text:
Why do we think chronic inflammation can cause cancer?
Why do we think chronic inflammation can cause cancer? I know the pathway is not fully understood, but what makes scientists believe that inflammation causes cancer?

There are good epidemiological data for this.

Links between cancer and inflammation were first made in the
nineteenth century, on the basis of observations that tumours often
arose at sites of chronic inflammation and that inflammatory cells
were present in biopsied samples from tumours.
There are many triggers of chronic inflammation that increase the risk
of developing cancer. Such triggers include microbial infections (for
example, infection with Helicobacter pylori is associated with gastric
cancer and gastric mucosal lymphoma), autoimmune diseases (for
example, inflammatory bowel disease is associated with colon cancer)
and inflammatory conditions of unknown origin (for example,
prostatitis is associated with prostate cancer). Accordingly,
treatment with non-steroidal anti-inflammatory agents decreases the
incidence of, and the mortality that results from, several tumour
types.

Cited from Mantovani, Alberto, et al. "Cancer-related inflammation." Nature 454.7203 (2008): 436-444.
http://www.sld.cu/sitios/reumatologia/temas.php?idv=21500

We don't think inflammation causes cancer - we know inflammation causes cancer. The mechanisms are still being identified, but chronic inflammation causes cellular turnover and proliferation that appears to lead to the development of cellular damage and subsequent mutations.
Chronic inflammatory states are clearly associated with the development of cancer in a number of diseases. One of the most common that comes to mind is hepatitis, which literally means "inflammation of the liver". Chronic hepatitis B and hepatitis C infections are two of the most common causes of liver cancer (hepatocellular carcinoma) world wide. This is why we vaccinate people for hepatitis B - it has greatly decreased the incidence of liver cancer.
There are a number of review articles that discusses potential mechanisms available on Pubmed that are freely available and worth taking a look at for more information.

I don't disagree with your answer (we do know inflammation causes cancer) but HCC in viral hepatitis is more of a counter example. HBV is an oncogenic virus and causes cancer directly. HCV might be an oncogenic virus, but the jury is still out. HCC is very rare in autoimmune hepatitis, which suggests that, in HCV (and HBV) it's the viral infection rather than the inflammation that leads to cancer.

Inflammation and the inflammatory response can lead to tissue damage, and these stresses at the cellular and DNA level can lead to changes in the cell's programming. One example I can think of is neutrophils and macrophages--inflammatory cells--releasing reactive oxygen species (ROS)--reactive oxygen radicals--at the site of inflammation, which can damage normal tissue and their DNA. With enough changes and damages--in particular, mutations and translocations to genes that regulate cell growth--the cells can undergo anaplasia and ultimately dysplasia and neoplasia (cancer).
Check our wikipedia for these term, "reactive oxygen species" and the section on caner (https://en.wikipedia.org/wiki/Reactive_oxygen_species) as well as the textbook "Robbins and Cotran Pathologic Basis of Disease" if you can get your hands on it.

Welcome to Biology and thanks for your interesting answer. Would you happen to have some references to back your answer up?

Chronic inflammation also appears to mediate epigenetic changes that serve as a fertile ground for the evolution and origins of fully transformed, neoplastic cells. In fact, there are inflammatory conditions such as chronic periodontitis where this is pretty well established. Paper here
There is also evidence for genetic and transcriptional disruption induced by inflammation in model organisms. Paper Here


text:
What range of dose should be used?
This is a dose-response experiment testing a new cancer drug.  the darker line represents cancer cells.  what range of dose should be used? I think it's 2-4 because this affects cancer cells only.  is this correct?

Assuming that that's % cells rather than # then the ideal dose would be the minimum dose that killed 100% of cancer cells - minimum because you want to stay far away from the healthy cells line.  This would be a pretty amazing drug however, in real life those lines are likely to overlap long before 100% cancerous cell death, hence the problems of dosing chemotherapy.

In the most basic sense you want to kill the most cancerous cells whilst minimizing the regular somatic cell death. Almost all cancer medications affect regular cells, too - though the better ones do so at a minimum whilst being effective. In reality, it's also nearly impossible to kill all of the cancerous cells. The goal is to bring them below detectable levels, which can allow the body to finish the job. Leaving significant amounts of cancerous cells alive won't do the patient any good - they'll just continue to proliferate and the patient will be back for more operations or treatments soon.
So, with the goal of minimizing benign cell cost and completely eradicating the cancerous line, on your crude chart that falls at about "4".

so what would the range be? 0-4 or 2-4?

Probably 3-4. A dose of "2" isn't killing significant amounts of cancerous cells. Though everything is a bit vague about the question you're asking. Normally doses are determined by mg/kg depending on the utilization and persistence of the drug in the body.

source: Stack Exchange

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/

sort: votes


text:
By What Mechanism can Felines Reverse Diabetes?
To my knowledge house cats (and likely other felines) are the only animal able to go into remission after onset of Type 2 diabetes mellitus. I don't have a reference, this has been by peers in my research institution and by a veterinarian. Has this mechanism been studied, and if so, what is it?

Could you please provide any source of this information? And are you talking about type 1 or type 2 diabetes? Because I am pretty sure once you develop T1 you cannot get back, at least if you're a mammal.

I've just had a look at http://en.wikipedia.org/wiki/Diabetes_in_cats#Insulin_injections and I am not sure what more would you want. Although I do think that Wiki is wrong in saying that diabetic remission in T2 is unique to cats. Temporary remission happens even in T1 humans, and in T2 humans as well.

Thank you for pointing that out to me @yotiao. It seems I have been misinformed, and it is rather a case of early intervention to reduce glucose toxicity that allows felines and dogs to go into remission.

I spent a couple of years working in a diabetes research institute.  And you did hear right.
Cats dogs monkeys all can be susceptible to diabetes, although rats and mice don't seem to have diabetes that behaves the same way as humans - I don't think a mouse has ever been observed to get diabetes without specific gene knockouts.  One could argue that mice simply do not get diabetes the way people do.
There are two causes of type 2 diabetes in the research world.  The first happens because the animal may have a genetic susceptibility and environmental conditions induce the disease (like most people).  The second happens because of mutations in one specific gene or another pretty much cause it to happen when the animal gets to a mature age (google term: mature onset diabetes in the young (MODY)).  MODY genes have not proven to be a great model for type 2 diabetes treatment in most people (about 1% of diabetics have a MODY diabetes though).
Cats and dogs have been animals of interest as models of diabetes because their symptoms are human like and have shorter reproductive cycles.  Some cats (like Burmese) clearly have a greater genetic predisposition to diabetes, but cats who are obese, have high glycemic diets, or who get little or no physical activity are more likely to develop diabetes.
As with humans, the condition leads to the insulin secreting cells of of the pancreas to slowly degrade and if these cells are gone, there is no recovery from type 2 diabetes. All this given its likely that cats get diabetes that is similar to the human condition.
In treating cats its been shown that such diabetes can be reversed.  The most important thing to do - common to all treatments - is to change the cat's diet - restrict calories if the cat is obese and change high glycemic food.  Additionally, insulin or drug treatments that reduce insulin resistance (such as are given to humans) can restart the islet cells that secrete insulin if the animal is lucky and don't always have to be lifetime prescriptions.
The reference I have does not give remission statistics, but it must work a reasonable amount of the time.
But I wouldn't want to leave you with the impression that cats are special.  It turns out that human diabetes type 2 is often reversible.  This reference estimates 80% of the time. This study mostly focuses on the same treatments - change of diet and some fasting, but no exercise regimin as the cats.
There's probably nothing magical about cat diabetes 2... ;)

The main difference in practice is probably that it is easy to put a cat on to a high protein, low carbohydrate diet because, as a carnivore, the cat will be perfectly content. Humans on the other hand require dedication and willpower to reduce carbohydrate intake to the required extent.

@AlanBoyd that's true, cats are obligate carnivores and that diet requirement likely explains their remission capacity.

@shigeta Interesting answer. As an aside, there is a spontaneous mouse model of T2DM, called NSY mice. They seem to develop T2DM in an age-dependent manner, and do not present with hyperinsulinemia or common co-morbidities like obesity.

I think that if the human rate of remission were 80% that would be significant.  Animals are quite different though and its a lot of work to demonstrate that any animal model is the same as humans - they almost always have some operational difference.  Still the effect of lower glycemic index diet, weight loss, fasting and exercise is well understood in humans.

all_licenses: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/


text:
Are inflammation and anxiety connected?
I've been reading a curious paper about the use of cannabis, and one of the passages piqued my interest:

There’s also been a lot of work done on another constituent of
  marijuana, cannabinoid, which is not psychoactive by itself. A lot of
  research has shown that it’s a great anti-inflammatory, it’s a
  neuro-protectant, and it may be what gives medical marijuana patients
  relief from things like epilepsy and anxiety

Has there been any scientific evidence that links inflammation and anxiety?
Source:
Cannabis, Forgetting, and the
The Botany of Desire

See this paper on link between inflammation and anxiety.
Also, quoting one of the paragraphs of this paper

Clinical
  studies have shown increased serum inﬂammatory markers in patients with depression as well as a correlation
  between plasma cytokine levels and the severity of depression, and have described improvement in depression
  after anti-inﬂammatory treatment.

Even if you do a simple google search, you will get thousands of results on this.


text:
What is the armpit hair for?
Modern human beings, especially women, cut their armpit hair. It seems to me the armpit hair is trivial/useless. Shortly speaking, what is the armpit hair for?

While I won't answer fully at this time: Insulation is always one purpose. Bare pits = cold! Also, for men at least, we have glands that emit scents that correspond to our MHC allele makeup (immune system variation) - and women tend to prefer scents that differ from their family which results in more MHC diversity in the bloodline. A mat of hair can act as a scent-sponge, increasing the effect. It can also be a sign of cleanliness; bad smells are often bacteria in origin - having hair but no bad smell = clean. Hope this helps!

There are three theories on Wikipedia: http://en.wikipedia.org/wiki/Underarm_hair

Hair has been used for defense, think of lions, horses and roman centurion helmets. It's hard to cut or bite through. I'm not an expert, but it may be that beards, pubic and underarm hair cover exposed parts of the body that have vital arteries under the skin(neck, armpit and groin).

