genetics - Chromatin shearing: what is it and what are the effects of high-sensitivity?

Shear forces are experienced by all molecules, and molecular complexes when they are treated roughly. So, for example, if you have a solution of high molecular weight DNA it will be very viscous, but if you treat it roughly by pipetting up and down through a narrow aperture the DNA strands will suffer shear forces strong enough to break covalent bonds and the solution will become less viscous. Another example of the use of shear forces in biology is lysis of yeast cells using small glass beads. As the slurry of beads and cells is vortexes the cells experience intense shearing forces (forces tending to pull different parts of the cell in different directions) and they break open. They are not being physically ground by the beads.

In the specific case that you quote, you apparently have a multimolecular complex (MSL-DCC) held together by weak (non-covalent) interactions and interacting with the nucleosomes through a component called MSL-3. Without looking at the paper, it seems that this complex is prone to falling apart (during isolation?) as a result of shear forces strong enough to overcome the non-covalent binding interactions. Think of a helicopter with a man hanging on to the undercarriage with both hands. Then imagine a second man hanging on to the first man's boot lace with his thumb and finger. Who will fall off first due to the shearing forces experienced as they are buffeted by the wind?

The helicopter is the nucleosome, the first man is MSL-3 and the second man is the rest of the complex.

added later in response to MattDMo
looks from this that I was wrong - it's actually a French press and other homogenizers that generate shear forces. I don't think I made the glass bead story up, but I can't remember who told me. The BeadBeater people also refer to "cell cracking" not shear. Apologies everyone, I think the rest of the post still holds up, and thanks to MattDMo for the challenge.

pathology - Why are antibiotics prescribed with a viral infection like a cold?

Antibiotics kill bacteria, not virus! So it's just plain wrong. If a bacterial infection appears after the cold, then the antibiotics should be prescribed because of the bacterial infection, not because of the cold. There is a serious concern about misuse of antibiotics promoting hyper-resistant bacteria through natural selection, but doctors keep ignoring alerts from WHO and prescribing antibiotics without even knowing the bacterial strain. It's absurd that a doctor should prescribe an antibiotic just because "the patient needs to get some medicine to be happy". In this case he/she should prescribe a placebo, not a real antibiotic (and there's still the point that killing most bacteria in our body destroy one of our defensive lines against pathogens). Confirming this point, according to American Medical Association, medical error is the third death cause in USA. So in many cases, yes, it might just be a medical error.

iris - Why Do Most Humans & Cats Have Blue/Bluish Eyes At Birth?

The generation of iris color is quite complex and the exact color of the eyes depends upon many different factors, not just melanin. In fact, blue coloration does not depend on a specific chemical, but on the structure of the eye itself.

This very nice review (free) summarizes our current understanding:
Genetics of human iris colour and patterns - Sturm and Larsson, 2009

From the Introduction (bold is mine)

In the brown iris there is an abundance of melanocytes and melanin in the anterior border layer and stroma whereas in the blue iris these layers contain very little melanin. As light traverses these relatively melanin-free layers, collagen fibrils of the iris scatter the short blue wavelengths to the surface, thus a blue iris is a consequence of structure not of major differences in chemical composition. Different shades of blue, and in irises with a limited amount of melanin, different shades of grey, green and hazel, are determined
by the thickness and density of the iris itself and the extent of accumulation of white collagen fibres, as well as patches of tissue loss in the anterior border layer and stroma.
However, a careful examination of people’s irises makes it clear that there are characteristics other than eye colour that present in the human iris. The iris has been analysed to show that it can display a degree of complexity encompassing over 240 degrees of freedom (Daugman, 2003).

botany - What controls leaf senescence in deciduous tree species, and how can I predict it?

If I want to predict litterfall, what data do I need to collect, and what statistical model might I use?

For example, I might use the following coding to record phenological stage every other day, or perhaps once per week:

|value| description
|-----|--------------
| 0   | all leaves fallen
| 0.5 | most leaves fallen
| 1   | no more green in canopy half of leaves have fallen
| 2   | most leaves yellow or red few leaves have fallen
| 3   | noticeable reddening or yellowing, green still present
| 4   | summer condition

Once I have these data, I can also collect weather data. Now, say I want to predict the day on which each of the transitions ($4\rightarrow 3$, $3\rightarrow 2$, etc) occur.

