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How to find miRNA binding sites on a specific gene?
I am trying to find miRNAs that bind to the 3'UTR of a specific gene. What is the best way of doing that (that is, with a good scoring analysis that is most commonly used by researchers in this area)? I would also like to know the other possible methods if there are multiple ways of doing this.

Good question here

Did you get the answer that you wanted ?

Bioinformatic part of your answer may be better that is why i did not give full credit. For those who also would like to know more about tools for finding miRNA target site they could check this article. It is really good: http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00023/full
Thanks for reminding me of the question by the way.

@user1445 I don't understand what you mean? Do you want to have details of these bioinformatics tools? If you are asking that then I would consider the question as broad. As you can see that it takes an entire article to explain these things.

There are some tools for predicting the binding:

TargetScan (based on seed match [primary], extra pairing, sequence context 1 — nucleotide composition around the site etc [secondary])
miRanda (based on hybridization stability and seed match[primary] and sequence context [secondary])
PicTar (adds a layer of evolutionary conservation criteria)

1 Context means the position of the target site in the 3'UTR and the surrounding nucleotide composition (which is also considered an indirect metric of secondary structure)
miRanda and TargetScan also have classes called conserved and non-conserved targets. miRanda reports miRSVR scores and TargetScan reports context scores but these measures are based on few experimental results and may not always be meaningful. miRSVR is based on change in target expression upon miRNA overexpression/knockdown. It also uses metrics for target site context. Context+ score of TargetScan includes many metrics which include target abundance and conservation along with the regular context scoring. Some of these metrics may be more useful than the others. But scores based just on miRNA OE/KD experiments can be misleading- especially if target expression is quantified just at the RNA level. Target abundance also varies between different cell types. For more details on these metrics refer to the papers corresponding to these tools.
There are some experimental procedures for target determination which mainly involve Protein-RNA crosslinking followed by immunoprecipitation of Ago and subsequent quantification by RNA sequencing. See HITS-CLIP and PAR-CLIP. These techniques do not really find the targets. All they do is to correlate the levels of miRNA and their predicted targets attached to Ago (you won't exactly know if the ternary mRNA-miRNA-Ago complex really formed or not).
CLASH is a more recent technique which tries to address this issue by ligating mRNA with miRNA. This way you can capture the miRNA-mRNA interaction. However, I am a little skeptical of CLASH; I myself was working on this principle some time back and faced this one challenge. CLASH roughly involves the following steps:

Crosslink protein-RNA
Immunoprecipitate Ago
Use RNAse to digest unbound regions of mRNA (and make it small enough for a short read sequencing experiment)
Ligate miRNA and mRNA bound to Ago using RNA ligase
Degrade Ago using protease
Sequence the miRNA-mRNA ligated pair

My doubt was how would miRNA and mRNA be ligated when the footprint of Ago is bigger than an miRNA (reported ~50-60 nt in HITS-CLIP and PAR-CLIP). When the RNA is nuclease protected then how can it be accessible to ligase. When I was thinking about it then I thought that a partial protein degradation was necessary (after RNAse step and before ligase step) to give some space for ligase to act. Eventually I did not work on it further. Three years later CLASH paper was published and I was happy that someone made it work. But the ligase issue was not addressed (It seems to have worked but I don't know how!!).
To test the predictions you can use a reporter assay (such as GFP or Luciferase) with the 3'UTR cloned downstream of the reporter. These can have artifacts too. Overexpressing the miRNA should be avoided and seed mutations should be done to ascertain the targetability.
Another technique to determine a target mRNA is to mask its predicted miRNA binding site and see the effect on the expression. This has been done in zebrafish using morpholinos complementary to target sites but not on other models AFAIK. This seems to me as an elegant assay- no overexpression and you can precisely determine the target site.

I would thoroughly check the literature on the UTR you are interested in, a lot of this has already been done for many  genomic regions since nextgen seq began.
You will want to first off use computational prediction algorithms to help guide you in getting a good Candidate list of miRNAs
The interaction between a miRNA and its target mRNAs is usually studied by co-transfection of a reporter expression vector containing the 3'-UTR region of the mRNA and an inhibitory or precursor molecule for the miRNA.
But, this does not measure the direct and physical interaction between a miRNA and a specific mRNA. To more specifically measure binding you will need to do a ElectroMobility Shift Assay.
Here's a commercial tool which will work well if your just trying to identify it.
http://www.activemotif.com/catalog/905/lightswitch-synthetic-mirna-target-reporter-collection
I don't think there are any other very effective/easy methods.
I guess you could do something like hybridize it, run the hyb on a gel, pop out the band and seq it

Thank you for the answer but my question was actually a lot more simpler. For the time being i am just looking for a good candidate list of miRNAs. I have found a website (http://www.microrna.org/microrna/home.do) for this and it is based on mirSVR score. Is this a good way of picking candidate miRNA's? Are there other ways of finding candidate miRNA's that are based on different scoring algorithm?

I thought you wrote specific gene?

yes "For the time being i am just looking for a good candidate list of miRNAs for a specific gene (the gene of my choice)". So, i want to choose a specific gene in the database and i want that database to show me a list of mirna's that can bind to that gene's 3'UTR . Also, I want to see the accountability of mirna binding via a scoring method such as mirSVR. I have so far found only mirSVR and the mentioned website but are there other ways and what is the best way to search for that in the literature? sorry if i am not maintaining correct terminology, i am relatively new in this.


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What is the name of the condition where no pacemaker cells are active in the heart for a short-time?
Assume that the heart is beating, but no pacemaker cells are working for at least 15 seconds.
This would be a very long compensatory pause if extrasystole started it.
There may be some low frequent cells working at lower frequency (less than 10 Hz) but I do not understand what.
What is the name of condition where main pacemaker cells are not beating?
Main pacemakers are SA-node, AV-node and Purkinje-fibers/His-bundle.
Raoul is correct.
This is called asystole.
It is temporal in the above case.
My definition in research but note the difference to current Clinics so you do not get confused: Asystole is a state of no cardiac electrical activity from pacemaker cells when the conduction system and cardiomyocytes can be still functioning (so the case in my thread). The conduction system and cardiomyocytes of the ventricles are responsible for the bradycardia in my case for short-term.
What do you think about this case?
Some bradycardia?
Can you suspect asystole there between?

Please, do not make diagnoses based on just this picture (which is often the current standard).
Assume case where you see Time-Frequency of the heart perfectly and where you can see exactly the functioning of pacemaker cells at different frequency levels.

Masi I have edited the question title which was confusing, please feel free to roll back

If there are no pacemaker cells active, no muscle contraction will occur. This condition is named asystole. It can be a temporary or definitive condition. Some would call it "extreme bradycardia" in temporary cases, but this is just an euphemism.
Edit:
Ok, so let's try to clear up the confusion a bit. Technically, there is no asystole involved here (not even temporary). This rhythm is regularly irregular (irregular, but has a pattern), while asystole has no pattern by its very nature.
What you are seeing here is not the consequence of low frequency firing from pacemaker cells. The supraventricular extrasystoles (every 3rd QRS complex) are a consequence of early ventricular depolarization not triggered by SA node activity. The P wave that would normally trigger the 3rd complex does in fact occur, but it is synchronous with the abnormal QRS complex, which is why you cannot see it. The compensatory pause is due to lengthening of the hyperpolarized state in pacemaker cells, and is a consequence of the addition of the hidden P wave and the extrasystole in a short time.
In conclusion, this pattern is not the result of delayed pacemaker firing, but of early depolarization of cardiomyocytes by an accessory pacemaker.

I have marked on this strip the maximal time interval of SA node hyperpolarization. Depending on when the P wave hidden in the extrasystole occurs, the real time may be shorter than the above interval.

Thank you for your fast answer! You are right. It is temporal asystole. I added a case picture which I think is little bradycardia and suspect asystole. What do you think?

As you can see, there are 12 QRS complexes on this 14 sec. time interval, which yields a ventricular frequency of 51/min. This is termed bradycardia. Furthermore, every third complex has an altered signal, is not preceded by a P wave, and is followed by a compensatory pause. Those complexes are supraventricular extrasystoles, and the rhythm on this strip is termed "trigeminism".

I think the case is extreme bradycardia and asystole. What can give frequencies of 5 Hz for 10 seconds? Probably something starts to excite when bradycardia reaches its maximum at 3s (first missing P wave).

I suggest that you read a bit on supraventricular arrhythmias, and especially trigeminism.

Let's define extreme bradycardia as the condition which starts asystole for some period of time. I think it is not now blunt.

Thank for the edit! Please, see my updated definition of the asystole. What do you think? I defined it as no cardiac electrical activity from Pacemaker cells.

You are right. There is extrasystole just about at 3 second (early depolarisation), after which no action potential is done from main pacemakers for the rest of the time and bradycardia. So the condition when main pacemakers do not work (like for 10 seconds) is called temporary asystole, right? During this time, I agree with you what you describe, but I am just interested on the condition when main pacemakers do not work for 10 seconds although QRS complexes can be seen but with those conditions you describe.

On the above strip, the inactivation (hyperpolarization) of the main pacemaker (the SA node) starts on the 3rd P wave (hidden in the abnormal QRS complex) and ends on the subsequent P wave, triggering a new (normal) QRS complex. If the pacemaker did not work for 10 seconds, you would have either an escape rhythm than can be junctional (SA node inactivation only), ventricular (SA & AV node inactivation), or a 10 second asystole. This is not apparent on this strip. Here, the inactivation can be estimated to be 1.4 sec. at most.

Yes, I think this is a escape rhythm where a 10 second asystole. You should visit me in some conference such that you could see my research. I know that the temporary asystole is not apparent in the strip. By current guideline, you estimate the inactivation to be 1.4 seconds if you take risks - this is a boundary case!

I accepted this answer because of the phrase Escape rhythm with a 10-second asystole where the last choice of the type is backed by my research.

Bradycardia is a heart rate under 60 beats per minute. Your strip shows a heart rate of ~54 BPM (so, yes, it's bradycardia), and the rhythm is trigeminy. There is no asystole involved.
In the following rhythm strip, initially it shows supraventricular tachycardia (of >150 BPM). After adenosine administration, a short period of asystole occurs, allowing the SA node to resume it's normal pacemaker rhythm., then resumption of sinus rhythm (at just under 100 BPM). Notice there are **no electrical complexes) during the asystole. It's not a matter different guidelines. There is no asystole in your rhythm strip.