I don't think trivial is the word you wanted to use... possibly redundant, or useless?

I have been trying to read up a bit on this. I started out looking on wikipedia and it seems there are three hypotheses which are not necessarily mutually exclusive.
1.Aid the wicking of sweat away from the skin
2.Reduce friction between the thorax and upper arm
3.Facilitate the release of sex pheromones
The first would seem possible because it would help to prevent over-heating of the lymph nodes under the armpits and that also fits with the fact there are a lot of sweat glands there.
The second, I can't find any citations which support this but I understand that people who shave their armpits tend to suffer from dry underarms. This could be a result of increased friction.
The third is apparently controversial although it seems perfectly reasonable and highly likely to me. There is a famous experiment by Claus Wedekind who got men to wear a t-shirt for a few days. He then got women to choose a most preferred male purely by the scent of the t-shirt and found interesting results relating to the MHC profiles. The armpit hair could help to trap the odour produced by the sweat and help with mate attraction, like some kind of scent sponge. I don't understand why this is so controversial, loads of animals influence mate choice with scent - perhaps people don't like to think we are genetically attracted to each other by sweat because it seems animalistic and less romantic.
In summary, there is no sure answer and it could well be all of the above, or something entirely different.

The third is controversial because modern men are more likely to (sexually) select women with less armpit hair. I can't say if it is purely due to media, though, or if there is genetic component.

Realistically that is too recent of a trend to have any noticeable effect on the natural presence of armpit hair.

It's not proper to think of evolution in teleological (purpose-driven) terms--armpit hair is probably a trait that was never eliminated because it is not harmful to the species, rather than a useful trait that was specifically "selected for".

Good point about avoiding thinking in teleological terms. I think what is difficult to explain is why most body hair has been lost yet some retained. I would have thought that the loss of body hair would have affected the armpits just as it has the rest of the body (I know we have hair all over our bodies but it is only so dense in a few places). It suggests that there is a reason the armpit hair (and other areas) has been retained and that the genes affecting hair growth are up-regulated in these localities. This would suggest to me that there is some purpose of having armpit hair. Any ideas?

ps, production/growth of the hair is an energetic and nutritional cost - though it is probably minor.

@rg255 Hair was probably retained in the most sensitive areas: the pubic area, the armpits, and outside various openings and membranes such as the eyes, ears, and mouth.

@rg255 To speculate further, it is possible that men on average have more body hair because they on average have a lower body fat percentage, leaving them more exposed. This could also explain the high prevalence of limb hair in both sexes: limbs and their appendages (fingers, toes) are farther away from the heart, and therefore more vulnerable to the cold.

I think that has a lot to do with testosterone (and other hormone) levels: give a woman testosterone pills and she will likely get rather hairy!

@rg255 Well, of course, but that is only the mechanism by which the exhibition of the trait is controlled--and while more efficient control mechanisms  for the "fittest" traits are certainly "weeded out", they do not dictate which traits are the "fittest".

sorry that wasn't meant to come across as a criticism if it did, the increased testosterone may well be, in part, selected for as an advantage in that way.

@rg255 I wish there were a more direct way of speaking on SE, I wanted to tell you I was intrigued by your profile. Where on here could we address science policy, psych. of interdisciplinary science, etc.?

my email is in there isn't it?

@QuietThud have you tried chat?

Yep! Is there a way to invite specific users, though?

Microbiome manipulation is a common theme in these answers/comments, and there are experimental methodologies for investigating such things. For example: "Topographical and Temporal Diversity of the Human Skin Microbiome" at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805064.
One selection pressure that hasn't been mentioned is the reduction of harmful bacteria that occurs when providing a growth advantage to more benign bacteria. Many hairy areas are those where bacteria in general can live and prosper. Various ways hair could impact the microbioime are are easily imagined, for example greatly increased surface area should favor aerobic vs anaerobic bacteria. More specific host-bacteria interaction, e.g. specific bacteria being selected for due to the presence of certain hair surface proteins or the microstructure of the hairs surface might be harder to investigate. How hair surface varies in different location might be informative.

The explanation I heard from the documentary called "Curiosity: World's Dirtiest Man" is that armpit hairs allows for the growth of microbes which allow for the production of smell. This smell is useful for the attraction of mates in primates (although this function is probably lost in humans as our society became more hygienic).


text:
Is there a timeline for the frequency of evolution of any species?
Evolution is traditionally spoken of as an inherited change over generations.
Does evolution happen one change at a time - or are there multiple changes occurring between two successive generations? Is there a known timeline for the frequency of such changes in any species?
Something like ...
20 Million years ago - Species X showed A, B, C.. Z characteristics
19 Million years ago - Species X following characteristics changed A'
17 Million years ago - Species X following characteristics changed B', C', Q', M'
16 Million years ago - Species X following characteristics changed A''

Your question presumes that species X is recognizable as species X for 4 billion years. And, the universe is only ~13.75 billion years old.

If not X, then it's most probable derivative. Homo Habilis, Homo Rudolfensis ... so on.

I think you want some kind of character mapping. e.g., http://mesquiteproject.org/mesquite_folder/docs/mesquite/CharacterEvolution/AncestralStates.html

It's unlikely that multiple independent, fitness-relevant changes would occur at exactly the same time. I mean, if getting a beneficial random mutation is like rolling a 1 on a 1000-sided die, then getting two of them is like rolling 1s on two dice simultaneously. However, you could have multiple changes in phenotype if they both trace to the same genetic change (e.g., an increase in metabolic efficiency leads to increased size and also changes in foraging behavior).

There can be multiple changes at the DNA level generation after generation, however most of these changes are insignificant (doesn't contribute for any specific character). But rarely, there can be a significant trait/change gained by an individual because of such changes in DNA level. Unfortunately such changes gets 'lost', unless it is fixed in the population (i.e., the gained individual should be successful in breeding and passing the trait/change to large number of progenies. Those progenies should further continue to pass on the trait till about every one (or most of them) in the population has those trait/change). Only such changes contribute for the species development (continuous accumulation of such changes, over time will result in the novel population that is very different from the original population).
Most of the timelines that we know are reconstructed from the DNA/protein sequences. Usually, DNA or protein sequences from the closely related species will be compared and looking at the differences they have, using suitable models, ancestral state of those sequences are determined. Once the sequence for the last common ancestor is known, mutational rate per unit time can be used to estimate the evolutionary time for those species.
A simple example would be the blue eye color in humans: it occurred about 10,000 years ago and it is still not fixed in the population.

Blount ZD, Barrick JE, Davidson CJ, Lenski RE. (2012) Genomic analysis of a key innovation in an experimental Escherichia coli population. Nature 489:513-8. doi: 10.1038/nature11514

Richard Lenski is conducting an experiment called the long-term evolution experiment (LTEE) in which twelve populations of E. coli are grown in a glucose-limited minimal medium. This experiment has now been running for over 40,000 generations (>20 years). If we take a human generation as being 25 years, this is equivalent to one million years of Homo evolution.
One of the diagnostic traits of the species E. coli is the inability to grow aerobically on citrate. The medium that is used in the LTEE does however contain citrate as a chelating agent (probably to solubilise ferric ions, although I haven't been able to confirm this). The Lenski group have recently reported on the appearance of a novel citrate-utilising mutant in one of the populations. The Cit+ variant appeared at around 31000 generations, and became dominant after 33000 generations. Because the LTEE involves storing samples of each population every 500 generations it has been possible to analyse in detail the emergence of this new phenotypic trait, and indeed to replay it.
The process that they describe has three phases:
1) Potentiation. This stage involved the appearance of mutations that were a necessary prerequisite for subsequent events. In this case it is thought that there were at least two potentiating mutations. These are as yet unidentified but their existence is inferred from replay experiments.
2) Actualization. This is the emergence of the new trait, and in this case is the event that took place at 31,000 generations. This involved a tandem duplication event at the citT locus, bringing citT under control of a new promoter, belonging to the rnk gene. The citT protein is a citrate transporter that is only expressed under anaerobic conditions in wild-type E. coli. The gene duplication event led to the expression of the transporter under standard aerobic conditions, opening up the possibility of taking up citrate and metabolising it. Replay experiments indicate that this event originally conferred a very weak Cit+ phenotype.
3) Refinement. This involves changes that strengthen the Cit+ phenotype. In this case these seem to have been further gene duplications of the rnk-citT module (with up to eight copies in one replay experiment). This eventually stabilised with the presence of four copies.
This may be the nearest that we can hope to get to defining a timeline of evolution of a new characteristic.


text:
Do effects of caffeine on human body change with habitual use?
I've been reading about homeostatic nature of a lot of neurobiological processes - the brain is trying to maintain a balance by desensitizing receptors, re-uptaking and breaking down neurotransmitters.
With this in mind, I'm interested in what happens to the receptors in the brain with chronic use of caffeinated beverages.  Let's say an occasional caffeine drinker likes the cognitive boost of caffeine and starts to consume it habitually/chronically - every day. Will the caffeine drinker experience the same effects day after day, or will the effect change over time?
If there is a change in how the body responds to caffeine, are there any time frames that can be used to estimate when the change takes place - is it X days/weeks of habitual use?
Thank you for your input!

Related CogSci question: http://cogsci.stackexchange.com/questions/111/does-caffeine-improve-performance-for-habituated-consumers

I don't have any references off hand (though if you like, I will find them). The body acclimates to caffeine intake, becoming desensitized to chronic caffeine use, analogous to chronic narcotic use. Habitual coffee drinkers, soda drinkers, and so forth must achieve the same level of daily caffeine intake to maintain a normal state of being. Taking in less caffeine leads to withdrawal symptoms, and taking in more caffeine leads to the familiar stimulatory effects. As for time frame of addiction, this likely varies, but I hazard a guess it's on the order of a few days to a week. Fortunately, caffeine is not nearly as strong and addictive as narcotics, however it is the most widespread.
Edit: Caffeine exerts high-affinity and low-specificity for adenosine receptors. This was a review article I fould that may help you out.

