text:
Why AZT is selective towards HIV and doesn't impair human DNA replication?
I've found this article, which is a very old one (from the time when nucleoside analogs where researched as a possible way to prevent replication of virus genetic material, before the HIV epidemics).
In the last page, the authors suggest that cellular repair enzymes could remove azidothymidine (AZT, zidovudine) from cellular DNA if it's incorporated, but viruses' polymerases lack this ability.
As it's an old article, I would like to know if this hypothesis was confirmed. As both azidothymidine and thymidine can form normal base pairings, how could human enzymes detect an azidothymidine was incorporated?
If someone is not familiar with AZT mechanism: basically, it's an analog of thymidine which has an azide group instead of 3'-OH

It can be phosphorylated by cell kinases and incorporated to the growing DNA chain; however, this will stop the polymerization because it depends on free 3'-OH. The natural question which follows is: why wouldn't AZT also block the replication of human cells' DNA?

it does and that is why the side effects

http://www.tandfonline.com/doi/abs/10.1080/15257771003741018 It has been shown to poison mitochondrial thymidine kinase, amongst other side effects.

Stalled replication forks can be repaired. See this paper, for example: http://cshperspectives.cshlp.org/content/5/5/a012815

@WYSIWYG it has side effects, but they're not compared to nucleotide analogs that target cancer cells, for example cytosine arabinoside.

Now that I'm getting a closer look at that structure, the AZT looks wrong, shouldn't that 3' amine be an azide?

@User137 indeed, it's $N_{3}$

Retroviruses depend on being able to convert their RNA genome into a DNA copy, and have a reverse transcriptase enzyme to do that. This unique activity is not found in human cells, allowing for potential antiviral therapy if a drug can be used to inhibit the reverse transcriptase while not affecting the human enzymes.
AZT is one such drug, by mimicking the nucleotide thymidine, it can it can act as a substrate for nucleotide kinases and become 5' phosphorylated. AZT is phosphorylated by host cell enzymes, specifically thymidine kinase, this means that the levels of AZT phosphates are similar between HIV infected and non-infected cells. Once the 5' triphosphate is formed, the drug is a substrate for the viral reverse transcriptase. If an AZT is incorporated into the DNA backbone, it terminates the DNA because the 3' OH is not available for further polymerization.
However, at high enough doses AZT can be toxic to healthy cells. One mechanism for toxicity is the depletion of thymidine, because AZT competes with thymidine for the kinase enzymes, but is phosphorylated at a slower rate. At high doses, >1mM, AZT can act as a substrate for human DNA polymerases. Thankfully, AZT is about 100 fold more selective for HIV reverse transcriptase than human DNA polymerase.
The mitochondrial DNA polymerase seems to be a little more sensitive to AZT than other human DNA polymerases. This can lead to toxicity in the heart, skeletal muscles, hepatocytes, or other cells that use a lot of mitochondria. This toxicity is generally reversible if doses are reduced.
For more information, read about other nucleotide analogs, such as acyclovir, ganciclovir, and others which work through similar mechanisms.

All you wrote is relevant, and thanks about the suggestion of the other nucleotide analogs. However, I still don't know the molecular mechanism that would explain that "AZT is about 100 fold more selective for HIV reverse transcriptase than human DNA polymerase". There are other nucleotide analogs (such as cytosine arabinoside) that actually impair human DNA replication, so they're used to target cancer cells.

Maybe (just a hypothesis) the higher rate in which the virus proliferate could make it more susceptible (by a similar mechanism for which the traditional chemoterapeutic drugs target cancer cells). However, just that doesn't appear to be sufficient, since AZT or acyclovir have fewer side effects than chemoterapeutic drugs...

@ElCid Even though the nucleotide analogs have the same general mechanism, they have different structures. This could explain why some bind to human enzymes more efficiently than others and account for the side effects. I'm not aware of any binding studies or crystalography to support this, but it probably exists.


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What is Mendelian Randomization, and how is it used to infer causality in epidemiology?
Studies of human traits and diseases are inherently confined to observational studies, known as epidemiological studies. This can make it very hard to determine what actually causes a particular disease or trait, and what is just a by-product or biomarker of the disease.
Mendelian randomization is a statistical technique used by genetic epidemiologists to determine causal effects, for instance whether a biomarker actually influences disease risk, or whether it is just a statistical association.
From basics, how can genetics be used to determine causal associations between traits (such as blood markers) and increased risk of disease, and on what assumptions is this based?

Epidemiological studies analyze human observational cohort data to try to statistically link disease risk and biomarkers. For instance, it is know a well know fact that smoking increases the risk of lung cancer, yet before the 1950s it was widely considered otherwise until observational evidence proved irrefutable (Levin, 1950).
Confounding
However, inferring causality using observational data can be tricky. For instance, there is a very strong statistical association between ice-cream sales and risk of drowning in the UK. In this example it is quite clear that the association is confounded - that is, there is a 'hidden' variable we have not accounted for that links the 2. It is easy to infer that ice-cream sales don't increase your risk of drowning, but the 2 are correlated because both ice-cream sales and risk of drowning increase at the same time of year; both are positively correlated with 'nice weather' traits.
In the above example it is easy to say that the relationship is confounded. However, in a hypothetical study on type-2 diabetes that finds higher blood hematocrit (% volume of blood made up of red blood cells) is associated with increased odds of being diabetic, it is less clear whether higher hematocrit increases susceptibility/risk of becoming diabetic, or whether diabetes increases hematocrit. Longitudinal studies that follow the same individuals for many years help determine which came first - this is based on the assumption that if raised hematocrit is associated with increased risk of diabetes 5 years later, it is more likely that hematocrit is causal, and you have a biomarker for diabetes risk (although you still cannot say it is causal, it may just be a proxy for another 'hidden' trait, or the effect may be mediated by another unmeasured marker).
Causality
Genome-wide association (GWA) studies have become increasingly popular since the completion of the human genome project, and there are currently (15th August 2012) 7039 genetic variants (SNPs, single-nucleotide polymorphisms) documented in the catalogue of published GWA studies (www.genome.gov/gwastudies). These SNPs have been robustly associated with traits such as 'risk of type-2 diabetes', or 'blood adiponectin levels', by large genetic epidemiological studies, usually with many thousands of participants sampled.
The key point about SNP associations is that the direction of effect is always known; a particular SNP may affect your adiponectin levels, but adiponectin does not affect the SNPs you inherit.
Mendelian Randomization
In an observational study that finds an association between (for example) circulating triglyceride levels and type-2 diabetes (using fasting glucose and insulin as 'proxies') it is not possible to determine the causal direction; do triglycerides increase risk of diabetes or vice versa? (This is an actual case study by De Silva, et al. 2011).
Using the assumption that the inheritance of SNPs is essentially random (i.e. not affected by the trait you are measuring - in this example triglycerides) it is possible to determine the causal effect of triglycerides on the risk of diabetes. Note: this is only possible for traits (such as serum triglyceride levels) that have SNPs identified by GWA studies.
First of all, you have already calculated the association between triglyceride levels (in this study a 1 standard-deviation (SD) increase in triglycerides was associated, with an Odds Ratio (OR) of 2.68, with type-2 diabetes in almost 10,000 human participants). Because it is a cross-sectional study, only an association is reported, with no causal implications... yet!
Enter the SNPs
Having identified the SNPs that increase triglyceride levels (at the time of the study, 10 were reported in the literature), each participants genotype for these SNPs needs to be measured or inferred (generally this is performed in large cohort studies, which are then used for many different individual projects).
A combined 'score' is then derived for each individual. This is conceptually very simple; if an individual has 4 of the 10 triglyceride raising alleles, they are given a score or 4, and so on. This is complicated by the fact that the SNPs have different effects on the triglycerides, so a 'weighted allele score' is derived instead (simply put, the coefficient of the SNP~triglyceride association is taken into account when adding risk allele scores). By using this kind of score, a 'per allele' estimation of the effects can be estimated;
The association between the triglyceride levels and the allele score is then determined (by linear regression analysis - adjusted for age and sex, as these are known to affect triglycerides). There are actually 2 ways of performing the next analysis, the first of which is conceptually simpler, but the second of which is more robust.
Method 1: the 'triangulation' approach
The two observed associations calculated so far (per-SD trig. levels are associated with diabetes, and the per-allele SNP score are associated with per-SD trig. levels) can then be used to calculate an expected association. This is simply derived by multiplying the 2 coefficients together. Below is the 'triangulation' representation of this;

This expected association between the triglyceride-raising SNPs and risk of diabetes is only true if raised triglycerides increase the risk of diabetes. The observed association between the SNP-score and diabetes can then be calculated. If the expected and observed estimates are similar, then triglycerides raise diabetes risk, and are a causal biomarker. If the observed association is null (or, at least, much smaller), then triglycerides are likely to be secondary.
Method 2: the instrumental variable analysis
This method is for the more hardy statisticians. Instrumental variables are derived variables, and represent an intermediate between a proposed 'cause' and the 'effect', or outcome (in this case the triglyceride raising alleles are proposed to 'cause' diabetes, and this is mediated by the triglyceride levels themselves).
Using a linear regression, the "fitted values" from a model with triglyceride levels as the outcome, and the weighted SNP score as the only independent variable, are extracted. These fitted values represent the variance in the triglycerides that is predicted by the SNP score. We are using the SNPs as the instrument here, as they directly influence the biomarker (exposure, i.e. triglycerides), and are not affected by either the exposure or the outcome (diabetes). The important assumption here is that the effect of the SNPs on the outcome is not confounded, and can only be mediated by the exposure - this is true for genotypes (Lawlor, et al. 2008).
By then determining the association between the derived variable and diabetes, you will know whether the proportion of the triglyceride variance predicted by the SNPs is associated with diabetes - if so, then triglycerides increase the risk of diabetes.
Results
The study performed both types of Mendelian Randomization analysis and found no evidence to suggest a causal association between triglycerides and diabetes phenotypes.
So Mendelian Randomization is a useful tool for inferring causality with biomarkers. It is not necessarily conclusive evidence, but it can help distinguish biomarkers of particular importance and interest (with regard to interventions) from those that are just markers of the disease.

