Do all microRNA isoforms need to be known and sequenced to obtain microRNA expression? From what I understand, microRNA are short "hairpin" shaped nc structures. When sequencing and counting miRNA, isoform miRNA are "found" which are subsections of varying length and possibly with some mutations or other differences to the "canonical" microRNA. The total counts for a miRNA are the sums of the counts for the isoforms which relate to that miRNA. [Please correct me if this is all wrong]

With regards to Next Gen Sequencing, a 'library' needs to be added which tells it what to sequence. Does this mean only "known" isoforms be read and counted or can "new" sequences (i.e. mutations) also be read and counted which were not known before sequencing started?

With regards to qPCR - does this technique only look for individual isoforms? In which case, if I want to know something about a particular microRNA expression would I need to do qPCR for each known isoform relating to that microRNA. OR, is it in fact easier to sequence microRNA expression with qPCR since sequences can be matched to the main hairpin structure with higher probability. (By easier I mean compared to say wanting to get the expression for a particular isoform since it needs to be matched exactly).

I had worked on a similar problem and I am telling my experience.

First, you have to consider the fact that a mature miRNA can arise from multiple genomic locations i.e. many pre-miRNAs can give rise to same mature miRNA.

As you said there are products of pre-miRNA cleavage with heterogeneity at their ends i.e. there are sequences that do not exactly match the annotated mature region. While products with 3' heterogeneity can be called isoforms, products with 5' heterogeneity are likely to have different targets as the seed sequence is disrupted and hence they are technically different miRNAs (by definition).

Now, the best technique to analyse isoforms is small RNA sequencing (NGS). qPCR would not be a good technique as primers cannot always differentiate highly similar sequences (worsened by the fact that miRNAs are too small). A NGS library is a set of DNA sequences that you obtain from shearing the RNA/DNA followed by adapter ligation (reverse transcription for RNA). Since the adapter sequence is known, the sequencing reaction does not require you to know the sequence of the products. However, you would need to know the reference genome for finding novel miRNAs. This is primarily due to the fact that it is very difficult to sequence pre-miRNAs (low abundance and hairpin structure). You can identify new small RNAs very easily but cannot say that they are miRNAs unless you can map them to a stem-loop precursor (pre-miRNA).

You can very well discover new reads and people have discovered a lot of new miRNAs using NGS. I can tell you the methodology I followed to find atypical products of the same pre-miRNA. I for simplicity I call the 5' heterogeneous products as badseeds (because they have disrupted seed sequence) and 3' heterogeneous products as isomiRs. I used a methodology that is similar to that of a well known program – miRdeep.

Get the pre-miRNA sequences from miRbase
Get mature miRNA sequences from miRbase
Use bowtie-1 to build an index from the pre-miRNA sequences
Remove adapter from your fastq reads and remove low quality reads. There are many tools to do that. You can try Trimmomatic.
Map mature miRNA sequences to pre-miRNA index using bowtie to find the exact location of mature miRNA in pre-miRNA
Map reads to pre-miRNA region. Filter reads that do not map in a pre-defined window around mature region.
Classify the reads as badseed or isomiR

Now, isomiRs and reads that perfectly map to mature miRNA region can be considered as contributors to total miRNA expression. However, badseeds should not be considered as an isoform. You can likewise allow a certain level of mismatch and count these reads. Sequences with mismatch in seed region would again be badseeds. You can additionally have scoring schemes for your reads.

There are not many studies on such analysis. I did not get any publishable result with our data but the methodology is reasonably correct. You can go ahead an apply it for your study.


How have single-celled organisms learned to survive? Upfront: I am a computer science student trying to understand evolution and its implications.

I've been pondering the concepts of evolution for some time, especially related to neuroscience / how the brain works / how to emulate brains. I wonder how single-celled organisms evolved at all. I know, they don't "think"; but once their ATP levels get low, they know they must find food to sustain their system, aka staying alive. This is probably no active decision, more like: "The enzyme concentration tells me to find food".

Question: Was the entropy just high enough that at some point those organisms had the property that finding food somehow is preferable to death? Edit: How can an organism perform something without "knowing" it needs to perform it?

I hope, this isn't a terribly stupid question.

Nothing more than physics

Simple physics

If you drop a rock, the rock will fall to the ground. If there was a table underneath, the rock would stop its fall when reaching the table. Clearly the rock response to the environment but the rock does not need to be conscious (whatever you mean by "consciousness") of anything in order to response to the environment.

Explanations for a programmer

As you are a programmer, you will agree that when you do std::cout << 3+2 << std::endl;, nothing more than physics is happening so that the value 5 followed by a newline gets printed to the screen. It is relatively complex though. So complex as it may feel quite magical before having spend many hours learning about computer engineering.

You understand that if you write a, say, boids program, all that is happening is just a bunch of addition and multiplication (eventually a power). The program does not need to be "aware" of what it is doing (nor do the individual agent) in order to respond to the change of behaviour of a predator.

You could even write a self-learning algorithm and you would still accept that there is no consciousness involved but only very simple operations.

Biology

Living things are pretty much the same. They are relatively complex (more like a computer than like a rock) but essentially the same. Also, the response tot he stimulus is often (not always) adaptive as it has been selected. But at it's core there's nothing more than physics involved!

More info

If you want to learn more about the mechanism of living things in general, you might want to just open an intro book or have a look at an intro course such as Khan Academy > Biology for example.

You can as well pick a simple response to an environmental stimulus and study its mechanism. How about having a look at chemotaxis for example!

Note that you might also want to follow a short and introductory course to evolutionary biology such as Understanding Evolution for example.


What is the difference between taxonomical aids Flora, Manual and Catalogue? The three type of books mentioned above are taxonomical aids that offer information about species found in an area. However, the exact difference between them is not clear to me. Please explain.

A Flora describes plants and where they live. Floras typically include a dichotomous key for identification purposes and often times will include range maps as well. Floras are almost always designed to be simultaneously regionally constrained and regionally exhaustive/complete (i.e., includes all plants that grow in that region or at least all taxonomic divisions of specified taxa). See Example.

A manual applies much more broadly to plants, and typically instructs you on a subject (e.g., identification/differentiation of species).  A manual does not need to be exhaustive and its scope is typically user defined (though often based on the scale/range of it's underlying subject). However, some have used the term manual to be more or less synonymous with Flora or otherwise similar document (e.g., see here).

A catalog is simply a listing of all species organized in some way. These are usually alphabetical (vs. taxonomically organized like a typical Flora). You will also never find a key in a catalog and will often find less phytographic detail.

See Chapter 6 in Describing Species: Practical Taxonomic Procedure for Biologists by Judith Winston for further assistance.


Regression to the mean and evolution I don't have a strong biological background but, in studying statistics, I met the idea of regression to the mean. e.g. children of tall parents tend to be shorter than their parents, and so on.

Does this interact with evolution ?

TL;DR answer: Regression to the mean doesn't always occur (children can be taller than either parent, as can be easily observed at any high-school basketball game), so it doesn't affect the theory of evolution through natural selection.

The observation of regression to the mean was of great concern to Darwin and early thoughts on natural selection (don't confuse "evolution", which is the observed phenomenon, and "natural selection", which is one of the theories proposed to explain evolution).  The problem has been effectively resolved since the rediscovery of Mendel's genetic work at the end of the 19th century.

"Regression to the mean" is inevitable if inheritance works through blending of features.  That was how everyone believed inheritance to work in the mid-1800s, and Darwin understood that it presented an insuperable obstacle to his theory.  That is, if blending inheritance was true, then natural selection could not be true.  Darwin puzzled over this quite a bit, and came up with some unsatisfying suggestions to overcome it, but at the end of the day, one of the predictions that his theory of evolution through natural selection made, was that blending inheritance could not be true.

Of course, blending inheritance is not true.  Mendel showed that in fact inheritance is quantal, not blending.  We now know that many traits of interest look, superficially, as if they're blending (which leads to regression to the mean), but are actually the result of multiple traits interacting.

With blending inheritance, the variation that is required for natural selection to work is lost, generation after generation; regression to the mean in an inevitable consequence.  With gene-based inheritance, variation (can be) preserved generation after generation; regression to the mean is a common but not inevitable consequence, because the variation in the original population is still present and can be re-created given appropriate selection pressure.


Can parts of a human brain be asleep independently of each other, or vary in the times required for them to fall asleep? I know that some birds and marine animals can continue complicated activity (swimming, flying?) while one hemisphere of their brain is asleep.

I'm interested if human brain has some parts of it that can be asleep while others are awake? In other words, can a human brain be only partially asleep while experiencing insomnia or similar sleep disturbances?

If human brain can have different parts "sleeping" independently of each other, is it possible that the times to "fall asleep" vary between these different parts of the brain?

I would appreciate research articles on the topic or just the names of brain regions that may exhibit behavior described above.

Update: I've taken a look at R&K "principles and practice of sleep medicine"' and it mentions the following parts as involved in sleep:

Medulla, preoptic area, hypothalamus, thalamus, entire neocortex involved in NREM.

Neurotransmitter systems: histaminergic, orexinergic, serotonergic, noradrinergic

Sleep factors: adenosine, interleukin-1 and other cytokines, prostaglandin D2, growth hormone releasing hormone, nitric oxide, all promote sleep in or around preoptic area.

This makes me hypothesize that drugs that modify the effects of these systems (ex- caffeine affecting adenosine) could result in sleep- related disturbances in these systems, potentially causing them to fall asleep later that usual. But I'm looking for more info to fihre out if this is true

Have you ever tried to read a complicated book after several hours of hard work that required a high concentration? Imagine that you have forced a particular area of your brain. After a hard work, the areas of the brain that we used to finish a work seem don't respond to any stimulation and make us feeling tired and as we can't understand what we are doing anymore. This happens because we have forced that particular area of the brain and it needs to reinforce the connections it made and to do this, it has to sleep, such as we do during the conscious (you know you are going to sleep) sleeping. Eventually we can say that some particular areas of our brain must sleep if forced to a hard work and they do it when you feel like you can't get something which you know you can. A recent study has demonstrated this by understanding physiological functions of sleeping.