How can you say that there is no asystole involved? Do you have evidence?

Ok, I am doing research here. In clinics,only clear asystole  can be detected. I am trying to detect asymptomatic asystoles which occur only short time.

Please read about event-triggered cardiac monitoring.

I know Holter but it is very cumbersome and errorprone, even single important beat can be missed. Current approach in clinics tries to take bigger sample of data - this is ok with current imaging technology, but requires much resources. 48h Holter is now standard. I am researching cardiograms and developing their imaging technologies. I can propose that the case has partial asystole with pacemakers of extremely low frequency active (not even Purkinje/His fibers). And this is confusing me, since I do not understand what can cause so low frequency.

This is what electrophysiology is all about. Event triggered monitoring can be for 30 days, is different from Holter.

Yes, you are right. We are actually doing the same things, just different point of views how to approach these challenges. I am doing algorithms for these devices and trying to use significantly less data to the analysis. It would be nice to have some good Review article about Electrophysiology with right sources. I have an intuition that the problems of missing significant peaks in Holter cannot by completely bypassed by these Event triggered monitoring (just taken longer data - you must have much simpler algorithms). It is probably about particle-swarm-optimization with simpler application.

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Gastroenteritis virus causing mutation of the Enterochromaffin cells
I am working on the solution to a worldwide problem: IBS or chronic diarrhea following a viral gastroenteritis infection. I think I have an answer. The only missing piece to the puzzle I found in a research paper discussing the genetic mutation of the Enterochromaffin cells by a gastroenteritis virus. I believe the paper was from Japan.  I had it, but I lost it.  Any help in finding this paper again would be greatly appreciated.

Maybe this can be a jumping-off point?

Gastroenteritis virus + chromaffin + mutation gives no result on pubmed. I tried all combinations and variations. The closest is this article.

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What controls gut motility?
I have two different papers. One claims that gut motility is reduced by stimulation of the Opioid κ and δ receptors. The receptors are activated by Morphine and certain derivatives, specifically Codeine, Fentanyl, Hydromophone, Methadone, and Oxycodone.
The second paper claims that gut motility is reduced by blocking the 5-HTb3 receptors.  Antagonists or competitors to the 5-HTb3 receptors being Morphine and certain derivatives.
Are these two different theories, two different action mechanisms, or am I missing something?

They are two different mechanisms.

Opium is arguably one of the oldest herbal medicines, being used as analgesic, sedative and antidiarrheal drug for thousands of years. These effects mirror the actions of the endogenous opioid system and are mediated by the principal μ-, κ- and δ-opioid receptors. In the gut, met-enkephalin, leu-enkephalin, β-endorphin and dynorphin occur in both neurons and endocrine cells. When released, opioid peptides activate opioid receptors on the enteric circuitry controlling motility and secretion. As a result, inhibition of gastric emptying, increase in sphincter tone, induction of stationary motor patterns and blockade of peristalsis ensue. Opioid receptors in the gastrointestinal tract

Roles of 5-HT in health include control of normal gut motor activity, secretion, and sensation, and regulation of food intake and cell growth. Abnormalities of serotonergic function contribute to symptom genesis in functional bowel disorders, inflammatory and infectious diseases of the gut, emetic responses to varied stimuli, obesity, and dysregulation of cell growth. Therapies acting as agonists or antagonists of 5-HT receptors or that modulate 5-HT reuptake play prominent roles in managing these conditions... Serotonin and the GI tract.

Interesting. Gives me some more reading to do.  I assume at this time, the opioid receptors only work in one direction, to slow the gut.  Because not taking morphine does not cause diarrhea, but too much serotonin such as in carcinoid syndrome does cause diarrhea.

Don't rule out endorphins and their receptors in the GI tract.

What really burns me is that a treatment exists for IBS and depression that really works, Tianeptine (a serotonin re-uptake enhancer).  But is not legal in the US.  I have a trip planned next week to Nogales, Mexico.

When discussing the control of gut motility there is more to mention than the use of serotonergics and opioids - a number of peptide and nonpeptide neurotransmitters are important. Somatostatin and nitric oxide are two examples which each happen be inhibitory of intestinal motor function, but by two completely different mechanisms. A bit of understanding in cell biology, specifically cell signalling would be helpful to fully grasp this, but the former acts by inhibiting the release of Acetylcholine and Substance P while the latter increases levels of cAMP/cGMP. And don't forget about the basics when it comes to motor control - the cholinergics and adrenergics (including dopamine) are logical opposites.

References
Leung, P.S. 2014, The Gastrointestinal System: Gastrointestinal, Nutritional and Hepatobiliary Physiology, Springer, 19/03/2018, http://www.springer.com/cda/content/document/cda_downloaddocument/9789401787703-c2.pdf?SGWID=0-0-45-1491980-p176563984

This is a nice answer about gut motility, but the body of the question specifically asks about opioids and opiates, which you don't address at all. I don't mean to be condescending, but there's more to a question than just the title. I see you're new (Welcome!) Maybe you're not too familiar with the SE model? In any case, nice to have you here.

Hi, looking back at my answer I didn't really address serotonin either, thanks for the feedback. Can you tell me more about the SE model?


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How fast can a human run?
I'm a runner (cross country) and I'm always amazed at how fast Olympic sprinters are. There's a lot of hype about those in the 100-meter dash being the fastest in the world, and we're constantly seeing the 100-meter time dropping. But is there a limit? How fast can human being, propelled only by its own energy (i.e. without any external assistance) run?

Me about 13km/h average, or by sprint about 18km/h :D I guess far from olympic ranges...

An older answer that referred to the physiological feats of ancient humans, and why modern humans are wimps made me look up a couple of papers on running speeds a while ago. One of the examples used to support the statement that modern humans are "wimps" is a study of ancient fossilized footprints from Australia, which claim that the individuals making the footprints were running close to Olympic record times. The footprint studies (Webb, 2007) basically attempts to describe the humans that have created the footprint paths, and also tries to calculate the speeds they were running at. For one of the individuals (T8), the estimated running speed is 37 km/h (i.e. 10.3 m/s). The interpretation by Peter McAllister in his book Manthropology seems to be (I haven't read the book) that these barefoot individuals running on mud could easily have outrun current day sprinters, especially with training and on a rubber track (also see this huffintonpost article on the book). If the estimates in Webb (2007) are close to accurate, it would seem that modern top-trained athletes might not have reached the edge of what is humanly possible when it comes to top speeds.
There is also a biomechanical study on potential human running speeds (Weyand et al., 2010) that you will probably find interesting. This paper looks at factors such as gait, stance, force application etc, and includes empirically estimated values from 10 subjects to discuss the limits to human speed. They conclude that (natural) human speeds are likely to be limited to ~50 km/h (as reference: Bolt's top speed during his 9.58 WR was ~44 km/h).

Consequently, human running speeds in excess of 50 km/h are likely to be limited to the
  realms of science fiction and, not inconceivably, gene doping.

They also look at different scenarios and e.g. point out how important limb length is for top speed:

Second, limbs lengthened through evolution or perhaps prosthetically could
  substantially increase the top running speed attained at the minimum period of foot-ground force application. For example, a relatively small increase in leg length of 10 cm would
  increase contact lengths by 9 cm and the top speeds of the subjects tested here from 9.1 to 9.8 m/s.

In general, important factors for maximum speed in animals are ground  reaction force and ground contact time. An earlier study by Weyand et al. (2002) also show how faster human runners in general have shorter ground contact times compared to slower runners. As a sidenote, this seems to be in contrast to cheetahs, which have longer ground contact times than greyhounds, while still being much faster (Hudson et al. 2012 and popular summary).
View these as a couple of interesting examples and a starting point. This is not my area, and I do not know the literature well.

This is a superb answer! On reading the question, I actually felt that it was hard/impossible to answer.

Fantastic answer. Very comprehensive.

Recent article from New york times, on the same subject: https://www.nytimes.com/2020/01/21/science/human-running-speed-quadruped.html

Also Kinugasa & Usami. 2016. How Fast Can a Human Run? − Bipedal vs. Quadrupedal Running. Front. Bioeng. Biotechnol.

It is interesting to look at the pre-motorized past when it was very common for people to travel on foot great distances since horses were expensive. I have read that some suspect mile records may have been beaten much earlier in history. On the other hand, older olympic marathon times are significantly worse than modern which may imply better training, nutrition and technique play a big role.


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What are the reactions in the body that triggers dizziness after cigar(nicotine) smoking in non-smokers?
Suppose there is a person that has never used nicotine in any form in his/her life. Why does the person get dizzy after a few "shots" from a cigar(nicotine)? What's the difference between using other plants(e.g. marijuana)?

It's all about the synapses, the places where separate neurons connect to one another. All psychoactive drugs act in some way so as to modulate the signals that are passed from one neuron to another. Nicotine acts by increasing the effect of signals that pass through a particular type of synaptic receptor called nicotinic acetylcholine receptors (they're named after the fact that they're affected by nicotine). The dizziness and other effects of nicotine are caused by this interference with normal neuronal communications.
The reason why regular users of nicotine don't get dizzy is because they've gained a tolerance to the drug. Tolerance isn't super well understood at the molecular level, but it has been associated with long term changes in the quantities and types of receptors that are present at synapses in certain regions of the brain, it particular the nucleus accumbens.
Marijuana is similar to tobacco, only its main psychoactive component, THC, acts on the cannabinoid receptors.


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Sequencing a specific region of a genome
First off, I'm new to bioinformatics and I am learning about DNA sequencing.
Let's say that I knew that a specific region of a genome which contained information about a disease (whether it a person had the disease or not).
It would make sense that we would only want to sequence that part of the genome in order to make a detector for this disease.
Would it be possible to 'cut-out' this region of the genome and only sequence that part (so we don't have to sequence the entire thing)? If not, how would we sequence only this part of the genome (it doesn't make sense to sequence the other parts as they don't give us information).
Thanks in advance.

Yes, it's possible to sequence a certain region. Probably the most straightforward method would be PCR amplification.