Dunwiddie TV, Masino SA. The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci. 2001;24:31-55.

While not an opioid, caffeine IS most certainly a drug (not sure what you mean by narcotic). It is also quite addictive as I can state from personal experience, but if that is no enough see, for example, here. In any case, it is certainly more addictive than many narcotics.

Just illustrating that like opiods (which are known to be highly addictive, and change neural receptor regulation), caffeine (an alkaloid) has similar pharmacological effects and similar addictive qualities.

It is the receptor regulation that I'm most interested in.

@AlexStone I've added a review article for you.


text:
High Glucose vs Low Glucose DMEM for Cell Culture
I've noticed that in mammalian cell culture, there are often two types of DMEM available. High Glucose and Low Glucose. Does it matter which type I use for culturing of cells (e.g. Hela or HEK293)? Which is the type people normally use?

We typically use High Glucose as cells grow faster.  One caveat is that there are concerns that certain protein modifications (specifically OGlnAc-ylation) may be upregulated in non-physiological (25mM or high glucose) media.


text:
DAM enzyme distances move along the genome
I am fusing a protein with a Dam enzyme (http://en.wikipedia.org/wiki/Dam_(methylase)).  The idea is that when the protein binds to the DNA, the Dam enzyme will start methylating nearby GATC sites, thus helping identify the protein binding region (using DpnI later on, and microarray technology).  However, I have no idea, in theory, how many (bps) will the enzyme traverse across the genome from its starting location.  I.e., how far (in terms of bp) from its starting location will the enzyme methylate the GATC sites.
There are methods for finding protein binding regions along the genome that use such technology, such example here: http://www.nature.com/nbt/journal/v18/n4/abs/nbt0400_424.html

I am not sure about this but I believe there is not minimum or maximum distance. Each Dam protein will cut and then disassociate from the DNA. I don't think it moves along while remaining connected. If this is correct (again, I am not sure, not my field) then there will be no min/max distance between restriction sites. It will just float around until it finds another DNA molecule and cut the first site it finds. This could be adjacent to the previous one or kilobases away.

get it, thanks terdon.  I think you may be right, in my case completely not my field I am a EE...

Is there a restriction enzyme called Dam? It isn't included in the rather extensive list on Wikipedia. The only Dam that I know of is the Dam methylase of E coli which modifies the A at GATC sites immediately after replication.

@Alan Boyd - my apologies, I misread your question about Dam, thinking you were referring to DpnI (which is indeed a restriction enzyme with preferential cleavage of methylated DNA). My apologies.

I'll second Alan's comment, please clarify which enzyme you mean exactly. Dam is a methylase, it doesn't cleave anything.

guys you are all completely right, there is not such a restriction enzyme but rather a methylase enzyme!

Dam methyltransferase methylates large DNA molecules in a processive manner, with an effective range of up to 7 kb on either side of an initial methylation reaction.
My answer is taken from this paper:

Urig, S. et al. (2002) The Escherichia coli Dam DNA Methyltransferase Modifies DNA in a Highly Processive Reaction J Mol Biol 319 1085-1096

The authors report on a kinetic analysis of E. coli dam methylase. For anyone using this system as described by the OP, this paper is essential reading. Their conclusion is that the methylation process is highly processive, which is to say that a single dam-DNA interaction leads to multiple methylations before the enzyme dissociates from the DNA.
I'll restrict myself to describing just two of their experiments:
Figure 5
In this experiment they analysed the time course of methylation of an end-labelled 879-mer with 4 GATC sites, using DpnI digestion to detect methylation. In this experiment all DNA was found to be either fully methylated or unmethylated - no evidence for the presence of partially methylated DNA molecules was detected.
Figure 6
In this experiment they analysed the methylation of λ DNA (48.5 kb) and were able to detect partially methylated molecules. A kinetic analysis of the data results in the following conclusions (MTase; methyltransferase):

From these simulations, we [determine] a processivity of nav=3000. This means that after binding to the λ-DNA and starting the one-dimensional diffusion process, one MTase on average meets 3000 dam sites before it dissociates from the DNA. Since the enzyme performs a random walk, it will hit many sites more often than only once and the effective range of processivity corresponds to the square root of nav. Therefore, the dam MTase is able to methylate approximately 55 GATC sites on λ-DNA in a processive reaction in vitro. In this simulation, 4.6 associations of an MTase molecule to the same molecule of λ-DNA are required to obtain fully methylated DNA.

In a random DNA sequence GATC should occur on average every 44 = 256 residues. This suggests an approximate range of (55/2)*256 = 7 kb on each side of an initial methylation reaction.

couldn't ask for a better answer!  thanks so much.

After re-reading your question, I suspect you are conflating DNA methylation and restriction digestion. For a more detailed overview of how these two relate to each other, please read the summary page at New England Biolab's website.
The crystal structures of common restriction enzymes do not suggest that they scan along the double-stranded DNA looking for a recognition site. Their reaction kinetics can be thought of as being a more random interaction, whereupon the enzyme comes into contact with a recognition site, then cleaves the DNA is and free to float around until the next reaction.
DNA methylation comes in three common flavours: Dam (DNA adenine methylation), Dcm (DNA cytosine methylation) and CpG methylation. The addition of any of these methyl groups changes can interfere with enzyme recognition of the site. Many enzymes are partially or completely blocked by at least one kind of methylation, while other are completely uninhibited. This is due to the shape of the enzyme and of the DNA.
Now here is where I think you are conflating the two. REbase (Restriction Enzyme database) is indeed the authoritative list on restriction enzyme. You mention Dam cuts at GATC. The sequence GATC is the canonical adenine methylation (Dam) site. As you pointed out, no known restriction enzyme contains Dam. If we instead look up the recognition site, GATC will match with DpnI, a restriction enzyme that produced blunt ends. I think it is DpnI that you are speaking of, which preferentially cleaves Dam methylated DNA (hence why the recognition site GATC also matches Dam mythyltransferases). If the absense of methylated DNA (or if non-methylated DNA is more abundant), DpnI will also digest at GATC sites.

you are completely right, sorry for the confusion.  as a follow up, do you have any idea how far (in terms of bp) dam would move along the genome?   thanks!

I rephrased the question based on your perfect suggestion!  thanks so much!

It's still unclear to me whether Dam does in fact translate along DNA, or if it too acts like a restriction enzyme, in which case it's more like a probabilistic collision event.


text:
What mechanisms tell temperate trees when to drop leaves?
I've been looking around and cannot find a definite answer on what it is that tells trees to change their metabolism and drop leaves. I see that such activity is called Deciduous.
What interests me are the specific mechanisms by which a tree knows that it's time to drop leaves. Is it photoperiod shortening (day duration?) Is it temperature changing metabolism? Is it build up of some toxic compound?
Thank you for your input!

For answers, also see the duplicate what is the mechanism behind plants losing their leaves?.

FYI: "Deciduous" is not the activity itself of losing leaves.  (The activity is called "abscission.")  Rather, "deciduous" is an adjective that describes the types of trees that display abscission.

Here is a good USDA link:
http://www.usna.usda.gov/PhotoGallery/FallFoliage/ScienceFallColor.html
It would appear that the shortening days are a main trigger, and there are other factors. I did a basic search using Google for "what triggers leaf fall in deciduous trees?", since I always thought temperature and changing seasons were major triggers and wanted to double check.


text:
Could a fetus properly develop in micro/zero-gravity?
I suppose another way of looking at the question is: how important is gravity for the development of mammal fetuses?
And if things would go wrong, what sort of things would they be, and what would be the result?

Let me just say, it would be awesome to be the first scientist to breed mice in space. Just sayin...

There is some evidence that fetal development under zero gravity conditions might be problematic.

Wakayama S, Kawahara Y, Li C, Yamagata K, Yuge L, et al. (2009) Detrimental Effects of Microgravity on Mouse Preimplantation Development In Vitro. PLoS ONE 4(8): e6753. doi:10.1371/journal.pone.0006753

The paper is here.
These authors studied aspects of reproduction of mice in a clinostat under 10-3G. They found that fertilisation was unaffected, but that preimplantation development of the embryo was affected by the mG environment.
The introduction to the paper gives a good brief review of this area of research. Perhaps of particular relevance is this section:

In the STS-80 space shuttle mission, mouse 2-cell embryos were collected on the ground, launched into space and cultured for four days in µG. The control embryos on Earth developed to normal blastocysts, but in the space flight group, none of the embryos showed any sign of development, and all degenerated (Schenker & Forkheim, 1998) . A more reliable experiment was done on the Cosmos 1129 mission in 1979, when mature male and female rats were sent into orbit and then allowed to intermingle in a common breeding chamber (Serova & Denisova, 1982). However, none of the females gave birth, although postflight examinations revealed that ovulation had occurred. Two of the females were reported to have achieved pregnancy, but the embryos appear to have been resorbed.

Schenker E, Forkheim K (1998) Mammalian mice embryo early development in weightlessness environment on STS 80 space flight. Israel Aerospace Medicine Institute Report.
Serova LV, Denisova LA (1982) The effect of weightlessness on the reproductive function of mammals. Physiologist 25: S9–12.


text:
Is Leptin Stimulated by Insulin Alone?
What is the mechanism of insulin stimulation in the human body?
Is leptin release stimulated by circulating insulin directly? Which other factors are involved in the level of insulin release? My goal is to identify nutrients that aid/trigger leptin production and release without causing undue inflammation or body-fat storage.

Welcome to SE.Biology. I think that you need to expand your question - it seems a little ambiguous as it stands. Do you mean stimulation of insulin release? Or perhaps insulin action in stimulating something else?

Is leptin release stimulated by circulating insulin directly? Which other factors are involved in the level of insulin release?
My goal is to identify nutrients that aid/trigger leptin production and release without causing undue inflammation or body-fat storage.

@Alan Would that be specific enough? I can go into more detail but thought keeping the question fairly general would make the answers be of use to more people.

You can edit your question, I have done that for you.

