was used briefly in the 1960s and 1970s for species identification under a statistical distance method called "phenetics". However, phenetics has been rejected as a valid method of species identification. Similarly, although ecologists widely use the Biological Species Concept (Mayr) based on reproduction, taxonomists generally prefer some form of the Phylogenetic Species Concept. In addition, paleontologists find species concepts that require assumptions about reproduction in fossils to be difficult. The phylogenetic species concept uses the presence of fixed morphological characters to identify individuals as members of a species. Fixed characters need not be major, obvious differences. They need only be present in all members of a hypothesized species, and absent outside the species. That they are fixed in all members of a species implies a lack of gene flow, but the definition does not require that. So in the example you gave, juvenile T-rex must have some unique characteristic morphological feature that define them as members of the species (a synapomorphy). In addition, when there are a series of intermediate juvenile fossils, it becomes possible to link them together.


ID for red millipede swarm near my place Location:Hyderabad,South India.
These worms usually come out when it rains,these worms are the most common ones any help in figuring out them,they come in groups too.

Based on the body structure and double pair of legs per body segment, this is a millipede.

Based on the small size and spacing between body segments, it could possibly be in the Paradoxosomatidae family. You could check by examining the specimen more closely:

  Most species possess a groove or furrow ("sulcus") on the dorsal surface between the keels (paranota) on each segment.

National Geographic ran a story/video on swarming Paradoxosomatidae in Senegal in 2017:

  Some species swarm together during mating season or to hunt for food, and some studies have theorized juveniles swarm together for protection from predators.

Bellairs et al. (1983)1 studied a similar swarming species of millipede in India:

  The adults of Streptogonopus phipsoni (Pocock), an Indian polydesmoid millipede, emerge from the soil at the onset of the monsoon and mate. Eggs are laid in the soil and the adults die. The larvae leave the soil at stadium III and, apart from moulting periods, remain on the surface until the end of the monsoon. The larvae are aggregated in swarms, usually consisting of several hundred individuals. They are active on open ground, including metalled roads, during daylight, but usually spend the night in an inactive state under cover of stones or vegetation. If a swarm is disturbed, the individuals scatter but later reaggregate.

 Source: Bellairs et al. (1983)

I couldn't find any additional reputable (or really much of any) detail about S. phipsoni in English sources online. So I think I'll leave you with this information for you to explore in your native language more closely.

Though, Bellairs et al. cite Hoffman (1980) 2 and Attens (1937) 3 as their identification sources.
Also, Golovatch & Wesener (2016)4 provide a relatively up-to-date species checklist of the millipedes of India, so I'm certain that reference would be a good place to continue learning more.

 Citations:

1  Bellairs, V., Bellairs, R. and Goel, S., 1983. Studies on an Indian polydesmoid millipede Streptogonopus phipsoni Life cycle and swarming behaviour of the larvae. Journal of Zoology, 199(1):31-50.

2  Hoffman, R. L. (1980). Classification of the Diplopoda. Geneve:  Musee d’Histoire  Naturelle

3  Attems, C. (1937). Myriapoda 3. Polydesmoidea 1 Fam. Strongylosomidae. Tierreich 12:1-300.

4  Golovatch, S.I. and Wesener, T., 2016. A species checklist of the millipedes (Myriapoda, Diplopoda) of India. Zootaxa, 4129(1):1-75.


Is erythropoietin released when breaking down RBCs I came across the MCQ in my physiology book, it says:

Erythropoietin.....
i) may decrease the life span of RBCs.
ii) is not released on breakdown of RBCs.
iii) may stimulate the stem cells.
iv) is formed mainly in liver.
v) is lipid in nature

I think ii) and iii) are correct answers, as when breaking down RBCs we don't get erythropoietin, and erythropoeitin stimulated stem cells to produce RBCs, am I right?
Because the book says that only one choice is correct. Help me please! Is there something I don't understand?

Erythropoietin is a glycoprotein cytokine (v is wrong) secreted by the kidney (iv is wrong); it stimulates erythrocyte production (erythropoiesis, from multipotent hematopoietic stem cells through erythroblasts through reticulocytes to red blood cells; iii is correct; i and ii are wrong) in the bone marrow.


What kind of fruit is this? It is the size of a small avocado or a plum The flesh inside them seems ripe as it is squishy, and it gives off a strange odor. The smell at first reminded me of menthol. It's about the size of a small avocado, or a plum. A coworker of mine left a few on my desk before he left, but he didn't say what they were.

After doing a bit more research and asking a few friends, I found out that it was a feijoa, or pineapple guava. I think the ones in the picture aren't fully ripe yet, though.


Which literature/study/myth spurred the idea that urine is sterile? There is a seemingly unfounded mantra that a person's urine is sterile who is not suffering from a UTI.

So far I have found convincing evidence to the contrary; urine is not sterile. This poster abstract and publication by Hilt et al., 2014 shows that urine may not be sterile. They list 6 other articles (references 3-8) that also found evidence for microflora in healthy urine, the urethra, and the bladder. In some of those studies males were used, and some used females. This makes a convincing case for non-sterile urine.