Nature article of Vyazovsky V. et al. Vol. 472, pages 443-447, April 2011 (I am not copying the link anyway, have to search it by yourself). Or to Science of Bushey D. et al. Vol. 332, pages 1576-1581, June 2011. And on Nature Review Neuroscience of Diekelmann S. And Born J. Vol 11 number 2, pages 114-126, February 2010.


Why can one swim longer underwater by blowing out air? I am a human. I take a deep breath. I swim underwater... After some time, I need to blow out some air. I blow out some air... By doing so, I can swim underwater longer. Blowing out some air gives me more time underwater. Why?

Apparently, dolphins encounter this phenomenon too.

This is purely a psychological response, and it does not help in decreasing the speed of CO2 level rise. As CO2 level in your blood rises, you instinctively want to breath out the 'bad' air and breath in fresh one. The latter is impossible under water, but the former eases you psychologically a little; you have "started doing something" with your predicament of high CO2 level.

Most freediving courses (as well as my own experience - humble as it is) suggest not to have the last breath substantially larger than your normal one; this comes from people who train to achieve 6-7 minutes dives, so I would assume they meticulously tried various methods.

The key here is not to have a victory over physiology; the key is psychology. Most people fail at diving because they unnecessarily get into a positive feedback loop: they get excited, their brain and muscles become even more active, they produce more CO2, brain receives information about rising CO2 in blood, and it becomes excited even more, produces even more CO2, etc, etc, until a panicked diver surfaces or inhales water. Without such unnecessary excitation, each moderately healthy human would be easily physiologically capable of 3-4 minute dives.

My take is the amount of air you have in your lungs should be primarily the amount that eases your psyche the most and helps to stop needless stress.


To what extent do domestic animals understand language? Note: Please tell me to re-post this in Cogsci or pets if this doesn't belong here.

Hello All,

I want to know how dogs or other domesticated animals differentiate between normal chat and a command. Do they understand their master's language or body language?

If they understand the body language of the master alone, then how come they can do the same trick (in most of the cases) if some other person gives the same command?

And to what extent do they have this understanding, meaning how many words does a domesticated animal understand?

Yes, they can understand some words and even simple sentences.
Here is what Animal Planet says:

Studies show that the average dog can understand about 165 different words, in some cases more if you make a point of training them. This includes the basic commands such as "sit," "stay," and "go," as well as a range of other terms, assuming they're tangible words and not abstract ideas.

Here are some supporting studies:

Some domestic dogs learn to comprehend human words, although the nature and basis of this learning is unknown [1].
A female mongrel dog, Sofia, was initially trained to respond to action (point and fetch) and object (ball, key, stick, bottle and bear) terms which were then presented as simultaneous, combinatorial requests (e.g. ball fetch, stick point). Sofia successfully responded to object-action requests presented as single sentences, and was able to flexibly generalize her performance across different contexts [2].

References:

Tempelmann S, Kaminski J, Tomasello M (2014) Do Domestic Dogs Learn Words Based on Humans’ Referential Behaviour? PLoS ONE 9(3): e91014. doi:10.1371/journal.pone.0091014
Ramos D, Ades C (2012) Two-Item Sentence Comprehension by a Dog (Canis familiaris). PLoS ONE 7(2): e29689. doi:10.1371/journal.pone.0029689


What problem does the Dobzhansky-Muller Model resolve? This page describes the Dobzhansky-Muller model and I can follow the illustration of the split leading to incompatible hybrids.

But at the start of the page the author states "[Dobzhansky and Muller] both realized that hybrid inviability or sterility was unlikely to arise from a single change at one locus." I don't really understand the explanation that follows i.e. what exactly is the issue with having a single change at one locus?

I wonder if someone here could explain the issue more clearly.

If reproductive isolation was to be caused by a single mutation, then the first individual to carry this mutation would likely have a very low fitness. At the extreme, in a purely sexually reproducing species without hermaprohiditism, this individual carrying the first mutation causing reproductive isolation would have no-one to reproduce with and would have a fitness of zero.

Hence, reproductive isolation is unlikely to arise from a single mutation as these mutations are unlikely to raise into appreciable frequency. Hence, Dobzhansky and Muller (and Bateson) created this minimalist model involving only two loci with negative epistatic interactions.


Why is ATP used as a source of energy rather than glucose? I'm struggling to pinpoint a misconception, but I don't think I understand why ATP is used as an energy molecule instead of glucose. I understand that glucose is respired, oxidised or combusted and produces energy in the form of ATP so I guess what I don't understand is why glucose isn't hydrolysed (like ATP is) when energy is needed instead of having to convert its energy to ATP first.

Well the mechanics of this can actually get pretty complicated, depending on how far into the biochemical weeds we want to go, but there are a couple of very simple reasons at the core... Well they actually aren't that simple, but they can at least be analogized in simple ways.  The first, and easiest to illustrate is this.  This is a glucose molecule:

And This is an ATP molecule:

If you want to get some energy out of an ATP molecule, all you have to do is break off one of those phosphate groups.  If you want to add more, you just stick another phosphate group back on.  This can be done without significantly changing the structure of the molecule itself.  That Adenosine base never gets touched.  Only the chain of phosphates is manipulated.  It is much more energy efficient to add and remove those phosphate groups than to add and subtract elements from a glucose molecule, as there is no way to effectively break it down without significantly changing its structure, which makes it harder to build back up.  We want a molecule that it is just as easy to add energy to as it is to pull energy out.  The glucose molecule just doesn't have a chain sticking off that's easy to remove and put back at will.  The CH2OH group on the end looks like an attractive energy sink on its face but getting the whole thing off isn't nearly as easy as it looks, and it doesn't contain as much energy as a phosphate group either, which brings us to the second easy to illustrate reason ATP is more attractive than glucose as an energy carrier.

If you look at that chain of phosphates, you will notice that they are each separated by an oxygen atom.  There are also a bunch of convenient hydrogens and OH groups floating around that make hydrolysis and dehydration very easy.  Where would you hydrolize the glucose molecule to produce a low energy molecule that can be converted back to glucose more efficiently than ADP can be converted back to ATP?  Just compare this process:

To this one:

The ATP hydrolysis looks more like the breaking down of polysaccharides into glucose than the catabolism of glucose itself, and this is at the core of the difference between the two molecules.  It is always easier to add and subtract links from a chain than it is to make direct modifications to one of the links themselves.  Glucose is great for energy storage.  You can pack a lot of energy into a glucose molecule, but once you get it out, it's very hard to put it back.  It's much easier just to throw out the waste and start over by making or eating another one.  We don't have this luxury with ATP.  It has to be able to drop off its energy load and go pick up more.  For this, the structure of ATP is much more appropriate than the structure of glucose.


Common Ancestry of ETCs and ATP Synthase complexes Rickettsiales are widely regarded as the ancestor of eukaryotic mitochondria through endosymbiosis.
Cyanobacteria are widely regarded as the ancestor of eukaryotic chloroplasts through endosymbiosis.

These two organelles bear striking similarities in terms of structure and mechanics. There seems to be plenty of information regarding speculation on the endosymbiosis that led from these free-living organims to the organelles. However I can't seem to find much on speculated relationships between these organisms in terms of common structures.

My Quesions : Are the electron transport systems and chemiosmosis simply ubiquitous phenomena in prokaryotes, or are these similarities evidence of highly conserved common ancestry? Or is there another answer?
Is there any information regarding the phylogenetics of Rickettsiales and Cyanobacteria. Do these two organisms belong to a single small clade or were these biochemistries (ETCs, ATP Synthases, etc) ubiquitous at some point and have simply been preserved in these two organisms today?

Rickettsia and Cyanobacteria are not part of a small clade that share these features.  ATP synthases are present across all domains of life, and they are all homologous, i.e. derived from a common ancestor.  The means its fairly likely that the last universal common ancestor had some form of ATP synthase.

ETCs and ATP synthases are part of the chemiosmotic theory put forward by Mitchell.  Whats beautiful about this mechanism is that you just need a single ATP synthase to make your energy, and it can be used regardless of your metabolism, be it a Cyano or a Rickettsia.  All you need to do is somehow couple your metabolism to a proton motive force across your membrane, and then you just let the protons fall back down their electrochemical gradient, powering the formation of ATP.

Organisms from all corners of the tree of life use this strategy, so this is not some special common feature linking the organisms that ultimately became eukaryotic organelles.  Its worth noting that there are alternatives to ETCs and proton motive force-based ATPases, you can make ATP by substrate-level phosphorylation like in fermentation metabolisms.


Role of Prevalence in Estimating Coronavirus Mortality Let there be a sample of 10,000 people.

100 of them have a fever. You test them for COVID19 and they all come out positive.
5 of them die, 9 of them end up in intensive care.
The estimated mortality is 5%, and estimated intensive care rate is 9%.
What about the 9,900 asymptomatic people who did no get tested?

Scenario A: All 9,900 asymptomatic people would test negative for COVID19.
Scenario B: All 9,900 asymptomatic people would test positive for COVID19 because of a combination of high rate of asymptomatic carriers and high false positive rate.
End result:

Scenario A: true mortality rate is 5% and true intensive care rate is 9%.
Scenario B: true mortality rate is 0.05% and true intensive care rate is 0.09%.
the numbers are fictitious, but the point is simple - we can't estimate mortality without knowing the prevalence

Question:

Where are we right now between scenario A and scenario B? Or put another way, are there any ongoing studies/reports which take into account this factor?

I think you're talking (setting aside false-positive/low-specificity testing problems for the moment) about the difference between infection fatality ratio (IFR, fraction of infected people who die from disease) and the case fatality ratio (CFR, fraction of clinically defined "cases" who die from disease). The difference between these two depends completely, as you suggest, on the difference between the population that gets infected and the population that is defined as a "case" (which could vary a lot: is it people who have a cough? fever & cough? request testing? are admitted to the hospital? are admitted to the ICU?).