Nice weather? In the UK? Ridiculous.

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Athletes: nature vs. nurture?
Having watched a lot of olympians the last few weeks, I was struck by how many of them have actually spent their wholes lives/careers training for their one event (be in running a marathon, or throwing a javelin). This is of course unsurprising - a lot of people take their sport very seriously - but I wondered to what degree these athletes are predisposed to becoming atheletes, and to what degree they just 'happened' to end up doing it.
I've had a bit of a search around, but have been unable to find any studies (although there is an awful lot of media attention to the topic) that actually study the interaction between nature (genetics) and nurture (environment/training etc) in the context of top-end athletes.
It is quite clear to me that the answer is of course 'both', but to what degree? Have any common genetic variants/loci been identified, or is 'athleticism' a far too complex trait for this? Thanks.

All I can think of is http://abcnews.go.com/Health/MedicineCuttingEdge/story?id=7231487&page=1#.UCow92NYvis

@LanceLafontaine That is very interesting - I've seen the mutant animals before, but did not know there were naturally occurring variants in humans! These individuals would certainly be predisposed to become strong-men!

I'm wondering if there are currently or going to be Olympic "policies" against people like that. It's gives an unfair advantage (that's for sure), but it's not like it's anyone's fault.

@LanceLafontaine you have to remember there will be a gaussian distribution, and these people are just at the very tail of it. I imagine that most athletes will also be close to it, but with a not so pronounced phenotype? At what point labeling these 'extremes' as 'mutants' becomes acceptable, and deem them unsuitable to compete in sports is an interesting thought

The Oregon Project might also be interesting to look at, as a means to counter the seemingly 'superior genes' of the, say Kenyan, runners with high-tech equipment.

All these fantastic atheletes on the record breaking levels are a combination of hard work, good funding and a good genetic predisposition.  Swimmers have flexible joints, Lance Armstrong has an extra large heart.  You can train to increase fast twitch muscles and reaction times, but a few extra mutations in your favor makes the champion I think.  Horses have been bred to champions for centuries.  Human champions also need a genetic advantage.  This is just my opinion, but not so controversial in my opinion.

@shigeta I completely agree - there is definitely an element of nature and nurture in the predisposition and development of athleticism. I am interested to know of any scientific studies on athletes, and whether there is any enrichment for genetic traits, or environmental traits (other than the 'obvious' - training very hard. Although this is not always the case - Usain Bolt famously does not train as hard as his competitors. This is a good example of natural advantage).

@Luke good question. not my field, but i'd be interested to know if all these superstars would have donated their genetic material to a study....

@shigeta Yeah it would require that they participate in cohort studies, but it would be so interesting to know of any conserved traits between them (presumably they would mostly be cardiovascular? as the muscle groups, etc, would be sport-specific).

you have to be careful though - its likely the genetic and physiological traits are so complex that no single group will stand out.  it looks as if there are many ways to make a tall person, there are probably an infinite number of ways to make a great ball player/runner etc. @Luke

I wonder if a case/control genetic study would be informative here: obtain genetic information from athletes (cases) and compare against the same genetic marks in the general population (controls).

For all types of athlete, their ability is determined by both genetic and environmental factors (nature and nurture). The degree to which each contributes ultimately depends on the demands of the sport.
As an example let's compare basketball and golf.
Basketball is likely to have a strong genetic component because players tend to be exceptionally tall (average is over 2 metres and there are only a handful who have played NBA under 1.75m). Because height is strongly genetically (but not entirely) determined by the genes, they have a big influence on whether someone can poses the physical qualities to play in the NBA. However, a large part of their technical capabilities are due to their environment. If you give a basketball to someone who has played 2 games a week their entire lives and ask them to take 10 shots it is likely they would score more than someone who has never seen a basketball!
Comparing basketball to golf, there are all sorts of body types within the PGA tour, and they is no/few obvious genetic traits which golfers tend to have over other people. This would suggest that golfing ability is more affected by environment.
So an easy way to get a rudimentary test of genetic contributions to sporting ability would be to compare frequency distributions of focal traits in the athletes to distributions of regular people. Obviously the phenotypic trait you measure has both genetic and environmental contributions (e.g. childhood diet) which could affect them but it would be a good starting indicator which could give some candidate traits to test.
As a scientist I would also consider sequencing some athletes and some non athletes and seeing which genes the athletes have more often then the regular person's genome. However, such studies are likely to be complex - linking phenotypes (in polygenic traits) to the single allele variants relies on large sample sizes. Generally it will be more difficult if:

There is large variance in the trait
The gene has a small effect (see major and minor effect genes)

Both of these problems going to be positively correlated with the number of genes affecting a trait (how polygenic is it?) which for athletic ability is probably quite a substantial amount of genes.
EDIT:  Here are some possible studies for your further exploration of the topic-
Candidate genes for Specific Genetic Markers of Endurance Performance and o2max
Rowers have an excess of the ACE I allele
Elite Italian footballers with "explosive" leg strength also reveal ACE and other genetic markers
A precautionary tale about Genetic tests for athletic ability

I am thinking that another good example could be 'sumo wrestlers', who are also very different in body types to the average population.

here is a paper which finds a candidate gene for physical athletic superiority (http://www.springerlink.com/content/hwllqyy12x29tpde/) in a method similar to that which I suggested. However, I can't find anything suggesting a gene leading people to being predisposed to being an athlete psychologically. The genetics of behavioural psychology is incredibly complex and hotly debated, classic example being "the gay gene."

@Luke, does this answer your question?

Hi @rg255 - thanks for the information and your opinions, but I was hoping for links to studies (like the one in your comment) where authors have tested for genetic contributions. I am of course expecting a large environmental contribution, but as you suggest the genetic contributions may be sport specific (e.g. height-increasing alleles for basketballers, bulk-increasing alleles for sumo-wrestling... etc). When I have some time later I will follow-up the paper you have sent, as this is quite an old study and have been cited almost 200 times! Clearly some other studies too. Many thanks.

@Luke there you go (see edit to answer) hopefully these will give you some help - looks like there are a few alleles that regularly come up in these studies (e.g. ACE I). Sorry it took a while to get around to it!

Yes, candidate genes like those found by these types of experiment could also be linked to mental attributes.

Two hints:

Do a google search for the ACTN3 gene (alpha-actinin-3)
Go to the fitness.stackexchange.com site and search for "fast
twitch" muscles, for example. There you'll find many similar questions
answered.

You can get an answer for you personally by genetic testing.
This is a quote from a genetic testing site 23andme.com (sorry it's behind a paywall). Note there are other companies who can do this equally well.

Genes vs. Environment
Athletic performance has different estimates of heritability,
  depending on what aspect one examines. For example, differences in the
  relative proportion of fast-twitch and slow-twitch muscle fiber are
  thought to have a heritability of about 45%. Although it is not yet
  clear whether ACTN3 genotype affects this proportion, it has been
  shown that the SNP in ACTN3 that we report accounts for about 2.3% of
  the variation in sprinting performance. However, at the molecular
  level, whether you have 0, 1, or 2 working copies of alpha-actinin-3
  is highly heritable. Lastly, muscle fiber only contributes a small
  part to your overall athletic performance. Other physical
  characteristics, such as lung capacity, and behaviors, such as regular
  exercise, also make important contributions to your prowess in sports.

This is considered "established research for 1 reported marker". It is still subject of much ongoing research, though.
So there you have it: around 2% of a difference in sprinting performance. For the general population this won't matter much. But for prospective professional athletes these 2.3% might matter a lot for developing the full potential of their athletic performance (assuming all other environmental factors, are of  equal top quality, e.g. technical equipment, coaching efficiency, etc)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255226/ - talking about genetic tests like the one for ACTN3 "this is a gross over-simplification of the science, according to many critics of these types of consumer genetic tests, including Timothy Caulfield, a Canada Research Chair in Health Law and Technology. “There are so many factors that contribute to something as complex as performance in sports that it seems ridiculous to narrow it down to this one type of genetic test,” he says."

so I'd suggest we can't call it a comprehensive test - individual loci only have minor effects on the overall ability.

@rg255: What the law school professor said is "I don't like questions like this narrowed down to 1 genetic test". That may be righteous, but I'm not narrowing it down. The original question asked for a quantitative estimation. Hence, the quote in my answer: we are talking about 2.3% differences here (which won't matter much for the general population) and the quote also says there are many factors.

I just don't think we can call it a comprehensive test

i removed the "comprehensive" word.

I meant to say that if you got a test result from any direct-to-consumer-genetic testing company, you'd also get a long reading list of science papers, probably carefully selected. Another aspect of "comprehensive" is the "established research" thing. The state of the science is that it's not a single geneticist who speculated about some ideas, there are many teams who have found similar results.

It's an interesting area of research - I just had a population genetics book discussion group for 2 hours and we talked about the difficulties in accurately connecting single allele variants to phenotypes particularly in polygenic traits. The finding of ACE I and ACTN3 could suggest that they are major effect genes. The ability to link a gene to polygenic phenotype depends on the strength of effect on the phenotype by the allele variant and the variance within the population for that trait.

I don't think this will ever be answered, mostly because studying the long-term effects of athletic training is very difficult. People constantly change their training methods, habits, and schedule, so controls are nearly impossible to construct.
My opinion, is that the nurture component is the strongest, because of the amazing plasticity of the body in response to stress: bones grow/reform differently, neural networks become trained, muscles change. Over many years these can be enormous. This is true of all humans, absent those with severe genetic faults.
Genetics probably has a stronger influence on the psychological traits which might induce someone to train so hard. Though parenting could certainly override this.

It is difficult but not impossible to quantify. Could you give us some solid scientific references?