But why does this mantra persist; where does it come from? Is there a paper that demonstrates the sterility of urine that I have missed? Even if it is old literature, or pop culture, I'd appreciate it.

But why does this mantra persist; where does it come from?

Behind this line of inquiry is a fascinating observation about the disconnect between the laboratory and the clinic. The basic answer, from my perspective, goes like this:

It is doctors who talk with people about their urine, and any testing thereof;
for doctors, urine is practically1 sterile; and
among those who are aware of the microbiologic reality, doctors inevitably gloss details when explaining laboratory results to patients.

The average clinician learns most of what he knows about his patients' urine from urinalyses. Most clinical urinalysis assays show negative nitrites and negative leukocyte esterase in normal people. A glance at the reference ranges for a clinical assay will demonstrate this. (See also the clinical review below.)

Ideally, urinalyses should not be performed in patients without relevant symptoms, but they are sent anyway, and they're mostly negative.2  Even in people who have symptoms possibly suggesting a UTI they're frequently negative.  Furthermore, urine cultures from properly collected specimens grown on the media used in clinical laboratories mostly return at 72 hours: "no growth". This point is emphasized in the abstract by Hilt et. al. linked in the question. Of the cultures that grew in their "expanded quantitative urine culture" protocol,

  90% of these specimens were deemed "No Growth" by the standard urine culture technique, highlighting its limitations.

The last phrase "highlighting its limitations" is an interesting one. It appears to me to be yet to be proven that this is a clinically meaningful "limitation" of such assays. Without attempting to refute these data  — fortunately this question doesn't require me to do so — I will note that the two linked studies aimed to show that people with overactive bladder are characterized by increased urinary flora. The explicitly stated hypothesis is that this may contribute to symptoms. Even in this study demonstrating the existence of such a micro-biome even in normal people, then, it is understood as a potentially pathologic state.

The reason this "mantra persists", then, is that it remains true for clinical purposes. In contrast to most (all?) other bodily discharges, urine is not packed with bacteria, and the commonly used assays reflect this fact.  Medicine and laboratory science have different "modes of discourse", each calibrated to convey levels of precision that are appropriate to the outcomes of interest.

Notes

1. In American English at least, that adverb is ambiguous, meaning either "for practical purposes" or (idiomatically) "almost". Both senses are intended here.

2. Of course, there are plenty of data in various populations demonstrating that some substantial minority of urinalyses among asymptomatic people return positive, "proving" that we shouldn't be checking them (amen!). But this is not the point. The gestalt remains: normal = negative.

3. The nitrite parameter in particular is not especially sensitive. It is, however, quite specific (92-100%), meaning it reliably returns negative in people without infection. (See review, below.) Of course, negative nitrites does not mean sterile in the sense that the OP has used it; see "modes of discourse", above.

Reference

Simerville JA, et al. Urinalysis: A Comprehensive Review. Am Fam Physician. 2005 Mar;71(6):1153-1162.


To have TBE vaccine during allergic times with mild asthmatic symptoms? My assistant says that if you have asthmatic symptoms you cannot have TBE (Tick Born Encephalitis) vaccine, although you are living in the active zone of TBE.

Cases

mild allergic symptoms
allergic symptoms under control of Montelukast (asthma in control)
asthmatic symptoms (bronchitis, rhinosinutis, repeated cough)

What are the risks of having this vaccine during allergic symptoms when you have mild asthma medication (Montelukast)?

I still think the risk of encephalitis is higher if you get TBE from nature than from vaccine.
Are there really some cases where encephalitis is caused by the TBE vaccine?

Interesting question!

The Tick Borne encephalitis vaccine is an inactivated vaccine. It is therefore impossible to get the infection from the vaccine. Reports of fever have been noted but that is due to the body mounting an immune response not due to infection. There are therefore no reports of encephalitis or other markers of infection following the vaccine.

Not only may you have the TBE vaccine if you are asthmatic, but if you are at risk due to your lifestyle and location then, particularly if you have chronic asthma, the TBE vaccine might be a good idea.

Asthma is usually treated by inhalers and montelukast is reserved for uncontrolled/severe asthma. However in the rarer case of aspirin induced asthma, it is much more first line and used for mild asthma. Montelukast is not considered a mild medication.

I hope this answers your question :) if not, comment below!


Queen ant identification I'm planning to start an artificial ant nest and I'd like to learn something about this specific species of ant that I captured in central Colorado.

Could you tell what kind of queen is that? Is there any image reference that would help me find out? Ideally with some location search possibility.

The picture is unclear but this ant looks like a Solenopsis queen. Maybe a Solenopsis invicta! Sorry if I'm wrong, I've only ever kept Camponotus and Lasius queens. I hope this is helpful though


Inbred mice has no severe phenotype outcome? Why does 20 generation of inbred mouse have no particular strange phenotypes, but on the contrary, when on purposely inbreed dogs or tigers for specific phenotype cause severe deformation of the bone structure or cranial structure?