In the new version do you mean "Which other factors are involved in the level of insulin release?" or did you mean to say "Which other factors are involved in the level of leptin release?"?

I'm looking for how circulating insulin effects leptin levels in humans

This is a strange question, it is difficult to understand what you are really getting at. You should make it a bit clearer because at the moment it is an unintelligible series of poorly connected questions.

Okay: I want to know which foods best induce high leptin levels in humans.
If insulin is the primary simulator of leptin production and release then high GI carbohydrates will be more useful, and possibly some amino acids. If not, there might be other foods that can do a better job without spiking insulin.

I have to say that this seems like a really odd approach to figuring out your diet.  The question of whether insulin increases satiety has been more specifically studied in the literature, as has the satiety generated by equicaloric portions of various kinds of foods, as have the actual effects of various specific diets in human feeding studies.  If you do a bit of digging, I'm sure you can find studies relating high/low GI diets to medically important outcomes (weight loss, blood lipids, fasting insulin levels, etc.), as opposed to their effect on one proposed satiety/fat regulation hormone (leptin).  Your approach also ignores leptin and insulin sensitivity, which might be as important as the levels themselves.  As someone concerned with which foods to actually eat, empirical studies of actual diets seem like the best place to look.
Anyway, here are a few relevant citations to help answer your question:
This study found a increase in serum leptin levels in type I diabetic children who started insulin therapy:
Flück CE, Kuhlmann BV, Mullis PE. "Insulin increases serum leptin concentrations in children and adolescents with newly diagnosed type I diabetes mellitus with and without ketoacidosis." Diabetologia. 1999 Sep;42(9):1067-70.
http://www.ncbi.nlm.nih.gov/pubmed/10447517
A slightly smaller study asked the same question, and found no increase in leptin levels:
McCormick KL, Mick GJ, Butterfield L, Ross H, Parton E, Totka J. "Leptin in children with newly diagnosed type 1 diabetes: effect of insulin therapy." Int J Exp Diabetes Res. 2001;2(2):121-7. http://www.ncbi.nlm.nih.gov/pubmed/12369715
An in vitro study of rat fat cells does indicate a direct increase in leptin secretion/production when given insulin:
Barr VA, Malide D, Zarnowski MJ, Taylor SI, Cushman SW. "Insulin stimulates both leptin secretion and production by rat white adipose tissue." Endocrinology. 1997 Oct;138(10):4463-72. http://www.ncbi.nlm.nih.gov/pubmed/9322964 http://endo.endojournals.org/content/138/10/4463.full
...and in human fat cells:
Wabitsch M, Jensen PB, Blum WF, Christoffersen CT, Englaro P, Heinze E, Rascher W, Teller W, Tornqvist H, Hauner H. "Insulin and cortisol promote leptin production in cultured human fat cells." Diabetes. 1996 Oct;45(10):1435-8. http://www.ncbi.nlm.nih.gov/pubmed/8826983
Leptin levels are positively correlated with insulin levels and BMI (presumably as a proxy for fat mass?):
Lambrinoudaki I, Christodoulakos G, Panoulis C, Botsis D, Rizos D, Augoulea A, Creatsas G. "Determinants of serum leptin levels in healthy postmenopausal women." J Endocrinol Invest. 2003 Dec;26(12):1225-30. http://www.ncbi.nlm.nih.gov/pubmed/15055477
Thierry Thomas, Bartolome Burguera, L.Joseph Melton III, Elizabeth J. Atkinson, W.M. O'Fallon, B.Lawrence Riggs, Sundeep Khosla, "Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women" Metabolism Volume 49, Issue 10, October 2000, Pages 1278–1284 http://www.sciencedirect.com/science/article/pii/S002604950041783X
This study found a positive relationship between changes in insulin levels and leptin levels, though it sounds like only in women. (I don't have the full text to check, and the abstract was ambiguous):
Widjaja A, Levy JC, Morris RJ, Frayn KN, Humphreys SM, Horn R, von zur Mühlen A, Turner RC, Brabant G. "Determinants of within-subject variation of fasting serum leptin concentrations in healthy subjects." Exp Clin Endocrinol Diabetes. 2000;108(3):208-13.
http://www.ncbi.nlm.nih.gov/pubmed/10926318
So based on an incomplete and cursory literature search, it seems likely that injecting insulin increases leptin production, as do some other activities that tend to increase insulin.  The evidence for causation in humans is not totally clear cut, though suggestive.

As you hinted, you must also consider Glucagon-like Peptide 1 (GLP-1), a hormone which upregulates inusulin synthesis and secretion.

I agree - an odd approach to diet. Leptin does a lot and has several modes by which its expression is regulated. While the connections to insulin are well documented, I've brought to light here several other interesting characteristics of leptin.
LEP exerts its effects in the brain via the gene MC4R - see this.
HMGA1 strongly potentiates the capacity of the CEBPB (CCAAT/enhancer-binding protein beta) transcriptional factor to transactivate the LEP promoter (Esposito Fusco 2009 J Biol Chem 284:25998)
Subjects who watched a humorous video had changes in blood pressure and showed decreased levels of LEP as the level of GHRL increased, much like the acute effect of moderate physical exercise that is often associated with increased appetite.
After adjustment for gender and age SERPINF1 SNP rs12603825 revealed significant association with MRI-derived total adipose tissue mass and fasting leptin concentrations, as well as nominal associations with bioelectrical impedance-derived percentage of body fat and clamp-derived insulin sensitivity in humans, thus contributing to overall body adiposity, obesity-related insulin resistance and circulating leptin levels (Böhm Ordelheide 2012 PLoS One 7:e34035).
Leptin influences the development of eyes and ears in zebrafish and was shown by knockout to affect eye and ear development in mice (Londraville 2012 General Comparative Endocrinology J). There are many connections between blood lipids, lipid homeostasis and eye health; many genes important to both blood lipids and eye health are shared.
Lastly, the LEP gene shows altered H3K9/K14 acetylation in response to hyperglycemia (Pirola Balcerczyk 2011 Genome Res).

Leptin may not be as important as we think. A review in 2001 concludes:

Conversely, it is unlikely that leptin has evolved to prevent obesity
  when plenty of palatable foods are available because the elevated
  plasma leptin levels resulting from the increased adipose tissue mass
  do not prevent the development of obesity. In conclusion, in humans,
  the leptin signaling system appears to be mainly involved in
  maintenance of adequate energy stores for survival during periods of
  energy deficit. Its role in the etiology of human obesity is only
  demonstrated in the very rare situations of absence of the leptin
  signal (mutations of the leptin gene or of the leptin receptor gene),
  which produces an internal perception of starvation and results in a
  chronic stimulation of excessive food intake.

However, in a newer review it looks as if leptin is involved in more processes than mere survival:

Cloned in 1994, the ob gene encodes the protein hormone leptin, which
  is produced and secreted by white adipose tissue. Since its discovery,
  leptin has been found to have profound effects on behavior, metabolic
  rate, endocrine axes, and glucose fluxes. Leptin deficiency in mice
  and humans causes morbid obesity, diabetes, and various neuroendocrine
  anomalies, and replacement leads to decreased food intake, normalized
  glucose homeostasis, and increased energy expenditure. Here, we
  provide an update on the most current understanding of
  leptin-sensitive neural pathways in terms of both anatomical
  organization and physiological roles.

Jéquier, Eric. "Leptin signaling, adiposity, and energy balance." Annals of the New York Academy of Sciences 967.1 (2002): 379-388.
http://www.ncbi.nlm.nih.gov/pubmed/12079865
Gautron, Laurent, et al. "Sixteen years and counting: an update on leptin in energy balance." The Journal of clinical investigation 121.6 (2011): 2087. http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21633176/

Would it be correct to say that this abstract indicates that leptin could be involved in preventing the decline of metabolism when a person has restricted calorie intake for a period of time?

It looks like it. However see the other review I added.


text:
Are genes associated with obesity selected for?
I've read that there are several SNPs associated with increased risk of clinical or morbid obesity. I was wondering if there is any evidence that these are under positive selection. Would you expect them to be so?
I guess I'm interested to know if they would previously offered a selective advantage and only recently, say in the post-war period in the West morbid obesity become a problem due to differences in the diet.
Related question:
How many, and how severe, are known single gene polymorphisms for obesity?

There are reasons beyond aesthetics why obesity is dangerous. Do not confuse obesity with "chubbiness", the latter can indeed be quite healthy and confer a selective advantage.

This is called the "Thrifty Gene Hypothesis" which was first used to explain why diabetes is so common. Basically it suggests that these alleles would have provided some kind of advantage, over the other possible alleles at that loci, until the environment changed. Then the environment changed and the allele became harmful. Environments are always changing and therefore favour different alleles (variant of a loci).
I suggest the genes linked to obesity in the modern world would, if tested on the old world populations would have been linked to being of a healthy weight. Further, those without it may have been skinnier and more likely to suffer from the disadvantages of being in such condition.
However, this paper present some counter arguments to the thrifty gene hypothesis. Speakman suggests that the genes responsible spread via genetic (allelic) drift rather than by positive selection. It is worth remembering that drift is very poor at spreading new mutations through large populations so there are also weaknesses to his arguments.
One example of a change in the favoured allele caused by an environmental shift is the DDT resistance gene in Drosophila which was present in the population at very low levels for a long period of time. As an aside, it possibly remained this way because it was subject to sexually antagonistic selection - beneficial to females whilst detrimental to males. It then spread through the population when DDT pesticides were used because it obviously became highly beneficial.  Many other examples of environmental change leading to different selection are around, this is just one off the top of my head. Another is the Galapagos Finches in a drought in the late 20th century.
HTH, if not please ask more and if it does then please accept it!

Hi, thanks for the answer and the explanation of the general theory explaining how this would happen.