I have been doing a little researching, and I also found something called 'Targeted Resequencing', do you know whether this has anything to do with PCR amplification?

Resequencing is basically sequencing something that has already been sequenced. This means that instead of assembling all of your sequence reads from scratch, you can just align them to the reference sequence (the entire human genome has been sequenced). Targeted resequencing means your sequencing a specific region, such as a gene. The targeting can be done by PCR or by other methods.

Yes, it is possible to sequence a specific region of the genome. The method, as you mentioned, is called targeted sequencing. Resequencing is basically sequencing something that has already been sequenced. This means that instead of assembling all of your sequence reads from scratch, you can just align them to the reference sequence (in your case, the entire human genome has been sequenced). Targeted resequencing means you're sequencing a specific region, such as a gene. This requires concentration of the specific DNA you wish to sequence and can be done by PCR amplification (using primers that flank your desired sequence) or hybridisation (using probes complementary to your desired sequence that are fixed to a surface), among other methods.
For information on methods for enriching a DNA sequence, give this a read:
Mamanova, L. et al. Target-enrichment strategies for next-generation sequencing. Nat. Methods. 7, 111-118 (2010).

So, let me get this straight: we PCR amplify the region of interest. Then use straight forward DNA sequencing on the PCR'd region?

Yes, basically.


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Why do physicians try to match HLA complexes for organ transplant?
My understanding of acute transplant rejection is that donor dendritic cells present donor antigens on MHC1 to host naive CD8+ T-cells resulting in an immune response against the graft. If you match MHC1 complexes between donor and host, wouldn't t-cell activation actually be more likely than the case where MHC1 complexes between donor and host are different?
Reasoning: I imagine in the case where MHC1 complexes between donor and host are different that the  t-cell receptor is unable to bind the MHC1 complex in the first place..making the transplant essentially invisible. In the case where MHC1 complex between donor and host are the same, the t-cell receptor would bind the MHC1 complex, and increase the likelihood of an immune response. Given that HLA mismatch is a major cause of transplant rejection, something is wrong with my reasoning. Thoughts?

There are no T cells in a host that attack foreign MHC1?

Cells with low MHC1 or non-recognizable MHC1 are destroyed by NK cells, so e.g. viral infections, intracellular bacterial infections and cancer cells cannot hide with their "abnormal" proteins...

I seem to remember from my (far behind) immunology that such is also the case with T CD8+ cells. Is that not the case?

@Raoul I don't think so, but I am not sure. Afaik TCR-MHC1 connection is required to activate CD8+ T-cells, and TCR does not necessary connect to non matching MHC1. Afaik anergy happens when it is connected to the MHC1, it recognizes the oligopeptide pattern with the TCR, but it does not have enough stimulus for activation. It needs costimulation e.g. B7 protein from an APC or cytokin from a CD4+ T-cell to lower the activation threshold. If it does not get it, it will die after a while. I'll check what happens when a CD8+ T-cell meets with a non MHC1 cell.

@Raoul It seems like much more complicated than we both thought. I'll edit my answer later.

@Raoul Still reading articles in the topic. ;-) Just a short report: it seems like there are multiple cell types with NK ability, e.g. NK cells, NKT cells (subgroup of T-lymphocites), etc... (possibly more). These cells can kill other cells if they don't recognize the MHC1 (MHC1 does not exist or not compatible). Regular T-cells (without NK receptor) seems like having the same ability by not compatible MHC1, but I am not sure yet about the mechanism. I think I'll need a weak more to read all articles I opened and come to a conclusion about how the immune response works in this case.

@Raoul Have you finished this work? I've been citing  you at https://biology.stackexchange.com/questions/104879/transplant-rejection-through-direct-allogenic-antigen-detection-where-do-the-t/104976#104976

In short, if a T cell does not find its corresponding MHC 1 complex on a particular cell, its default behavior will be to attack it. Binding to the MHC complex will cause a period of anergy in the bound T cell.

"Binding to the MHC complex will cause a period of anergy in the bound T cell." - I think this refers to T cells that encounter their specific antigen while strolling in the blood without having been primed/immunisized before by APC/dendritic cells, cp. Janeway's.

T-cells are selected against self reactivity so those that react to self-MHC are selected against and die by anergy. That's why they try to match the donor and the recipient's MHC molecules, to diminish the immune response.

On activation of host cells by foreign APC/dendritic cells with non identical MHC1

It cannot be ruled out that there do exist host T cells that do not bind to host MHC1 and have not been sorted out by so called positive or negative selection. They would not be activated by any presentation of antigen on host type MHC1 (conversely, presentation on foreign, non identical MHC1 might acitvate them, and there would be no sorting out of non-tolerant cells). Cp. comment above
inf3rno:  "it seems like there are multiple cell types with NK ability, e.g.  (...) NKT cells (subgroup of T-lymphocites), etc... (possibly more)."
To sum up: assuming that there are T cells that react to foreign, not host MHC, there is no need  for antigens being presented on (identical) host MHC1

On presentation on (identical) host MHC1

a. in case some antigen is presented on host MHC1 that there has been a process of inducing tolerance for
there would be no specific host T cells "left" to mount a reaction, as they would have been sorted out.
Apart from pre-tolerance, your reasoning should apply, as there is no process of tolerization after a certain period of "youth".
"Given that HLA mismatch is a major cause of transplant rejection, something is wrong with my reasoning."  - To sum up, nothing's wrong, as there is rejection with identical MHC1 too, according to my reasoning above (with the exceptio of "tolerance").
However, refering to first part of my answer,  this (rejection with self MHC1) does not imply that there is no rejection with non-identical MHC1. There is no  either/or. Both situations know rejection. From "self MHC1 has rejection" does not follow "foreign MHC1 doesn't".

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DNA methylation on the forward vs reverse strand?
I'm wondering if there are meant to be differences in DNA methylation between the forward and the reverse strand of the gene? I'm wondering because in primer design for bisulfite pyrosequencing one might only design primers for the forward strand. Should this matter for human/mouse DNA?
cheers and thanks in advance for any advice.

In most tissues, close to 100% of DNA methylation occurs at CpG sites. This provides a straightforward mechanism for epigenetic inheritance. Since C and G are complementary, both strands have the CpG site at the same locus and methylation is either present on both strands or on neither. During replication, each daughter DNA molecule inherits a parent strand with the (un)methylated CpG sites. Enzymes can recognise when there is asymmetrical CpG methylation and subsequently methylate the new strand where required. So, for CpG sites, both strands are methylated or not.
In embryonic and induced stem cells, however, ~25% of the total methylation occurs at non-CpG sites (especially CpA). Thus, methylation at a specific locus would only occur on one strand. As far as I know, how/if this methylation pattern is inherited has not yet been elucidated. Furthermore, this type of methylation occurs throughout the chromosome and is particularly high in exons whereas CpG methylation generally occurs upstream of a transcription start site.

There is also a phenomena called hemimethylation where one of strand is methylated while the other one is unmethylated or vice versa. There have been various research questions associated with hemimethylation, you can find more about it in here: http://nathansheffield.com/wordpress/what-is-hemimethylated-dna/

Recent work showing functional role of hemimethylation: http://science.sciencemag.org/content/359/6380/1166


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What is happening physically when I get sleepy and when I wake up?
After a week of too little sleep, I slept about 12 hours last night to "catch up". It made me wonder: what is happening physically that signals that I'm done sleeping,  or conversely,  that I need to sleep. I read this question and its answers, which explain how brain waves indicate different sleep stages: Why sleep? No, actually, why wake?
But what causes the changes in these brain waves? I'm curious about the mechanism by which my body determines that it needs sleep, and not just a set amount,  but a specific amount based on my previous week's lack of sleep. is it something in my brain or is it a hormone or something else?

During sleep the cerebrospinal fluid clears out the waste products of brains cells. Sleep fragmentation or sleep deprivation can prevent this process, or reduce its efficiency. So I think the accumulation of waste products cause that you have to sleep more after sleep deprivation and extreme sleep deprivation (e.g. by fatal insomnia) can cause death. Low quality sleep and sleep deprivation can cause or worsen both neural (e.g. Alzheimer's disease),  and metabolic diseases (e.g. diabetes mellitus, etc...), so you should avoid it, if you can (I cannot :D).
Daily sleep is regulated by the circadian clock. Many hormones can affect that clock, e.g. melatonin (dependent on blue light), insulin, etc...

The conservation of sleep across all animal species suggests that
  sleep serves a vital function. We here report that sleep has a
  critical function in ensuring metabolic homeostasis. Using real-time
  assessments of tetramethylammonium diffusion and two-photon imaging in
  live mice, we show that natural sleep or anesthesia are associated
  with a 60% increase in the interstitial space, resulting in a striking
  increase in convective exchange of cerebrospinal fluid with
  interstitial fluid. In turn, convective fluxes of interstitial fluid
  increased the rate of β-amyloid clearance during sleep. Thus, the
  restorative function of sleep may be a consequence of the enhanced
  removal of potentially neurotoxic waste products that accumulate in
  the awake central nervous system.

2013 - Sleep Drives Metabolite Clearance from the Adult Brain
2013 - Sleep Facilitates Clearance of Metabolites from the Brain: Glymphatic Function in Aging and Neurodegenerative Diseases

According to the traditional understanding of cerebrospinal fluid
  (CSF) physiology, the majority of CSF is produced by the choroid
  plexus, circulates through the ventricles, the cisterns, and the
  subarachnoid space to be absorbed into the blood by the arachnoid
  villi. This review surveys key developments leading to the traditional
  concept. Challenging this concept are novel insights utilizing
  molecular and cellular biology as well as neuroimaging, which indicate
  that CSF physiology may be much more complex than previously believed.
  The CSF circulation comprises not only a directed flow of CSF, but in
  addition a pulsatile to and fro movement throughout the entire brain
  with local fluid exchange between blood, interstitial fluid, and CSF.
  Astrocytes, aquaporins, and other membrane transporters are key
  elements in brain water and CSF homeostasis. A continuous
  bidirectional fluid exchange at the blood brain barrier produces flow
  rates, which exceed the choroidal CSF production rate by far. The CSF
  circulation around blood vessels penetrating from the subarachnoid
  space into the Virchow Robin spaces provides both a drainage pathway
  for the clearance of waste molecules from the brain and a site for the
  interaction of the systemic immune system with that of the brain.
  Important physiological functions, for example the regeneration of the
  brain during sleep, may depend on CSF circulation.