Because most of the people aboard the Diamond Princess cruise ship were tested (3063/3711), we can have a reasonably good idea of the fraction infected (unlike the usual scenario where most asymptomatic cases are never noticed). The authors of this (not yet peer-reviewed) study concluded that:

  the all-age cIFR on the Diamond Princess was 1.2% (0.38–2.7%) and the cCFR was 2.3% (0.75–5.3%)

(where 'c' in cIFR and cCFR stands for 'corrected'; these are estimates that account for the fact that we don't yet know the outcome for all patients).

Other issues to think about:

sensitivity and specificity of testing (false positive/negative rates)
variation with/adjustment for age (discussed in the paper)
variation by medical/social context (e.g. Wuhan vs Iran vs places where cases are caught early and the medical infrastructure isn't overwhelmed)

Russell et al., "Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship". https://cmmid.github.io/topics/covid19/severity/diamond_cruise_cfr_estimates.html


In this illustration about CRISPR function, what do these objects mean (image provided)? In the paper on CRISPRs, the following figure is shown:

I added the light-green boxes.

What do the red arrows and the line with a filled circle on the far left mean?
What does the arrow in the middle mean (also just infront of cas9)?
Is the purple square to be understood as the RNA section in the B plot (blue arrow)?

Taken from here.

The caption is (cited):

  The type II-A system from S. pyogenes is shown as an example. (A) The
  cas gene operon with tracrRNA and the CRISPR array. (B) The natural
  pathway of antiviral defense involves association of Cas9 with the
  antirepeat-repeat RNA (tracrRNA:crRNA) duplexes, RNA co-processing by
  ribonuclease III, further trimming, R-loop formation, and target DNA
  cleavage. (C) Details of the natural DNA cleavage with the duplex
  tracrRNA:crRNA.

The arrow direction denote transcription direction and its location denotes the transcription start site. The circle is probably the transcription terminator (I cannot access this article at the moment, but this is what it should mean).

The purple boxes refer to the protospacers which are derived from foreign DNA. These elements help in recognizing and cleaving foreign DNA. These are transcribed as RNA which in turn guide the Cas complex to the target DNA. In a way, these protospacers provide some kind of immunological memory to the bacteria. See the below figure (From Nuñez et al. 2015 ):


What type of mushroom/fungus is this? I had someone gift me some old firewood along with some other wood I had purchased from them.  I was told the wood in question is popple.  However, it was in pretty bad shape and much of it had a mushroom/fungus growing on it.

Does anyone recognize this fungi?  The trees lived in central Minnesota, and sat close to a lake for a year or so.

These are shelf (or bracket) fungi. They love dead or diseased wood, and are as common in woods as dirt.

Yours are kind of in rough shape (it looks like they're experiencing some problems of their own.) It's hard without examining a specimen to determine exactly which it is.

Some are edible, some are beautifully colored, some are hard, some soft, some plump, etc. But they are all shelf fungi.


Why do some bacteria have most genes on the leading strand of the genome? Genes in the (+) strand are black and genes in the (-)strand are red.
The gene distribution in E. coli genome is somewhat expected: transcribed regions would tend to alternate with non transcribed regions, as a consequence of (random) evolutionary process. Also, genes don't overlap (it would be highly  unlikely that two complementary strands both carried useful information).
In B. subtilis, on the other hand, there seems to be a preference for one of the strands in each side of the chromosome. What sort of evolutionary pressure could give raise to such a pattern?
I have a guess, but I'm not sure, that this may be related to bacterial transformation.

The pattern we see in B. subtilis is quite common in prokaryotes. The origin of replication is shown at the top of the genome diagram. DNA replication proceeds bidirectionally from this point. In the B. subtilis diagram, most genes are located along the leading strand in each direction. Even in E. coli, by the way, important genes, including all rRNAs, tend to appear on the leading strand.

Why is that? Rapidly growing bacteria are replicating their genomes most or all of the time, so you've got replication and transcription happening at the same time.  If genes are on the lagging strand, RNA transcription proceeds in the opposite direction from DNA replication, and the DNA polymerase will often collide with the RNA polymerase. If the genes are on the leading strand, however, RNA transcription proceeds in the same direction as replication and collisions are minimized. Hence the selective advantage to positioning most genes along the leading strand.

Some genes may also be on the lagging strand in order to target them for mutagenesis (Paul et al. 2013, Million-Weaver et al 2015). This goes back to the concept of transcription-replication collisions where the head-on collisions are worse than co-directional collisions. Head-on genes actually have a higher mutation rate and incidence of convergent mutations which suggests that they are mutated and evolve faster than leading strand genes. This is a controlled process in that it only occurs in lagging strand genes, and only when the gene is transcribed (i.e. when it is needed). It was argued that this is a way bacteria can control and ratchet up or down the rate of evolution in a controlled way. This was argued against by Chen and Zhang based upon computer based modelling. It is an interesting concept that has been hotly debated.

EDIT for additional clarification and references:

This diagram from Chen and Zhang (2013) helps show what is going on:

Caption: "Schematic drawing of a collision between a working DNA polymerase and a working RNA polymerase in bacteria. (a) Codirectional collision when a gene is encoded on the leading strand. (b) Head-on collision when a gene is encoded on the lagging strand. Arrows show the directions of movement." (Chen and Zhang 2013)

A few references

The original idea goes back almost 40 years to Nomura M. and Morgan,E.A. (1977) Genetics of bacterial ribosomes. Annu. Rev. Genet., 11, 297–347.
An early paper about highly transcribed rRNA on the leading strand: Ellwood M. and Nomura,M. (1982) Chromosomal locations of the genes for rRNA in Escherichia coli K-12. J. Bacteriol., 149, 458–468.
A recent overview: Rocha, E. P. (2004). The replication-related organization of bacterial genomes. Microbiology, 150(6), 1609-1627.
Why some genes remain on the lagging strand: Chen, X., & Zhang, J. (2013). Why are genes encoded on the lagging strand of the bacterial genome?. Genome biology and evolution, 5(12), 2436-2439.
Paul, S., Million-Weaver, S., Chattopadhyay, S., Sokurenko, E., and Merrikh, H. (2013). Accelerated gene evolution through replication-transcription conflicts. Nature 495, 512-515.
Million-Weaver, S., Samadpour, A.N., Moreno-Habel, D.A., Nugent, P., Brittnacher, M.J., Weiss, E., Hayden, H.S., Miller, S.I., Liachko, I., and Merrikh, H. (2015b). An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis. Proc Natl Acad Sci U S A 112, E1096-1105.


What is vascular cambium? I'm confused over the two terms vascular cambium and intrafascicular cambium.

Is vascular cambium the same as intrafascicular cambium?

I know nothing about plant physiology but I googled your question and here is what I found
Vascular cambium
From wiki

The vascular cambium (plural cambia) is a plant tissue located between the xylem and the phloem in the stem and root of a vascular plant, and is the source of both the secondary xylem growth (inwards, towards the pith material at the center of plant, often dead and/or deteriorated, that is composed of parenchyma tissue) and the secondary phloem growth (outwards [to the bark, rough or smooth, of the plant]). It is a cylinder of unspecialized meristem cells that divide to give new cells which then specialize to form secondary vascular tissues.

Intra fascicular cambium
From Biology.easlife

The cambial strip which is present between the primary xylem and primary phloem is known as the intra fascicular cambium. The intra fascicular cambium is also known as the vascular cambium. During the secondary growth the cambial ring is formed by the inter connection of the intra fascicular and inter fascicular cambium. - See more at: http://www.biology.lifeeasy.org/5040/what-is-intrafascicular-cambium#sthash.aY3SPblI.dpuf

What is the difference between fascicular cambium and inter fascicular cambium?
From biology.lifeeasy

The cambium present within the vascular bundle is called intra fascicular cambium or vascular cambium. It is present between the primary xylem and primary phloem. The intra fascicular cambium is primary in origin.
The new strip of cambium which is formed from the permanent cells of inter fascicular parenchyma is called the inter fascicular cambium.  The inter fascicular cambium is secondary in origin since it is derived from the permanent cells of medullary rays.

Need more?
If the above definitions don't help, you should include in your question why these definitions don't help and what is unclear.


Is the frequency at which a species mutate affected by natural selection? As per natural selection, is it safe to assume that some species will have it genetically encoded so that they produce a certain 'perfect' rate of mutation so that they can adapt to an environment that changes quickly?

Another way to put this; does every type of organisms have  roughly the same amount of mutations each time they reproduce (relative to the size of their DNA)? If so, is/can/could this be governed by natural selection?

Drake's rule

Let $L$ be the size of the genome. Let $\mu$ be the average per nucleotide mutation rate, then the genome-wide mutation rate $U$ is $U=L \mu$. There is a general relationship between the genome size of an organism and the nucleotide mutation rate that makes that the genome-wide mutation rate is often approximatively 1. There is of course several orders of magnitude of variation around this value of 1 among organisms.

This rule is called Drake's rule after the name of the author who first discovered it (Drake, 1991).

To my knowledge, this relationship is not fully well understood. Because you are looking for an adapted mutation rate in your question, I would like to highlight that I would not go about assuming this is adaptive. I could imagine that some molecular genetic constraint of the replication process could be causing this type of relationship between $L$ and $\mu$.

You will probably want to read this post about Drake's rule.

Mutation rate in humans

In humans, the average mutation rate is estimated to be around $\mu=2.5 \cdot 10^{-8}$ (Nachman and Crowell, 2000; see also this post), with a genome size of about $L=3 \cdot 10^9$, leading to an estimate of the genome-wide mutation rate of 80.

Interestingly, the mutation rate is in fathers is age-dependent. See the post Gender and age-specific mutation rate in plants.


Can germs develop surfactant resistance in a harmful way? Germs can develop antimicrobial resistance. It is a problem serious enough to deserve an FAQ page on the WHO website (http://www.who.int/mediacentre/factsheets/fs194/en/).

But how about surfactant resistance? We wash our body, our dishes, our clothes, and pretty much anything that is washable with soap/detergent, which means surfactants.

So can germs develop surfactant resistance in a way that is harmful to human health? If so, is there any recorded experiment about it? If not, why not?