I would think that genes favouring obesity nowadays in contexts of constant food abundance were in the past useful to store extra nutrients, when the food availability was irregular. One day you get something, you eat as much as you can of it and store the extra in the form of fat, and then you starve for some days, living on the fat you stored on the good day. I think I heard or read about such theories, but I have no reference for it.


text:
Have there been any experiments that duplicate chromosome copies from 23*2 to 23*3 or 23*4?
Deinococcus radiodurans is an amazing bacterium with a fantastic survival rate. It can survive to high doses of radiation, in a complete vacuum and in hydrochloric acid.
How does this bacterium manage to restore damaged chromosome?
It is polyploid with 4 to 10 copies of the genome which are packed in a highly ordered manner.
Does this imply that creating multiple copies of the genome or inceasing DNA base repair activity would increase life span?
Is that even conceivable on bigger life forms?

Could you please try to clarify your question, I have a hard time understanding what exactly you are trying to ask.

I have tried to edit your question. I still can't understand what you are asking. Do you believe that simply increasing ploidity will boost life span?

Upon reading the article: yes seems rigid packaging, no less important than the number of copies of the genome. Over time, the chromosomes are scattered and pile

Polyploidy works out in certain lineages, most famously in plants, but mammals aren't one of them. https://en.wikipedia.org/wiki/Polyploid#Animals

It's an idea that doesn't hold much promise.
Individuals who show diploid/tetraploid mosaicism present "failure to thrive and multiple minor anomalies." according to:

Alonso L et al (2002) Tetraploid/diploid mosaicism: case report and review of the literature. Annales de Genetique 45 177-180

On the other hand, complete tetraploidy is apparently lethal:

Nakamura, Y. et al. (2003) A Tetraploid Liveborn Neonate: Cytogenetic and Autopsy Findings. Archives of Pathology & Laboratory Medicine 127:1612-1614.
Abstract
Cytogenetic and autopsy findings of a nonmosaic tetraploid male neonate, alive until shortly after birth at 37 weeks' gestation, are described. Oligohydramnios, intrauterine growth retardation, cranial abnormalities, and Dandy-Walker malformation were noted prenatally. Autopsy findings included cleft lip and palate; overlapping fingers; low-set ears; simian creases; hypoplastic external genitalia with undescended testes; Dandy-Walker malformation; slightly dilated lateral and third ventricles; hypoplasia of the cerebrum, pons, medulla, pituitary gland, thymus, lung, adrenal gland, and kidney; large ventricular septal defect; and enteric cyst behind the urinary bladder. The placenta was hypoplastic and showed no remarkable abnormalities, except for mild syncytial knots. Chromosome analyses of amniotic fluid cells at 31 weeks' gestation and the umbilical cord blood cells at delivery revealed a 92,XXYY karyotype. G-, C-, Q-, and N-banding heteromorphic studies demonstrated duplication of paternal chromosomes 1, 3, and 15, and maternal chromosome 22. In addition, the results of an analysis with 16 CA repeat polymorphic markers were consistent with duplicated inheritance of 1 paternal and 1 maternal haploid sets to the tetraploid patient. Therefore, it is most likely that the tetraploidy was caused by a cytoplasmic cleavage failure at the first mitotic division.

full text available here.


text:
What is the benefit of near-emptying the bloodstream in the mammalian kidney?
In the normal function of the kidney, the bloodstream is near emptied of fluids as it moves through the glomerulus, in which glomerular filtrate is formed.
As it proceeds through the Nephron, a significant amount of this material is returned to the bloodstream, and only a comparatively timy amount goes into the urine.
Why, in evoultionary terms, is it not more favourable energetically to remove only the small number of molecules, perhaph using specialised channels made of protein and activated only by a certain molecules which need removing, at a potentially huge energy saving?

Probably because it's easier to retain what the body wants than get rid of what the body doesn't want.
What does your body want to keep from your Urine? Pretty much water and selective ions (Cl-, K+, Na+, Ca+2, etc.). Maybe a few other things, depending on how healthy you are.
Now, what does your body want to get rid of in your Urine? Well, anything it can't get rid of in your solid waste. That includes pretty much anything water soluble that could harm you, whether it's Urea, chelating agents for heavy metals, ions your body doesn't want (excess minerals), excess vitamins, sugars (to maintain insulin levels), hormones, liver byproducts, and whatever dark horrors mother nature is concocting for us in the forms of virii or whatever else.
That's just the beginning of the list, but already you should start to see the impracticality of having active transport or coupled transport for everything. The list of transmembrane proteins needed to ferry all of the items your body wants to get rid of is a lot longer than the list of transmembrane proteins needed to keep what the body needs.
Then you have the "unknowns" - whatever else your body hasn't encountered yet, but will still be water-soluble. If the body required some sort of transport across membranes for everything it didn't want, then it would need to adapt to every single new compound it encounters. Given the relatively slow generation periods for humans, if a new compound turned out to be significantly fatal then the slow adaptation could spell disaster for any small populations and create serial bottlenecking events.
So, while it may not be energetically favorable to let water and ions pass into the Nephron and subsequent tubules to be reclaimed, Evolutionarily speaking it's probably strongly selected for. We may expend a lot of energy reclaiming water against its concentration gradient, along with whatever else we want from Urine, but at the same time we get rid of everything else we don't need that's filtered through the glomerulus. It doesn't matter what the "everything else" is - but we know we don't need it, and that's the big key.
With my current level of knowledge (B.S. - Biology) this is the best explanation I could think of, but I haven't read any specific papers nor heard any particular theories on why the kidney's components act as they do.

This is a great answer. Usually biological arguments based only on logic are a little questionable, but you make a very persuasive argument that the alternative arrangement is just not feasible.

I've spent a while thinking about this, but it makes a lot of sense, and before I read this answer, I was thinking along similar lines. With the time that changes due to natural selection take, it must make sense to remove everything that isn't exactly what it needs, so newly synthesised or evolved poisons can still be removed, even without the body knowing their sturcuture.

I would argue from an evolutionary perspective: not all kidneys are created equal. The mammalian kidney has a long evolutionary history and potentially a lot of phylogenetic inertia. Mammals do what they can with what they inherited from their ancestors.
The metanephric kidney, which is what mammals have, is thought to have evolved with the first amniotes (terrestrial, cleidoic-egg-laying tetrapods). However, the metanephros, from when the definitive metanephric kidney evolved, was (is) present in most fishes as well as amphibians. These groups live all or part of their lives in fresh water, so their tissues are hyperosmotic relative to the water. Their problem is not retaining water, but getting rid of all the water that enters their tissues via osmosis. (Marine bony fish have small, aglomerular kidneys.) They produce large volumes of urine, and their kidneys are set up to reclaim essential minerals, etc., as @MCM describes.
So the first amniotes, although now living on land, had a kidney that had evolved in conditions where water was in excess. It evolved for filtering large volumes and reclaiming minerals. Amniotes simply adapted it for a water-poor environment.


text:
Why does vision go blurry after microscope use, and how to prevent it?
After using a binocular microscope recently for about 20 minutes, my vision went blurry and for an hour or so it was much harder to read small text. This occurs to a (far) lesser extent whenever I use it for a shorter time.

Why does this occur?
Which is the optimal microscope light intensity so this does not happen?
What other variables should I beware of?

Wow, I use microscopes daily and I never had this problem. What type of microscope / light source are we speaking about?

@nico It's an 'apex researcher' microscope. For lighting it's a small lamp mounted underneath the slide hole and lens. I don't know what's the standard for microscopes so I can't really comment if it's anything out of the ordinary.

Could it be because you are focusing at a fixed distance for a long time? I would try changing my focus every 5 mins by looking someplace far away.

@Alyosha: OK, that is a fairly standard brightfield microscope. The only thing I can think of is that your problem may be due to the fact that the lenses of the microscope are not top quality and may give some optical aberrations that your eyes got used to during the 20 minutes.

I'll try Memming's idea in the future.
Thanks all.

@Alyosha If you have gotten reliable answers to the problem you faced and you no longer have the same issue, I would request you to close the question.


text:
Is there such thing as "half-life" of dopamine?
If a dopamine is released at T=0 and binds to receptor D2, what determines the time when the concentration of this neurotransmitter bound to the receptor reaches half of the original concentration? In other words, when will the effect of neurotransmitter on the intercell signalling fall in half?
Is there any time estimate of how quickly the brain thinks that neurotransmitter has "fulfilled its purpose" and is to be re-uptaken? Or is this process completely random?
Thank you for your input!

All processes involving reuptake or metabolism of biological molecules are completely random. However, when you look at a large number of molecules over time, the random events combine into a stable, predictable rate of decay. This rate is usually either exponential decay (a half-life) or, more rarely, a constant amount per second.

I don't know what the answer is for dopamine, and individuals probably vary in how zealous their brains are about dopamine reuptake.

The half life of dopamine in the extracellular space is of the order of 200 milliseconds.
Yavich,L. (2007) Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum. J. Neurosci. 27:10196-10202
In Figure 1 of this paper the authors present values for the half-life (τ) of dopamine elimination from extracellular space in the caudate nucleus and prefrontal cortex of mice as:
caudate nucleus: 0.2 +/- 0.03 sec
prefrontal cortex: 1.92 +/- 0.22 sec
Apparently this is because dopamine is usually inactivated when the presynaptic cell takes it back up using the dopamine transporter, but in the prefrontal cortex uptake is instead via a lower affinity norepinephrine transporter on neighbouring neurones. Thus the value of 200 milliseconds seen in the caudate nucleus is probably more typical.

Interesting. Does this mean that upon release, dopamine has 200ms to either bind to a receptor or be reabsorbed?

If we think of release as instantaneous, we now have a pool of extracellular dopamine. This will begin to bind to receptor, setting up an equilibrium between free and bound. The free dopamine will also be taken up by DAT, and because the binding to receptor is a reversible process, as the external pool shrinks the level of DA-receptor complex will shrink. An individual molecule could be taken up without ever binding to a receptor, or could undergo multiple receptor binding/release cycles before being taken up. The half-life reflects the interaction between these processes.

If I understand correctly, the DAT cleans up extracellular and bound DA, and deposits it back within the neuron. As less and less extracellular DA is available, there's a higher chance that bound DA will be recovered. Is this correct?

Dopamine (DA) secreted by neurons is selectively reuptaken by the dopamine transporter (DAT), present on nerve terminals.