Some information on inbred strains of laboratory mice:

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

http://what-when-how.com/molecular-biology/pure-line-molecular-biology/

A relevant quote on the consequences of inbreeding:

  Inbreeding in allogamic organisms bring the deleterious recessive alleles to homozygosity; the immediate consequence is an increase in the frequency of defective offspring, or, in another words, an increase in the genetic load of the population. This phenomenon is called inbreeding depression or inbreeding degeneration. As inbreeding continues, the deleterious alleles are selected out and eventually disappear. The original heterozygous populations are often more fit than the resulting pure lines because they profit from heterosis and balanced polymorphisms; the main advantage of pure lines is the quick production of many individuals with the same well-adapted genotype, while the allogamy continuously generates new genotypes.

In other words, inbreeding is harmful because it makes it more likely that offspring will have two copies of bad recessive alleles, meaning those alleles get expressed, meaning the organism gets the bad consequences that wouldn't show up if they had only one copy. This is what happens over a single generation however; over many generations the bad alleles are selected against, precisely because they are harmful to the organism so it reproduces less, and after enough generations of inbreeding you hit a point where all individuals are genetically identical and have all the "good" alleles (if they were lucky; otherwise they die out or stay stuck with some bad-but-not-fatal alleles). They still may be worse off than their more diverse ancestors, but they're not completely messed up like their unfortunate great-aunts and uncles who didn't make it either.

The big difference between inbred mice and dogs or tigers is the "for specific phenotype" aspect. Laboratory organisms are inbred so that you get a large pool of genetically-identical individuals, meaning they're much easier to experiment on. The aim is the inbreeding itself, not any particular phenotype. For example if you look at the page for the most popular strain of laboratory mice, C57BL/6, you can see it has many different properties and is used for many different things.

On the other hand, dogs aren't inbred for the purpose of inbreeding or of being genetically identical; the aim is to get desirable phenotypes, and inbreeding is just an efficient way of achieving that aim. It also isn't obvious that many of the problems purebred dogs have is inbreeding (i.e. lack of genetic diversity, high levels of homozygosy) per se, but the fact that the traits being bred for are just plain unhealthy for the dog, or part of a bell curve that include bad outcomes at the edges. For example, Syringomyelia in the Cavalier King Charles Spaniel:

  Some researchers estimate that as many as 95% of CKCSs may have Chiari-like malformation (CM or CLM), the skull bone malformation believed to be a part of the cause of syringomyelia, and that more than 50% of cavaliers may have SM.* It is worldwide in scope and not limited to any country, breeding line, or kennel, and experts report that it is believed to be inherited in the cavalier King Charles spaniel. CM is so widespread in the cavalier that it may be an inherent part of the CKCS's breed standard.

(emphasis mine)

Same thing for that spine malformation that's related to selecting for corkscrew tails. The genes that make the tail corkscrew also mess with the spine.

In other words, the issue isn't inbreeding or not but whether the genes themselves are harmful. When organisms are selected for traits that are directly harmful in their extreme, or are associated with harmful genes that just happen to be next to those that are selected for in the chromosome, then the harmful consequences will spread through the population. Inbreeding is only a problem insofar as it allows the process go faster (more offspring per generation have the desired trait). On the other hand when you're just inbreeding with no specific focus on phenotype, or not phenotypes that have obvious harm associated (i.e. no lab would select for a frivolous trait that also causes harm. They're either selecting for the harmful trait on purpose, or they're selecting against it, because they'll want animals that are as healthy as possible except for the one variable they're interested in), then you'll end up with populations that are fairly normal except for some of the direct consequences of genetic uniformity.

It should be noted that most purebred dogs probably aren't inbred strains the same way many laboratory animals are; those are genetically identical, so the whole point is that their offspring will be like they are. So while they may be less fit than a non-inbred version of them might be, their offspring won't be any less fit than they are. And this is not what's observed with purebred animals like dogs and horses; individuals aren't identical, and looking at the page on Syringomyelia it seems the problems are getting worse.


Why is it called "Ebola virus disease", not just "Ebola" or "Ebola disease"? Why do scientists (pretty consistently) call it Ebola virus disease, rather than just Ebola, or Ebola disease?

Many other diseases are caused by viruses, but they don't seem to have this detail of terminology.  Nor do you hear the analogous terminology for bacteria.

For example:

Rubella is caused by the rubella virus.
Influenza is caused by various influenza viruses (genus names Influenzavirus A/B/C).
Some strains of E. coli (pathogenic E. coli) cause disease, but you never hear E. coli bacteria disease.

This is now how new viral diseases are being named, possibly because one can have/carry a virus without having a disease (e.g. HIV, herpes simplex, etc.). It is not as uncommon as you think.

A bit of googling will turn up reputable sites which discuss the epidemiology of Hantavirus disease, Hendra Virus Disease, Powassan Virus Disease, Lake Victoria Marburgvirus disease, Lujo virus disease, Ross River virus disease, Nipah virus disease, respiratory syncytial virus disease, Kunjin virus disease, Chikungunya Virus Disease, Heartland virus disease, St. Louis encephalitis virus disease, West Nile virus disease, Eastern equine encephalitis virus disease, Western equine encephalitis virus disease, and California serogroup virus disease (includes infections with the following viruses: La Crosse, Jamestown Canyon, snowshoe hare, trivittatus, Keystone, and California encephalitis viruses) and others, but I'm stopping here.