Never say never indeed!
a three part answer to the question:

Bacteria can develop resistance.  These researchers did a screen for Staph and Pseudomonas which survived a detergent/soap treatment and indeed were able to select for many strains.  I'm not sure that their explanation of why they are resistant is a final answer, especially for the Pseudomonas strains which have no hypothesis at all.

Nearly all bacteria do this all the time #1  Most bacteria can go into spore or plaque forms which basically hibernate.  These plaque colonies are matrices of crosslinked bacteria and are resistant to extremes of conditions in the environment or lack of food.

Even Normal Resistance is a relative thing.  Alcohol sanitizers kill 99.9% of bacteria.  That sounds like a lot but that 0.1% can come back to full strength in a relatively short period of time.  0.1% is still millions of individuals surviving after a shower.  Resistant bacteria have a higher proportion of survivors and should improve the bounce back rate.  So resistance is a term which you need to define for a given situation.

Surfactant (soap) resistant bacteria can be nearly any sort of bacteria and a certain percentage of them are ready for a scrub down at any given time.  To get a surface completely free of bacteria takes a good deal of work.
As far as a danger to human health - resistance to being killed by soap is a real problem because the few of them which also have resistance to antibiotics and are pathogenic will be pretty much unstoppable.  Its not likely that surfactant resistance will itself make a bacteria pathogenic (never say never!) but if such a 'triple threat' emerges we'd all be in trouble.


What is "chain identifier" in PDB? The PDB file format is explained here. My question is what "chain identifier" is exactly? What is the difference between two residues which have the same sequence number but different chain identifiers?

The "chain identifier" does exactly what it says: it identifies the polypeptide or other molecular chain. For some structures, there is only one, so you'll only see an identifier A. However, many structures show two or more proteins bound together, or an enzyme complexed to a substrate, or a small molecule inhibitor in a binding pocket - there are many different possibilities. Each individual chain of atoms has its own identifier.

For example, 1VKX shows my favorite transcription factor NF-κB bound to the κB DNA enhancer sequence. There are four chains in the structure: two polypeptide chains, the p65 subunit A and the p50 subunit B, and two DNA chains C and D, one for each strand (forward and reverse).


Wearing sunglasses during a solar eclipse Note: I had asked this on Physics, but it is off-topic there due to being about safety.

On the BBC's guide to eclipse-watching, Dr Lucie Green says:

  Watching an eclipse with normal sunglasses provides virtually no protection. In fact, they trick your eyes to let in more light, so they can cause even more damage.

This doesn't seem right, because proper sunglasses should block UV to a safer level. Surely wearing proper sunglasses at any time is safer than not? Whilst I can understand staring at the sun with sunglasses on still allows too much UV in, why couldn't someone just glance at the eclipse from time to time?

Your eyes can dilate behind sunglasses, especially when the main source of light (the sun) is blocked, and ambient light decreases. Regular sunglasses offer some protection against certain UV wavelengths, but not enough to protect your eyes when looking directly at the sun (or, during an eclipse, the corona). Most sunglasses are mainly designed to, first and foremost, look good. After that, there is some protection against UVA (400-315 nm) and UVB (280-315 nm) light. Some sunglasses also offer "UV400" protection, which is short-wavelength blue light longer than 400 nm. Polarized sunglasses do not protect against UV at all, only reflected light (such as shining off the water or from an automobile's body or glass) and glare. Different sunglasses tints (or colors) also do not protect against UV, but they can affect color perception.

  Surely wearing proper sunglasses at any time is safer than not?

That is true, it is safer, the question is to what degree? Sunglasses offer some protection from indirect UV and visible light that has been scattered by the atmosphere and reflected off of things around us. However, the number and energy of photons (the "particles" of light) reaching your eyes when looking directly at the sun is dramatically greater, and so much more dangerous. Eyes can be damaged quite quickly by high-energy light of many wavelengths, including UV and visible, with the magnitude of the damage correlating to the energy of the light. Damage is also cumulative, accruing over a lifetime. Even small peeks directly at the sun will contribute to your overall lifetime risk of eye damage, and may cause permanent, irreversible harm very quickly.

There are a number of much safer alternatives for watching solar eclipses, including pinhole projectors, welding goggles rated higher than 14, various solar filters for cameras, telescopes, and binoculars, and fully exposed and developed black-and-white film (good luck finding that nowadays), among others.

Above all, make sure you're safe, and if you have any doubts consult with an expert, such as a science/natural history museum or local university's astronomy department.


What is the proper pronounciation of the scientific name of the ground elder / Aegopodium podagraria? A audio sample would be great. As a kind of bonus: I would appreciate a kind of database, which contains a lot of botanical plant names.

Here is a american database which offers sound samples for a lot of scientific plant names.


Can undigested food proteins enter the bloodstream? I know that food proteins in our digestive system are denaturated and broken down into amino acids or very small peptides that are then absorbed in the small intestine. If some proteins stay undigested they move to the large intestine and either gut flora eats them or they are excreted.

But lately, I've been hearing a lot of stuff like "if you eat a lot of eggs there will be egg proteins in your blood" or "drink liquid collagen and it will travel to your skin through the blood". It seems really stupid to me. I imagine if all sorts of food proteins entered our blood they would wreak havoc there catalyzing random reactions, triggering immune responses, etc. So it cannot be a very frequent event. But I've been wondering if some of the food proteins can on occasion end up in the blood of relatively healthy people. Does this ever happen? With food allergens maybe?

Sort of.

Proteins can enter the body through the intestines by exploiting a few transport mechanisms, They are not truly crossing the cell membrane but are transported across the cell in vesicles. Though not into the bloodstream but into the lymph system.

M cells in particular will move antigens across the intestinal wall, a few more durable proteins (like prions) have been shown to piggyback on this system to cross in tiny quantities. Some viruses also exploit it. Collagen definitely does not enter this way but there are likely egg antigens that may.

Note this is very rare for non-antigens, the vast majority of food you eat will not contain anything that can exploit this although they may contain antigens that get passed to the immune system.

Source

Source 2


Are gene variants at different loci also called alleles? I think the title says it. I always read that alleles are gene variants at a given locus, which confuses me. Thanks!

EDIT:
Short answer : Yes: "allele" is a synonym for "gene variant", irrespective of location (locus).

Background
Original answer: From About Education I found this definition for an allele:

  An allele is an alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome.

EDIT:
Hence, two alleles are located at the same locus, but are situated on a different chromosome.

ADDITION EDIT: Given the many high-quality comments (and the downvote) I erased the concluding sentence of my first attempt and I will elaborate below:

Feero et al. (2010) gives the following more elaborate definition of "allele" (text relevant to the question is bolded out):

  Specific locations in the human genome where differences between individual people
  are found are generally referred to as variations, and the term “normal” or “wild type” is often used to refer to the most common variant at a location in a given population group. In its simplest form, the variation has two different spellings, referred to as “alleles.” If the frequency of the minor allele is greater than 1%, such variants are called polymorphisms. The word “mutation” is generally reserved for changes in DNA that are believed or known to be pathologic [...] or for changes that are [very] recent (e.g., not inherited DNA changes).

Hence, from my understanding, the original quoted definition from About Education still stands.

As to the critical comments placed by the PO, @fileunderwater and @WYSIWYG:

(1) [...] what is a copy or a variant of a gene at a different locus on the same chromosome? - That is a very interesting question, and I think Feero et al. (2010) deals with that simply by saying

  In its simplest form, the variation has two different spellings, referred to as “alleles.”

In other words - perhaps the gene duplication is a step too far for this terminology. And in fact, although I regret having to cite wikipedia here, it does provide a very enlightening sentence:

  [...] [A]t the gene locus for the ABO blood type [...] classical genetics recognizes three alleles, IA, IB, and i, that determine compatibility of blood transfusions. Any individual has one of six possible genotypes (IAIA, IAi, IBIB, IBi, IAIB, and ii) that produce one of four possible phenotypes [...].

Hence, what this implicitly tells us is that an allele is, as Feero et al. (2010) also says, simply a gene variation.

This means that it basically boils down to what is a "chromosome locus"?

An article by Proulx & Phillips, 2006 entitled "ALLELIC DIVERGENCE PRECEDES AND PROMOTES GENE DUPLICATION" mentions:

  [...] [H]eterozygotes at a single locus are broken up by segregation, whereas for duplicate loci an individual can carry copies of alternative alleles at separate
  loci.

Hence, what the authors implicitly say is that an allele is a gene variation and that a locus is a fixed position on a chromosome. Hence, a gene duplication means 2 loci that can carry the same or a different allele. This should answer

(2) Are the alleles at the two duplicated loci then named differently, even if their DNA sequences are identical (as well as the protein they might be coding for), namely no, an allele has a name (e.g. IA) that remains unchanged when duplicated. The locus is then different for the duplicate, but the name of the allele stays the same (as an allele is, by definition, simply a gene variant wherever on the chromosome).

(3a) [...] two versions of a gene at two different loci are alleles (not paralogs)?: yes

(3b) What about the same identical version at two different loci: same allele or not? yes, same allele, allele has nothing to do with locus. Just a gene variant. Where ever.

Reference
Feero et al. N Engl J Med 2010;362:2001-11
Proulx & Phillips. Evolution 2006;60:881-892


Effect of pupil responses on the electroretinogram The electroretinogram (ERG) is a measure of electrical activity of the retina. It is typically recorded from the cornea with a wire electrode or gold-foil electrode. Generally, the the ERG is considered to reflect the retinal processing of a light stimulus, typically a photoreceptor response followed by secondary neuronal activity and electrical activity evoked by supportive Muller cells.

I am wondering if the pupil response will add signal on top of the ERG? Firstly, there is the direct pupil response, which causes the pupil to constrict when the eye is subjected to bright light. Pupil constriction may, perhaps, induce electromyogram (EMG) activity when the smooth sphincter muscle around the pupil contracts, which in turn could theoretically contaminate the ERG. Secondly, there is neuronal activity involved in constricting the pupil, as light is processed in the retina by ganglion cells that in turn drive the pupil reflex. Furthermore, there is the consensual pupil response as well. This response causes the contralateral pupil to constrict when the ipsilateral eye is subjected to bright light. The consensual response is mediated by efferent input from the brain following stimulation of the other eye and causes both eyes to restrict. Hence, neural input arrives in the contralateral retina from the brain. This activity is not directly related to the processing of the light stimulus and may disturb the ERG proper when ERGs are recorded with a flash and both eyes are open.