(source: inist.fr)
Image source: Plasma membrane monoamine transporters: structure, regulation and function - Torres et al. - Nat Rev Neurosci., 2003
DAT acts as a symporter, using the Na+ and Cl- gradients to generate the energy required to transport DA back in the cytosol.
The mechanism of reuptake has been investigated in vitro allowing the description of a model for DA reuptake by DAT.
In particular, from the abstract of this paper:
A multisubstrate mechanism of striatal dopamine uptake and its inhibition by cocaine. - McElvain and Schenk, Biochem Pharmacol., 1992

Dopamine uptake was found to be first order in dopamine with a Vmax of 582 pmol/sec/g wet weight and a Km of 1.2 μM. The results of experiments in which choline and isethionate were substituted for Na+ and Cl−, respectively, suggested that the uptake process is second order in Na+ and first order in Cl−. Multisubstrate analyses of the initial velocities of uptake over the concentration range of 0.025 to 1.5 μM dopamine suggested that the mechanism of binding of dopamine to the uptake carrier is a partially random, sequential mechanism where dopamine or Na+ binds first with the uptake carrier and Cl− binds last.

A transport scheme is reported in:
Dopamine Neuronal Transport Kinetics and Effects of Amphetamine

Scheme 1 is a kinetic scheme for a simple carrier adapted from that of Stein (1986) for the DAT. The subscripts o and i represent the outside and inside, respectively, of a DA neuron. Scheme 2 describes a possible mechanism for
  the cotransport of another species. All symbols are as in scheme 1 except that A corresponds to amphetamine.

From the text

This scheme describes transport as a series of steps: the competition between binding and dissociation of the substrate to the transporter on the  extracellular side, a similar process on the cytoplasmic side, and an equilibrium between the unoccupied transporter facing toward the extracellular or cytoplasmic side. The driving force for inward transport arises from the cotransport of Na1 and Cl2 as well as the membrane potential difference
  (Stein, 1986; Sonders et al., 1997). Biochemical (Krueger, 1990) and electrophysiological (Sonders et al.,1997) studies have established that DA transport is accompanied by transport of at least two Na1 ions and one Cl2 ion and that DA transport can be bidirectional in isolated preparations.

If I'm reading this correctly, then Dopamine is randomly extracted from receptors, right?

Not really "extracted"... dopamine will randomly detach from the receptor, and randomly bind to DAT. The speed of this may depend on the actual concentration of dopamine, dopamine receptor and DAT present in the system.

This is an attempt to illustrate how a system like this behaves kinetically, to help Alex visualise it. The model shown below contains external dopamine which can bind reversibly to a receptor. The unbound dopamine is subject to irreversible reuptake.

I built a quick simulation using Copasi. I haven't made any attempt to refine the parameters to fit the information in my previous answer - I'm just trying to illustrate qualitatively how the three different pools of dopamine (free external, bound external, internalised) behave in this kind of system. As @nico says, there is no question of extracting the receptor-bound dopamine - it will dissociate as the free dopamine concentration falls due to reuptake.

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


text:
Nucleotide frequencies in Kimura's two-parameter model
Here's an excerpt about Kimura's two-parameter model from Felsenstein's Inferring Phylogenies:

"The model is symmetrical, and one can immediately see that, after
  enough time has elapsed, it will be equally likely for the base to be
  a purine or a pyrimidine."

I think I understand the assumptions of the model but it's not obvious to me why the equilibrium frequencies are equal. Why is that so?

If sufficient time has elapsed, there will be a large number of transversions present between the original base and the final state. The initial state will therefore not matter.
Say, you flip (turn over, not toss) a coin at random intervals. For short time and few flips, the initial state will matter. But if you go on flipping it for millenia, the final state will be essentially random -- you will not be able to tell what was there in the beginning.

Good answer. In the case of the model, am I right to think that equilibrium frequencies are equal because there is an equal chance of a base being a pyrimidine or purine in both the initial and final states? With enough time the base will mutate multiple times and can also mutate back to it's original state, therefore, the initial state does not matter. ... Imaginary sequence of events for a single nucleotide: A>G>C>A>G is just as likely A>G>A>C>T and in this example there is one transition and one transversion. Am I correct in my thinking?


text:
Interpreting SNP-in-gene associations from GWAS studies
For most SNPs identified in GWAS studies, is the underlying assumption that if it is indeed associated with a phenotype (and lets assume its associated because it affects protein function), that you don't need two knocked out copies of that gene for it to confer susceptibility risk to the individual?
In other words, is my assumption that GWAS is likely uncovering alleles that confer risk in single copy, correct?

Why would a SNP ID tell you anything about its effects? To my knowledge you couldn't say anything about phenotype from just a SNP, but I'm not professional on this.

@Armatus, there are plenty of diseases with disease phenotypes from a single SNP (e.g., sickle-cell anemia as a classic example, but there are many others).

@leonardo Of course, I wasn't saying that a SNP can't have an effect; but that you can't predict the phenotype just knowing there's a SNP [unless you investigate its effect] (cf. your answer)

In short, yes.
If a gwas study links a SNP to a particular phenotype then yes, it is an effect of a single copy. Bear in mind, however, that a SNP is not a knockout or even a knockdown. It can be, but it is not always the case.  SNPs can produce a change in the protein sequence or in the regulation of the production of that protein. Both types of variation can result in a phenotypical change.
In any case, SNP information is always about a single allele, I imagine that you can find cases where a cell is homozygous for a particular SNP but is is not necessarily, or even often as far as I know, the case.


text:
Why is Botulinum toxin the most potent poison known?
Botulinum toxin (trade name Botox) inhibits acetylcholine release in neurons and causes botulism, an acute paralytic disease which leads to nerve degeneration and takes a long time to recover. I've read the statement that Botox is the most potent poison we know a few times now and was wondering why exactly it is. All sources I've found only claim that it is, without explanation.

do you want to know the mechanism? Or numbers for comparison?

A quick search for a list of LD50 (median lethal dose; half of the people will die with that dosage) gave me 1 ng/kg for Botulinum toxin. This is pretty darn small amount, and in fact the smallest amount within that table.

True. Also look at the potency page on Wikipedia

This doesn't seem to answer the why, it doesn't explain the reason for the high toxicity.

@MadScientist I didn't know if OP wanted to know "why it is known for the most potent poision" or mechanism of Botox. I asked OP via comment, but with no answer so far.

Thanks for this answer, LD50 is a good criterion for a statement like this and I expect many of the sources where I've read it are probably referring to this. Though the question remains what exactly gives BT such a low LD50 - it's not the only neurotoxin out there, and some members of the BT family have much higher LD50's despite a very similar mechanism of action. I'm afraid that might be a question yet unanswered by science though.

The biochemical mechanism of BT is pretty well laid out at Wikipedia already. The toxin is likely very potent because (1) it is targeted to neurons; (2) neurons endocytose BT; and (3) the BT light chain's protease activity is able to cleave a wide range of SNARE-complex proteins which effectively disrupt the neurons ability to secrete monoamine neurotransmitters, and peptide hormones. Basically, the neurons are completely inhibited from transmitting nerve impulses.

Many poisons simply bind to and deactivate their target proteins. BT proteases can bind to, damage, and unbind to find other targets. Good answer.


text:
Multiple sequence alignment - how to align everything to 1 gene sequence?
I'm having trouble aligning 3 sequences together - the total gene (~2500bp) and the forward and reverse sequences that are ~1000bp in length. Now I'm using Clustal X2, but the problem is that the program does complete alignment, which is useless for me right now.  Could anyone recommend or suggest any parameters or methods on how to align more that 2 sequences together, but that each sequence is aligned to the first one (the total gene)?
Thanks!

Which kind of result do you want to have? One alignment with three sequences, or two pair-wise alignments? If the former, what would you do if one of the 1000bp sequences causes a gap in the reference sequence?

Could you please clarify your question? The reverse strand of a sequence is not alignable to the forward strand. Also, i don't understand what you mean by complete gene, forward and reverse sequences. Do you mean the genomic sequence, the transcribed transcript and the reverse complement of that transcript?

Like the others, not sure that I understand, but if these 1000 bp sequences are perfect matches to the 2500 bp sequence then can't you generate what you want just by editing a file which shows the dsDNA sequence? Shouldn't take too long.

Your question is not very clear, but I think what you are trying to do is align sequencing results to a reference gene sequence.
Your total gene sequence spans ~2500 bp. It sounds like you have a forward sequence at the start of gene, reading only about 1000 bp and the reverse strand reading in 1000 bp from the end (if this is Sanger sequencing, you likely only have 800-900 bp of accurate base reads by the way). Therefore, you have a gap of about 500 bp in the middle of your gene of interest.
There are (at least) two ways to do the alignment, and I would suggest the manual method if you are trying to verify gene sequencing.
Manual Method:

In a word processing document, paste in your gene-of-interest (or the recombinant gene you are trying to make), as well as the base reads from the forward strand, and the reverse complementof your reverse strand. Make sure you remove any whitespace like line breaks and spaces as this will disrupt the rest of the process.
Manually select a small portion of your forward read (20-30 bp for example) and search for the same "phrase" in your gene-of-interest. If you find it, highlight it in both the sequence it came from and the gene-of-interest so that you know you have already matched them.
Carry on with adjacent bases for the forward strand. Repeat for the reverse complement of the reverse strand.

Semi-Automated Method:

Go to NCBI Blast, and under the heading Basic Blast, click "nucleotide blast".
Check "Align 2 or more sequences."
Enter your Query Sequence as your 1000 bp sequences, entered in FASTA format. FASTA format will allow you to enter multiple sequences, but if you just enter one at a time, that will work perfectly well. Results will only display one at a time anyway.

For example:
> sequence name here
ATCGATCGATCGATCGATCGATCG....

Enter your gene of interest as your Subject Sequence. Format does not matter here, but for consistency, I use FASTA format.
Keep "Highly similar sequences (megablast)" selected. You shouldn't need to play with these parameters, they just change how the alignment method penalizes alignments for gaps and mismatches.
Hit BLAST.
Interpret your results. I've included an example of BLAST results below.