2014 - A new look at cerebrospinal fluid circulation

Sleep fragmentation is present in numerous sleep pathologies and
  constitutes a major feature of patients with obstructive sleep apnea.
  A prevalence of metabolic syndrome, diabetes and obesity has been
  shown to be associated to obstructive sleep apnea. While sleep
  fragmentation has been shown to impact sleep homeostasis, its specific
  effects on metabolic variables are only beginning to emerge. In this
  context, it is important to develop realistic animal models that would
  account for chronic metabolic effects of sleep fragmentation. We
  developed a 14-day model of instrumental sleep fragmentation in mice,
  and show an impact on both brain-specific and general metabolism. We
  first report that sleep fragmentation increases food intake without
  affecting body weight. This imbalance was accompanied by the inability
  to adequately decrease brain temperature during fragmented sleep. In
  addition, we report that sleep-fragmented mice develop glucose
  intolerance. We also observe that sleep fragmentation slightly
  increases the circadian peak level of glucocorticoids, a factor that
  may be involved in the observed metabolic effects. Our results confirm
  that poor-quality sleep with sustained sleep fragmentation has similar
  effects on general metabolism as actual sleep loss. Altogether, these
  results strongly suggest that sleep fragmentation is an aggravating
  factor for the development of metabolic dysfunctions that may be
  relevant for sleep disorders such as obstructive sleep apnea.

2012 - Sustained sleep fragmentation affects brain temperature, food intake and glucose tolerance in mice
2014 - Sirtuin 3: A Molecular Pathway Linking Sleep Deprivation to Neurological Diseases

Inadequate sleep simultaneously modulates the levels of multiple
  hormones that govern metabolism, In general, with sleep deprivation,
  the following hormones are decreased: insulin, growth hormone (GH),
  growth hormone releasing hormone (GHRH), and leptin levels. In
  contrast, ghrelin and somatostatin are increased. Essentially,
  hormones that signal that the body has plenty of energy are decreased,
  while those that signal energy need are increased. Experiments
  utilizing knockout animals as well as pharmacological agonists,
  antagonists, and immunodepletion of the proteins, illustrate that
  these hormones affect sleep regulation. Diabetic rats have decreased
  sleep time and consolidation while replacement of insulin increases
  increases slow-wave sleep.

2013 - The Genetic Basis of Sleep and Sleep Disorders (book)

In humans, melatonin is produced by the pineal gland, a small
  endocrine gland[26] located in the center of the brain but outside the
  blood–brain barrier. The melatonin signal forms part of the system
  that regulates the sleep–wake cycle by chemically causing drowsiness
  and lowering the body temperature, but it is the central nervous
  system (specifically the suprachiasmatic nuclei, or SCN)[26] that
  controls the daily cycle in most components of the paracrine and
  endocrine systems[27][28] rather than the melatonin signal (as was
  once postulated).

wikipedia - melatonin

Maybe some explanation about the downvote? :D I guess I have a fan...

I've linked to your answer in How widespread among mammals is the glymphatic system's metabolite clearance in the brain during sleep currently known to be?


text:
Earliest and latest onset of Huntington's Disease(Chorea)?
Huntington's disease can hit at any age, although it tends to hit middleaged people most often. What is the youngest and oldest person that has exhibited Huntington's?
Clarification: By oldest I mean with no prior symptoms until the age.

Huntington's disease may become symptomatic starting from as low as 2 years old [1] and rarely after 55 years old [2] (yet there is evidence of onset at 65 years old [3] and even more according to newer studies).

Figure: Copyright © 2004, The American Society for Experimental NeuroTherapeutics, Inc.
Richard H. Myers. Huntington’s Disease Genetics. NeuroRx. Apr 2004; 1(2): 255–262. doi:  10.1602/neurorx.1.2.255. PMCID: PMC534940
Factors [4]:

CAG number (65%-71% of the variance in age of onset)
siblingship (11%-19%)

[...] paternal age is negatively associated with age at onset of HD (Huntington's disease), particularly among subjects who inherit the mutant gene from grandfathers [5].

References:

Huntington's Disease Society Of America. What is Huntington's Disease (HD)? Available from http://www.hdsa.org/about/our-mission/what-is-hd.html (accessed 26.10.2014)
National Institute of Neurological Disorders and Stroke. Huntington's Disease: Hope Through Research Available from http://www.ninds.nih.gov/disorders/huntington/detail_huntington.htm (accessed 26.10.2014)
Myers RH, Madden JJ, Teague JL, Falek A. Factors related to onset age of Huntington disease. Am J Hum Genet. 1982 May;34(3):481-8. PMID: 6211092. Full text available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1685335/
Rosenblatt A, Brinkman RR, Liang KY, Almqvist EW, Margolis RL, Huang CY, Sherr M, Franz ML, Abbott MH, Hayden MR, Ross CA. Familial influence on age of onset among siblings with Huntington disease. Am J Med Genet. 2001 Jul 8;105(5):399-403. PMID: 11449389. Available from http://www.ncbi.nlm.nih.gov/pubmed/11449389
Farrer LA, Cupples LA, Kiely DK, Conneally PM, Myers RH. Inverse relationship between age at onset of Huntington disease and paternal age suggests involvement of genetic imprinting. Am J Hum Genet. 1992 Mar;50(3):528-35. PMID: 1531729. Full text available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684271/

Any exact dates? Like a child of 612 days exhibiting it? Or a woman of 72 years?

I first experienced Huntington's Chorea at 7-1/2 years of age. My father took me to Vanderbilt Hospital in Nashville, TN where it was confirmed by testing. I am now 71-1/2 years old, and have suffered Rheumatic Fever, a stroke, 4 heart attacks, and atrial fibrillation, along with many other less serious diseaes. I still have occasional bouts of Chorea, but am leading a mostly normal life.  During my earlier life at age 60, I completed a Bachelor of Science and an M.B.A. degree, so my reasoning faculties and ability to organize and study successfully are still intact. I may be on borrowed time, but don't worry about it.


text:
Identify the pink mold infecting refrigerated lemons
I made lemon juice 6 month ago.

I just washed the lemon using brush and then cut them into pieces.
Then I put one layer of lemon in the bottle followed by one layer of
sugar
Again one layer of lemon and one layer of sugar.
Then I close the bottle and put it in the refrigerator.

When I opened it, I observed some pink colored mold on the lemon slices.
Can anyone can identify the mold or tell me how to identify it?
PS: in the 6 months, I never opened the bottle. The bottle was clean and I did not add water; just lemon and sugar.

Whatever it is, I would not consume the lemon juice. The chances of toxins being present are just too high.

It can be Neurospora crassa....cause the fungus is pink, can live in anaerobic conditions, & can survive on carbohydrates, like sugar...but it's only a wild guess.... The pickle in your case got spoiled because it got in contact with water, only a few drops, but enough to cause those scattered microbial infections...

The S.E is gradually becoming a "Show & Tell"-site...somebody or the other is watching a vid or a pic or something weird in their kitchens...& thinking " Let's-just-post-it-in-BiologyS.E-&-ask-for-an-answer"....

Additional details are necessary to answer this question. Can you please provide them?

I would say that it is very hard to impossible to identify a mold simply by photos. There are a number of different molds that can grow under the actual conditions.

I checked citrus diseases on wikipedia, then "ctrl+f" and typed in "pink mold". The result was Gliocladium roseum which is really a pink mold, but it is hard to find any image of it, where it is on fruits... So this is just a guess. Btw. I think it is rarely possible to identify microorganisms just by checking an image of them.

citrus disease refers to mainly diseases on live citrus trees or fruits still on trees...the q is talking about a dead, refrigerated citrus...

@souvikbhattacharya "It colonizes living plants as an endophyte, digests material in soil as a saprophyte and is also known as a parasite of other fungi and of nematodes." - according to wikipedia. So I think it can survive on a dead lemon as well and likes anaerob conditions. Before cutting into slices the lemon was pretty alive (like every other fruit). The freezing not necessary kills microbes. Btw. I think it is impossible to find out what it is without laboratory tests...

If the mold was already there before pickling it...then why pickle it in the 1st place???....neway the q is pretty frustrating...why don't she try it out to find what actually it is,"great 1st hand experience"..;)


text:
Redundancy of the genetic code
One particular codon codes only for one amino acid, but an amino acid can be coded for by several different codons. Now according to the genetic code, the codon UUU codes for the amino acid phenylalanine and UUA codes for leucine. But, according to the Wobble Hypothesis, the base on the third position of the codon and that on the anticodon need not be complementary (which helps explain why there are very few types of tRNA molecules, inspite of there being 61 codons). If this hypothesis is true, then we could have a phenylalanine placed in a position which was meant to be for leucine, and vice versa (since the codons coding for them differ only in their third base). The same holds true for pairs like aspartic acid & glutamic acid and serine & arginine. So how does translation of a particular mRNA molecule result in the right polypeptide sequence?

Related question: Why 22 amino acids instead of 64?

Wobble pairing is just a phenomenon and not a hard and fast rule. There are some justifications for why it should exist and that is why it is still called a hypothesis. And this statement is not true:"the base on the third position of the codon and that on the anticodon need not be complementary". The anticodon residue corresponding to the third residue of codon can be a promiscuous base which can pair with two or many different bases.  The tRNA for Phenylalanine has an anticodon - GAA which can pair with both UUU and UUC but not UUA.
So the statement of wobble hypothesis is that the first base of the anticodon (often is a modified/atypical nucleobase) can show promiscuity of binding.

You are correct in saying that Crick, in his Wobble Hypothesis, proposed that “the base on the third position of the codon and that on the anticodon need not be complementary”, but the “need not be” in your statement is a paraphrase of the “some” in Crick’s original statement:

￼“It is suggested that while the standard base pairs may be used rather strictly in the first two positions of the triplet, there may be some wobble in the pairing of the third base.”