I have no references because I don't think these data exist. Certainly you can get quantitative data, but it doesn't mean that it will be useful. My main point is that there are too many ill-defined variables that need to be tracked for many years. This is nearly impossible to do.

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how much grass does a sheep eat in square meters per day?
I want to buy some sheeps in order to eat my garden's grass.
How much grass does a sheep eat each day ??

What species of sheep? How old? In what climate?

This: http://www.urbanshepherds.com might have the answer.

@sheep agree with terdon, some more detail would be nice.


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how do we prevent restriction enzyme of bacteria to cut and destroy our new recombinant?
Based on cloning principle, the new DNA recombinant will be introduced to host cells, commonly bacteria, how do we prevent restriction enzyme of bacteria to cut and destroy our new recombinant ?

I have a few questions: What do you mean by "cloning principle"? What is a "DNA recombinant" for you, a plasmid?

You're essentially looking for a restriction modification system. You modify the restriction sites with methyl groups in a way that blocks restriction enzymes from accessing them. The DNA methylation should also be maintained through replication. So if you have an EcoRI site, you can use an EcoRI methylase to block the action of EcoRI.


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Do transcription factors block transcription entirely?
Transcription factors bind to the DNA to block the transcription of a certain gene, right? But while they are bound to the DNA, do they completely block any transcription of this gene for as long as they stay there or can they also partially block transcription?

Different transcription factors have different effects: they can increase or decrease transcription. Your question is probably too broad, because there are so many different transcription factors which can interact with DNA at different distances from the influenced gene, or interact through protein complexes, etc. See wikipedia for more on the diversity of transcription factors.

Of course it's never 100%. The protein still has a measurable Kd for the DNA, meaning that there's always some part that's not bound (or some time that it's not bound.
Besides that, you're talking about repressors. There are also activators, and they use many different mechanisms. The same regulator protein can even recognize different sequences of DNA and repress one gene more than another. Some can bind and actually recruit a RNA polymerase, some work only while they're binding small molecules.
https://en.wikipedia.org/wiki/Transcription_factor or your molecular biology textbook might be a good place to learn more.

Like Bryan had said in the comments, transcription factors can perform different types of work. Sometimes, binding onto the template DNA strand can cause the RNA polymerase to be activated while sometimes, vice versa.
According to Wikipedia, transcription factors are:
"...protein[s] that binds to DNA and regulates gene expression by promoting or suppressing transcription"
So both promoting and suppressing is possible.
Transcription factors are combinations of multiple types of proteins, therefore it would depend on what protein you mean.

Please add a link to that Wikipedia page and consider adding something from a slightly more reputable source.


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What decides between the synthesis of eumelanin and pheomelanin on a biochemical level?
MC1R is a very well known gene where a loss-of-function mutation will cause the synthesis of pale/redish pheomelanin instead of black/brown eumelanin. MC1R is only a receptor which doesn't directly participate in the synthesis. it affects the expression and transcription of several important enzymes for melanin synthesis (Tyrosinase, TYRP1, TYRP2).
In one study (Ito, 2003) they proposed that increased tyrosinase activity and decreased cysteine levels would promote the snythesis of pheomelanin. Since MC1R controls the expression and transcription of tyrosinase I think it makes that mainly the increased tyrosinase activity is responsible for the decision between eumelanin and pheomelanin.
The question is whether this is correct or false or if we just don't know yet.

Let's have a look at the pathway first (this figure is figure 2 from reference 1), which shows the basic pathway of pigment biosynthesis:

The first important step, the oxidation of the amino acid tyrosine to Dopaquinone (DOPA) by the tyrosinase is the same for both pathways (eumelanin and pheomelanin production) and rate limiting.
The important step is the next one: Either the formation of Cyclodopa (for eumelanin) or Cysteinyldopa (for pheomelanin). As long as the concentration of cysteine in the melanocyte is above 13µM (see reference 1) the formation of pheomelanine is favored and biochemically much faster than the cyclisation of DOPA.
If there are high levels of tyrosine and normal to low levels of cysteine, the cysteine will be depleted at some point and only eumelanin is made.
The opposite will happen if either a lot of cysteine or little tyrosine is available. It will also happen, when the available tyrosine cannot be oxidized into DOPA when there is little or reduced Tyrosinase activity.
And this is actually what happens in the case of the MC1R mutation. MC1R is a receptor on the pigment producing cells which regulates the production of pigment upon external signals (as UV radiation to the skin) (see reference 2 for more details). When mutated is is not or much less functional leading to much less (or no) signals to the downstream gene (MITF) which regulate the enzymes for the pigment production.
Low signals lead to low tyrosinase production which then can only produce little DOPA. Since the cysteine stocks of the cells will not be depleted then, only pheomelanin is produced causing people with MC1R mutations to be red haired and having light skin and freckles.
References:

Chemistry of mixed melanogenesis--pivotal roles of dopaquinone.
MC1R, Eumelanin and Pheomelanin: their role in determining the
susceptibility to skin cancer


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Is there a website that shows population sizes?
I'm looking for a website that shows the population sizes of a species (doesn't matter which) as a function of time at a geographic coordinate. Is there a government website or other free database with such information?

Will humans do? You can probably get this from the OECD site.

You can access the Imperial College global population dynamics database.  They will have time series data at specific locations.  http://www3.imperial.ac.uk/cpb/databases/gpdd
There is a sister database as well that might be useful. http://lits.bio.ic.ac.uk:8080/litsproject/
These contain several hundred time series, and you can see a paper that used them here:  http://onlinelibrary.wiley.com/doi/10.1111/j.1461-0248.2011.01702.x/abstract

My first idea as well, and definitely the best source around.

Would you happen to know one with more recent data (e.g. 2005 and above)? Thanks.


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What happens to potassium after an action potential?
If I understand right, after repolarization, much of the potassium is outside the membrane and much of the sodium / calcium is inside. How does it get back to the original concentrations (i.e. potassium inside and sodium/calcium outside)?

During the repolarization, relatively few ions need to cross the membrane for the membrane voltage to change and therefore the change in ions concentration outside and inside the cell is neglible. After repolarization, the concentrations are restored by the continuous action of Na⁺/K⁺-ATPase. The same happens for calcium, but I don't know exactly what kind of pump is used.


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How to increase pheomelanin production?
How can you increase the pheomelanin production in your body, while decreasing the eumelanin production? In other words, shifting the balance towards pheomelanin.
From what I see, sulfur and cysteine can help with this. MSM and glutathione caps can be a good way to do this, since these are used for skin lightening.
But is there another way? Something more scientific? Like deactivating the MC1R? Is that even possible?
Thank you!

Since Eumelanin is the protective form of melanin and there is some research available that Pheomelanin contributes to the generation of reactive oxygen species which are harmful to the cell (see reference 1, which contains a lot of further references on this topic), I don't see any reason to do so, but ok. Additionally removing Eumelanin from your skin will lead to a higher risk for skin cancers as Melanoma. Let's think through this:
If we look at the biosynthesis pathway of the Melanins, they both start with the same two reactions (see the figure from here):

The routs parts at the DOPAquinone, which in the presence of Gluthathione or Cysteine goes into the pheomelanin direction. The concentration of Cysteine available to the cell needs to be higher than 0,76 µM (see references 2 and 3 for details), otherwise the reaction goes exclusively into the Eumelanin direction.
There are some skin whitening (or better lightening) products available which contain L-Cysteine or GSH. This will work to some extend, but once the level drops enough, the ratio will shift back to the more natural ratio between Eumelanin and Pheomelanin. There is also no data available on the risks of doing this, so I would strongly advocate against it. See the review in reference 4 for details and additional references on this topic.
If you now think, ok, taking some pills is enough, I would call this a false hope, since this process is highly regulated. This happens on one part through external signaling through the MC1R receptor (which as you already mentioned is of importance here) and also through the availability of key enzymes in the process as well as stability of them and their regulation.
Signaling through the MC1R receptor is highly important for pigmentation and also the amount of enzymes available (the transcription factor MITF is regulated by it). If the signaling is strong, the cysteine storage is soon depleted bringing on the production of Eumelanin. If this signaling is weak
this will not happen and the production of pheomelanin is favoured. Mutations in MC1R are the reason for people having red hair and and fair skin. See reference 5 and 6.
Interfering with the signaling cascade which is activated by MC1R is certainly not a good idea either, since this will interfere with other processes in the cell as well. These pathways are also disregulated in cancers, so I would not touch these.
Summarizing I think there will only be a way of influencing this by taking some supplements, but how safe this is, is unknown. All the other possible ways are certainly more dangerous.
References:

How does pheomelanin synthesis contribute to melanomagenesis?: Two
distinct mechanisms could explain the carcinogenicity of pheomelanin
synthesis.
Rate constants for the first two chemical steps of eumelanogenesis.
Chemistry of mixed melanogenesis--pivotal roles of dopaquinone.
Systemic skin whitening/lightening agents: What is the evidence?
UV signaling pathways within the skin
The melanocortin-1 receptor: red hair and beyond.

Thanks for clearing that up!That figure surely makes things more simple.So basically the only effective solution would be interfering with the MC1R signalling.I am not talking about completely screwing it up,but making it slightly/moderately less effective.IN THEORY,how can this be done? About supplements:what would you consider effective?Vitamin C,glutathione and MSM?Or basically any form of cysteine and sulfur? My main goal is to reduce brown/black (eu)melanin and the best way to accomplish this seems by increasing/shifting towards pheomelanin production.

But I have found other approaches as well.One main approach which stood out to me is inhibiting the tyrosinase activity.For this there is a list of tyrosinase inhibitors,but two stood out to me especially: ZINC SULPHATE and CAPTOPRIL.I will attach links to the studies.What do you think about this approach of reducing (eu)melanin? And the third approach I came across was directly inhibiting melanogenesis.Messing with MSH by using MSH inhibiting drugs/supplements,like melanostatin or resveratrol. What do you think,which one of these is the most effective,and respectively the safest?