Many studies use a temperature metric of growing degree days $GDD = (T_{max}+T_{min})/2-T_{base}$, but I have also seen chiling days and photoperiod used to predict changes in phenological stage. I would like to develop a function (statistical model) $f$ that would allow me to predict a date of state change from environemental variables, such as $$D_{4\rightarrow 3} = f(GDD)$$

My questions:

• what controls litterfall? Is it photoperiod, temperature, other?


• do the controls vary by species?


• is there a "standard" approach to modelling senescence?

microbiology - Aerobe or facultative anaerobe organism that metabolizes acetate?

I'm assuming bacteria, but will take any suggestions. Organism must survive primarily on the acetate (plus trace elements), but I can give/take electrons, if necessary. Not interested in strict anaerobes. I've tried Shewanella oneidensis, but have not succeeded in getting it to eat any acetate (just lactate). Feel free to give journal refs. Self-promotion won't be frowned upon if it's helpful. :-) Opportunity for joint pub, if successful.

bioinformatics - Organize sequence database

I recently took up the task of organizing the sequencing database for a research project. I am still quite unsure of which database type I should use for this. Some advices/recommendations would be wonderful.

This research project is more like a class where students are taught how to sequence a piece of plasmid via Sanger sequencing method, with paired end primers. For each plasmid there will be two entries (~1kbp each). Then the students would BLAST the sequence, mostly to see if there is any close match with certain related organisms.

The main purpose of this database I'm creating is to monitor the sequencing progress, as well as to single out the samples that need to be redone. So far, the record-keeping is not exactly accessible, hence the need for re-organization. Additionally, the students would need to be able to view their own results and enter the BLAST results themselves. The last condition seems to necessitate a web-server type of thing that the student can connect to enter their information.

The total number of bacteria clones containing plasmids are ~18k, which means there will be ~36k entries in this database. It would be great if there is anyway to manage the trace files of the entries, or if not, I think I can add a column for the file path.

Is there a database management program that is appropriate for organizing sequence and trace file, with easy access for data entry by multiple users? It would also help if the program don't have a high maintenance need.

Disclaimer: I have very limited knowledge with database structure, having only taken an online intro to database class. About programming language, I am still learning Python. This project is a way to force myself to learn more.

vision - Possibility of orthogonal view for a creature?

The answer depends on the distance between eyes, and width of the objects you are viewing.

The view of a separate object is close to the orthogonal view when the width of the object is equal to the distance between your eyes.

Hence the creature that has variable distance between eyes, and has large maximum distance between eyes, has most possibilities to view objects in orthogonal view. Snail comes to mind when I try to think about animal with variable distance between eyes, but its maximum distance between eyes is not that large.

When object is narrower than distance between eyes, you see it in "anti-panoramic view". You will see both left and right side of the object, which is impossible both in orthogonal view and in panoramic view.

Speaking about whole 180 degrees wide visble scene (wider for some animals), the answer is No. You cannot view the whole scene without perspective view, unless you have large number of "eyes" (sensors) that are spread over a large plane. There is no such animal, but you can artificially construct such "perceptor plane" using large number of photocameras.

When looking at the objects of width equal to distance between eyes, if your brain can direct eyes such that their viewing axes are parallel, and could integrated two pictures, then it would view perfectly orthogonal view. This is not what our brain normally does, though. But even with non-parallel view axes of eyes, what we eventually see when brain integrates different pictures the result is not par from orthogonal projection.

medicinal chemistry - Why does ice reduce swelling?

Swelling is one of the signs of inflammation. Inflammation involves release of histamine by mast cells present in the tissues. Histamine causes vasodilation and leads to leakage of fluid from the blood, along with which neutrophils and other WBCs also enter the area. They phagocytose microbes that might have entered with the injury.

Applying ice would cause vasoconstriction* (i.e. narrowing of blood vessels.) which would reduce the leakage of tissue fluid and hence swelling.

*If you wonder why ice(or any cool thing) causes vasoconstriction think why you turn pale in winter ? Vasoconstriction reduces blood flow to the particular area and hence the exchange of heat is reduced which conserves body heat in cold environments.

microbiology - Highly spherical Radiolaria; does this image accurately depict the organism?