If you read that paper — or consult the Wikipedia entry under Wobble — you will become aware that Crick is using the word “some” to indicate that:

(i) The wobble proposed is specific for certain base pairs.
(ii) That such wobble base pairs will only be found in cases where they
  do not violate the genetic code.

The Wobble Hypothesis — as stated above — has been unequivocally shown to be correct. The specific Wobble Rules that Crick proposed to satisfy point (i) were based on an examination of the chemistry of the bases, and have been shown to be partially correct:

Wobble Rules: Crick’s origin predictions compared with observed 5'-anticodon bases and their base-pairing with codons.
Thus, the prediction that the 5'-tRNA anticodon bases, G and I could wobble (and C could not) have been borne out. Crick was aware of the paucity of A at this position in anticodons, and both it and U are normally found in chemically  modified forms, the base-pairing of which he did not attempt to predict (he was unaware of most of them) and which is different in different cases. The point to remember is that there is a scientific rationale for this in terms of the three-dimensional structure of the anticodon in the tRNA (which holds the first two bases in position by base stacking) and the proximity of the potentially hydrogen-bonding groups in the various bases.
Point (ii) is that Nature will only use Wobble where the genetic code allows. G pairing with C or U always works, whereas I pairing with A, C or G will work with amino acids encoded by all four bases in a block (e.g. Leu, Val, Ser), but not where there are blocks of two (e.g. Tyr, His, Asn).
One final point that emphasizes the chemical basis of all this. Mammalian mitochondria have a different set of wobble rules on account of their peculiarly truncated tRNAs.

I appreciate that this is an old question that has already been answered (it came to my attention on a 'related' listing. However as I had some material on the topic I thought it would be useful to flesh the previous answer out a little.


text:
Does sociality evolved before or after the ability of motility?
According to book Life Ascending: The Ten Great Inventions o Evolution.
(Lane, N.;2010),

Motility has indeed transformed life on earth in ways that are not
  immediately apparent, from the complexity of ecosystems.

As I understand it, when animals had begun to actively use their bodies to locate resources and thus left the sedentary way of life the amount of information they received has increased exponentially. It induced the rapid evolution of additional physiological, morphological and behavioural adaptations such as specialized brain regions enabling spatial memory, vision or cognition.
Was sociality also additional adaption induced by motility?
Is sociality as a life strategy present only in mobile animal species, or they exist also a social sedentary organisms?
Working definition of sociality: Forming of animal group where information transfer enable cooperation among individuals.

I think a working definition of sociality would be useful, since the question covers a large range of organism types.

Hi @fileunderwater. An edit was made, I hope this definition of sociality is sufficient.

@LadislavNado The question is interesting but it indeed deserves some definitions to be correctly addressed. Would you consider multicellular organisms to be a society of cells? The concept of motility also needs a working definition. For example, sponges are motile in the sense that they have cells with flagellates (and they can follow a chemical gradient). Bacteria are motile as well.

Do you restrict your question to animals or do you welcome consideration from other clades? Note that plants produce GLV (Green leaf volatiles) to warn other plants from predators which really seems to be a cooperative action.

I'm going to hazard that primordial sociality by this definition and this question proceeded primordal motility in cells.
Algae started to form physically attached groups like these filaments, giving them some of the advantages of higher organization.

Its easy to see how this is a relatively simple adaptation - just have proteins or carbohydrates on the cell surface that stick together.  This might also have evolved from large cells compartmentalizing since we're talking about very ancient stages of life on earth.


text:
How do the quantities of ATP formed during aerobic and anaerobic respiration compare?
How do the quantities of ATP formed during aerobic and anaerobic respiration compare?

What do you mean by compare? The amount of ATP made in each process? Is this a homework question?

@Aly I guess you are referring to glycolysis and its switch to lactic fermentation in anaerobic conditions?

You means fermentation and respiration?
In aerobic,1 mol glucose trough respiration and get about 38 ATP
In anaerobic, 1 mol glucose through fermentaion and get 2 ATP

I think you mean 1 molecule, not 1 mol.

Yes! I means that.


text:
Is it possible to simulate the effects of high altitudes for plants?
Note- I considered asking this on gardening.stackexchange.com but i believe it is better suited for this site since it deals with more complicated material.
As I understand it, certain plants (Camellia sinensis, Coffea, etc.) grow best at higher altitudes. What factor, biologically speaking, is responsible for this?
I know that the oxygen concentration at higher altitudes is lower, is this the reason?
If so, is it possible to use machinery to alter the gas concentrations in a grow room and simulate the effects of high altitudes? Are there any other factors such as pressure or anything that can also be altered? Would simulating this environment be practical for large scale applications?

The higher altitude means lower atmospheric pressure which in turn means lower oxygen concentration. Just pumping the air out of a sealed chamber would simulate this. Temperature, humidity and sunlight intensity/composition should also be taken into account.

I'm not sure that it's known which factor is responsible for this. Altitude changes the air pressure, but it can also drastically change the temperature, rainfall, drainage, soil type(no silt on mountaintops), etc. You can simulate almost anything with varying degrees of difficulty, but most would be impractical for fields on fields of crops.


text:
Hamming distance between two DNA strings
By definition from Wikipedia, the Hamming distance between two strings of equal length is the number of positions at which the corresponding symbols are different. In other words, it is the number of substitutions required to transform one string into another. Given two strings of equal length, compute the Hamming distance.
So to find the how many differences there are between two strings, say we have two DNA strings A and B:
A = TGACCCGTTATGCTCGAGTTCGGTCAGAGCGTCATTGCGAGTAGTCGTTTGCTTTCTCAAACTCC
B = GAGCGATTAAGCGTGACAGCCCCAGGGAACCCACAAAACGTGATCGCAGTCCATCCGATCATACA

Throw them to two arrays A and B. Therefore, If
(= count 0)
(cond
   [(symbol=? A[1] B[1]) /do nothing just move on to the next pair of string]
   [else (add1 count)] ;; counter:= counter + 1;

output would be the counter.
Is this the right logic flow to go with this problem? Any suggestion to write this on python or Scheme?

I think for the programming side of things, this question should be asked (at least in part) in http://stackoverflow.com

This question does fit into bioinformatics, which is on-topic here. That said, it really has nothing to do with DNA and you might get a better response at stackoverlow.

By the way, this sounds a lot like a homework question and there is a tag for that here.

Your logic on the problem seems correct. The wikipedia article about the Hamming distance describes both a python and a C implementations. The python version assumes two strings of equal length:
def hamming_distance(s1, s2):
    #Return the Hamming distance between equal-length sequences
    if len(s1) != len(s2):
        raise ValueError("Undefined for sequences of unequal length")
    return sum(ch1 != ch2 for ch1, ch2 in zip(s1, s2))


text:
How exactly can dsRNA be introduced to a cell?
Is it just by viruses or are there other means by which it gets into cells, such as plasmid uptake?

Artificially or naturally?

Besides viral infections there are different pathways for cells to take up dsRNA. Inside the cells these dsRNA are processed by Dicer which processes these RNAs into small interfering RNA, which play an important role in the regulation of gene activity.
These pathways have mostly been researched in Drosophila and C. elegans, I am indicating where evidence for them in humans is available. The different possibilities for the uptake are:

Uptake via transmembrane proteins: In C. elegans two different transmembrane proteins have been discovered which passively transport
dsRNA into the cells. They are called SID-1 and SID-2 (systemic RNA-interference defective protein), at least for
SID-1 a homologue exists in humans as well. These receptors are important for the uptake of systemic (produced by the own organism) dsRNA. See references 1-3 for
details.
Uptake via Endocytosis: In drosophila cells active transport happens through the scavenger receptors SR-CI and Eater. They bind
the dsRNA and are then internalized. Knockdown of these genes
inhibited the import of dsRNA and inhibited the endocytosis mediated
knockdown of genes. This process seems to be evolutionary conserved,
as knockdown of the orthologous genes in C. elegans led to similar
results. This mechanism seems to be more important for the uptake of environmental dsRNA. See references 4 and 5 for more details.
Uptake via Phagocytosis: At least for drosophila, there is evidence for a phagocytosis mediated uptake mechanism, which is
independent of endocytosis. See reference 6 for details.

References

SID-1 is a dsRNA-selective dsRNA-gated channel.
Uptake of extracellular double-stranded RNA by SID-2
RNA interference: a mammalian SID-1 homologue enhances siRNA uptake
and gene silencing efficacy in human cells.
The endocytic pathway mediates cell entry of dsRNA to induce RNAi
silencing.
Double-stranded RNA Is Internalized by Scavenger Receptor-mediated
Endocytosis in Drosophila S2 Cells
A phagocytic route for uptake of double-stranded RNA in RNAi

SID-1 looks interesting. Do you think there's a size limit or would it take up long dsRNA molecules?

@user137 This paper suggests that very different length (they tested from siRNA length to 500bp) are taken up. The longer the dsRNA gets, the more effective (meaning smaller concentrations of the dsRNA outside the cells lead to a downregulation) the process seems to be.


text:
If hermaphrodite C. elegans can reproduce with females?
C. elegans can self fertilize, or they can mate with males. But are they able to mate with females? Or is there some kind of morphological barrier that prevents that?

By "females" you probably mean hermaphrodites: C. elegans have no females.

There are female mutants, actually.

Since only the male tail is equipped with various specialized sensory and copulatory structures that enable him to locate the vulva and successfully inseminate the hermaphrodite.  Hermaphrodites can self-fertilize, but only males can cross-fertilize a hermaphrodite.
sources: Wormbook: Male development
C. elegans II (2nd edition): Sexual Dimorphism

The C elegans hermaphrodite is basically a female, except that she makes some sperm of her own. (Judith Kimble likes to say that a hermaphrodite is a female who's learned to be independent.) C elegans is derived from male/female species by a small change in sex determination in the female germ line. As you'd expect for a female, she can mate with males, but not other females.


text:
For how long can a raven stay airborne (a week or more)?
I'm wondering for how long a raven can stay continuously airborne, if strained to do so? If it makes a difference, I'm mostly interested in the Common raven, Corvus corax. Are there for instance any information on long-distance dispersal (wind-blown individuals over sea?) that can be used to roughly estimate this? Information on other corvid species could also be interesting, as a rough proxy.
If you are wondering, my motivation for asking is the biblical story in Genesis 6–8 (the deluge of Noah). Here, Noah sends out a raven and a dove to look for land. From the story it appears as if the raven can stay airborne for a longer time than the dove, which returns to the ark to rest. Is there any realism in the claim that a raven can stay airborne for one or maybe even two weeks?
Some background from Genesis 8 (this translation):

After forty days, Noah opened the window he had made in the ark. He sent out the raven, and it departed. It went back and forth until the water had dried up from the land's surface. He then sent out the dove to see if the water had subsided from the land's surface. The dove could not find any place to rest its feet, and it returned to him, to the ark. There was still water over all the earth's surface. [Noah] stretched out his hand, and brought it to him in the ark. He waited another seven days, and once again sent the dove out from the ark. The dove returned to him toward evening, and there was a freshly-plucked olive leaf in its beak. Noah then knew that the water had subsided from the earth. He waited yet another seven days and sent out the dove [again]. This time it did not return to him any more.