The links:Zinc sulphate: http://www.ncbi.nlm.nih.gov/pubmed/16792750 Captopril  & other tyrosinase inhibitors: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705500/ MSH inhibitor: https://en.wikipedia.org/wiki/Melanocyte-inhibiting_factor alpha-MSH inhibitor: http://www.hindawi.com/journals/ecam/2013/632121/    As you can see,I have done a little bit of research on this,but there is quite a mess in my head since I don't know which route would be more effective.I am looking for OVERALL reduction of black/brown (eu)melanin,and I don't care if this is achieved by pheomelanin increase or other ways

It sounds like you're planning to experiment on yourself. This community is not for medical advice, although I'd strongly advise against self-experimentation.

Also, the second two papers from your comment are from publishers accused/suspected of predatory or unscrupulous publishing (MDPI, Hindawi). Frankly I don't know anything about the science in these two papers but that was an immediate red flag for me when I opened them.

@Luigi Scientifically these are ok - also I have no personal problem with Hindawi. I think Frontier Science is worse...


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Glycoprotein hormones metabolism
Why do the carbohydrate groups in glycoprotein hormones decrease the rate of metabolism? And increase the half-life?

can you give some specific examples of how glycosylated hormones have altered half lives and affect metabolism?


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Extinction of non-mammal Synapsida
I am following M.J. Benton's Vertebrate Palaeontology, which explains how many groups of Synapsida were already extinct in the Mesozoic Era, with one obvious exception being the group of Cynodontia, which includes modern day Mammalia.
Nevertheless, I cannot find when the last non-mammal synapsids got extinct and I would be very grateful to anybody giving more information about the topic.

OK, I don't know how I did it but I misread your question as being why all the non-mammalian Synapsids went extinct. I answered your question at the end, but I'm leaving the rest as-is until I figure out how to rewrite it (it was rather too much work to delete).
According to The Wikipedia page for Synapsids, the answer really depends on the Synapsis since there are quite a gap between the start of the Synapsid clade and the appearance of Cynodonts.
The first big "culling" of Synapsids (i.e. the extinction of all groups except one clade that led to mammals - Therapsids in this case) seems to occurred over the Permian era. Some groups went extinct in the early Permian but most groups went extinct at various points during the Middle Permian. No clear reason is given for these various extinctions (though the page for Dinocephalia suggests "disease, sudden climatic change, or other factors of environmental stress may have brought about their end"... which basically covers all possible extinction reasons so that's helpful); it's probably various reasons specific to each. Most species do go extinct after all.
Among Therapsids, the only clade that survived the Middle Permian, most seem to have been wiped out in the Permian-Triassic extinction, the largest extinction event in Earth's history, of which only three Therapsid clades survived: Therocephalians, which went extinct soon after, Dicynodonts, which were extinct by the Early Cretaceous, and Cynodonts. Aside from the usual environmental factors, a reason for the extinction of those two clades could have been competition from the then-ascendant Dinosaurs, and Cynodonts themselves.
As for when the last non-mammal Synapsid when extinct, it appears to have been a member of the Tritylodonts, which survived into the Cretaceous (and arguably having a representative after the K/Pg extinction, emphasis on "arguably"). Mind you these are very close cousins to Mammals indeed:

Tritylodontids ("three knob teeth", named after the shape of animal's teeth) were small to medium-sized, highly specialized and extremely mammal-like cynodonts, bearing several mammalian hallmarks like erect limbs, endothermy and lactation. They were the last known family of the non-mammalian synapsids.

Very interesting and exhaustive answer. Thank you so much!


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5-HTTLPR polymorphism and Depression
I am reading about the biology of depression and came across something I can't understand. Here is the thing:
Lesch K-P, et al. (1996) say that people with short alleles of 5-HTTLPR are more prone to anxiety and depression. Pezawas (2005) also say that short allele carriers have worse anterior cingulate cortex - amygdala connectivity, which is observed among MDD patients. This, however, doesn't make much sense to me, since I'd expect people with short allels to have underperforming serotonin transporter - and isn't it overperforming serotonin transporter that contributes to depression by preventing serotonin transmission by sending it back to the presynaptic neuron? So, wouldn't you expect people with long alleles then to be prone to depression more?
To complicate things further, Willeit et al. (2008) do say that enhanced 5-HTT is observed in Depression. And enhanced 5-HTT would be found in people with long 5-HTTLPR?
So my questions are:

Do I understand it right that Willeit's (2008) results contradict
Lesch (1996) and Pezawa's (2005) results?
To the best of today's knowledge, is it the people with short or
long allels who are more prone to Depression? If the answer is -
with short, could you please clear up my confusion about it (see 2d
paragraph)?

I hope my question makes sense.
References:

Lesch, K., et al.(1996). Association of Anxiety-Related Traits with
a Polymorphism in the Serotonin Transporter Gene Regulatory Region.
Science, 274, 1527-1531.
Pezawas, L., et al. (2005). 5-HTTLPR polymorphism impacts human
cingulate-amygdala interactions: A genetic susceptibility mechanism
for depression. Nature Neuroscience, 8(6), 828-834.
Willeit, M., et al. (2008) Enhanced serotonin transporter function
    during depression in seasonal affective disorder.
    Neuropsychopharmacology, (33), 1503-1513


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What is the lifecycle of hanging woody vines?
In the first ten seconds of this video, you can see a vine that appears to have started its life 60 feet up in a tree and has now grown down almost close enough to touch the ground. I have seen similar vines that do make it to the ground and start curling around, but don't sink roots. Why do they create this long woody stem? Or do they start at the bottom, grow up the tree, and then release their roots somehow so they can swing free? They're sometimes not wrapped around the trunk at all, just hanging from the very upper branches, as if their seeds found purchase there and started stealing nutrients to grow. Is that possible?
I have swung from these in several locations in Wisconsin and Iowa. They're very tightly attached.

There are no epiphytic vines in the US. Most likely, if it's sturdy  enough that you can swing from it, it's the vine of a wild grape. (The vine in the video is classic wild grape.)
They grow like most other flowering plants: they start innocently enough with a seed that takes root in the ground. They are initially tender and small stemmed.

From there, they grow along the ground, sending out tendrils. If they find something growing vertically, they cling to it (a shrub, tree trunk, or a low hanging branch) and grow upwards towards the light. If they have enough light (they are shade intolerant), they continue to grow, branch, and elongate. because they can become quite heavy, they break canopy branches of their supporting tree and fall in long loops toward the ground.

If the loop breaks for some reason, you have one swinging vine. But if you diligently follow it back, you'll find either the continuation of the vine near the canopy (the part after the break) or the trunk growing from the ground alongside of a nearby tree.
Though cool-looking, they are very destructive, bringing down not only branches but often entire trees (plural. They intertwine different tree branches, and if they bring down one tree, others fall in a domino-effect.)

Imagine that SOB hanging onto your upper arms for support (not the guy, the grapevine).
Smaller vines (which can also be destructive) that climb up the sides of trees are Oriental Bittersweet, Poison Ivy, Virginia Creeper, etc. (Probably Kudzu as well, but we don't have that here yet.) But these aren't likely to become large or sturdy enough to swing from if they come loose from the tree.

This is a photo of two common offenders: a wild grape (dark shreddy bark, about 2.5 inches in diameter) being slowly strangled by an oriental bittersweet (lighter bark), both climbing this large oak. If you look carefully, the base (roots) of both these vines are behind the tree (about five feet), one on either side. (You might have to take my word for it...)
Wild Grape


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Identify this spider
I found this spider on my balcony in Sunnyvale, CA. It sat in a irregular net. The body was approx. 6mm long. Which species does it belong to?

That's a Western Black Widow subadult female.  The banded legs, with dark 'knees' and lighter brown intervals, become all black as the spider matures, just as the bands on the body disappear as it becomes all black.
Below is a slightly older one, where the center stripe is beginning to turn red.
Your first clue is the irregular web, characteristic of the Theridiid cobweb spiders.  The second clue is the robust body and legs, with especially long first and last pairs.  The key field mark, if you had seen the underside, is the red or orange hourglass.  It is clearly not any kind of orbweaver, simply from the web; and none of the several sorts of Argiope look anything like this spider.
Be aware that this spider can give quite a potent bite (although they often don't, preferring to hide, and not biting unless endangered).  Like the other Black Widows, they are best not handled, just in case.
https://bugguide.net/node/view/1458045/bgimage


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What to do with a DNA sequencer?
My school is very fortunate to have a DNA sequencer, and I want to find an opportunity to learn how to use it. I'm currently taking AP Biology this year, and I hope to do an independent study in biology next year, concerning DNA. I'm sure there's plenty I can do with the sequencer, but do you have any cool project ideas?

You might want to narrow that down a little. What kind of equipment do you have access to (apart from the sequencer)? How much time would you have for this project? Do you plan to do this alone or will there be a teacher to help?

Agree with @terdon, but you'll have to do a bit of scouting out of possible options (based on time limitations and supplies), and then maybe this will have a concrete answer based on those.  This is not to discourage you, just to get you a better answer.  IOW, Way to take the initiative so early in your education!

Also, will there be some money available for the project, and if so how much? That may be a limiting factor for certain experiments.

You can [edit] this post to respond to the feedback in the above commments

@Jack What we once did with a sequencer was to isolate bacteria from our rooms and take their dna out and sequence it and then compare the sequences using BLAST and RDP and construct a phylogenetic tree using that. But I think this is a really basic project with no importance except to learn the basic techniques which you can apply elsewhere.

@Jack I had also read an experiment where they isolated microbes from different soils and identified different microbes using PCR and sequencing and then tried to identify which are the most necessary.

Then there was one more experiment in which gut microbes from different people were isolated and it was found that different types of bacteria were present based on whether people were primarily veg. or non veg.

Deciding on your project will also depend on whether you want to use your sequencing machine as a main tool or as a supplement to your project and one more thing - all examples I gave u r regarding microbes but there are gazillion other organisms on which you could try sequencing....This was just to give u a start.


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Japanese Crab Identification?