Bacteria cause diseases, but many already had/have names: Typhus (Rickettsia typhi or Rickettsia prowazekii), Rocky Mountain Spotted Fever (Rickettsia rickettsii), Diptheria (Corynebacterium diphtheriae), Lyme disease (at least three species of bacteria belonging to the genus Borrelia), Pertussis/Whooping Cough (Bordetella pertussis), Tetanus (Clostridium tetani), etc.

Interestingly, I have started to see scholarly articles for Clostridium Difficile Disease, which was an entirely new name for what we used to call Antibiotic-Associated Diarrhea. So maybe there will be a shift in that direction as well; time will tell.

How diseases are named is another whole thing.


Why do we have more sweat glands in our palms? Why is it that we have more sweat glands in areas such as the palms of our hands and the soles of our feet? I just learned that there are more there but I am curious as to why that is.

You sweat much stronger in the palms of your hand and the soles of your feet, because they contain a much higher density of eccrine sweat glands. According to Sato et al., (see reference 1) there are something like 64 glands per cm² on your back, 108/cm² on your forearm and 600-700/cm² on the palms of your hands.

This is thought to have different reasons: First, sweating is an important way to control the body temperature.
Sweat works as a defense by anti-microbial peptide dermcidin, it is also seen as am important way to maintain the conditioning of the skin and as well as a lubricant for contact surfaces. (references 2-4)

Sweating is controlled by the sympathetic (autonomic) nervous system, and can be triggered by acetylcholine and adrenaline. This explains why you get wet palms when coming into stress.

References:

Biology of sweat glands and their disorders. I. Normal sweat gland
function
Systematic review focusing on the excretion and protection roles of
sweat in the skin.
Dermcidin: a novel human antibiotic peptide secreted by sweat
glands.
The human eccrine sweat gland: Structure, function and disorders


How do drugs enter synapses? Many psychopharmaceutical drugs change synapse chemistry or directly agonize neuroreceptors in the brain. For example, cabergoline is a D2 agonist.

How do these compounds enter the physical synapses? Are they simply lipid soluble and diffuse throughout all cells?

The answer is that cabergoline does not need to enter a cell in order to function.

Cabergoline (as well as most (possibly all?) other drugs that target synapses) interact with proteins on the surfaces of the synapses. For example, the D2 receptor that you mention is a dopamine receptor which in its active form is expressed on the surface of neurons near the synaptic cleft.


Do PC-12 cells have to be stored in nitrogen? My lab has been storing their PC 12 cells in the -80 freezer... upon arriving here and investigating a new project I see that it specifically stated to be stored in nitrogen vapor? Is this the absolute case or is -80 for short term storage okay as well?

The temperature at which nitrogen evaporates is about −195°C. Given the considerable difference in temperature between the current freezer and nitrogen vapor, I'm inclined to say probably not.

I suspect that it may be dependent on what exactly you are using the PC 12 cells for. Without knowing more detail about the situation, I would do my best to get ahold of some liquid nitrogen for your samples as soon as possible. When in doubt, it is always best to follow procedure.

Until you can acquire nitrogen, -80 is still far better than room temperature. Be sure to take note of the discrepancy in your notes and hope for the best.


Manufacturing toxoids Toxoids produced by tetanus and diphtheria bacteria are detoxified
  with formaldehyde, yet their antigen properties remain.

Source : Biological Science by Taylor

What does formaldehyde do ?

The toxins of both Clostridium tetani and Corynebacterium diphtheriae are so toxic that you cannot use them for immunization, since the amount needed for proper antibody production would kill the individuals. For that purpose the toxins are "de-toxified" by reacting them with formaldehyde which takes away the toxicity but the resulting toxoids are still immunogenic.
This happens by the reaction of the formaledehyde with the free aminogroups of the sidechains of the amino acids to form azomethin groups. This changes the protein so much, that it cannot bind to glangliosides any more which renders it untoxic. The immune system can still recognize unmodified parts (for this 8-10 amino acids in one stretch are enough) and make antibodies.


Reversal form of endosymbiotic theory? Cell's organelles give us evidence that they might have been independent organisms on their own.

Are there any single-cell microorganisms known to have gone so to say this way back as well, i.e. having some evidence to have their past as part of a larger organism?

Endosymbiosis leads to an irreversible loss of independence of the endosymbiont and the host.
For example, all members of the insect superfamily Aphidoidea (aphids) have an obligatory association with bacteria, commonly called primary endosymbionts (Munson et al., 1991; emphasis mine):

The primary endosymbionts are found in specialized organs, the
mycetomes, which consist of cells (mycetocytes) containing the
endosymbionts. The endosymbionts are enclosed within vesicles which
are derived from the cell membranes of the mycetocytes.
None of the [primary] endosymbionts has been successfully cultivated in
bacteriological media or in tissue culture. [These] organisms are essential
for the life of the aphids since the removal of the endosymbionts by
antibiotics leads to aphid sterility.
The endosymbionts are  maternally transmitted, and
there are complex mechanisms which assure that the progeny are
infected.