So the raven couldn't find a place to land, and it flew around until it could do so. A week later, the dove still couldn't find a place to land, but a week later it could. Thus, either (a) the raven was flying around for more than a week (as much as two weeks) or (b) the raven could more readily land in a wet area than the dove. Can either of these be true?

This question appears to be off-topic because it is about a mythical story and not based any real observation or scientific speculation.

It is possible to edit the post to make a scientific question without religious/mythical connotations.

@WYSIWYG not sure if off-topic. Although the religious part is evident, I think the OP is asking whether such a raven could exists in reality (i.e. if biologically a raven could fly for such a long time), and the religious reference serves simply as background of why he/she is interested in the question. I think, anyway, the question can be improved by focusing on the scientific part- as you suggest.

Quite apart from using a mythical story to ask a scientific question, I don't see what makes you think that the raven was flying around all that time. For all you know, and as seems more likely, it drowned. Could you [edit] your question, remove the biblical references and just ask something specific about an animal's behavior?

@terdon, I could just ask "Can it be true that either a raven flies for more than a week straight or doesn't mind ground as wet as a dove minds?" but that is a very odd question absent the background. Note that my question as currently worded does ask something specific about an animal's behavior -- but does so with some background to indicate why I'm asking.

I am sure you can count it by checking how much energy a bird needs to fly, and how much it has in its energy storages. The equation will be possibly an integral, because the energy requirement of flight will depend on the weight, which will drop, just by rockets. Water may not be a problem, because afaik guano contains very few water.

Hmm I think the answer can be much more complicated, because birds can extract energy from atmospheric phenomenons.

Can't be very sure about ravens but the maximum recorded flight duration is of Common Swift — 10 months.
Alpine swifts also remain airborne for up to 6 months.
Pigeons can fly up to 1800km in a long flight. From this article (pubmed):

In the United States, the longest pigeon races involve flights of 1800
  km and, because substantial financial rewards accrue to the owner of
  the fastest pigeon, there is severe selection for those pigeons that
  home the fastest.

Wikipedia article on pigeons says that they can fly at 80km/h but I suspect because the other wikipedia page on flight speeds says that average flight speed of peregrine falcon is 65-90km/h. So assuming that average speed of pigeon is 60km/h it should be able to fly for 30h. According to this paper, the speed with minimum power consumption is 8-9m/s (~30km/h). At this speed they should be able to fly for 60 hours. In the same paper it is estimated that the maximum continuous power output is ~10.5 W; if a pigeon has 11g of stored fat (per 400g body weight — assumptions from the same paper), and given the calorific value of fat — 38kJ/g, it can fly upto 38 × 11 ÷ 10.5 = ~40h. This means that the best trained ones can perhaps manage to fly for 2.5 days straight.
Now ravens are heavier (~3 times heavier) but are more aerodynamic and can fly faster. However, I guess they cannot perhaps fly 7 days straight.

Ah, but is that an African or European pigeon?

@terdon I urge you to add that as an answer ;)

@terdon In principle (if we assume no speciation events after the Flood), it could be any Columba species or even any other similar bird for which יונה was used as the closest term :)

Who needs land? These birds spend 10 months of the year in flight

@theforestecologist thanks. This seems like a recent report. I'll update.


text:
Are fish and reptilian scales homologous?
Wikipedia:

Fish scales are dermally derived, specifically in the mesoderm. This
  fact distinguishes them from reptile scales paleontologically.

So aren't reptilia scales also dermally derived?

No, fish scales are dermal (= formed in derma) bones like skull roof bones. Scales in reptiles are formed by epidermis and are made primarily of protein (from keratinocytes), being similar in derivation to hair, feather and nails.
On the other hand, in reptiles one must differentiate between scales and osteoderms (= scutes). Scutes are widespread among reptiles and they are similar to fish scales in that they are produced in derma and are ossified. Similar structures are found in some amphibians and in armadillo. Nevertheless, different types of osteoderms are currently considered as converges: "it is essential to recognize that osteoderms represent non-homologous structures that have been independently evolved a number of times" and have no direct homology with fish scales.

Do u mean fish scales disappeared and then reptilie scales re-emerged?

@Anixx I don't know anything about reptile and fish evolutionary history, but it's also possible that both developed after divergence. According to wikipedia, scales have evolved multiple times. Also, some reptiles have scutes which are derived from the dermis, like fish scales.

Scales must have been present in the ancestor of Tetrapoda. Actinistia (like Latimeria), for example, had/have cosmoid scales. Other elements of dermal ossification are skull roof bones and teeth, and only they are found in Tetrapoda. Hair, reptile scales (and feather on their basis) have absolutely no relation to dermal bony elements.

@canadianer can scales develop into scutes ever rather than other way around?

@har-wradim I thought skull originates as several vertebrae.

No, the bones of the skull roof have a completely different origin.

@canadianer Indeed, we have a terminological problem scales != scutes. I have modified my answer.

Are teeth bones?

The scales of reptiles are made of proteins not present in fish, and are regulated by genes not present in fish.
Proteins produced in the skin prevent amniotes from drying out. A specific kind of springy protein (corneous beta protein) produced by sauropsids (lizards, crocs, birds, etc.) produces what we now look at and call scales. This protein makes tiny springy bits that are ~50% smaller than the smallest bits in keratin proteins that we mammals make, so it may be critical for allowing the evolution of fancy feathers. Sauropsida mix these springy proteins into their hard skin bits to control how flexible, strong, etc. the pieces are.
I find this recent review paper super-helpful:
https://onlinelibrary.wiley.com/doi/epdf/10.1002/jez.b.22840
To summarize, the last common ancestor of a tuatara and a sparrow probably had some resistant skin material made with corneous beta proteins that formed in the upper layer of skin. Crown-groups evolved increasingly complex assignments for this material: claws, scales, shell, feathers, rhamphotheca.
I'm glad to see this review paper, because this makes the springy protein inside the scales of lizards and birds another good synapomorphy of sauropsids, which is easier for college freshman to see on the first week of class than the wacky regrown history of diapsid skulls.


text:
Poisonous plants, animals, mushrooms: is this always a kind of defense?
I wonder whether developing deadly toxins in the organism's body is always or usually a defensive strategy rather than a by-product.

I don't understand the question, spiders, snakes, etc... use it for external digestion of their prey.

@inf3rno I wouldn't say it that generally. Animal venoms tend to be a complex mixture of ingredients, with some components that paralyze a victim, while other components may cause death or digest tissues. Snakes don't use external digestion, they swallow the prey whole.

@inf3rno I do not refer to venom used as a weapon. I mean toxins in somatic tissues.

There's certainly a spectrum here, from the monarch butterfly(and others) who find their poisons in the environment and store them in their tissues, to some kinds of shark that have high urea contents as a result of their metabolism. The sharks probably retain some of the urea they would otherwise excrete for defense, but I'm not actually certain. If I understand the question correctly it's asking about poisonous organisms, not venomous ones. The difference is crucial to addressing this question.

@JeremyKemball +1 venom and poison are different terms, I forgot that too...

I think it always starts as byproduct, and after that if it is an evolutionary advantage it will help the organism to survive.

related: Why are some fungi poisonous?

Developing anything by the body takes energy so generally only useful products are conserved. If some sort of mutation caused an organism to produce some sort of by-product that also happened to be toxic to its predators, then that organism is more favored to survive. No species ever starts producing something with the intention of toxicity in a predator/consumer of said species.
These xenobiotics that the plant/animal produces then can either be selected for because they're useful in whatever pathway they are a by-product of. Or they can be conserved because then this by-product has a defense use, regardless of whether the pathway its part of is necessary. Or both could happen, it could be doubly selected for.

needs references..


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Why would an Eadie-Hofstee Plot be non-linear?
Besides cooperativity between multiple active sites on an enzyme, what are the other reasons for the Eadie-Hofstee plot to be non-linear?

Is this an assignment/homework questions?

The reason is that the inhibition models are inherently wrong.
Inhibitors bind to enzymes with the same mass action principles as substrates do so the term that should describe their binding should mirror the form of the MM equation i.e. ([S]/([S]+km)).  However all the traditional equations use (1+([I]/Ki)) rather than ([I]/([I]+ki)).
To compound this problem the (1+([I]/Ki)) term multiplies into the Km in competitive inhibition but divides into the Vmax in the noncompetitive equation.  It is therefore not affecting these terms in the same way in these separate equations and leads to the conclusion it is upside down in the competitive equation.
The plots above are deceiving as they allow the user to look at a linear plot and assume mechanism based on axis intercept pattern without analyzing the actual change in kinetic parameters produced by the inhibitor.  Kinetic models should be only fit using global data fitting to the proposed inhibition model.  This can be done quite easily using excel, for an example of how this can be done check out Kemmer and Keller 2010, or check youtube.
Kemmer G, Keller S. 2010. Nonlinear least-squares data fitting in Excel spreadsheets. Nature Protocols 5:267-281.
By realizing that the change in enzyme kinetic properties relates directly to inhibitor binding the logical hyperbolic shift in values exactly like the hyperbolic curve of the MM equation must be acknowledged and finite changes in the kinetic parameters must be accounted for.
i.e. Km = Km-((delta Km)*([I]/([I]+Ki)))
  Vmax = Vmax-((delta Vmax)*([I]/([I]+Ki)))

While I have been told this may be over fitting as the competitive, noncompetitive, mixed noncompetitive equations define inhibition with one or two inhibition constant (Ki alphaKi), these terms eliminate the need for all of these equations and the family of equations that they spawned as they proved ineffective over the years (such as uncompetitive, partial competitive, partial noncompetitive, partial mixed noncompetitive, I could go on but I think you get the point).
Additionally the competitive, noncompetitive and mixed noncompetitive equations define the effect of the inhibitor with the equilibrium binding constants and do not allow for the possibility that complete inhibition may not occur (no delta terms), leading to the family of equation to try to make up for this, i.e. partial competitive and partial noncompetitive.
Use empirical models and stop trying to force mechanistic models, the data will suggest the mechanism with good experimental design.