I saw a crab walking home from work the other night. We're by a river, but I was probably 500 feet away from the river when I saw this one. I apologize for the image quality, all I had was my terrible Ipad camera and no flash. I have provided the original image and one with brightness and contrast modified to make the crab easier to see. It's about 2.1 inches from leg to leg, I threw a 500 yen coin by the crab as a reference, but cropped it from the image.
I am located directly across from Haneda airport, which is on Tokyo bay. The river is close enough to the ocean that we get tides. I'd say the river level varies by as much as a meter, and there are many many crabs on the exposed riverbed at low tide. But again, this crab was far away, and would have needed to climb a three foot tall vertical wall at the river's edge.

The carapace shows the distinctive lines of Chiromantes dehaani (Kurobenkei-gani in Japanese). This species can be found quite far away from the ocean, commonly in brackish streams and rivers. The size fits your description, the width of the carapace is approximately 3-4 cm, giving the entire body roughly the same size as you observed. These crabs are also most active at night.
I have seen these crabs in sheltered areas slightly inland from the sea. Here is a photo of C. dehaani that I took in Tokyo:

While there is a slight possibility that this is Chiromantes haematocheir (Akategani in Japanese), your photo does not show the distinctive red claws and this species is less common in Tokyo Bay due to development and loss of its natural environment of mudflats. Therefore, I think it is save to identify this as C. dehanni.


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Amount of Na+ needed to be transfered in order to depolarize the membrane?
I found out that the number of $Na^+$ ions that is needed to be transfered across the membrane to make it depolarized is a small number.
In what way its proved? (Goldman equation maybe?)

You mean how the exact number of ions passing the membrane is measured?

One ion is enough to depolarize it. It depends on how much depolarization you are looking for and on the areal surface you want to depolarize and on the exact physiological ionic composition in and out of the cell at that time


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Why do some plant species have lobed leaves, while similar species in the same habitat don't?
Some plants have lobed leaves, like the English oak (Quercus robur), while other plants growing the same deciduous woodland habitats, and very often growing alongside oaks, such as the European beech (Fagus sylvaticus) don't have lobes. Here are two two leaves side by side for comparison:

These two species should be subject to most of the same evolutionary pressures. Why would one evolve lobed leaves, whilst the other has only tiny serrations?

Could I interpret this question as asking what is the function of lobes on a leaf?

The answer to that question could constitute part of the answer to mine, but a good answer will also explain why it might arise in one species and not in another, despite them both having similar evolutionary pressures.

This is a question for which, I think at the moment, we don't have a clear answer.
It is important to bear in mind that the leaf plays a number of important roles in the plant (photosynthesis, thermoregulation etc.) so leaf shapes probably evolved through a process of successive trade-offs. This may make it difficult to identify the exact selection processes operating on any one species. In contrast, something like the eye has a well-defined single function, which in principle at least, makes it easier to understand the link between form and function.
From Niklas (1988):

Life history and optimisation theory suggest that the number of
  phenotypic solutions that allow for different equally successful trait
  combinations increases as the number of trade-offs increases – a
  conclusion that applies to traits within the leaf (e.g. for shape) as
  well as to leaf–branch relationships.

However, there are a  number of ideas to explain leaf shape diversity which include:

Thermoregulation

It has been shown that by adding lobes to leaves, the rate of heat transfer across a leaf is greater than that of an unlobed leaf of the same area (e.g. Gurevitch and Schuepp 1990). So, lobed leaves may be selected for under certain environmental conditions.

hydromechanical constraints

Lobed leaves may have greater hydraulic efficiency. For smaller veins, hydraulic pressure increases as they present an increased resistance to water flow. This places stress on the deliate outer leaf tissues. If  lobed leaves have relatively less mesophyll tissue than large, highly conductive veins, they may have reduced hydraulic resistance compared  unlobed leaves (Sack and Tyree 2005).

optimization for photosynthesis
adaptations against herbivorous animals
random (non-selected) variation. This is a possibility, although probably unlikely due to the importance of the leaf in plants.

So, some or all of the above possibilities (which are not necessarily mutually exclusive) may shape the leaves of species which may appear to have undergone very similar selective pressures.
This is a good read by Nicotra et al. (2011) which summarizes the state of play.
Gurevitch J, Schuepp PH (1990) Boundary layer properties of highly dissected leaves – an investigation using an electrochemical fluid tunnel. Plant, Cell & Environment 13, 783–792. doi:10.1111/j.1365- 3040.1990.tb01094.x
Nicotra et al., The evolution and functional significance of leaf shape
in the angiosperms, Functional Plant Biology, 2011, 38, 535–552
Niklas KJ (1988) The role of phyllotactic pattern as a developmental constraint on the interception of light by leaf surfaces. Evolution 42, 1–16. doi:10.2307/2409111
Sack L, Tyree MT (2005) Leaf hydraulics and its implications in plant structure and function. In ‘Vascular transport in plants.’ (Eds NM Holbrook, MA Zwieniecki) pp. 93–114. (Elsevier Academic Press: Burlington, MA, USA)


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Evolution of sexually concordant genetic variation on the X-chromosome
It was theorised in 1984 that sexually antagonistic genetic (SA) variation should more easily evolve on the X-chromosome. This is partly because female beneficial/male deleterious mutations face less powerful selection against them; the X is in females twice as often as in males so mutations will persist up to the point where male cost is <2x the females gain. Furthermore, male beneficial/female deleterious recessive mutations (p) will always be expressed in males and, when rare, only very occasionally in females; if the frequency of p 0.1 then 1 in 10 males will express that trait and only 1 in 100 of the females.
It is therefore expected that the X-chromosome should become a hotspot for SA variation in comparison to the autosomes. A result would be increased persistence of genetic variation on the X- within sexually antagonistic loci. However, how would a sexually concordant (male & female beneficial, or male & female deleterious) fare in the X- compared to the autosomes? Just eyeballing it, it feels like the X- should be better able to select on recessive mutations because they are always expressed in males; removing deleterious and spreading beneficial mutations more rapidly. Should there then be less genetic variation on the X- than autosomes?

I dont really understand what Sexual Antagonism means. However this article may be relevant to your question. Just happened to see it some days back.

@WYSIWYG - I briefly touch on sexual antagonism in my answer to this question. See the last part where I talk about conflict.


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Heterochromatin production limitations
Currently playing with some ideas for a project and needed some guidance. I am wondering, both in Drosophila melanogaster and in general, is the amount of heterochromatin a cell/nucleus can produce limited/consistent or variable?
Does one cell in a D. melanogaster produce a similar amount of heterochromatin as another cell in the same fly or another fly (assuming same conditions - environment etc.) or is the heterochromatin production quite variable? How is heterochromatin production regulated?

Heterochromatin profile is of course different in different cells but I am not sure if absolute heterochromatin content will vary greatly. This DNAse hypersensitivity region data is for human cells but same principles apply to all organisms. If I have to take a guess then I would say that quiescent cells are likely to have more heterochromatin. Heterochromatin production is regulated by different epigenetic mechanisms but I cannot comment (I feel it is unlikely) if there is a mechanism to control absolute heterochromatin content.

Generally speaking, heterochromatin or euchromatin structures mark specific regions to regulate the transcriptional activity and these marks carry the signature of developmental processes as they differ in different tissues (or cell types).
Therefore, we should not ignore the developmental processes if we want to understand how such epigenetic marks are formed. But first, we should reconsider the question as it assumes that the heterochromatin is produced. The assumption is somewhat valid, there are many enzymes responsible to shut the chromosome off thru the histone modifications. On the other hand, heterochromatin strucure comes as a default (or as the factory settings). Before the mid-blastula transition, where no (or negligable) transcription happens, all the genome is heterochromatin due to the excess amount of histones. After certain amount of division, the amount of histone per cell reduces but the genome per cell remains constant which then titrates the histones and some transcriptional activity kicks in.
Then HATs, methyl transferases etc. help to clear up the necessary genomic regions depending on the extracellular developmental signaling. Then for many somatic cells, the ratio of heterochromatin and euchromatin regions more or less remain similar.

Thanks for posting but I don't think this answers the question at all


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What species have had their genomes sequenced/are being sequenced?
The human genome project released it's first complete genome nearly ten years ago. Since then many species have also been sequenced.
I am trying to find a list of completed (and possibly ongoing/initiated) projects sequencing other species along with some very basic summary data such as number of genes (divided amongst the sex chromosomes and autosomes), length of DNA, number of chromosomes etc.
This is for a presentation I am giving at a conference and would make a nice addition to my talk.

"ongoing/initiated" is data you just cannot collect. There are more sequencing projects ongoing at some university which have not been publicly mentioned (and often won't before they are finished) than I would be willing to count. I am involved in at least 2.

The GOLD database (Genomes Online DB) contains data on the sequencing status, and also some stats (number of chromosomes, genome size) -- but this extra data is not available for all species.

There are several lists on Wikipedia, for example for plants, bacteria and eucaryotes.

The Genome 10K project, in their words "aims to assemble a genomic zoo—a collection of DNA sequences representing the genomes of 10,000 vertebrate species, approximately one for every vertebrate genus.". Here is their species list.

At NCBI, you can find a table with genome Information per organism.
For each organism, you can find the Kingdom, group and subgroup it belongs to, the size in Megabases, the number of chromosomes, organelles and plasmids (if present) and the number of assemblies.


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Heterochromatin binding sites position information
I am working on a project and I'm trying to find data on the position of genes and heterochromatin binding sites such as HP1 in Drosophila melanogaster. Is this information available for the DGRP lines? Would I be able to measure the distance between a gene and its nearest binding site from such data?

Have a look at these ChIP-seq data for HP1 in Drosophila: 1, 2 and 3. From ChIP-seq data you can find the distance between the TFBS peaks and the TSS of the gene.
You can also look for nucleosome positioning and DNAse hypersensitvity regions; for the former, I am sure that data is available for Drosophila.