So my question is

Does a pupil-mediated EMG affects the ERG signal?
Does neuronal activity involved in the pupil reflex affect the ERG, for example the  efferent input involved in the consensual response?

I have had no luck after extensive searches in text books, Scopus, Pubmed, Google, Google Scholar.

Answer version1 (read the comments, I leave v1 for the those who can make the same assumptions in the future)

To answer the question we should clarify some general concepts and processes mentioned it the clause:

EMG is performed by means of direct placement of the electrode (the are two types here - surface-EMG and needle-EMG) on/into the skeletal muscles, this is why there is no such thing  "iris-sphincter-related EMG": the sphincter is inside the eye and there is no way to contact it without eyewall penetration somewhere. Thus, this part of the question is hypothetical.
ERG is performed after pharmacological mydriasis (pupil dilation to ensure retinal mass response or to perform multifocal ERG), so in the standard settings there is no substantial pupils reaction during the test. Thus, this part of the question is hypothetical too.
ERG measures electrical changes when one of the electrodes is directly attached to the cornea - here we should stress "to one cornea", and "reads" the current from only one side. This is why, the reaction of contralateral pupil, skeletal muscles, heart/defibrillator activity are irrelevant since they are out of the electrical loop existing between the electrodes (the second electrode is on the forehead).
ERG measures electrical activity only - there is no muscle contractions in the process, while EMG involves the time needed to acetylcholine to be released and muscle contraction to begin. This means that the time scopes of these tests are different. In addition, as stated, pupils react as an efferent organ (III nerve, mediator related), while retinal photoreceptors react directly to the light stimulation, so there is a clear delay between these two processes. Theoretically, one can perform full cut of the optic nerve with the resultant loss of afferent signal and consequent loss of efferent pupil reaction, but the ERG will still detect the normal curves if the photoreceptors are intact.

Back to question itself: according to the mentioned facts we should state that the question is more hypothetical and theoretical, thus answering it directly is problematic and the answer should not be assessed without facts mentioned above.

So, the final answer - 1+2: No, pupil reaction does not affect the ERG in the real and standard settings and should not be counted as an interfering factor.

Version2

I've found an interesting patent claiming that pupillary responses can contribute to eERG (electrical stimulus instead of light). These influences stated to be artifacts, thus the authors raise the question how to diminish/filter them out.

They say

  Eye movements and pupil responses may contribute to the eERG;

  Pharmacologic dilation abolished these pupil responses;

  Bilateral artifacts, such as pupil responses, in the corneal eERG
  cannot be sufficiently reduced by using dilation drops; Even after
  dilation, a residual, but substantial electrical response persisted in
  the contralateral eye.

So, I should convert my answer to yes/yes. Taking into account the obscure nature of the subject, I hope you will agree that by making mistakes we can learn something new. I personally learnt a lot trying to answer this excellent question.

Patent application number: 20120143080 (if the link will be broken in future, one can find the patent by this number).

Direct link
http://www.faqs.org/patents/app/20120143080


Evolution of long necks in giraffes In this question, the OP uses giraffe necks as a supportive example of evolution. Is the mechanism described in this post accurate? At some point, I thought I remember hearing that giraffes did not evolve long necks to reach higher food resources, but instead longer, stronger necks gave some sort of mating advantage (male competition perhaps?).

Is there a consensus in the scientific community as to evolutionary mechanism(s) that contributed most to the evolution of long necks in giraffes?

There seems to consensus that it is not competition for tall food.  Giraffes actually often feed on resources that are lower than their maximum possible height.    See:

Simmons, R. E. & Scheepers, L. 1996. Winning by a Neck: Sexual Selection in the Evolution of Giraffe. The American Naturalist 148: 771–786

This paper put forth the idea that sexual selection is the reason behind long necks.  The idea is that longer necked males are dominant.  But this  theory has also been questioned.  See:

G. Mitchell, S. J. Van Sittert, J. D. Skinner. 2009.Sexual selection is not the origin of long necks in giraffes. Journal of Zoology 278, Issue 4: 281–286

So in the end there's no clear consensus.  Some papers have returned to the theory of competition for research in the past few years.To put it simply, no there is no consensus.


Major effects on cells grown with 5% FBS supplemented media instead of 10% FBS? I maintain a few cell lines in the laboratory (industrial R&D) that I use regularly for experiments. I realized today that the media i prepared for the week on monday was only supplemented with 50 mL of FBS into 1 L of DMEM, instead of the usual 100 mL that i usually do. I was in a hurry and absentmindedly didn't add the second 50 mL autopipettor's worth.

My cells are fine morphologically but I think they're growing a bit slower than usual, my guess is due to the 1/2 concentration of all the FBS growth factors, etc. Are there any other effects that would be pronounced in these?

I understand that it will be apples to oranges to do compare results with these cells to, say, an experiment done with a batch of cells grown in complete (10% FBS supplemented) media.

If you were to run a flow-based viability assay (annexin V, live/dead fixable dyes, 7-AAD) or dual-fluorescence count (like acridine orange/propidium iodide, popular method as of late), you might find that more cells are undergoing apoptosis, or an increase in dead cells. I say this because trypan blue often overestimates viability. Your most pronounced effect should simply be a reduction in viable cells or a slower growth curve if you take those data points. Otherwise you'd need to run some test (fair example).

The problem being, these observations vary wildly based on what cell line you're using, lot-to-lot variability of the serum, and reagent handling. For example, the serum was heat-inactivated improperly, medium was degraded, bad lot of serum, and so forth. So take this as a generalization and a good reason to validate your serum lots.


Can trichoptera and lepidoptera be distinguished with the naked eye? Are there any tell-tale signs which one could use to distinguish adult trichoptera from lepidoptera? To me, trichoptera just look like moths:

One method would presumably be to touch its wings and see if scales come off, but what if we assume we don't want to catch it?

The etymology of the names will help you there: trichoptera means "hairy wings", whereas lepidoptera means "scaly wings".

If you can get a close shot (maybe with a powerful tele lens) of any possible trichoptera or lepidoptera, you can tell that it either has hairs or scales on its wings, without having to touch its wings.

Examples:

Note the hair visible above the wings. Taken from https://www.inaturalist.org/observations/18660283

Now, there are lepidoptera species that also seem to have hairy wings, such as the tussock moth:

Note the hair as well. However, the shape of the antennae would be a dead give-away: as far as I know, trichoptera shouldn't have feather-like antennae. Furthermore, the wings still have noticeable scales, besides the hair. Taken from https://www.inaturalist.org/observations/18652111

Other lepidoptera species may also seem to lack scales, such as the Syntomoides imaon:

Parts of the wings of the Syntomoides imaon are transparent. However, anywhere that has scales should exhibit some kind of iridescence. You can use your phone's flashlight and try to illuminate the insect from different angles, and you should notice some iridescence. Trichoptera wings, in contrast, should just reflect the light flatly, due to the lack of scales. Taken from https://www.inaturalist.org/observations/18652111

Also, (most) butterflies and moths have a proboscis (the "straw" that can coil up, used to suck nectar). That's usually easy to spot if you can look at the head from the side. Caddisflies don't have that. Instead, caddisflies have mandibles (used to chew through their pupal case as they emerge as adults).

I did mention using a tele lens at the beginning of this answer. Of course, that's not "naked eye" like you asked. The point is that you begin by using a tele lens. As you see more caddisflies vs moth/butterflies, you'll build up a sense of the cues to look at. And at some point you may be able to distinguish them with your naked eye (depending on how close you can get your face to the insect and how good your eyesight is).


Are Triceratops and Eotriceratops similar enough to be considered as the same genus? Everybody knows Triceratops, the horned dinosaur from Late Cretaceous North America, who lived 68-66 MYA.

In 2007, Eotriceratops xerinsularis was named and described (Wikipedia). It lived in (what is now) Canada about 68 MYA. It is a little bigger than Triceratops but in many aspect very similar, e.g. they both have long horns and solid frill, and postcranial skeleton. Gregory S. Paul, in his Princton Field Guide to Dinosaurs 2016, suggested putting Eotriceratops xerinsularis in the same genus as Triceratops, renaming it to Triceratops xerinsularis. I find this suggestion appealing, but I know Paul's taxonomy is unorthodox and not mainstream (e.g. I do not agree with the thesis that Torosaurus is merely a full adult Triceratops).

So the question is: can Eotriceratops xerinsularis be put in the same genus as Triceratops and is this suggestion is plausiable enough?

Taxonomists have wide leeway over assigning higher taxa. The publication process in which Eotriceratops was described as a new genus made it a new genus. However, given a different set of reviewers, they may have rejected the new generic description, and suggested that the author put it into Triceratops. The process is somewhat arbitrary, and there are some random elements to higher taxon assignment. But it is the system we use. If somebody were to write a paper to synonomize Eotriceratops with Triceratops, and that paper were accepted, then Eotriceratops would cease to be a valid name. Its all about publication precedence. Gregory  Paul may have good reason for his suggestion, but it must be published before a change is made.


Molecules, Targets and Isoforms I have a question. Given a molecule A and two isoforms of a gene X, Y, and the knowledge that A targets X. Can I infere from this anything about whether A targets Y?

As a motivation think about Furosemide (= A) and SLC12A1, SLC12A2. From Drugbank I know that Furosemide targets SLC12A1, and from KEGG I know that Furosemide targets both genes. I wonder whether I can infer the KEGG knowledge already from the Drugbank knowledge...

Best,
Alex :)

The short answer is no.  What matters is whether the sequence and folding (if you are talking about binding of A to proteins instead of DNA) of each isoform of your gene still results in the binding of A.