Munson et al. (1991) Buchnera gen. nov. and Buchnera aphidicola sp. nov., a taxon consisting of the mycetocyte-associated, primary endosymbionts of aphids. Int J Syst Bacteriol 41: 566--568.


Can I figure out the identity of my grandparent from this information? I know all my family up to my grandparents, with the exception of the grandfather on my mother's side. At the time my mother was conceived, my grandmother was having an affair so no one in my family knows for sure who the grandfather was.

In high school we learnt that blue eyes are a recessive trait and brown eyes are a dominant trait, as such I should be able to figure out who my grandfather is, but I only studied up to that level and I want to check with someone more knowledgeable than myself if it is correct.

So here's my reasoning:
I have blue eyes, meaning I have two blue eyed genes and got one from my father and one from my mother.
My mother has brown eyes, meaning that she has one brown eyed gene and one blue eyed gene to pass it on to me.
My grandmother has blue eyes, so she passed one on to my mother.
One of my potential grandfathers had blue eyes, so if it had been him my mother would have received two blue eyes genes and have blue eyes. But she has brown eyes so it must be the other potential grandfather (who's eyes I don't know the colour of).
Can someone tell me if this is correct, and if not, why not?

One of my potential grandfathers had blue eyes, so if it had been him my mother would have received two blue eyes genes and have blue eyes.

No, this does not necessarily follow, because eye color genetics are more complicated than just one dominant-recessive gene. See, for example this article from a someone at  Stanford University on How Blue Eyed Parents Can Have Brown Eyed Children. It isn't common, but apparently it does happen.

Solving your inheritance just based on eye color with 100 percent certainty is not possible.


Are there any neurotransmitters that trigger all neurons? I'm reading into the basics of the nervous system, and am intrigued by neurotransmitters. I understand that certain neurotransmitters can trigger more than one neuron type, and may be used as inhibitors or regulators (antagonists). Conversely, are there any types of agonists that trigger excitation in all neurons, regardless of type? If so, what functions do these play?

There is no such  promiscuous neurotransmitter. There is always some difference between central and peripheral nervous system w.r.t neurotransmitter usage.

Glutamate is one neurotransmitter which acts as an excitatory agonist in most neurons (but still.. not ALL neurons)


Genotype of children conceived after stem cell transplant? If you have sickle cell disease and have a succesful stem cell or bone marrow transplant, your blood type changes to AA. But what about your future children? Do your sperm or egg cells continue to express the SS genotype or do they become AA as well?

Spermatozoa are produced in a process called spermatogenesis. They come from germ cells, which in the human males are located in the testes. These are not affected by stem cell transplants.

In females, the equivalent oocytes are already present at birth. They undergo meiosis later, but since their genetic composition is already set at birth, they, too, are not affected by stem cell transplants.

This might make the process clearer: Primordial Germ Cells and Sex Determination in Mammals

  In all vertebrate embryos, certain cells are singled out early in development as progenitors of the gametes. These primordial germ cells migrate to the developing gonads, which will form the ovaries in females and the testes in males. After a period of mitotic proliferation, the primordial germ cells undergo meiosis and differentiate into mature gametes—either eggs or sperm

A stem cell / bone marrow transplant only affects the bone marrow, where the blood cells are produced.


Which Enzymes are Responsible for the Biodegradation of Beta-endorphin? Which enzymes are responsible for the biodegradation of the endogenous opioid peptide, beta-endorphin?

As far as I have been able to find out, there isn't a definitive answer to this question.

β endorphin is a peptide, and it would seem that there are numerous brain peptidase enzymes that are implicated in the hydrolysis of β endorphin and other peptide neurotransmitters. These include aminopeptidase N, membrane-dipeptidase A, angiotensin-converting enzyme and neutral endopeptidase (also called enkephalinase).

For an early (1984) review of this topic see here; there doesn't seem to be a more up-to-date review, but there is quite a bit of literature on the effects of inhibitors of these various enzymes.


Why can't intermediate filaments be used as tracks by motor proteins? A motor protein like kinesin-1 cannot use an IF as a track because it lacks polarity.

Can someone elaborate on this answer?

Polarity essentially means a plus end (growing/polymerising) and a minus end (depolymerising). Look at microtubule (MT) (http://en.wikipedia.org/wiki/Microtubule). So molecules such as Kinesin-1 (http://en.wikipedia.org/wiki/Kinesin) use the hetero-dimeric nature of MT (alpha and beta subunits) and its polarity to orient themselves and move directionally along MT in an energy dependent manner.


Why do you die if you cannot breathe? I was wondering what the actual reason for death by suffocation is. Obviously it is related to oxygen deprivation. But what is the underlying cause of death?

Is it due to insufficient oxygen for aerobic respiration, and the resulting lack of ATP (as anaerobic respiration forms less ATP)?
Or is it because of the build-up of lactic acid, causing enzymes to denature?
Or is it the lowering of the pH of the blood because of a build-up of carbon dioxide which forms carbonic acid and subsequent denaturation of enzymes?

Short answer
This is a difficult question to answer. As far as I am aware, asphyxiation results in excitotoxicity, which causes unconsciousness, brain damage and eventually, death.