As the previous answer said, there are some public HP1 ChIP-seq data from D. melanogaster if not from the DGRP, from modENCODE and maybe others. In the case of modENCODE, they've published not only the reads, but also their peak calls (mapping with Eland + calling with MACS).
BEDTools ( https://github.com/arq5x/bedtools2 )is a nice command line tool for manipulating intervals with genomic coordinates, and the bedtools closest command can calculate the distance to the closest feature. It would look something like this:
bedtools closest -d -a genomic_features.gff3 -b peak_calls.gff3

Where the "genomic_features" part would be any subset of genome annotation that you're interested in.
I've worked through a small example with modENCODE data, Flybase transcript annotation and BEDTools:
http://martinsbioblogg.wordpress.com/2014/07/04/finding-the-distance-from-chip-signals-to-genes/
Cheers,
m.


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How many traits can a multivariate breeders equation handle?
The multivariate breeders equation (MBE) by Lande predicts the change in a trait $\Delta \bar z$ (response) as
$\Delta \bar z = G \beta$
where $G$ is a genetic variance-covariance matrix and $\beta$ is a vector of the selection coefficients. What are the limitations on the number of traits the MBE can tolerate? Is there a theoretical limit on the number of traits $G$ and $\beta$ could contain? Or does the calculation lose power with increasing complexity?
Theoretically as an example, could I take the expression of 10000 genes, compare them to fitness to to make a 10000 row $\beta$ vector, and generate a 10000 * 10000 G-matrix from estimates of male and female gene expression in some lines, and then put them through the MBE?

(this may be better on or cross posted on maths SE)

I guess there is no theoretical limit on how many dimensions you should have. But it makes sense to reduce the dimensionality of the model if possible. Having too many variables makes a) the system look complicated (and clumsy) b) consumes more computational resources c) in some cases makes the dynamical model stiff (makes it difficult to solve)

This is still fine because it is a linear equation. And 10k x 10k matrix is not that huge for computers these days. But you would end up storing more information than needed.

@WYSIWYG Thanks, I guess there is a trade off to be had, on one hand we want to include as many traits as possible to ensure we have all traits affecting fitness (which is almost impossible, particularly in natural populations, and especially if we consider all ontogenetic and environmental variants). But on the other it becomes rapidly more complex, conceptually difficult and less general in its meaning.

Noting that the right hand side can also be written $\mathbf{G}\mathbf{P}^{-1}\mathbf{s}$, we see that the only theoretical limitation of the multivariate breeders equation is the invertibility of the matrix $\mathbf{P}$. This happens when the measures of two traits are the same for all individuals, making two columns of the matrix the same I.e. It becomes singular.
This theoretical concern can become a practical concern quite quickly when multiple traits are measured. The solution is to effectively consider two traits as one.
The 'power' of the equation, by which I assume you mean something like 'accuracy of prediction', actually improves with the number of traits measured. Indeed, a big concern with measuring only a few traits is that the response to selection on those traits is actually 'caused' by selection on some other correlated but unmeasured trait.


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Collective name for the X- and Z-chromosomes
Chromosomes are grouped as sex chromosomes or autosomes, with the X, Y, Z and W all falling in to the former category. The Z and X are present both in the homogametic and heterogametic sexes, and the Y and W only in the heterogametic sex.
Is there a collective name for the chromosomes in such groupings (X/Z & Y/W)?
I want to talk about Z- and X- (and analagous) chromosomes in general. Rather than having to write "The X-chromosome, and analagous chromosomes such as the Z-, are present in both sexes...." I'd like to say "The blank chromosomes are present in both sexes...."

I can suggest one for Y/W- meiomorphic : Smaller in size. Heteromorphic is anyways used for dissimilar sex chromosomes.

I'm not aware of collective names but you could define one for the purpose of your paper. Inspired by @WYSIWYG you could try macro- and micro/meio- prefixes. I don't know if those terms would apply broadly to your needs.

majo- prefix means greater.. But majomorphic sounds weird. Macro/micro also seem fine (but macro/micro are not comparative prefixes). You can actually ask this in a Greek/Latin forum :P

I think you can safely use the terms heterogametic (Y/W) and homogametic (X/Z) chromosomes, meaning that a heterogametic chromosome is the chromosome which makes one of the sexes heterogametic (i.e. defines the difference between the two types of gametes of the respective sex).
These terms applied to chomosomes do have some usage in the literature, e.g. in this article.

heterogametic/homogametic is used only in the diploid sense. What else could be an appropriate name for the gene-rich/deficient of the sex chromosomes?

@WYSIWYG: 1) How many cases of sex-chromosomal sex determination in haploid organisms are known? Or do you mean something else? 2) I don't know. By the way, the differences between the two (or three) sex chromosomes are not always pronounced to such a degree as observed in mammals.

you mistook me.. I meant it is said in reference to the genotype of the sex rather than the chromosome itself

@WYSIWYG My point was that the same terms can be also applied to chromosomes. E.g.: "... the heterogametic chromosome (Y or W) has repeatedly lost many genes ..." (p. 1646).

I just tried a search of major and minor sex chromosomes and found a paper here by Judith Mank who refers to the X and Z as the Major Sex Chromosomes and Y and W as the Minor Sex Chromosomes.

I will therefore refer to the W and Y as minor sex chromosomes, and
  will use the term major sex chromosomes in reference to the X and Z.
  These terms are based on abundance and do not refer in any way to size
  (discussed below) or relative effect. In fact, the effect of the minor
  sex chromosomes is, in many ways, anything but minor.

I think I will go with this naming as the hetero-/homogametic chromosomes distinction could become confusing in the context I am using it (Talking about expression of the X/Z in the homogametic and heterogametic sex).
EDIT:
Further I think it is wrong because, while "heterogametic chromosome" would be somewhat suitable for Y/W chromosomes, to call the X and Z the homogametic chromosome is wrong because the X/Z can be present in both a homogametic sense (in females/males respectively) and a heterogametic sense (paired with a Y or W).
Calling the X/Z the homogametic chromosome implies that it is only present in homogametic sexes no less than "minor sex chromosome" might imply a minor role for the Y.
Another suggestion could be to call the Y/W chromosomes the sex-limited chromosomes, but then the question of what to call the X/Z remains... non-limited? shared? sex-unlimited?
Or recombining and non-recombining sex chromosomes.

I'm not a fan of this usage since the mechanism of function varies so widely and the major/minor distinction implies something about the functional role of the two types.

@JackAidley that's why I put in the Mank clarification "the effect of the minor sex chromosomes is, in many ways, anything but minor."

I agree with @JackAidley regarding meaning but at least you have precedence to cite and it appears to suit your needs.

@JackAidley Thanks for your input so far, please see the edits..

@MikeTaylor Thanks for your input so far, please see the edits..

@caseyr547 Thanks for your input so far, please see the edits..

While your point about hetero/homo is valid, I think that it's likely to be a more readily understood and less confusing term than major/minor.

Regarding the meio/majo or micro/macro suggestion, I do not think it is the way to go for the following reasons:

Micro and macro-chromosomes are terms already used in species such as chicken whose genomes combine very small and big chromosomes
Although this is more the exception than the rule, bear in mind that sometimes the Y chromosome is bigger than the X chromosome (e.g. in S. latifolia)

As for the initial question, I do not know of a term the X/Z - Y/W groups. What comes to my mind is the term sex-restricted sex chromosome for the Y/W (as it is normally present only in one sex) although it does not seem to be widely used according to Google.
You could also oppose them as recombining vs non recombining sex chromosome which would hold true for most heteromorphic sex chromosomes (if we do not take PAR into consideration). It might be confusing as some persons would think you speak about the pair and not the individual chromosome. However, it seems to be used in the literature.
I checked one of my manuscript on the topic and we used X/Z when needed.
Edit: first sentence clarified.

instead of size sex chromosomes should be classified by their gene content.

I did not say we should classify by size (my second bullet point clearly shows this is not a general rule). Gene content of any of their property (e.g. recombination, segregation,...) is definitely a better way to go.

Not you. I was saying in general (after considering your example)

Based on answers and discussion so far and my own searches, I think there is no widely understood and used term for grouping the X/Z and W/Y chromosomes. You could coin your own term or pluck one from obscurity in the literature, however, I think you would probably be better off not doing so and simply writing X/Z and W/Y wherever you need to refer to the grouping.

I've mentally decided to start using WYsomes (pronounced why-somes) and ZXsomes (pronounced zicks-somes) for collective use.  Of course, I'm not trying to publish a paper. :)


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Evolution (Reductionism)
My recent post was tagged as unclear so I wanted to re frame my question. Though I am a layman, I would love to read books and find the stuff, if I get an overall picture of intelligence factor. My question is, how come evolutionary mechanism of protecting ones species made them adapt to their environment ?
The answer comes by the genetic mutation, the switch genes and so on. But how are these cells intelligent to cause such mutation ? For instance, cells don't have intelligence of their own, so presented a situation where in you have to see, but have no eyes, or have to walk but have no legs, how come cells know that they have to work against gravity and develop such structures and hollow bones in birds to make the flight easier ? Does it mean that nature is intelligent ? How come matter itself create gravity, space etc., on one side, and creating beings to overcome it ? Isn't the matter altogether ? If that's the case, imagine a thought experiment, where in we all have dangerous predators which are 4D beings. So since our cognitive and visual percepts  are just designed to perceive 2 dimensions at a time, we being 3D creatures. So over thousands of years, since we have to live and survive, would we develop a vision that can see 3D ? It would be amazing then. It then means that there is an intelligence factor in nature that tells the creatures how to change !
Please do answer, and again repeating I want to hear, how Genes know that they have to work against gravity, or develop a particular efficient thing, that can solve the problem. Otherwise it's as if Genes permute infinitely, and then develop all possible models, and only those which serve the purpose will stay.
Please do clarify.
Thanks !

Hi! It's wonderful that you are thinking about evolution! Could you clarify on what you mean by evolutionary mechanism of protecting ones species ?

if Genes permute infinitely, and then develop all possible models, and only those which serve the purpose will stay. appears pretty close to what is actually happening.