I other words, A may bind to X. Y, an isoform of X may not have the same sequence that A likes to bind to. Or, in the case of proteins and A, Y may fold slightly differently, preventing accessibility of A to Y.


Why do chain identifiers in PDB have no standard starting chain id type? At first I assumed that PDB chain identifiers are just uppercase letters (A, B, C,..) but found out there are protein chain ids that are numbers (0-9) and lowercase letters as well.

For example,

1NAL only has chain ids (1 - 4). It starts with chain '1' (number).
103L has chain identfier 'A'. It starts with chain 'A' (uppercase letter).
5afi's chain id's range from [a-zA-Z0-6] since it has 52 unique protein chains. It starts with chain 'a' (lowercase letter)

Can someone please explain? Or are id's just arbitrarily assigned?

Chain IDs are assigned by authors who submit the structure to the wwPDB.
According to the PDB spec:

  Non-blank alphanumerical character is used for chain identifier.

Usually, the chains are assigned uppercase letters.
But since digits and lowercase letters are also allowed, some people will use it.
And a good reason to allow more characters is to accommodate for structures that have more polymer chains than there are letters in English alphabet. With lowercase letters and digits the limit is 62 chains.
Which is still not enough for some structures.
(Many programs can handle two-character chain IDs, but this common extension has not been embraced by the wwPDB.)


Cell division - meiosis Really confused. How many chromosomes pairs do humans have in their sex cells? How many single chromosomes do humans have in their sex cells?

Terminology is what is holding you back.
What chromosome implies depends on context, i.e. is it replicated or not.

In Meiosis. Gametes arise from Germline cells that have 23 PAIRS of chromosomes. That means, that while there are 23 different chromosomes they come in doubles/pairs. This is the typical X like shape we think about when we hear chromosomes.
Another way, chromosome can means either 1X or 2 single chromatid

MEIOSIS I -- 23X chromosome pairs are duplicate and end up as 46X chromosome pairs (46 pairs of X OR, 92 separate chromatid)

These 46X are divided equally among two daughter cells just like in mitosis. Where now each daughter cell receives 23X = 23 pairs.

MEIOSIS II. The daughter cells in end of Meiosis I divide without DNA replication and the 23 pairs are split among 2 new cells. So now each new daughter cell (in total 4) has 23 individual chromatid (individual chromosomes)
and these are the gametes.

When the gametes fertilize to form a zygote, the zugote product ends up 24X each.

Each X contains, 1 chromatid (|) from the father and 1 chromatid {|} from the mother.

Haploid means once copy of each chromosome.
23
Diploid means two copies chromosomes or 23X

Ref
- Allison Q.N,.(2015), Freeman Biological Science.


When can a virus modify DNA in every cell of a living organism? I've recently heard about experiments with brain tissue, where a virus is introduced in a rats brain, causing a "glow when electric charge is present" protein to be created. This protein then helps to study the brain using optical techniques to detect this glow. As far as I understand, not all cells in the brain were affected by this virus.

It seems like this kind of "virus operation" on DNA is pretty powerful, so my question is : at which point in an organism's life can a virus operation be done in such a way as to affect the entire organism for the rest of its life?

In other words, will a virus is introduced into a young embryo(or sperm), affect all cells and stay with an organism until death? Can it be introduced later and still have "complete effect"?

The answer depends on two factors:

The type of vector (virus) you are using
How well your vector can be integrated.

The bottom-line is that there is no guarantee the vector will work even if you start from the embyro.

As far as I know, the problem of using vectors in general is that the vector you are using might not be integrated into the genome of the host. (Not necessarily get into the DNA, but just keep replicating during each S phase.) Therefore doing it earlier gives you a better chance to actually get them in the organism.

For example, there is a linear vector used in C. elegans that was injected into the oocyte even before fertilization. The cell later treats the vectors as broken DNAs and linages them so they could be pull to one side of the cell during mitosis. However, the huge chunk of vector DNA is mosaic. (i.e. only some of the cells in that worm have the vectors.) Other vectors like engineered HIV have better chance to integrate themselves.


Is it possible for humans to digest and live on food that isn't based on DNA or RNA? Our bodies digest food using enzymes that have evolved to convert food here on Earth. Could we even possibly get nutrients from something we haven't evolved alongside? - Is it possible for humans to digest and live on food that isn't based on DNA or RNA?

This might be flagged for being somewhat of a subjective question, but to survey human diet:

Mnemonic SPONCH can be used to sum up the necessary building blocks of life, in the elements Sulfur, Phosphorus, Oxygen, Nitrogen, Carbon, Hydrogen. There are others, trace elements, which are necessary and come from diet (selenium, for example). These elements are used in building our biological macromolecules: Carbohydrates, lipids, nucleic acids, and proteins. The molecular interactions between these macromolecules, their cofactors, etc. are essential for life. Some of these compounds, however, can't be made in the human body from scratch; hence essential amino acids, and the necessity to consume foods which provide metals, carbohydrates, fats/triglycerides, etc.

So, at this point our body is optimized to incorporate terrestrial foods. Sometimes, though, we can see that the body will sometimes accept analogs to normal compounds, although this is often to disastrous effect (like chemotherapy in cancer). The real question, then, would be: does said extraterrestrial food compose of necessary biological elements or analogs in a way our body can actually use this food for sustenance? That, however, is 100% speculation as we have no reference in even a single case to base our assumptions.


Why can't my body deal with cold-sores I am not a biologist, but I have always wondered why my body hasn't learnt to deal with the HSV-1 virus. I understand it reamins dormant for a while and things like stress or the common cold can trigger it. I get cold sores about twice to even four times a year and I have had them since being quite young.

Why hasn't my immune system learnt to recognise it and eliminate it?

HSV-1 has evolved mechanisms to thwart the immune system's surveillance.  A number of genes in the viruses genetic material code for proteins that can disrupt the process by which a cell alerts the immune system that it has a foreign virus within in it.

For technical readers, the reasons are described in the links above in detail.

For the non-biologist....

PART ONE  As you note in the question, HSV-1 can remain dormant in an infected cells for a long time.  In general, there is nothing for the immune system to respond to at this time.  So the infection persists in a dormant state.  Whats more, when it spreads, it can spread between cells, without entering the bloodstream.

PART TWO If the virus re-activates. In order for cells of the immune system to recognize and destroy a cell infected with a virus, the infected cell first chops up bits of the virus that are inside the cell and transfers these pieces (called antigens) to the outside of the cell so they may be presented  to immune system cells. At the same time, the infected cell attracts and activates immune system cells using 'distress' molecules.    However, HSV carries genes that make proteins that can thwart the presentation of antigens by a cell as well inhibiting the distress molecules that help activate an immune response.

PART THREE  What about antibodies ?  During the body's response to an HSV infection, antibodies can be produced and persist.  In many infectious diseases, antibodies can be protective as they mop-up any circulating virus and may prevent re-infection.  However, since HSV is already present inside cells, antibodies may have little effect in the reducing the amount of virus-infected cells in the body and may not prevent flare-ups.

Paradoxically, some of the symptoms of HSV flare-ups are due to the immune system's response!  (looking for a good reference)

The good news is that drug options to treat HSV have improved.


How exactly are gaps defined in genomics? My understanding is that when sequencing a genome, "gaps" refer to fragments which were not sequencing in the sequencer.

Is this correctly? What are there other meanings to the term "gap"?

You're not wrong but gap can mean more than that. A good recent reference is this paper: Genetic variation and the de novo assembly of human genomes.

Essentially, a gap occurs if something happens in our genome that can't be explained by uniformity. Since our genome is highly complicated, you can expect gap is also more than just mis-sequencing. The gap you mention is the sequence-coverage gaps mentioned below.

This paper has a section about the types of gaps.

1. Sequence-coverage gaps

Sequencing gaps occur, under the simplest condition, where no sequence reads have been sampled for a particular portion of the genome.

2. Segmental duplication-associated gaps

Over one-third (206/540) of the euchromatic gaps in the human reference genome (GRCh38) are flanked by large, highly identical segmental duplications.

3. Satellite-associated gaps

These include short and long runs of tandem repeats designated as short tandem repeats (STRs; also known as microsatellites), variable number of tandem repeats (VNTRs; also known as macrosatellites) and Mb-sized centromeric satellite repeats.

4. Muted gaps

Muted gaps are defined as regions that are inadvertently closed in an assembly but that actually show additional or different sequences in the vast majority of individuals

5. Allelic variation gaps

Some regions of a genome also show extraordinary patterns of allelic variation, often reflecting deep evolutionary coalescence.


At what temporal scales do forest structures change? At which time scales do forest stand characteristics (i.e. stand density, species composition, & diameter distributions) change in a temperate European forest which is not managed?

Ideally, I'd like to conclude if a certain quantitative description (based on the variables I've mentioned above) of a forest stand is valid for e.g. 10 years or even 20 years.

A peer-reviewed reference would be ideal.

This question is too broad. What type of temperate forest?

The European Environment Agency recognized dozens of temperate forest types:
 Acidophilous oak and oak‑birch forest types
 Mesophytic deciduous forest types
 Beech forest types
 Mountainous beech forest types
 Broadleaved evergreen forest types
 Floodplain forest types
 Non‑riverine alder, birch or aspen forest types

Community types will experience different patterns and rates of change based on numerous properties including climate, edaphic conditions, stand density, species pools, specific species characteristics, land use history, etc.

See Wright & Fridley (2010)
-Rate at which woody species colonize and dominate old fields decreases significantly with latitude.

Rates of woody succession were highly correlated with both annual temperature...and measures of soil fertility

See Fridley & Wright (2012)

suggest that climate plays a relatively minor role in community dynamics at the onset of secondary succession, and that site edaphic conditions are a stronger determinant of the rate at which ecosystems develop to a woody-dominated state.

See Peet & Christensen (1980)

Examined thinning rates based on initial stand densities -- found rates to be higher in denser stands and later densities became similar regardless of initial density (after 40 years).

Further compounding all of this are issues such as invasive species, shifts in herbivore pressure, plant pathogens/pests, etc.
Also, it's hard to find European forests w/out some type of historical major human influence.