Background
Asphyxia is a condition of the body that occurs from severely inadequate oxygen supply, or because of excessive carbon dioxide in the body (First Aid and CPR courses). The brain is the organ most sensitive to hypoxia (Medscape). Nerve cells in the brain can survive only up to four minutes without oxygen (First Aid and CPR courses). Consciousness is lost after approximately three minutes (Forensic Pathology). Permanent brain damage begins after approximately 4 minutes without oxygen, and death can occur as soon as 4 to 6 minutes later (Medline). Asphyxial deaths typically involve respiratory arrest with bradycardia / asystole (low heart rate / cardiac arrest) because of the hypoxia-induced dysfunction of the respiratory centers in the brainstem (Forensic Pathology).

Despite the small size of the brain (2% of body weight), it is, however, the largest consumer of total body oxygen (20%) and glucose (25%), which are delivered by 15% of the total cardiac output (Schur & Rigor, 1998).

A lack of oxygen may result in so called hypoxic-ischemic encephalopathy (HIE), i.e., neuronal cell death due to hypoxia. Its pathophysiology is related to the lack of energy because cellular respiration diminishes. This initially causes neurons to stop firing, and eventually in an arrest of cellular functions and cell death. Even sublethal HIE can set in motion a series of toxic reactions that kills injured neurons and even neurons that have not been damaged during the initial insult. Thus, following global brain ischemia, neurons do not die suddenly or all at once. In some of them, damage develops hours or days after the insult. Most neurons undergo necrosis. In some neurons, HIE triggers apoptosis (Neuropathology).

Specifically, energy depletion is believed to result in a failure of the Na+,K+ ATPase, leading to depolarization of the neuronal membrane (Fig. 1). Synaptic function and conductivity cease at this point. Depolarization causes neurons to release glutamate (Glu) into the synaptic cleft. Glu is the most common excitatory neurotransmitter. In small amounts, it is indispensable for neuronal function. In excessive amounts, however, it is neurotoxic. Some Glu receptors, such as the NMDA and AMPA receptors, are non-selective cation-permeable ion channels. Initially, over-activation of these channels causes a passive influx of  Cl- (and Na+) into cells causing osmotic (cytotoxic) edema and rapid death (Neuropathology).

Additional structural damage develops hours or even days later as a result of Ca2+ influx into neurons through NMDA and AMPA receptors (Fig. 1). This delayed cell death is caused by an over-activation of NMDA and AMPA receptors by the excessive release of glutamate, which causes massive influx of Ca2+ into neurons. Ca2+ activates catabolic enzymes (proteases, phospholipases, endonucleases), and also NO synthase. NO is a free radical and other free radicals are generated due to the impairment of oxidative phosphorylation. Free radicals and activated catabolic enzymes destroy structural proteins, membrane lipids, nucleic acids, and other cellular contents, causing neuronal necrosis. DNA damage from endonucleases and mitochondrial injury from free radicals trigger apoptosis (Neuropathology). Collectively, these effects are referred to as excitotoxicity (Choi, 1992). When enough brain cells die, the person perishes with them.

Fig. 1. Schematic showing the excititoxic effects of excess glutamate in the brain. Source: Neuropathology.

References
- Choi, J Neurobiol (1992); 23(9): 1261-76
- Schur & Rigor, Dev Neurosci (1998); 20: 348-357


In the diffraction pattern of a protein crystal what exactly determines the intensities of the spots? What I have read is that the contents of the unit cell affect the intensities, but how? I am also unclear on why you need to know the symmetry of the unit cell, what is that used for?
I understand segments of this topic (x-ray crystallography) but I am having trouble piecing all the segments together to make a complete picture. I've been spending hours every day on this on this, any help would be really appreciated!

Two questions here:

1) What does the symmetry of the crystal mean?

The symmetry of the unit cell is the symmetry of the crystal.  Its really useful thing to know about the crystal in practice.  You can always pretend that any crystal is space group P1 - with no internal symmetry.  This implies half of the diffraction data is needed to get a complete set.  Why half? The Laue symmetry of typical X-ray diffraction shows that the diffraction should be centrosymmetric  I(hkl) = I(-h,-k,-l).

If you do this and the crystal has more symmetry than that you are collecting too many data.  Here I take the example of a 2-fold axis.  Along that axis the space group shows that the symmetry of the crystal should be 4 fold along the x axis (x axis is chosen by convention):

I(hkl) = I(-h,-k,-l) (as above) and I(hkl) = I(h,-k,-l)

This fact means we actually can collect less data and know the crystal diffraction pattern easily.  In practice we collect from more than just the unique data, but the more diffraction data we take it also means that we can assume equivalence and have taken more  measurements, giving us better experimental accuracy for the same effort. It also means that when we build a molecular model for structure in the crystal we have a simpler model - one only creates a model for the unique assymmetric unit of the crystal unit cell. Fewer atoms in the structure, fewer degrees of freedom and less error in our resulting model.

There's more... screw axes 2(1), 3(1) and non primitive lattices create systematic absences which helps us collect more accurate data and do refinement more easily in the same vein...  but maybe this gives you an idea...