"these terms eliminate the need for all of these equations and the family of equations that they spawned as they proved ineffective over the years" - Can you add a reference please!

Walsh R. (2014) Are improper kinetic models hampering drug development? PeerJ 2:e649 http://dx.doi.org/10.7717/peerj.649           http://cdn.intechopen.com/pdfs/36518/InTech-Alternative_perspectives_of_enzyme_kinetic_modeling.pdf

Wikipedia where these equations have been up for several years although people still try to make the old methods coexist side by side http://en.wikipedia.org/wiki/Enzyme_kinetics http://en.wikipedia.org/wiki/Enzyme_inhibitor

One thing I hardly understand, why don't they use the Vmax + (Vmax2-Vmax)*(...) form?! It is much easier to understand x than --x... Btw. nice article, thanks again! :-)

On Eadie-Hofstee plot, you can draw enzyme activity changes for example inhibition in a linear form:

Figure 1 - inhibitions on Eadie-Hofstee plot

left-top: competitive inhibition
right-top: non-competitive inhibition
left-bottom: uncompetitive inhibition
right-bottom: mixed inhibition

(Btw. they are linear on Hanes-Langmuir, Lineweaver-Burk plots too.)
edit:
According to review "enzymatic" linked (2012 - Alternative Perspectives
of Enzyme Kinetic Modeling) these plots were important only before the development of the unified enzymatic activity modulation equation (2007). (I had learned about this topic somewhere between 2004 and 2009 that's why I weren't up to date.)

Can you explain this and not only drop in a image and some links? This will not help someone who is not familiar with the topic.

@Chris The question was very specific so I wrote a very specific answer. For those who did not know the topic I added wikipedia links, so if they are interested they can read a detailed description there. Why should I write more? It wasn't the question to explain how enzyme kinetics work, and how to draw an Eadie-Hofstee plot...


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The sex of the offspring of twins?
Given identical twin males, Michael and Douglas, Douglas and his wife have four children, all of whom are girls.  Michael and his wife have only one child, a boy, and are expecting another. What are the chances it will be another boy? If Michael and his wife have more children, what are the chances they will all be boys? Is there any support/evidence for, or a study about, one twin of an identical pair will have children all of the same sex and the other twin will have children all of the same (or opposite) sex?

Personal medical questions aren't allowed here, but you can easily edit it to make it not personal. The gender of your children is determined by chance.

This is NOT a PERSONAL medical question, rather a question regarding research of identical twins and their offspring.  Gender is not determined "by chance", as chance is defined as "a possibility of something happening,fortuitous, accidental".  There is no accident in the gender of a child.

@MichaelPrice in this context chance refers to the fact that something happens without observable cause, not that is accidental. Gender is defined by chance determined by the probability of an ovule being fertilized by an spermatozoid carrying an X or Y chromosome. Different fertilization events (i.e. for each child) happen independently of one another. I am not aware of any research proving gender bias, yet I am not an expert in that field.

I know what you're asking, you should just remove the details about you, your wife and your brother. It might seem trivial, but that is the policy of the site. Anyways, a male's sperm is equally divided into gametes carrying an X chromosome and gametes carrying a Y chromosome. The gender of a child is determined by which sex chromosome is inherited from the father (since the mother only passes on X). So the gender of the child is determined by which sperm fertilizes the egg out of how ever many hundreds of millions. That's where chance comes into play.

@canadianer Afaik it is not just about chance, there is some regulation about the gender, for example after wars the boy/girl ratio is not 1:1. However I never investigated this, so it is maybe just an urban legend...

Note: This is based on literature searches I've done a while ago out of general curiosity. I'm in no way an expert on human reproduction.

If I understand you correctly you are basically asking if there are any evidence for sex biases in offspring between families, that has a heritable genetic basis. This has been an active research topic for a long time and there are a number of proposed mechanisms for how this can be achieved. Historical data sometimes shows deviations in sex ratios over time, e.g. in 20th centrury Europe after WWI and WWII (see data in Gellatly, 2009). There are also other reported/hypothesized deviations in sex ratio e.g. trends in sex ratio due to paternal age (e.g. Jacobsen et al, 1999), sex biases of offspring due to earlier insemination in the menstrual cycle, and the child rank. However, from what I've seen, the evidence hasn't been conclusive and different studies point in different directions.
As Irving et al (1999) point out, possible mechanisms for sex ratio biases can be:

deviations in X/Y-ratio of sperm
selection of sperm within the female reproductive tract
biases in implantation success and/or survival for embryos of different sex

Most evidence seems to point against explanation one, see tests in e.g. Irving et al (1999) and Graffelman et al (1999). Graffelman et al (1999) also tests for an effect of male age, but do not find support for this idea.
Another interesting study is Curtsinger et al (1983), which tries to look at vertical population transmission of sex ratio variation in Japan. They conclude that there is a marginally significant effect on the paternal side, which would support the idea that sex biases might run in families.

An analysis of vertical transmission of sex-ratio modifying factors that excludes effects of birth order in both the parental and offspring generations has detected a marginally significant paternal effect.

However, they also conclude that the genetic variability in sex ratio is very small, if there is one. This study also does not find support for effects of e.g. paternal age or child birth order.
Gellatly (2009) provides a model of how an autocorrelation in sex ratio between generations could be explaned (while still having a stable population-level sex ratio), using an autosomal gene modifying male sex ratio. Note thought that this is a proposed model, and not empirical evidence. However, Gellatly (2009) also use genealogical/pedigree data from North America and Europe to show that there is an heritable component in the human sex ratio (an association between sex ratio in F1 and F2 generations). However, from what I can see the evidence is weak, and the models only explains 0.5% of the variance in the data. The introduction to this paper also has a useful overview of the subject with more references you might want to check out.
All in all, my perception is that there are some evidence that certain sexes can be overrepresented in families, which could potentially mean that the sex ratio in the offspring of a twin brother can contain information on the probablility that his brother will have a son or daughter. However, to me, the evidence is far from conclusive and the estimated effects seem rather weak. So as a null hypothesis, you should definately go for a 50/50 chance of a son/daughter, irrespectively of what the sex ratio of the twin brother is.
As for the general calculation of probabilities of different scenarios, you just use the product of probabilities and sometimes summation of birth orders. For instance (if assuming 50/50 sex ratio), the probability of having three sons is $0.5^3= 12.5\%$ (births: MMM) and the probability of having 2 sons and one daughter is $3*0.5^3= 37.5\%$ (births: FMM, MFM or MMF, i.e. three ways to achieve this scenario out of eight).

I heard of a theory, that X chromosome is heavier than Y, so it is more likely that the child will be boy. But I guess there are many other theories in the topic...

The question you're asking is essentially a version of an old riddle:

If you flip a coin ten times and it comes up heads each time, what are
the odds that the coin will
come up heads when you flip it for an eleventh time?

And of course the answer is that the odds are fifty-fifty. You could instead argue that 10 heads in a row is evidence that the coin is weighted somehow, and the way you would deal with that is by flipping that same coin 1000 more times, or (somewhat less reassuringly) by finding 100 coins identical to your first one and then flipping them each 10 times.
It's the same thing with children's genders. For every family with 6 girls there are hundreds more families with more mixed genders. The only effect known to skew the male-female sex ratio at birth significantly is wide scale sex-selective abortion (it tends to reduce the number of females).

While I agree with you in a practical sense, your answer is assuming that the sex ratio is 50/50 for all couples/populations and that variation in sex ratio lacks a heritable component, which is an open empirical question. Heritable variation in sex ratio is known in many non-human animals.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/


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How do C. elegans manage nutrition?
If there is ample amount of food, do C. elegans worms know when to stop eating or do they store extra energy? Could they put this extra energy to use by moving faster or putting more eggs?

The answers are:

Yes, they know when to stop eating. See this paper.
Yes, they store extra energy as fat in the intestine.
This one is a little more complicated. They can use extra energy, but not to move faster. Movement doesn't take much energy, and until they're close to death from starvation, they continue to move quite well. As for eggs, they do indeed slow down the rate of embryo production when nutrition is inadequate. But the total number of eggs is limited by the supply of sperm, so there is an upper limit on how many they can produce, even in unlimited food. Probably the main benefit of stored nutrients is to allow them to survive longer if the food runs out. They are very, very good at dealing with a variable food supply -- much better than you, for instance -- and they do it partly by storing up extra energy. This paper and references therein describe some starvation responses. You can also look up L1 diapause, the dauer larva, and adult reproductive diapause.

Any references available for 2) and 3)?

@Chris Stronks: I added some references. Unfortunately, some of this is just common knowledge among C elegans researchers that's hard to track down in published form.

Great. I understand, it is not my expertise. Looks good.+1


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Functions of the CFTR gene?
I am a senior in high school and I am studying cystic fibrosis.
I don't quite get the function of the CFTR gene as this is my first time dealing with this type of heavy scientific  info.
I had searched up its function on a website like this:
http://omim.org/entry/602421?search=cystic%20fibrosis&highlight=fibrosi%20cystic
By reading the gene functions section, I learned that CFTR regulate the formation of a chloride channel, changes the regulation of other transport pathways (i.e increase sodium ion absorption in sodium ion absortion). At the same time it also regulate the chloride-coupled bicarbonate receptor. And that is about all I got from that section.
I would greatly appreciate if someone can summarize all the functions of the CFTR gene listed in layman terms (i.e grandma language)  and also explain to me why decreased  chloride channel leads to thicken mucus or increase sodium ion absorption leads to CF Symptoms. In addition I would also appreciate it if someone can tell me does decreased CFTR gene function also lead to other diseases on top of Cystic fibrosis.
Thanks

I don't have enough expertise to have a real answer right now, and may have some info wrong. CFTR is an ion channel that moves chloride and bicarbonate ions into the extracellular space. This adjusts the viscosity of mucous and other fluids that line the lungs, intestines, pancreas, bile ducts of the liver, and reproductive tracts. In cystic fibrosis, the mucous becomes thick and hard to move. This can trap bacteria in the lungs, obstruct the bowels, cause diabetes and liver failure, infertility, etc. Studies on mice, pigs, and ferrets have also revealed changes in immunity and inflammation.