From Parviainen 2005:

Latest estimates show that there are about 0.3 million ha of virgin forest (0.4 % of the total forest area) left in strict forest reserves and other protection areas in the temperate zone of Europe.

So given all of that, it's hard to definitively nail down specifics to answer your question.

Each of these above characteristics/variables/issues will influence both individual growth rates (i.e., tree diameter and height) as well as population and community dynamics.

To answer your question a little more directly:

As shown in the paper linked above (Peet & Christensen 1980), stand density rates vary dramatically based on initial stand densities and succesional stage; high-density stands can see HUGE loss of stems/ha in < 40 years, while low-density sites might see very little change.

Diameter distributions can change drastically, but will likely take multiple decades to shift to the "late-succesisonal reverse j". However, this is strongly dependent on frequency and magnitude of disturbances -- large canopy-clearing disturbances such as major wind events will accelerate this shift in distribution.

Species composition can certainly shift fairly quickly (1 or 2 decades), but typically only in transitional stages of succession or due to major disturbance. Late-stage successional forests (i.e., "mature forests") will typically see very little change in species composition in this time frame, but again so many facotrs will influence that. Because of changing climates, mass introductions of invasive species (both competitors and pathogens), etc., forests appear to be changing more rapidly. [See Israel (2011)].

Overall, forests change continuously, with most processes occurring on the time-scale of decades. However, this depends on scope b/c understory plants can change from year to year, while canopy trees can live for centuries. Noticeable shifts in community composition and biomass are visible on decadal timescales, but only long-term evaluation will demonstrate the effects of past disturbances. The takeaway, then, is that forests chnage on multiple time scales and as a result of many variables; as a rsult, one can never consider a forest as a static community or as a climax type.

However, we have more long-term data sets available and numerous advances in sampling methods that are aiding our ability to understand forest change across time scales. So we are just now beginning to truly understand some of the phenomena on a deeper level.

I'd recommend you start with an overview of the topic:

van der Maarel & Franklin (2013) should provide a number of citations for you to follow:

covers the composition, structure, ecology, dynamics, diversity, biotic interactions and distribution of plant communities, with an emphasis on functional adaptations;
reviews modern developments in vegetation ecology in a historical perspective;
presents a coherent view on vegetation ecology while integrating population ecology, dispersal biology, soil biology,
ecosystem ecology and global change studies;

Citations
 - Fridley, Jason D., and Justin P. Wright. 2012. “Drivers of Secondary Succession Rates across Temperate Latitudes of the Eastern USA: Climate, Soils, and Species Pools.” Oecologia 168 (4): 1069–77. doi:10.1007/s00442-011-2152-4.
 - Israel, Kimberly A. 2011. Vegetation change in Duke Forest, 1977 – 2010. University of North Carolina at Chapel Hill Masters Thesis. 120 pp.
 - Parviainen, J. (2005). Virgin and natural forests in the temperate zone of Europe. Forest Snow and Landscape Research, 79(1-2), 9-18.
 - Peet, Robert K., and Norman L. Christensen. 1980. “Succession: A Population Process.” Vegetatio 43 (1): 131–40.
 - van der Maarel, E. & J. Franklin. 2013. Vegetation Ecology, 2nd Edition. Oxford University Press, New York, New York. Pages 28-70.
 - Wright, Justin P., and Jason D. Fridley. 2010. “Biogeographic Synthesis of Secondary Succession Rates in Eastern North America.” Journal of Biogeography 37 (8): 1584–96. doi:10.1111/j.1365-2699.2010.02298.x.


Why doesn't the herbicide 2,4-D damage lawn grass? I sometimes use 2,4-Dichlorophenoxyacetic acid to control broadleaved weeds in lawns. It is selective, and quickly kills the dicot weeds, while other plants are unharmed.

2,4-D is a synthetic auxin, a class of plant hormones. It is gets taken in through the stomata on the leaves, and is transported to the meristems of the plant. This causes uncontrolled, unsustainable growth, and the plant wilts, and dies.

Why doesn't this affect most monocotyledons?

According to this link from Purdue, the seed of the answer is this:

  The herbicide is used to kill broadleaf weeds, which are dicots, while monocot grasses, such as sorghum and corn, are more resistant. That's because grasses inactivate 2,4-D inside the plant, while broadleaf dicots do not.

But on the other hand, Song 2014 has this to say about 2,4-D:

  However, the underlying molecular mechanism of how auxinic herbicides selectively kill
  dicots and spare monocots is not
  understood yet (Grossmann 2000; Kelley
  and Riechers 2007; McSteen 2010). The mechanisms of auxin biosynthesis, transport,
  and signal transduction
  are conserved in monocots and dicots make this question more complex (McSteen 2010). Early research has
  proposed that the selectivity of auxinic herbicide is because of
  either limited translocation or rapid degradation
  of exogenous auxin, altered vascular anatomy, or altered perception of auxin in monocots (Monaco et al. 2002;
  Kelley and Riechers 2007). Auxin transport is influenced by plant vascular
  systems (Mattsson et al. 1999;
  Scarpella et al. 2006). The difference in vascular tissue structure between dicots
  and monocots may contribute
  to the selectivity of auxinic herbicides. In monocot
  stems, the vascular tissues (the phloem and xylem) are
  scattered in bundles, and lack a vascular
  cambium; in dicot stems, the vascular tissues are form
  ed in rings and
  possess a cambium.

So in other words, we don't know yet. It seems to be very strongly tied to auxin transport, but we do not have the full mechanism of action; since auxin is such an important plant hormone, and the pathway is therefore highly conserved (that is, the genes tend to be nearly identical on the parts of the sequence that affect the phenotype), the general conclusion is that the pathway itself is not affected, but an accessory pathway clears up auxin in levels excess of any normal amount in monocots.

Edit: Whoops, got the author's first/last names mixed up.


An experiment to test if a bacterial resistance gene is on the plasmid or chromosome? So I have an E.coli strain phenotypicall resistant to the antibiotics ampicillin and rifampicin. How do I test if the AmpR gene is carried on a plasmid and not on the chromosome?

In summary, I thought perhaps you could isolate the plasmid, put it in an ampicillin sensitive bacteria, then see whether or not the bacteria die.

I also thought you could use PCR on the plasmid with primers complementary to sequences adjacent to the AmpR gene. I'd use a positive control with the gene of interest and a negative no template control.

Do these sound about right & are there any other methods or controls I should consider?

Based on the situation you have described, isolating the plasmid from the ampicilin-resistant strain of E. coli and allowing it to be taken up by a separate, non-resistance strain of E. coli would be the most efficient, and cost effective method of determining whether or not the AmpR gene is located on the plasmid or the bacterial chromosome itself.

In order to do this, you would need to first grow a culture of the ampicilin resistant strain, from which you could induce lysis of cells in order to obtain a solution containing free plasmids.

Several different plasmid isolation or mini-prep procedures exist that are typically quite effective, if done correctly.

Additionally, many specific "plasmid-isolation" and "plasmid-purification" kits exist that would offer the materials and instructions needed to undergo this process: Isolating your Addgene Plasmid DNA from Bacteria

After properly isolating the plasmid from your ampicilin-resistant strain, you would then need to insert that plasmid into a non-resistant E. coli strain. Bacterial transformation via electroporation is a commonly used technique that causes increased permeability of bacterial cell membranes, enabling the plasmid to enter or be taken up by the cells.

Once these cells have been allowed to "recover" they can then be grown in liquid or solid culture containing ampicilin. Growth would indicate the AmpR gene is present in the bacterial strain, and that the plasmid is responsible for carrying this resistance. Likewise, no growth would suggest that the gene must have be present on the bacterial chromosome instead.


Is it possible to create DNA of a species that could be any animal I was thinking about a fiction world in which all animal (at least vertebrate) could crossbred because they share same number and layout of chromosome but differ in hereditary detail (like human skin color) and/or using epigenetic modifications.

Is it actually possible? And how large of DNA it could be to code all vertebrate form and function?

I'm programmer so I just think DNA as a code. And it seem we could refactor and reuse most of DNA code between tetrapod species (also between arthropod-arthropod species)

Suppose genome A generates organism oA and genome B generates organism oB. Their phenotypes pA and pB are quite different from each other.

Because genome A and B are not similar enough, organism oA and oB cannot sexually produce viable offspring.

Your question seems to boil down to: "Would it be possible to generate oA/pA and oB/pB from genome A, or a genome similar enough to genome A such that it can still sexually reproduce with genome A?"

So you basically ask whether any genome A could simultaneously produce pA and pB under different external conditions.

Answer: Possibly? The genes involved in the development of organisms typically don't respond to external stimuli but to genes which were active before them (in time). Various genes produce proteins which sense temperature, osmotic pressure or particular chemical species or ions. If those were factored into very early developmental programs, feeding into transcription factors to modify gene expression according to external factors, the same genome could produce drastically different organisms.

To speculate more about this yourself, it would probably help to go away from a code-based understanding of DNA and think more about what it is physically and biologically. Unlike computer programs, DNA "programs" can modify themselves and other programs or the functions they execute.

Biologically, DNA is an information carrier that is transcribed into RNA, which can have functions of its own and/or be translated into proteins. DNA interacts very tightly (physically) with a lot of RNA and protein components, and most things that happen in cells and tissues around them end up modifying the way DNA is handled in some way. Keywords that you could look up are "gene expression", "gene regulation" and "developmental biology".


Why have plants evolved to photosynthesize glucose instead of another molecular compound? I think this question can be broken down into two sub-questions:

Why do plants produce $C_6H_{12}O_6$ as opposed to another molecule following the formula of $C_nH_{2n}O_n$? Why not $C_8H_{16}O_8$, $C_4H_{8}O_4$, or any other of the many possible variations? Does it likely have something to do with stability or some other property that glucose has that many other variations on the formula do not?
Why have they evolved to produce a molecule following the formula $C_nH_{2n}O_n$ at all? In short...why carbohydrates as opposed to another family of compounds?

My assumption is these are questions that have been researched extensively in biology and evolutionary biology and have at least tentative answers.