2) how does the unit cell contents reflect the diffraction intensities

X-ray scattering from crystals is the result of the photon causing an elastic scatter from atomic, inner shell electrons - Bragg scattering.  By considering the crystal as a series of slits in 3 dimensions, it can be shown that the average positions of atoms in the crystal reinforce each other to give the reciprocal lattice that is diffraction data in 3D.

In the picture above from Wikipedia you can see a beautiful protein crystal diffraction pattern.  The rings of spots are a spherical section from a 3D orthorhombic lattice of spots.

Rather than digress into the reason the diffraction appears this way, back to your question: what causes the intensities to vary from spot to spot and crystal to crystal.  The crystal lattice contains atoms which are in the same position in every unit cell which are creating the diffraction by Bragg scattering.  As such, it is the positions, relative electrons in orbit that dictate the diffraction intensities measured.

The models built to model diffraction typically translate a set of atomic positions to the structure factors (square roots of the diffraction intensities), but this is an approximation that works pretty well - the full model is not atomic positions, but an electron density function in space.

There are other sorts of scattering methods, more that could be said about all these subjects, but I hope that gives you some help with your specific questions. If you want clarifications in this, I can edit the answer from comments...


Photolysis in the Light Reactions of Photosynthesis I'm a bit confused concerning photolysis. During the light reactions, photons are used to excite the chlorophyll molecules so they are passed to the primary electron acceptor. The electrons initially come from a split water molecule. Is water split by the photons?

A catalytic site on a subunit of Photosystem II is responsible for splitting water via photo-oxidation. This site, called the Oxygen-evolving complex (or OEM), uses energy from sunlight (which is converted to electrochemical potential energy in the photosystem's reaction center) to accomplish this task.

 Source: Wikimedia

See Barber (2012)1 for an explanation. The abstract (my emphasis):

  The oxygen in our atmosphere is derived and maintained by the water-splitting process of photosynthesis. The enzyme that facilitates this reaction and therefore underpins virtually all life on our planet is known as photosystem II (PSII), a multisubunit enzyme embedded in the lipid environment of the thylakoid membranes of plants, algae, and cyanobacteria. During the past 10 years, crystal structures of a 700-kDa cyanobacterial dimeric PSII complex have been reported with ever-increasing improvement in resolution--the latest at 1.9 Å. Thus, the organizational and structural details of its many subunits and cofactors are now well understood. The water-splitting site was revealed as a cluster of four Mn ions and one Ca ion surrounded by amino-acid side chains, of which seven provide ligands to the metals. The metal cluster is organized as a cubane-like structure composed of three Mn ions and the one Ca2+ ion linked by oxo bonds. The fourth Mn is attached to the cubane via one of its bridging oxygens together with another oxo bridge to an Mn ion of the cubane. The overall structure of the catalytic site provides a framework to propose a mechanistic scheme for the water-splitting process and gives a blueprint for the development of catalysts that mimick the reaction in an artificial chemical system as a means to generate solar fuels.

My understanding is that we are still not totally certain how this actually works...

Cady et al. (2008)2 wrote a review in 2008 of various functional models trying to explain the chemistry of the oxygen-evolving complex of photosystem II.

A quick Google Scholar search reveals plenty of proposed mechanisms published since.

Most currently proposed mechanisms do, however, incorporate the 4 oxidation steps proposed by Kok et al. (1970)3 (now referred to as the Kok Cycle, or Kok's S-state cycle).

From Kern et al. (2013)4:

  The oxidation equivalents generated by the absorption of four photons by the PS II reaction center are stored in the four consecutive redox states of a Mn4CaO5 cluster, known as the Si (i=1 to 4) states. The accumulated energy is used in the concerted oxidation of two molecules of water to form dioxygen (1) returning the catalyst to the most reduced S0 state in the Kok cycle (Scheme 1).

 Scheme 1 from Kern et al. (2013) explaining states of Kok Cycle.

You can learn more here.

Works Cited:

1 Barber, J., 2012, January. Photosystem II: the water-splitting enzyme of photosynthesis. In Cold Spring Harbor symposia on quantitative biology (Vol. 77, pp. 295-307). Cold Spring Harbor Laboratory Press.

2 Cady, C.W., Crabtree, R.H. and Brudvig, G.W., 2008. Functional models for the oxygen-evolving complex of photosystem II. Coordination chemistry reviews, 252(3-4), pp.444-455.

3 Kok, B., Forbush, B. and McGloin, M., 1970. Cooperation of charges in photosynthetic O2 evolution–I. A linear four step mechanism. Photochemistry and photobiology, 11(6), pp.457-475.

4 Kern, J., Alonso-Mori, R., Tran, R., Hattne, J., Gildea, R.J., Echols, N., Glöckner, C., Hellmich, J., Laksmono, H., Sierra, R.G. and Lassalle-Kaiser, B., 2013. Simultaneous femtosecond X-ray spectroscopy and diffraction of photosystem II at room temperature. Science, 340(6131), pp.491-495.


Difference between Appendix and the Cecum? What's the difference between an appendix and a cecum, and what are their functions?

In herbivores the Cecum is an area that stores plant matter and helps digest it via symbiotic bacteria. Carnivores have smaller Cecums because meat is easier to digest than plant matter. In humans the Cecum is also an anatomical landmark that delineates the change from small intestine (a digesting organ) to the large intestine (mostly a capacity/storage organ).