K thanks, is the extracellular space the surface of the lumen of the small intestine or bronchi,  in the case of Cystic fibrosis?

Also another clarification, the CFTR gene plays  three roles in the body.  The 3 roles are mucus thickness, minor regulation of inflammation in the body, and a minor regulation of immunity in the body?

Yes, the extracellular space is the lumen of both those organs. And what should be pointed out that I didn't really see in the answers is that almost all people with cystic fibrosis acquire chronic pseudomonas aeruginosa infections in their lungs. These are very hard to kill and if untreated the patient usually dies before 30 years old. With modern medical care, they are living long enough for the other organ problems to become noticeable, but still aren't living normal life spans.

CFTR is the gene which encodes the "Cystic fibrosis transmembrane conductance regulator", which is a membrane protein. Its function is to transport chloride and other negatively charged ion like thiocyanate ions from the inside of the cell to the outside (into the extra cellular space). This happens along a gradient, meaning the ions flow from the place of high concentration (inside the cell) to the place of low concentration (outside the cell). Since this would mean that a negative charge would build up on the outside of the cell, positively charged sodium ions follow the chloride ions by passive diffusion. This ions are secreted into the mucus in the extra cellular space.
This leads to a higher concentrations of electrolytes (salts) outside of the cell, which causes water to leave the cell (following the higher concentration of electrolytes), which makes the mucus thinner.
When the CFTR gene is mutated, this function is impaired and ions cannot be transported across the membrane. This causes a higher electrolyte concentration inside the cell and water stays there. This causes the mucus to get thicker (due to less influx of water), which then can block fine channels of the lung. Additionally bacteria can grow in the thicker mucus, which can cause severe problems as pneumonia. The process functions as shown in the figure below (from here), the sodium ions are not shown here:

If you want to read further about cystic fibrosis, I recommend this website.
Regarding the immune system there are different functions affected. First, the reduced (or prevented) secretion if thiocyanate ions lead to a reduction in the production of Hypothiocyanite ions which kill bacteria. Then different cells which are of importance to a proper immune reaction are impaired in their function, as shown in the figure below (from the first reference):

The function of CFTR is impaired in all cell types, not only in epithelial cells in the lung (although these are the most obvious consequences). In the cells of the immune system (T-cells for example) the intracellular ion concentration is disturbed including Ca2+ which plays an important role in the regulation of other genes. Other observations show that the activation of the immune system itself is also affected.
Further informations can be found in the articles I linked below. They require some knowledge of immunology, but when there are question, ask.
References:

Immune Responses in Cystic Fibrosis
The innate immune system in cystic fibrosis lung disease

The CFTR gene is coding a protein called CFTR (Cystic fibrosis transmembrane conductance regulator). This protein is an ion channel, which allows passive transport of the Cl- ions through the cell membrane in both directions. This allows the cells to transport water due to the active transport of Na+ ions. The Cl- ions follow the Na+ ions with passive transport to even up the electric charges, while the water will follow the higher osmolarity created by both ions. (Something similar happens with glucose when you put grapes into water. The glucose cannot go through the membrane of grape cells, but the water can. So the higher osmolarity in the grape cells will suck in water and the grapes will crack.)
Without working CFTR the cells cannot transport too many Na+ ions, because their membrane potential changes too much when the Cl- ions cannot even up the charges, and so the cells would possibly die because of this. (Another possible explanation that the energy barrier would be too much for the Na+ transporter to send through another Na+ ion.)
Without sufficient ion transport the water transport is not adequate in many regions of the body. By cystic fibrosis the most important affected organs are the skin, the lungs, the pancreas and the reproductive organs.

The skin cannot reabsorb Na+, so it will be salty.
The lungs cannot send water to the mucus, so it will be too sticky, and because of that it prevents the cilias by cleaning out the pathogens from the lungs. The results are infections, probably pneumonia and cysts in the lungs.
The pancreas is usually not able to do its job as well. The result are poor digestion, and due to that vitamin absorption problems, e.g. vitamin-D deficiency (and because of that osteoporosis). In many cases the pancreas is completely cystic, and it loses the ability to produce insulin, which leads to diabetes.
The reproductive organs are affected as well, most of the males with cystic fibrosis are infertile, and about every fifth female as well.

As you already know this is a hereditary disease caused by mutations in the CFTR gene. What you probably don't know that only homozygotes are affected. The prevalence of the mutant alleles is around 1/25 in my country (Hungary), so every 25th person is an asymptomatic carrier and by every 625th marriage there is a 25% chance that the child will be homozygote. The prevalence is dependent on the region, e.g. North- and West Europe is more affected than South- and East Europe.

Figure 1 - cystic fibrosis homozygote prevalence - Epidemiology: Mutational Diversity–Patterns of CFTR Mutations

Because of the region dependent prevalence of the heterozygotes (and homozygotes) there are theories, which claim that probably there is (or was) a negative evolutionary pressure on the CFTR gene, and the heterozygotes have evolutionary advantage, just like by sickle-cell anaemia and malaria. The CFTR is target of many infectious diseases e.g. cholera, typhoid fever, tuberculosis, etc..., so there are many candidates. Afaik there is no decision yet in this topic.


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Gene Therapy for Cystic Fibrosis
I have another question regarding cystic fibrosis.
I understand that gene therapy is currently being talked about in the cure for cystic fibrosis. I know that Eric Alton at imperial college London is working on delivering genes using liposomes and viruses like lentiviruses but I am confused over the advantages and disadvantages of those two methods.
In addition, is there an alternative 3rd method for injecting genes that don't involved viruses or liposomes. (An alternative type of vector) ?
Thanks

There are many types of non-viral vectors. They generally fall into cationic lipids and cationic polymers. The positive charge binds to the negative charges on DNA and forms stable particles. Getting these to work in the body is harder. I've been working at it for 5.5 years and far better scientists than me have spent far longer. Some researchers working on non-viral gene delivery include Dexi Liu, Leaf Huang, and Mark Kay.

Just thought of a couple guys who are doing research on cystic fibrosis specifically, John Engelhardt has a ferret model and Joseph Zabner is using pigs. Neither animal perfectly replicates the human form of the disease, but they're both better than current mouse models.

Why are the ferret and pig models better than mouse models?

I don't exactly know, but Engelhardt and Zabner have papers describing the animal models. If I remember right the mice don't exhibit the same inflammation and immunity symptoms.

There are many other methods that are used for transfecting cells in culture. These include:

Cationic lipid mediated (as mentioned by user137)
Calcium Phosphate mediated transfection
Biolistic methods
Electroporation

Newer techniques include optical transfection (using lasers to bore a hole through membrane) and impalefection (using nanotubes). Wikipedia page on transfection nicely summarizes these techniques.
Induced pluripotent stem cells can be cultured from a patient, transformed using the plasmid and transplanted back to the tissue where it can replace the old cells with "corrected" cells.
There is another somewhat recent technique called in-vivo electroporation using which Nucleic Acid can be delivered directly in to the desired tissue.
However, to fix a mutation or introduce a transgene, just transfection is not enough; you have to make sure that the desired gene is inserted in the chromosome at the right location. Faulty gene can be replaced by the transfected functional gene via homologous recombination(HR), but rates of recombination are generally very low. Targeted gene insertion methods using genome editing tools such as Zinc-Finger Nuclease (ZFN), TALEN, and Crispr-Cas can increase this rate by introducing a break in the DNA at that region; this causes DNA repair systems to "repair" the break using HR.
There is another type of DNA repair system called NHEJ (Non-Homologous End Joining), and this is not what we are interested in. NHEJ can, in fact cause mutation through indels. Presence of the transfected DNA would shift the preference towards HR, however it has also been shown that different stages of cell cycle have different preference towards HR and NHEJ (cant find the reference as of now but I am sure about it because I was thinking at some point of time, to work on this).
Having said that, I would add that it is essential to screen the cells to see if the gene is incorporated or not. If some optimal protocol is devised then one can proceed to in-vivo electroporation.

Consider adding viral transduction to the delivery methods. If that could be effective to silence the mutation. Then introduce the wt gene by viral delivery again. It's done in vitro, even with CFTR However the pathophysiology behind CF would not allow something this simple to work.  Otherwise +1 for good answer

@rhill45 OP was interested in non-viral methods, that is why I did not include it

Your methods are all in vitro; are there in vivo methods being tested? +1

@ChrisStronks In vivo electroporation has been used for experimental purposes (I have provided a JOVE link for it) but I don't think they have been used for therapeutic purposes. As such gene therapy is still in its inception. Stereotactic injections are also used to deliver a gene to a desired tissue but afaik, they mostly use viral vectors

All of these methods are good for delivery in vitro, but in vivo is a much harder problem, especially for nonviral methods. I've reviewed a paper about endoscopic electroporation in pig intestine, but never heard of it in the lung, which would be where you want the DNA to go for CF. Hydrodynamic Injection is a fun one that works well in mouse liver, but in larger animals it turns into a major surgical hassle, and probably wouldn't translate well to the fragile tissues in the lungs, not to mention pumping them full of fluid.

I think this is that electropration paper, looks like it got published.

@user137 Yeah lung tissue is a little difficult. I think better technique would be to implant corrected epithelial stem cells in the trachea. It will still be very difficult to eliminate the existing population of mutants. It is so much easier for blood cells.
For delivery to lungs inhaling the DNA-complexes might be a solution. I had heard about a paper in which they delivered a small RNA to lungs via inhalation (shown its effects too). I am not very sure if transfections can happen that way.