I'm looking for either your best hypothesis or a currently popular hypothesis within the relevant scientific disciplines. I understand there is likely no "definitive" answer, but probably at best pretty good hypotheses.

This is a brief answer (for me) to point out that:

Your question is not really concerned with photosynthesis but is actually about the choice of the carbon constituents of living cells.

First you talk about photosynthesis as if it is a single process, however it is two separable processes:

The Light Reactions convert solar energy into chemical energy (in the form of ATP and NAD(P)H).
The Dark Reactions use the chemical energy to reduce carbon dioxide and elaborate it to more complex molecules.

Photosynthesis is so elaborate chemically that it clearly was not the first process by which living organisms managed to convert environmental energy into a usable form. So the question becomes:

  Q. Why is chemical energy trapped by living organisms used to make
  compounds such as glucose 6-P?

and giving what may at first sight seem to be a frivolous answer

  A. Because glucose 6-P and its precursors and metabolites were suitable molecules for building the structural components of cells, that had arisen early in evolution.

So the question becomes:

  Q. Why did the structural components, energy storage, genetic information
  etc. of cells evolve to employ the particular molecules that we find
  today, most of which can be formed from glucose metabolites?

And that is a very broad question about a very speculative area of chemical evolution, which cannot be summarized here.

In general one would imagine that the answer is related to the carbon components available in the environment and the possibilities of chemical transformations. However the trap is that one ends up arguing that things are the way they are because that was best. Which is all very well until one discovers dirty little secrets such as the fact that archaea evolved different chemical constituents for their cell membranes.

Footnote

My first degree was in chemistry. Since becoming a biochemist/molecular biologist I have almost never talked in terms of overall chemical formulae of molecules in the manner of the question. It has seldom been a useful way to approach biochemical reactions or intermediates. What has been more important is to look at their structures and ask how they lend themselves to their functions or interconversions.


Is greed an evolved trait? I am not a biologist, but I am fascinated by evolution.

I was watching the news this morning and, as so often is the case, there was a news story about a corrupt politician who was accepting bribes.

This started me thinking about how greed can become such a strong factor in one's life that it cancels out empathy for your fellow human beings.

So I was wondering--is greed an evolved trait?  Maybe some result of an evolutionary pressure to hoard food for example?

The whole point about your question is to define what is an "evolved trait"? The concept of "evolved trait" does not exist in evolutionary biology. Here are various definitions I can think of that could apply to the expression "evolved traits".

Heritable Traits

Does evolved traits mean heritable traits?

A trait may be heritable or not. See for example my answer to this post to understand what heritable mean. You may want to understand the difference between the narrow and broad sense of heritability. Greed is probably heritable as several studies showed that many personality traits are heritable. This post will maybe give you more info.

--> Greed is probably a heritable trait

Traits that evolve

Does evolved traits mean traits that can evolve?

Any (existing) biological trait evolves. Not necessarily because they are selected for or against, neither even for genetic reasons, but traits change through times. Culture changes.

--> Yes, greediness can evolve

Traits that are adaptations

Does evolved traits mean traits that are adaptations?

The concept of adaptation is not always easy to define and its definition may vary from authors to authors. Simply speaking, an adaptation might be defined as a trait that is now fixed in the population (meaning that all individuals in the population carry this trait) but when it was not fixed yet it was beneficial. Such definitions would not fit the concept of greediness if we assume there is some genetic variance for greediness. But while I am not aware of any study on the subject, a level of greediness very probably influence the fitness  (=~ reproductive success) of its carrier. If someone is extremely greedy, he might not find a mate and may fail to reproduce. On the other side, someone that is extremely generous may give everything it has up to its life and would definitely fail to reproduce. Therefore, it seems at first though that there is what we call stabilizing selection on the level of greediness.

--> It depends on the meaning of adaptation. But yes, it seems intuitive that greediness is a trait that undergoes (stabilizing) selection.

Social traits

Greediness is the kind of trait that are particularly interesting because it influences not only the fitness of its carrier but also the fitness of other individuals in the population. We say that it is a social trait and the field that study such traits is called social evolution. You'll need to get in touch with Hamilton's rule (Kin selection) and evolutionary game theory to understand more about the evolution of social traits. This post may eventually help you.


What is the function of dendritic cell in immunity? I'm interested in how dendritic cells present antigens to  helper T-cells? I'm also interested in the molecular actions between a dendritic cell and a helper T-cell during the activation of the helper T-cell?  What function does the homing receptor on a T-cell have?

Dendritic cells are so called professional antigen-presenting cells (APCs) as pointed out by Sleepes in comment section. They express both MHC-I and MHC-II receptors on their cell surface on which they present small peptides. These small peptides come from digested proteins of their own (MHC-I) or antigens that were phagocited or taken up by receptor mediated endocytosis (MHC-II). They also express costimulatory molecules necessary for the activation of T-cells (eg. CD80/CD86).

source: http://journals.cambridge.org/fulltext_content/ERM/ERM2_09/S1462399400002143sup004.htm

As you can see in image above, activation of a T-cell requires two distinct signals: the recognition of an antigen and a co-stimulatory signal.

source: http://www.mhhe.com/biosci/ap/dynamichuman2/content/gifs/0158.gif

After activation T-cells undergo rapid division and diversification.

Details of T-cell activation by dendritic cells can be found in this article for example:
Immunol Cell Biol. 1997 Jun;75(3):223-30.
The role of dendritic cells in T cell activation.
Ni K1, O'Neill HC.


2 types of telomerases? As telomerase works by adding new nucleotides complementary to the RNA it contains, it cannot work for the complementary strand.

Say telomerase X has RNA complementary to the 5' to 3' strand it cannot elongate he telomere for the 3'to 5' strand.

So does a cell have 2 types of telomerases ? One for 5' to 3' and another for 3' to 5' ?

A second telomerase is not necessary, as the lagging strand is filled in by the DNA-Polymerase, see this figure:


Growing Penicillium Digitatum Mold I left a cup of tea with Lemmon on my desk and after a while green mold start growing on the water. From my understating this is Penicillium digitatum. I gave it some sugar and after one day black spots appeared. I read that it can be little bit dangerous to inhale mold so I wrapped the cup with saran wrap and make some holes in it in order to give the mold oxygen.

What do I need to do in order to give the mold better condition to grow?
Can it be dangerous growing it?

You could place part of the mould into a cut in a piece of citrus fruit to continue its growth. Citrus can also host P. italicum, the below website is one mentioning how to differentiate between them.
http://www.pestnet.org/fact_sheets/citrus_storage_moulds_197.html
Hazards.
Aspergillosis: (fungal spores growing in the lungs) which is uncommon.
Asthma: penicillium spores have been associated with increased chance of onset of asthma, and problems with breathing in people with asthma.
There may be other hazards.
I just cite one paper below, but a search using terms of penicillium and asthma shows lots more.
"Household airborne Penicillium associated with peak expiratory flow variability in asthmatic children"
published in :
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
by:
Kemp W. Bundy, MD, MBA, Janneane F. Gent, PhD, [...], and Brian P. Leaderer, PhD
doi: 10.1016/S1081-1206(10)60139-1


Why are prions in animal diets not destroyed by the digestive system? According to CBC:

  Mad cow disease is the common name for a condition known technically as bovine spongiform encephalopathy, or BSE. [...] The only known source of mad cow disease is from animal-based feed contaminated with tissue from a diseased animal. The original source of BSE is believed to have been feed containing tainted meat from sheep with a related disease called scrapie.

As prions are proteins, I would expect any that were contaminating food to be broken down to amino acids by the proteases in the digestive system. Why does this not occur?

Proteases are enzymes in your digestive system that help break down food, acting like molecular-sized scissors that cut up proteins.
Proteases have clefts, or subpockets, into which proteins fit, where the substrate (protein) gets cut.
Infectious or pathogenic prions are resistant to proteases, because of their three-dimensional shape, which hides away parts of the prion that would normally fit in proteases and which would cause the prion to be digested.
Prions that do not cause disease — normal prions — have a different three-dimensional shape that allow them to fit into proteases, and so they are not resistant to digestion:

A wealth of evidence contends that the infectious pathogen causing the prion diseases, also referred to as spongiform encephalopathies, is solely comprised of PrPSc, the pathogenic isoform of the prion protein (21-23). Both PrPSc and its normal cellular counterpart, PrPC, are encoded by a cellular gene (2, 19). Physical and molecular characterization of PrPSc and PrPC has failed to reveal any chemical differences between the two isoforms (32). However, PrPSc acquires distinctive conformational characteristics upon its conversion from PrPC. Whereas PrPC is soluble in most detergents and can be easily digested by proteases, PrPScis insoluble in detergents and maintains a protease-resistant core, designated PrP27-30, which polymerizes into amyloid (25).

Dr. Neena Singh also discovered that prions "piggyback" or attach to another protein called ferritin, as they make their way through the digestive system:

Disease-causing prions are thought to have passed into people when they ate beef from infected cattle, triggering the brain wasting condition called new-variant Creutzfeldt-Jakob disease, or vCJD. But researchers have not been sure exactly how prions enter the body.
To find out, Neena Singh and her team at Case Western Reserve University in Cleveland, Ohio, mimicked the process of eating and digesting infected meat.
They mashed up brain tissue that contained prions from patients who had a form of Creutzfeldt-Jakob disease. They then exposed it to a range of harsh digestive enzymes from the mouth, stomach and intestine, which normally break proteins into pieces.
Prions, which are known to be enormously tough, escape this attack almost unscathed, they showed, as does a second type of protein called ferritin, which stores iron and is abundant in meat. The two proteins seem to stick together, they report in the Journal of Neuroscience.
The researchers next added the digested slurry to a lab model of the human gut: a growing sheet of cells from the intestinal lining. By attaching fluorescent tags to the two proteins, they showed that they are transported through the cells hand-in-hand. "Prions probably ride piggyback" through the gut wall into the body, Singh says.

Attaching to ferritin may provide additional protection from digestion, insofar as this removes prions from the digestive system, where proteases are concentrated.