If I understand correctly, Cenosphaera spp. is a type of Radiolaria, which is a type of zooplankton. The following is an image of Cenosphaera spp. is from the supplementary material (Figure S2) of the following paper:

F. Lejzerowicz et al., Ancient DNA complements microfossil record in deep-sea subsurface sediments, Biol. Lett. (9) 2013.

Question: Does this image accurately depict the organism?

More specifically, in other images of this organism, there are numerous thorns pointing outwards. Is this thorn-less version a natural variation (or e.g. the result of the process of imaging the organism)? Also, is it largely a sphere with a hollow inside?

The authors give the following description of the process involved in obtaining these images.

Eighteen sediment samples were wet washed over 63 μm and 20 μm sieves. The >63 μm residua were dried and picked for radiolaria and foraminifera. From most samples all specimens were picked. Rich samples were divided with a dry microsplitter into fractions, from which at least 100 specimens were picked for each group. Specimens were arranged by taxa on micropaleontological slides. Radiolaria are classified on the generic level, according to the classification utilized by [8]. Foraminifera above the species level are classified according to [9]. In addition, for radiolaria, the 20-63 μm fractions were soaked in peroxide, then washed with tap water and propanol. For each sample, a few drops of suspended material was left on a glass to dry, covered with Durcupan ACM resin and a cover glass. The micropaleontological slides were analyzed under Olympus BX50 light microscope (electronic supplementary material, figures S2 and S3).

molecular biology - Just how light-sensitive is ethidium bromide?

Good question.

I found this reference in "Molecular Biology: A Project Approach"

A phenomenon called photobleaching occurs when ethidium bromide (EtBr) -stained DNA is illuminated by ultraviolet light.... This decreased fluorescence is presumably due to the dissociation of ethidium bromide from the DNA.

Ethidium bromide fluoresces when it is in a hydrophobic environment, such as when its stuck between two base pair stacks in DNA- water quenches its fluorescence.

I also found this article citing the fact that sunlight can break down EtBr but only when a catalyst of iron and titanium dioxide is there to catalyze the reaction.

A lot of the original characterization of EtBr as a stain is very old, so I couldn't access it directly online... It looks like the compound itself is pretty stable, but UV can, somehow interact with it when its bound to DNA to bleach it out.

evolution - Are genes associated with obesity selected for?

This is called the "Thrifty Gene Hypothesis" which was first used to explain why diabetes is so common. Basically it suggests that these alleles would have provided some kind of advantage, over the other possible alleles at that loci, until the environment changed. Then the environment changed and the allele became harmful. Environments are always changing and therefore favour different alleles (variant of a loci).

I suggest the genes linked to obesity in the modern world would, if tested on the old world populations would have been linked to being of a healthy weight. Further, those without it may have been skinnier and more likely to suffer from the disadvantages of being in such condition.

However, this paper present some counter arguments to the thrifty gene hypothesis. Speakman suggests that the genes responsible spread via genetic (allelic) drift rather than by positive selection. It is worth remembering that drift is very poor at spreading new mutations through large populations so there are also weaknesses to his arguments.

One example of a change in the favoured allele caused by an environmental shift is the DDT resistance gene in Drosophila which was present in the population at very low levels for a long period of time. As an aside, it possibly remained this way because it was subject to sexually antagonistic selection - beneficial to females whilst detrimental to males. It then spread through the population when DDT pesticides were used because it obviously became highly beneficial. Many other examples of environmental change leading to different selection are around, this is just one off the top of my head. Another is the Galapagos Finches in a drought in the late 20th century.

HTH, if not please ask more and if it does then please accept it!

pharmacology - Can a person become addicted to tea?

Yes, both tea (black tea at least, English speakers usually mean black tea when they say tea anyway) and coffee have caffeine which is addictive.

Apparently, being able to correctly reply to this question involves defining the word "addiction". My guess is that the negative connotation of the word "addiction" will cause some pressure to not use it.

Here's a recent review on caffeine addiction that says that caffeine is not addictive. I do not agree with their arguments but I'll leave it to the reader to judge.

human biology - How does Humira work when injected into patients with rheumatoid arthritis?