At the top of this window is a schematic, showing exactly how much of the the query sequence aligns with the subject sequence. The longer the line, the more bases align. Similarly, the closer the colour of the line is to right of the scale (e.g., red), then the more continuous the segment is indicating a longer, continuous alignment.
Below the graphic is a table of results. Briefly, the table highlights all possible alignments that the BLAST algorithm has found, including how much coverage there was, confidence of the alignment and length of alignment coverage.
Below the results table, are the detailed results which were summarized in the table. This detailed report shows you exactly which bases align or mismatch, or any gaps. The top line is the subject sequence; the bottom is the query sequence. The other thing to keep in mind here is the Strand line. In this case, it says "Plus/Plus, meaning that the aligned sequences were the forward sense, or plus strand, of each of subject and query sequence, respectively. If you entered a reverse complement sequence instead (such as the reverse sequencing results) then this would change to "Plus/Minus".
From here, you will still need to manually line these results up to your gene of interest to determine exactly which portion of the gene is missing sequence coverage, as well as any mutations that may have cropped up in the cloning process.

Multiple sequence alignment is a common bioinformatics problem and there are many tools available to solve it.
This paper provides a good comparison of the following tools:

Thompson, et al.  A comprehensive benchmark study of multiple
  sequence alignment methods: a current challenge and future
  perspectives

The paper addresses the following methods:

ClustalW
MUSCLE
DIALIGN-TX
KALIGN
ProbCons
MAFFT

this answer may be a bit sparse, but these are the most typical solutions to the question

If you want to align sequencing results over the reference sequence and check the sequences for presence of spontaneous mutations, the easiest way would be to use Sequlator.
Sequlator is a convenient because it has a pairwise alignment, reverse complement, editing and navigation functions but lacks irrelevant functions. With Sequlator one can manipulate any way existing alignments, or manually assemble sequencing reads into an alignment with the reference sequence. After elimination of poorly sequenced fragments, discrepancies with the reference sequence are revealed in the consensus of the resulting alignment. And it is free and Java-based meaning that it works on Windows, Linux and Mac computers

In Mafft, the command to align new sequences to an existing reference alignment is:
mafft --add new_sequences.fta existing_alignment.fta > output.fta

See this part of the documentation for more details.
It is a nice program to use for alignment, in any case...


text:
Why do living organisms replicate itself or procreate
Why do living organisms spontaneously replicate itself or "procreate" (my understanding is that it does).
From a uni-cellular and micro-organism point of view. Is there some sort of stimulant in the environment? A chemical reaction that causes it? Is is there a physical or emotional motivation? Is it by choice?
Note: I may have some terms used wrongly as I am not a biologist. In this question, I am interested at living organism nearer the forms of single smallest unit of life form.

Its unclear what you're asking. Do you want to know about the biochemistry of the cell cycle or how evolution drove organisms to replicate? "Is there some sort of stimulant in the environment?" Nutrition is required and some molecules can encourage rapid division. "A chemical reaction that causes it?" A complex biochemical one yes. "Is is there a physical or emotional motivation?" No. "Is it by choice?" No.

If there are enough nutrients, a unicellular organism will "eat" and grow until it reaches a certain size. Through different mechanisms, it can sense that it is large enough and has enough metabolites to divide. Then, the organism will duplicates its DNA, separate the duplicated DNA and divide. (This is called fission for prokaryotes.)
So why does it happen? One of the characteristics of life is replication. In favorable conditions, the organism replicating the fastest will out-compete all other organisms. So there is no motivation or stimulus of some sort needed (or possible), by their very nature cells are made to divide as soon as feasible.

"One of the characteristics of life is replication" is that part of the definition of life? i.e. if a thing has all characteristic of living organism except "desire" to replication, then it is NOT a living organism?

@Jake yes, well perhaps not "desire" but a thing must replicate itself/reproduce to be classified as alive.

Yes, reproduction is part of the definition of life. However, this doesn't mean that a sterile animal doesn't live.

@RoryM Thinking out loud: Due to pre-perception of a living thing, defining it with "ability to reproduce" seems to suggest that when the thing reproduce, it does so under its controlled will. However if i am asked WHY a kitchen sponge absorbs water with its ability to do so, I am unlikely to suggest that the sponge has a will. In a way, the sponge MUST absorb water. So to answer the "why", either living thing MUST reproduce, or the more approperiate question becomes, "does living thing desire to reproduce" or "can living thing inherently stop (temporarily) reproduction?" Hope I make sense...

In your words, living things "must" reproduce - they have the ability to do so, and if the environment allows it, reproduction will spontaneously (i.e. without "will", "intention" or "motivation") happen. Compared to the original first molecule that had this ability, even the simplest cell is an incredibly complex organism with highly sophisticated control mechanisms which integrate all the necessary requirements for favourable reproduction and scan the environment (both internal and external) for these conditions.

This is a very interesting question but the answer (or as much of the answer as is known) can fill a few books. There are many many signals that control cell division.
As a horrible simplification, the cell can be compared to a car parked on a slope with a driver's foot on the brake. If she lifts her foot, the car will roll downhill. In the cell, there are various proteins (P53 is the most famous) that have their metaphorical foot on the brake. Various external and internal stimuli can cause these proteins to stop suppressing replication and the cell will then continue its cycle and replicate.
So, a cell's "natural state" is to replicate, there is a complex network of interacting factors (primarily proteins) that actively block replication in resting cells. When the conditions are "right" (what that means depends on the cell in question) the block is removed and the cell replicates.

So in your metaphor, rolling down slope is the process of replication?

@Jake, yes, the point I am trying to make is that replication is the natural state of cells and needs to be actively prevented for the cells to not proliferate.


text:
What are the biological mechanisms behind the increase in cancer risk and alcohol consumption?
Alcohol consumption is known to be a risk factor for developing cancer. Compared to obvious causes like tobacco where one is exposed to known carcinogens, I don't see an obvious mechanism by which alcohol consumption would increase the risk of cancer.
Is there anything known about the mechanisms by which alchohol consumption affects cancer risk?

Am I missing something here or is it just for the rather obvious reason that alcohol is a strong cell toxin that, taken often, causes constant low-level inflammation and stress (and thus accumulating damage) in tissues?

Our pharmacology course taught alcohol essentially as "is an extremely unspecific molecule and doesn't really bind to anything, but we take it in doses high enough to drive random reactions everywhere" (its effects start at mM concentrations, 1000x higher than drugs tend to). It's tiny so I don't see a barrier preventing entry into the nucleus and randomly reacting with DNA.

Asian Glow is linked with cancer. Actually tackling alchol related cancer is a fairly hot topic these days.

There aren't many studies which associate between alcohol consumption and cancer to my knowledge. The association is more with metabolic diseases because the liver is affected.
Alcohol is oxidised to acetaldehyde by alcohol dehydrogenase. Acetaldehyde may also, in turn affect the cells by DNA damage if it is not metabolized quickly to acetyl-CoA (perhaps in a manner similar to formaldehyde or by formation of Schiff's base with nucleotides). The other way by which alcohol is metabolised is through cytochrome-p450 (CYP2E1) which produces ROS (Hydrogen Peroxide), that may lead to carcinogenesis.
You might want to check this review.

Welcome to the site. It would be great if you could provide citations for your statements if possible (e.g., low correlation between alcohol consumption and cancer).

@kmm.. corrected :)

I agree damaged is caused by acetaldehyde (also the cause of asian glow) but I believe that your selected enzyme is incorrect.

yeah.. i mixed it up slightly .. but cyt-p450 is also involved..


text:
How to get smallest subtree containing a set of nodes from BioPhylo?
I'm testing out various phylogenetic libraries in Python. I want to read in a Newick tree, then, given a list of taxa, generate the smallest tree that contains them all. This task is quite simple and efficient in dendropy and ete2:
newick = '((raccoon, bear),((sea_lion,seal),((monkey,cat), weasel)),dog);'
taxa = ['raccoon', 'sea_lion']

import ete2
tree = ete2.Tree(newick)
pruned = tree.prune(taxa)

import dendropy
tree = dendropy.Tree.get_from_string(newick, 'newick')
pruned = tree.prune_taxa_with_labels(taxa)

I'm trying but failing to find equivalent functionality in the Bio.Phylo package. Trees do have a "prune" method, but it prunes a single node from the tree.

The common_ancestor function should give you the result you want: it gives you the tree (I think) that is the most recent common ancestor of all the given targets.

Sorry for digging out this old question. But I think that given you have an unrooted tree, the common ancestor maybe not the correct answer.
What you need to do is this:
Suppose you have an unrooted tree with n tips (species), and thus 2n-3 branches. You should cut the tree in half in all these possible branches. By doing this, you will have 4n-6 subtrees. The smallest subtree containing all your selected species will be your answer.
This is different from common ancestor because for an unrooted tree, it could be put in a way that those species not picked by you are clustered first, all your selected species becomes the outgroup. But if you "re-root" the tree properly, you could still make your selected species cluster together as a small, exclusive clade.

You are right that this wouldn't be correct for unrooted trees, so thanks for responding. I failed to mention in the question that the trees I was working with were in fact rooted (so the example tree was perhaps a bit misleading.)


text:
Will a bone marrow transplant change one's blood type?
Will a bone marrow transplant change one's blood type?
Or is the donor blood type matched with the person before transplant?

Bone Marrow transplants are extensively matched in order to prevent rejection. Current matching methodology is HLA matching: Stanford Children's Hospital Guidelines

How are a donor and recipient matched?
  Matching involves typing human leukocyte antigen (HLA) tissue. The antigens on the surface of these special white blood cells determine the genetic make-up of a person's immune system. There are at least 100 HLA antigens; however, it is believed that there are a few major antigens that determine whether a donor and recipient match. The others are considered minor and their effect on a successful transplant is not as well defined.
Medical research is still investigating the role all antigens play in the process of a bone marrow transplant. The more antigens that match, the better the engraftment of donated marrow. Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin reproducing new blood cells.