The Appendix is a small, previously thought "superfluous" fleshy worm-shaped organ at the junction between the small and large intestines. Recent research posits that the appendix is sort of a harbor for a person's gut flora that can re-populate the intestines should the existing bacteria die or get removed (diarrhea being the most common cause). It can also become infected, inflamed, and require surgery to remove (Appendicitis).


V(D)J recombination on homologous chromosome V(D)J recombination is known to recombine IG locus of a B cell. Is anything known about how the recombinations on two homologous chromosomes are connected? For example, are the selected V(D)J couples(triples) the same on both homologues?

There are two alleles (variants of the same genetic region) for the Ig and TCR loci, one on each chromosome. The cell will try first with one allele to obtain a productive arrangement, and then with the other. If the cell fails on both alleles, the cell undergoes apoptosis. If at least one allele has a productive arrangement, the cells move on to selection.

Groups are still uncertain, however, how the cell chooses which allele to initiate recombination on, and ruled out parental imprinting as a culprit last year (1).

To be certain, the regions are the same, though not the same sequence. However, mechanisms during recombination ensure that recombination events among individual cells result in robust junctional diversity and a suitably diverse repertoire of immature antibody or TCR sequences (example).

In activated B cells, however, class switching and somatic hypermutation can result in gross changes to the Ig locus not seen in immature or pro-B cells.


Optimum pH of Catalase I am aware that certain organs in the body have specific pH environments to increase the activity of their enzymes. I'm also aware that enzymes only work at certain pHs due to the configuration of the amino acid in their active site and the way this is altered as the pH is changed. What I want to know, however, is why their amino acids are as they are to begin with - has it got to do with the substrate molecules they react with? Particular reference to catalase would be helpful.

The optimum pH for catalase can be found be a simple search. According to the Wikipedia entry for catalase it is approximately 7.

With the exception of extreme pHs, which can cause denaturation, the pH optimum of enzymes is often related to the ionization of the amino acid residues that participate in the reaction (and hence their pKa). Often what happens is that the reaction mechanism requires a residue to alternate between an ionized and non-ionized form, so that the optimum pH approximates to the pH of half-ionization. (This may not be the same as the pKa of the amino acid in solution, as the environment at the active site can alter this greatly.)

You need to understand ionization chemistry to appreciate this. If you do not, you could try this section from Berg et al. first. If you do, look at the mechanism of action of well-established enzymes like lysozyme and the serine proteases.

I cannot help you further with catalase. Apparently it is not well understood.


qTERT-pcr like qRT-pcr Is it possible to use a biologically active Telemorease Elongation Reverse Transcriptase (TERT) in the place of the Reverse Transcriptase (RT) for quantitative Reverse Transcriptase pcr (qRT-pcr)? Yes I do know that it would seemingly have no advantages. What kind of reverse transcriptase is used in qRT-pcr is there a standard like taq dna pol is used for qpcr?

What kind of reverse transcriptase is used in qRT-pcr is there a standard like taq dna pol is used for qPCR

M-MuLV (Monoley murine leukemia virus) reverse transcriptase

Some RT enzymes are engineered to remove the RNAseH domain so that template RNA persists for more rounds of RT.

  Is it possible to use a biologically active Telemorease Elongation Reverse Transcriptase (TERT) in the place of the Reverse Transcriptase

Perhaps it can catalyse an RT reaction in-vitro. But commercial enzymes need to be efficient and I think using TERT won't be that advantageous.


Why are there exactly four nucleobases in DNA? Does someone know why DNA is composed of four nucleobases? In particular, is there an explanation for the number? Why four and not two, or eight?

A now deleted answer put this down to an argument based on amino-acid coding in codons but, as pointed out by Konrad Rudolph in a comment, arguments based on codons cannot be correct because the 4-base system likely pre-dates the evolution of protein translation.

So why four?

I suggest that it comes from a combination of factors which make it a 'just right' fit for RNA-based replicators: more would be bad, and less would also be bad. The four bases are able to copy with high reliability because two features combine to exclude mis-pairings: there are two size classes - meaning any purine-purine or pyrimidine-pyrimidine pairing results in incorrect separation between the strands, excluding A-G and C-U bonds; and there are two classes based on number of OH-bonds - which limits the potential for A-C and G-U bonds. More bases must, inevitably, weaken the strength of these exclusionary approaches and increase the number of mispairings. RNA world replicators will have lacked the sophisticated repair and error checking mechanisms of modern lifeforms so this increase in mispairings would likely not be corrected.

Of course, a two base system would be even more capable of reducing errors. I suggest that the advantage of the four base system is that it allows for much more complex 3-dimensional structure to form in RNA and thus enabled a broader range of catalytic capabilities. I've only considered even-numbers because only even numbered systems could use the Watson-Crick style of base pairing.

I'd also suggesting reading Eörs Szathmáry's 2003 paper on this very question.

Addendum

A group in California has just published a paper in which they successfully added a third base pair stably into DNA. I think this could shed some light on why four - you can read about it here or get the full paper here (Nature, so pay walled).