Afaik. RA and psoriasis are probably caused by a malfunction of genes which regulate IL-23 production. IL-23 is required for Th17 cells to survive. Th17 cells produce a lot of things which result in inflammation and since TNF-α is a key mediator in inflammation and break down of joints, reducing the amount of available TNF-α reduces the inflammation.

(Th17 cells produce IL-17, IL-21, IL-22, IL-6 and TNF-α. Th17 cells are playing against Treg cells, which try to protect self cells. IL-17 promote osteoclastogenesis, and osteoclasts break down bone. According to serveral wikipedia articles IL-17 induces the production of other cytokines such as IL-6, IL-1β, TNF-α. IL-21 is required for sustained CD8+ T cell effector activity. IL-22 is a mediator of cellular inflammatory responses. IL-6 modulates the resistance of T cells against apoptosis, induces activation of T helper cells and promotes osteoclastogenesis. TNF-α is an endogenous pyrogen which is able to induce fever, apoptotic cell death, cachexia, inflammation and inhibits tumorigenesis and viral replication. IL-1β is a mediator of the inflammatory response, and it is involved in the regulation of apoptosis as well.)

Adalimumab is an immunoglobulin, which binds to TNF-α, and so it prevents it to bind TNF-α receptors and cause inflammation. After it is bound to its target you cannot reuse it, that's why you need daily doses of it. It is degraded by liver and kidney cells, or probably by phagocytes as well.

There are other TNF-α blocking pharmaceuticals as well. There are IL-23 inhibitors, one of them is called ustekinumab. It is an immunoglobulin too and it is used by treating psoriasis. By RA it is currently under clinical trial, but I guess it will work by RA as well. There is an IL-23 inhibitor which is not an immunoglobulin and can be taken orally, it is called apilimod. Sadly it failed the clinical trials, it had only mild effect. It probably does not reach the inflammation in sufficient amount. Maybe later there will be an effective delivery method and so a drug which can be taken orally.

There are alternative natural therapies: TNF-α inhibitors which you can take orally, for example γ-linolenic acid, ω−3 fatty acids, chondroitin sulfate, etc... These can be useful by mild cases of RA. Probably fever therapy works by mild cases as well. Afaik. cryotherapy has nice results in treating RA and its positive effect lasts much longer than the effects of any drugs, so if you aren't afraid of cold, that is a nice alternative therapy as well.

Blood Pressure: Significance of difference between systolic and diastolic

The difference between systolic (the upper number) and diastolic (the lower number) pressures is known as the pulse pressure:

Systemic pulse pressure = P_systolic - P_diastolic

For a typical blood pressure reading of 120/80 mmHg the pulse pressure is therefore 40 mmHg.

It is proportional to stroke volume, the amount of blood pumped from the heart in one beat, and inversely proportional to the compliance or flexibility of the blood vessels, mainly the aorta.

A low (also called narrow) pulse pressure means that not much blood is being expelled from the heart, and can be caused by a number of factors, including severe blood loss due to trauma, congestive heart failure, shock, a narrowing of the valve leading from the heart to the aorta (stenosis), and fluid accumulating around the heart (tamponade).

High (or wide) pulse pressures occur during exercise, as stroke volume increases and the overall resistance to blood flow decreases. It can also occur for many reasons, such as hardening of the arteries (which can have numerous causes), various deficiencies in the aorta (mainly) or other arteries, including leaks, fistulas, and a usually-congenital condition known as AVM, pain/anxiety, fever, anemia, pregnancy, and more. Certain medications for high blood pressure can widen pulse pressure, while others narrow it. A chronic increase in pulse pressure is a risk factor for heart disease, and can lead to the type of arrhythmia called atrial fibrillation or A-Fib.

botany - Why is the floral biodiversity of grazed grassland higher than that of mown grassland?

I have collected some data to compare the biodiversity of a field in which the plagioclimax is maintained by machine mowing with a field in which the plagioclimax is maintained by sheep grazing.

What I found was that there was a significant increase in floral biodiversity in the field which was managed by agricultural grazing when compared to the floral biodiversity of the machine-mown field.