However, because the HLA matching doesn't utilize blood-type and the recipient's marrow is destroyed in the process, then if the donor's marrow produces different red blood cells - then so will the recipient with time:

Does my blood type change after SCT or [Bone Marrow Transplant]?
Yes.  The recipients blood type eventually changes to the donor type.  That means if you had a blood type of A+ prior to transplant and your donor had a blood type of O, eventually your blood type would become O.  I may take several weeks, possibly months for your original blood type to disappear, but eventually it will.

What's interesting is that blood-typing is not be expressly necessary with the modern bone marrow transplant process. The danger of mixing two antagonistic blood types in vivo is that the recipient's immune system attacks the foreign red blood cells resulting in body-wide rejection. However, because the immune system's response capabilities are decimated by the destruction of the recipient's bone marrow (usually accomplished via chemotherapy or radiation), it can't mount much of an attack in the first place. That's not to say the body can't mount an attack, or that the donor's tissue can't mount an attack on the recipient (Graft-Versus-Host-Disease [GVHD]) - but the better the HLA match the less likely issues are to arise, which is why we do the more accurate and relevant HLA matching instead of blood-typing.

Great answer. And it's pretty amazing that blood type can change, I never would've thought of that!


text:
Where does an organism store reserves of amino acids?
Where does an organism store reserves of the amino acids it needs to build various proteins it needs:

in the liver?
in the blood?
in every cell?

In the sense that you have asked the question, humans have no stores of amino acids. Amino acids obtained from the diet are quickly incorporated into new proteins or are metabolised as fuel molecules.
Proteins are subject to continual turnover, and the amino acids that are released by degradation are either reused or metabolised in exactly the same way.
This is one of the reasons why the diet must contain appropriate levels of essential amino acids (those we cannot make for ourselves) since these are continually being released from proteins and used as fuel - we have no mechanism for storing them in case of future dietary deficiency.
During starvation the protein turnover process releases amino acids from muscle and these are mainly used as fuel molecules. This is why muscle wasting occurs in starvation, although the mobilisation of fat reserves helps to delay this as long as possible as tissues, including brain, switch over to relying on ketones (derived from fat breakdown).

In fact amino acids can't be stored as monomers, As monomers they would generate tremendous osmotic pressure. So they have to be stored as proteins but there is no good way to build an inactive protein without needing specific structure, which would defeat the purpose of storage. the closest we get is converting them to fatty acids and storing them that way.

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


text:
What makes urine smell acrid?
Occasionally, after someone's been, there is an awful acrid smell lying about long after them. What causes this? The food that they've eaten? Urea less dilute due to dehydration?
If it helps I've noticed it only with older males.

Acrid or like ammonia?

Acid (not ammonia on the basis that it doesn't smell like cat urine).

The odor comes from urea. Urea will slowly undergo displacement to become ammonia, but when it's fresh, it has a strong odor. Other odors do come from food, notably coffee and (in some of the population) asparagus.

I always thought that urea was oderless(thus urine not smelling when it is fresh) and that the reaction that urea goes through to be turned into ammonia is what gives that urine smell.

This answer lacks sources and as far as I understand contradicts two Wikipedia articles 1 2 that state that smell becomes stronger ("worse") with time but is weak in the beginning. Therefore imho this can not answer the awful acrid smell mentioned by OP, unless the toilet was not flushed.

Urea could be one. Also, be aware that there are other sources of urine. Asparagus is a famous one. I am still amused because I once thought something was really off with me ( a male, not older yet) when my urine smelled. I panicked and then found out that it was because I had consumed asparagus in a prior meal.
I am not sure if urine starts smelling differently in certain older males, but take diet into consideration.

Urine on the ground smells when there is no rain. Water evaporates, but solutes in it do not. Rain washes solutes deeper into the ground.
In the urine of a healthy person it is urea and bilirubin that smell.
Other causes of smelly urine:

Certain foods, like asparagus, onions, garlic and coffee can add to urine odor.
Dehydration (more concentrated solutes)
Untreated diabetics secrete glucose and ketones in urine
Urinary tract infection
Liver disease

Here's one source:
http://www.healthline.com/health/urine-odor#Diet


text:
Histone marks mechanism
I am slightly confused about the mechanisms that makes histone modifications associate with gene expression.
That is, H3K36me3 is believed to be present in actively transcribed genes, H3K27me3 in repressed regions, etc. What is the mechanism that makes the presence of H3K36me3 to be in active regions, etc.? Is it causal or just an association?

First we must remember what a nucleosome is: a segment of DNA packed with proteins called histones. This is the initial step to turn the DNA a more compact structure. Citing the advantages of an extremely compact but flexible structure like chromosomes would make this answer a little longer (if you want, I can add them later), and to answer your question faster, we'd better keep moving on the discussion. Epigenetics and gene expression are so beautiful that they have many mechanisms to regulate or change gene expression, and you mention one, which is done by reversible covalent modifications on histones. Such modifications are executed by especific proteins, that can do methylation, acetylation, phosphorilation in some aminoacids of histones. When an aminoacid of a histone is linked with charged groups (e.g: methyl, acetyl) its charge is altered, and depending of the resulting charge (negative or positive), it can reduce or increase the afinity between the histone tail and the adjacent nucleosomes, and therefore, make the nucleosome more compact and less accessible or less compact and more accessible, respectively. But the main effect of these covalent modifications on histones is that the groups added to the aminoacids act like markers indicating for proteins involved in expression (like transcriptional factors and RNA polymerase) that some genes are switched on or switched off. The patterns of this modifications (which one repress or estimulate gene expression) is not completely understood yet.An example of how a certain region is chosen to be marked for expression or repression: Consider an organism that has received a repressed gene related to obesity from its parents and this organism is lazy, eats a lot, has a sedentary life. As a result of all this stimulation, the proteins responsible for altering the histones of the gene related to obesity can be activated or recruited by others proteins, and make covalent modifications in a way that the histones of that gene now are marked for it to be expressed. This organism can pass the new mark to the its children and they will have propensity to obesity due to the activated gene. (This final example was an experiment of epigenetics using rats, I saw a long time ago, so I can't remember the reference).And about if it's casual or not, the marks of regulation in a sequence of DNA can't be casual. For each one or two modifications of histones there is an enzyme that will only do its function if some event is already triggered or if it's triggered during the cell life depending on the environment the cell is exposed to. So millions of cells of a same tissue that have the same function would not have the same pattern of expression for the main genes related with that function by chance. Therefore, regulation of gene expression is very refined and histone marks are one of the many mechanisms that together dictate if a gene is repressed or expressed.


text:
In a human, what non-germline cells have the highest/lowest mass?
I'm just curious which cells are largest/smallest in the human body other than sperm/ova.

Definitely by mass or by length?

Am I missing a clue or is this as straightforward as: biggest cell - ovum, smallest cell - sperm? Or are you only concerned about non-germline cells?

Sorry to move the ball @Armatus, but yes, I was thinking non-germline (I give you a comment upvote anyway for the "real" right answer).

Definitely by mass @Rory M♦

Large cells: adipocytes, the cells that store fat are possible the largest in humans, because after puberty they rarely divide and just enlarge if a person gains weight. A typical adipocyte is about 0.1mm in diameter, but may be a lot larger. Another good candidate is a megakaryocyte, which is a gigantic (up to 0.1mm), cell with multiple copies of its genome producing blood platelets. Depending on your definition of a single cell, also myocytes may be considered large cells, because during development several cells fuse to form one muscular fibre. Additionally, myocytes gain weight if a person excersises and strengthens muscles.
Small cells are more common, and it is difficult to point to some consistently smallest cells. The smallest kind-of-cells are definately platelets and erythrocytes (red blood cells - they are anucleated, thus may not be considered "real" cells). Generally, the part that determines the minimum size of the cell is the nucleus, so any cells, that are more-or-less metabolically inactive may be just a tiny bit larger than the size of their nucleuses. These may be for example polar cells, the tiny cells, that carry the excess of genome during meiosis in women and die soon afterwards.
If you are interested in all kinds of strange cells inside yourself, you might start by browsing this beautiful, though longish list.

If multiply nucleated cells count, the syncitiotrophoblast of the placenta is a big candidate :)

Right, I forgot about that one. I think I just focused on adult cells.

Are nerve cells not larger (1 meter or more)?

Quote: Definitely by mass @Rory M♦ – joseph_morris 2 days ago

If tissue density is constant, then volume is proportional to mass. I would posit that a very long axon has more volume than an adipocyte.

Long human axons are up to 20um in diameter, their bodies are very small, so I think we can assume, that such a very long human axon is a long, thin tube of 20umx1m. This means it's volume is about 31,400,000um^3. If a large adipocyte is 0.2mm (200um, same source as previously) in diameter and a sphere, it is 4,190,000um^3. So yes, an extremely long axon is larger than a large adipocyte, but I could go on searching for a largest adipocyte known to science and I'm almost certain, that I could find something larger ;)


text:
Do adipose cells divide in adults?
I have a dim recollection of having heard that when humans gain weight, adipose cells just get larger, rather than dividing.  True?

The Wikipedia entry for Adipocyte has a whole section on cell turnover. "If excess weight is gained as an adult, fat cells increase in size about fourfold before dividing and increasing the absolute number of fat cells present." citation

@QuietThud please consider fleshing out your comment a little and posting it as an answer.

My foray into the literature suggests that mature adipocytes do not divide. See, for example:

Lefterova, MI et al. (2009) New developments in adipogenesis. Trends in Endocrinology and Metabolism 20:107-114

In the context of looking at the possibility of stimulating the conversion of white adipose tissue to brown adipose tissue, the authors outline the way in which the expansion of adipose tissue occurs by a process in which fibroblast-like pre-adipocytes differentiate into cells capable of storing lipid droplets and responding to insulin.
It appears therefore that expansion of adipose tissue occurs by the generation of new adipocytes. Thinking of the morphology of a fully-loaded adipocyte (a lipid droplet surrounded by a narrow band of cytoplasm) it seems rather unlikely that these cells would be capable of division. The Wikipedia citation linked to by QuietThud in the comments to the OP is to a popular book on nutrition, not an authoritative source.