@biogirl, Thanks so much for your reply. I was mentioning that, in the sense, that evolution always occurs to safe gaurd one's species.

@SatwikPasani, Great ! Thanks ! Then do you mean that they permute infinitely ? Isn't it a bad model to explain the underlying enigma ? Someone said, seeing universe as a dice play, or someone throwing marbles on ground is not a good way of looking at it. As Einstein said, God doesn't play dice.. Continued

+1,"But what has convinced many people, including myself, that one should take models with extra dimensions seriously is that there is a web of unexpected relationships, called dualities, between the models. These dualities show that the models are all essentially equivalent; that is, they are just different aspects of the same underlying theory, which has been given the name M-theory. Not to take this web of dualities as a sign we are on the right track would be a bit like believing that God put fossils into the rocks in order to mislead Darwin about the evolution of life. - Stephen Hawking

@Iyengar Hmm! The statement you are saying(regarding the benefit to species) implies a misconception. Evolution does not happen to safeguard members of a species. It happens at the individual/at the genome level. If an old spider "sacrifices" itself,in principle, it is not so that a competitor of the spider species is reduced/ the species do not face overcrowding. There has to be a selfish advantage to the spider.

I also strongly recommend the book - The selfish gene by Richard Dawkins which explains the common concepts of evolutionary biology in an interesting way !

I think we may be missing a piece from Darwin's original hypothesis.
An outline of the first 4 chapters of Origin of Species form the kernel of the Theory of Evolution:
1: Variation under Domestication
2: Variation under Nature
3: Struggle for Existence
4: Natural Selection

Really you can't reduce evolution to less than variations; competition (struggle) ; selection.  that's about as far as you can go and still call it evolution.  Even genetic algorithms which don't use living organisms at all have these 3 steps.
Most people don't have an issues with Variation any more.  At one time it was thought that individual variations were not important, but now most people understand that one water bug might have significant individual differences from other water bugs and its not just people who look at each other and marvel at individual traits.
The struggle for existence was difficult for people to accept at the time, but its simply that most living things don't make it.  Darwin had noticed that each spring that a typical bird pair might have 3-4 eggs in their nest but if you do the numbers it tells a story of how much of a struggle life can be even if we don't see it on a walk in the woods.  If all eggs reached maturity and reproduced, a single pair of birds would generate enough birds to cover England in about 40 years.  That's just a squeak under 3.5^40 without death from old age.
The struggle for existence hints how competitive Selection is.  In their breeding lifetime, to have a static population of birds, a breeding pair produces 2 breeding offspring out of perhaps 14 eggs lain.
It's a given that genes don't know that they have to do anything, but if they don't work well they will not be seen again. Their host dies from a developmental issue, falls and hurts itself doesn't display the right plumage, isn't fast enough to catch its food, is so slow that it gets eaten, its seed falls on soil it cannot germinate in, etc etc.
The list is endless as to the things that can go wrong in the wild and would cause an individual to be removed from the gene pool and they don't produce offspring. All of the important qualities that genes need to have is mysteriously embedded in what we call the environment - the earth, the air, the water the behavior of other living things decide whether most genes make it or not.
If you need any more evidence that intelligence has nothing to do with evolution, then look at human beings... not getting along well with other living things well now - is that smart?
An example of selection
Since it was requested, let me expand and give a very simple example of random selection that I've always liked (Disclaimer: maybe because I made it up as far as I know!).
Take a box of 100 coins.  We want all 100 coins to be heads up, but we can't individually flip any of the coins over: we can only shake the box.  Note that when we shake the box - nothing is thinking or acting consciously.  Genes do permute randomly and, for all reasonable approximations of infinity, infinitely, but they tend to stick around when something works.  This makes evolution seem unnaturally quick to respond.
Method 1: shake the box, looking every time. There are 2^100 combinations.  Getting terribly lucky we'd have to shake the box 2^97 times before we accidentally caught a box of all heads up coins.  That's random chance.
Method 2: if we remove the coins that are heads up every time we shake the box, we'll be shaking the box 8 times or so.  That is similar to a strong selection case in evolution: the coins which are heads up are like traits which have an advantage so they stay around.  Its striking how efficient this can be and how many tremendous changes can happen in a short time if there is selection and advantage.
Note that we have plenty of bad traits here (tails up); they show up all the time - with great frequency.  They just don't stick around because the struggle for existence is so challenging.
You can further get an idea of weaker selection if you can imagine that instead of the heads always staying heads, you have a little stickiness on the tails of the coins.  80% or 60 or 52% of the time these coins stick and stay as heads.  It still will not be long before you find that the coins are mostly heads.  10 20 or 30 shakes of the box rather than 8.
Where do new traits come from then?
So taking all this and thinking about how new traits like eyes which had not been
seen before, the same blind and random process applies.  It is better not to think of humans and human traits - we're the product of over a billion years of selection and evolution!   Think how primal traits at the bacterial level emerge.
Below is a picture of salt pools in the San Francisco Bay.  Evaporation increases the salt concentration in the pools and as they become inhospitable, halophilic (salt loving) bacteria take over.

The pools are colored because these bacteria have an ancient mechanism which allows them to harvest light to pump the salt out of their bodies and help create energy as well.  The light is harvested in one well documented case by a retinol molecule which absorbs blue light.  Retinols are a variation on vitamin A and must be quite ancient.
Yet a similar molecule, retinal, is used in human eyes as the light sensor there.  A similar protein holds those light sensing molecules in both human and halophile as well. While the structure of the eye and the nervous system that processes information into the brain all came later, you can see at one point the interaction with a bacterium with light became so useful that once it evolved, it has stayed in the gene pool since the days of bacteria to be the light sensor.  Vitamin A is the product of a biosynthetic pathway that very easily makes a variety of molecules.  The light sensing genes that used them evolved once, but variations on it sense light in our eyes today.

+1, @shigeta, Thanks for your answer. Anyway, it answered my question, but I didn't understand how genes adapt themselves to the environment ! I mean how can they create eye to grasp light and other things. How do they know that ? Where does the interaction start from ? For instance take beings without eyes, how did they get eyes from ? What caused the genes to create such structure ? How are they intelligent on their own ?

On a side note, loved this very comment of you. "I believe that biology and other stackexchange sites should welcome newbies and encourage dialog about science, evolution, technology and etc, not kick them back down the stairs when questions are not worded quite right. " Love to see that day, where in people in scientific field encourage layman, and where the knowledge is free. Thanks a ton !

Hi @Iyengar - yes welcome to biology.stackexchange!  Richard Dawkins wrote an entire book called the 'blind watchmaker' to try to dispell this idea that genes are active participants somehow.  let me expand the answer a bit.

The most wonderful piece of example, I have ever read. Can't stop voting it as perfect answer. You should seriously consider writing up articles and giving expositions for layman, which will benefit people like me ( You can look at my background in about me ). I would love to stay in touch and can't thank you enough. Can we exchange emails ? Do you have website ? @shigeta

Hi Iyengar - thanks - i use stackexchange to sharpen my writing skills and i teach classes locally here.  I've updated the url on my profile - you can contact me through the info there. anyway i'm glad you like the answer!

I read your answer many times, and it's so useful. But still there is some doubt, because you didn't comment about the thought experiment I have stated. So in the beginning cells had no eye. How did they understand that they have to develop something related to photons and absorb them, there by encoding all the distance ? So isn't it a very complex phenomenon, and it has something to do with nature's interruption as well ? Sorry if I am sounding foolish. @shigeta

Hi @Iyengar.  there is no answer that will remove doubt I find. Evolution is not intuitive to people and its a process to understand it.   Nevertheless I'll add a paragraph about this case explicitly.  Its getting a bit long though. go ahead and ask other questions if you are still curious.

Now, I got the overall picture. Can't be a clearer picture than this, unfortunately I can up-vote only once. I was asking this question to my friend as well, who is doing his PHD in biology. He said, it's impossible to explain in an hour. I challenged him, and showed this to him, which is less than say 1000 word. He was flabbergasted. People like you should be there in every field, to bridge the gap between experts and layman, there by bringing science to common man. Thanks so much @shigeta

youre welcome! One of the best ways to learn is to explain to others. stackexchange is a good place to learn to write and challenge yourself on things you don't understand...

This is a superb answer! Clear, well-written and just detailed enough. Plus, that picture of the salt pans is just gorgeous! Let me echo the OP and say I wish I could upvote this more than once!

You know what, I can upvote this more than once. @shigeta: bounty coming your way in 24 hours.

hey @ChinmayKanchi - thanks - I really appreciate that you like my writing.   Lets all talk more - post some more questions..  surely there are other issues.  Common questions are; 'If its selecting fit individuals, why can't evolution make us able to digest any kind of food/super strong/ live forever?'  'if we're always competing, why do people form civilizations and cooperate?' 'are people still evolving? is selection still operating?'  there is a lot more about the evolution of eyes too - that's been a hot story.   etc etc

@shigeta: I'm a biologist myself, so I don't often have questions I can't answer with a quick Google/Pubmed search. Re evolution of the eyes, I remember that Walter Gehring gave his last pre-retirement talk at our University. Best talk I've ever been to! It was only rivalled by this fantastic woman who came to gave a talk about explosives and actually blew things up during the talk :D

Hey @ChinmayKanchi well maybe you would like to write that one up? if I ask will you post?  biostack needs a nice reference to it. PAX8, crystallins etc... its one of the best stories of this kind of evolution around...

Too long for a comment:
Evolution and mutation has nothing to do with intelligence and is not influenced by the cells itself. It happens by chance and if the mutation turns out to be beneficial (or at least not harmful for the moment) it will be a selection advantage.
Something to think about: If a mutation in an enzyme which is responsible for Glucose metabolization allows bacteria to also metabolize another sugar (lets say Galactose) with the same enzyme, this will not change anything for the moment. If these cells are living in a substrate where glucose gets a limiting nutrient but which contains still a lot of galactose, these bacteria will have a growth advantage and overgrow the other strain. Eventually the strain, which can only metabolize glucose will disappear completely.
Evolution is also a very gradual and slow process. So it is not boom suddenly birds appear on the sky, it is a process which took millions of to happen. All the things which allow birds to fly (hollow bones, feathers and so on) developed slowly.
Genes do not know anything, since they have no consciousness. They are "simply" building blocks. They also don't solve any problems, they are only expressed, not more.
It is like you write, genes acquire mutations, which allows changes in function or morphology. As stated above: This is a slow and steady process with a lot of dead ends.

Wonderful ! What about my thought experiment ? Any answer/comment to that ? Thanks so much +1. @Chris

@lyengar: I expanded my answer.

Nature isn't intelligent, genes aren't intelligent, and evolution doesn't have a purpose or a goal.
Mutations are random, and roughly 97% of them are deleterious while roughly 0.03% are advantageous for the species. This is the first prerequisite of evolution.
The second one is differential survival. An organism with a better chance to survive or reproduce (because of a random mutation which was advantageous) will have a better chance of passing on that trait to his offspring.
We're talking about billions of years, and billions and billions of organisms, and that's how complex structures evolve. The most notable example would be the eye. First, by random chance, an organism evolved a light receptor cell and had a better chance to survive. Then there were several light receptor cells, then there was a chamber, and so forth. Eventually you have the eye as we know it. It took billions of years.

No.  That can't possibly be right.  The vast majority of mutations are NEUTRAL, or nearly neutral.  See Bromham & Penny (2003)

There is an average of 2.2 new deleterious mutations per human zygote, and 0.02 new advantageous mutation per human zygote.

Citation?  How does that compare to the # of neutral or nearly neutral mutations?

A mutation is an error, to put is simply, and you are correct that some of them have no visible effect. But you misunderstood the paper you linked to.


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How to design primers contanining random "NNNN" nucleotides?
I need to synthesize this primer: GACCATCTAGCGACCTCCACNNNNNNNN. This primer contains eight random nucleotides in the 3' end. This primer can be used for viral metagenomics, and the last 8 "N" nucleotides are similar to a random primer that is used for RT-PCR. My question is if I submit this sequence for oligo synthesis, say to IDT, will they synthesize one primer that contains random 8 nucleotides at the 3' end, or will they synthesize multiple primers containing all possible nucleotides at every position?

That's a question you should ask the IDT customer support. There may be someone on here who can answer as to what IDT can do, but your best bet is to ask the source.

You will get 48 different primers in a single tube.
Oligonucleotide synthesis is a cyclical process which adds nucleotides one position at a time.

image source
All that’s happening when an N is encountered in the sequence is, during the coupling step, instead of adding a single type of nucleotide to the reaction, they add all four (which are incorporated stochastically).

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How many plants arise from a polyembryonic seed?
When I asked this question to my teacher she said that she doesn't know. So I wanted to know? Is there any use of polyembrony in plants?

In plants due to programmed cell death only one plant arises.
Here is a good article

The enigma of plant monozygotic polyembryony is that only one embryo in a polyembryonic seed usually survives while the others are eliminated at an early stage.

If that is so, what is the need of polyembrony (Sporophytic budding). It's there any use in the process?@JM97


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Why do humans have irregular teeth and impacting wisdom teeth?
Imagine that horses, dogs, bears, and gorillas had teeth as unreliable as humans do, The interruption in behaviour and stress brought by teeth would cause them to be more prone to sinus infections, jaw abscesses, and general poor performance.
The stress from cavities and wisdom teeth growing sideways would affect their survival rates.
Humans have evolved slow maturation times, including teeth, have shortened jaws with compressed teeth, and errored, unvariable, DNA from inbreeding after near extinction 100k years ago (lake toba caldera) which makes us biologically quirky and unreliable.
Why does our jaw have to be so short that we could live with impacting wisdom teeth? because it places strain on the neck to have a long jaw?
Why didnt face infections and tooth misalignment cause humans to select each other strongly with straight teeth?
Are wonky teeth a feature of cold climates, where people dont have so much fruit, and in hot countries, ethnicities have straigher teeth?

Teeth first:
The vast majority of people have no problems with their wisdom teeth, whether they emerge or not. Impacted wisdom teeth are very common and are usually painless. They do, however, sometimes mess around with other teeth and throw off our bites (which will always readjust, not necessarily in a cosmetically pleasing manner, but the bite will adjust). Today, because we value straight teeth, impacted wisdom teeth are often removed prophyllactically, even if we have no proof that it/they will cause any problems.
Since impacted wisdom teeth are not evident until well after reproductive ability is attained, there is no reason to believe that malocclusion from wisdom teeth should be evolutionarily selected against. If problem teeth are so bad as to cause disability for an individual, that individual is removed from the gene pool.
Given two equivalent males, there's no reason not to entertain the notion that a female did not choose the one with better occlusion. So, it is theoretically possible that what we have now is an improvement over what was the state of our occlusions long ago. But there is rarely only one reason for two individuals to choose each other as partners, so... the teeth are relatively unimportant evolutionarily.
Or, if impacted wisdom teeth hurt enough to interfere with reproduction ("Not tonight, Og, I have a killer toothache.") the individuals who don't reproduce because of it will be dropped from the gene pool.
There may have been selection against wisdom teeth, because there are populations who have a lower incidence of third molars.
80% of all people will have problems with their backs at some point in their lifetime, which is a direct result of bipedalism in humans. You might ask why we became bipedal with that painful trade off. But bipedalism gave us some distinct advantages in survival. So did the expansion of our brains. The greater advantage has precedence in evolution.
Impacted tooth
Ancient Mutation Explains Missing Wisdom Teeth


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Can a young voice have physical causes?
I have noticed that some older adults (40+ range) can have voices that sound much younger than their actual age (i.e. an adult sounds like an adolescent).
My question is: could any physical aspects play a part? For instance the size of the throat, the tongue or something else? I am assuming that there are no external factors that are influencing this (smoking, exposure to chemicals, physical trauma, etc).

every aspect of an organism has a physical cause, there is nothing about an organism that is not ultimately physical.

In general, a grown up man will have a voice with a lower pitch than when he was an adolescent (Cleveland Clinic). The pitch height basically depends on the length of the vocal cords. According to Wikipedia:

Adult male voices are usually lower-pitched and have larger folds. The
  male vocal folds...are between 17 mm and 25 mm in length. The female
  vocal folds are between 12.5 mm and 17.5 mm in length.

So, the shorter the cords, the higher the pitch. There are other anatomical structures in the throat, mouth and nose that may contribute to more adolescent-like voice. To know what exactly is the cause in a particular man, an examination by an ear, nose and throat (ENT) specialist would be probably required. Additionally, a voice specialist could have a good insight even without physical examination.
There can be reasons associated with self-image that make one to consciously or subconsciously insist in speaking with a voice unusual for his age. Sometimes you can see this in singing competitions, when a young man introduces himself with a child-like voice but then sings as a grown-up man.

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Are pulp cells (in oranges) normal plant cells?
Does a pulp cell contain all the elements that a 'normal' plant cell contains?
I've searched for an hour to find more information about this but couldn't find anything useful. Is the pulp cell the exception from the general size range of most eukaryotic plant cells, normally between 10 - 100 µm?
Please include link to a reputable website.

They are not individual cells. In fact, the "juice sacs" (as they are known) are actually specialized, multicellular hairs:

Juice sacs originate as multicellular hairs in which the interior of the enlarged distal part breaks down and fills with liquid. The juice sacs constitute the fleshy, edible pulp of an orange and are the source of the sweet juice.

(Quote and image from Fruit Terminology, palomar.edu)
This is from a botany course; if for some reason that isn't reputable enough, check out the book Anatomy of Seed Plants by Katherine Esau (1960).


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Why do neurons die so quickly (relative to other cells) when deprived of oxygen?
This question could be considered a follow-up question to Why is a lack of oxygen fatal to cells?, although the top answer there does not address why damage starts to pop in.
The answer says this:

Neurons are also highly metabolically active, which means they
  generate more waste products. A buildup of nitrogenous waste products
  in the cell (and bloodstream) can be potentially fatal due to it's
  effects on pH (screws up enzymes and a whole slew of biochemical
  reactions)

But when the brain is deprived of oxygen, metabolism shuts down. So waste products aren't being generated anymore.
====
Basically I'm wondering - what causes neurons, in particular, to die so quickly (relative to other cells, like kidney cells) after they're depleted of energy?

who said anything about metabolism shutting down when the brain is deprived of oxygen? Brain cells die, sure, is that what you mean by "shut down"? Are you implying that they go into some kind of dormant state before they die?

Doesn't metabolism shut down before death occurs? Or does the metabolism start causing damage, which causes death in the process?

this isn't very scientific, but metabolism shutting down is death in some sense. Our neurons aren't designed to be shut down, so if that happens they start to fall apart (die).

FYI: I've opened a related question on how much our brains' metabolic rate varies. My guess is that since neurons consistently use lots of energy, they are totally unprepared to exist in a low-metabolism state.

But on the other hand, some organisms can be frozen and revived. In that case, metabolism is shut down but death does not occur.

There is a good review in the Journal of Experimental Biology (Bickler and Donohoe 2002, JEB 205, 3579–3585) I will just summarize for those that do not have access to the review.
Neurons use lot of energy to maintain their polarized state, this is not required to other cells. When O2 or blood flow is reduced, the neuronal ATP levels breaks down very fast, with 90% ATP depleted in less than 5 minutes. Without ATP, the neuron can not maintain the correct ion flux, so depolarization occurs causing glutamate excitotoxicity, cell swelling and finally cell death.

+1. Neurons use a lot of active transport pumps that consume ATP to maintain ion gradients and to shuttle neurotransmitters.

What about cardiac myocytes? They also need to maintain a depolarized state for synchronized contraction