I am trying to explain my findings, and I believe that it is due to the comparitively short amount of time that machine-mowing has been a grassland management technique, so there has been little time for natural selection to take place and for species to develop adaptations to machine-mowing (such as being low-lying, or extremely fast-growing). Whereas the field which is managed through sheep-grazing, contains multiple competing species which have adapted over time to grazing sheep, such as Cirsium arvense.

Moreover, the field which is managed by grazing has nutrients returned to it through defecation of the grazing animals, allowing for more favourable conditions for growth.

Is my explanation valid? Are there any other reasons why the floral biodiversity of a field managed by sheep grazing would be higher than one managed by machine-mowing?

Thanks in advance!

evolution - Why was polyploidy not lethal in certain octodontid rodents?

Actually, that is not what is discussed in the question you linked to. The following is a quote from the very comprehensive accepted answer (emphasis mine):

Polyploidy arises easily in both animals and plants, but reproductive
strategies might prevent it from propagating in certain circumstances,
rather than any reduction in fitness resulting from the genome
duplication.

In fact, try rereading that answer and the references therein, it answers your general question.

There is a popular theory (mostly accepted) that there have been whole genome duplication events (WGDs) in the vertebrate ancestry. If true, it means that all mammals are the descendents of polyploid ancestors. For a very nice review of WGDs in vertebrate evolution, see here [1]. Octomys is simply the only known mammal with a more recent WGD event. As for what makes it special (taken from [2]):

Our data demonstrate that parental-specific silencing of at least one
gene and normal X chromosomal dosage mechanism are conserved in the
tetraploid genome. We hypothesize a concerted action of genetic and
epigenetic mechanisms during the process of functional diploidization
of this tetraploid genome.

1) Van de Peer Y, Maere S, Meyer A., The evolutionary significance of ancient genome duplications., Nat Rev Genet. 2009 Oct;10(10):725-32.

2) Bacquet C, et al., Epigenetic processes in a tetraploid mammal, Mamm Genome. 2008 Jun;19(6):439-47.

human biology - How does sodium in one's diet affect blood pressure?

Salt will cause high blood pressure, but only under certain circumstance.

physiologic hormonal compensations for increased blood volume:

• Atrial natriuretic peptide -- increases sodium excretion, hence this is INCREASED with high blood volume


• Antidiuretic horomone -- ADH increases water reabsorption in the kidney, hence this will be DECREASED with high blood volume


• Renin/Aldosterone -- increases sodium reabsorption from ultrafiltrate back into blood, hence it will be DECREASED

these explainations are a bit reverse (saying that these horomones have these effects and that is why they are released) for the sake of simplicity, and I'm not discussing the mechanism of release of these horomones (aka under what circumstances they are released in the place where they are released from)...

while these horomones help with the kidney regulation of sodium balance and blood volume, this still depends on the kidneys being given the circumstance where they can be effective.

Pathologic circumstances, when elimination of excess sodium fails:

Some people simply have a higher sodium sensitivity and there are a variety of factors that have been statistically correlated to sodium sensitivity, but often the mechanism is unknown. Here are various factors statistically correlated to affect salt sensitivity:
http://physrev.physiology.org/content/85/2/679

the above article shows that no organ systems need be compromised for excess sodium to raise blood pressure, but just for the sake of discussing more macroscopic things I want to discuss these organ systems based reasons for the kidney being unable to compensate for excess sodium in the diet=

• The kidney:
  A patient with renal disease may not be able to regulate the excretion of sodium. Even in normal humans, the kidney's capacity to excrete sodium declines with age, and smaller increases in salt intake induce a rise in arterial pressure, as GFR (the renal filtration of the blood sent to the kidney) falls by about 40%, though individual variations are wide and some people lose less.

Other than the kidney:
Other diseases can also interfere with renal excretion of sodium. A problem with maintaining blood volume will cause constriction of the renal artery. This would occur before a drop in blood pressure would occur, as this is a way of preventing a drop in blood pressure. This occurs in congestive heart failure and liver cirrhosis.

• A patient with congestive heart failure may not have adequate renal
  perfusion. Hence, to maintain adequate blood pressure the renal artery is constricted.


• Also, liver cirrhosis may decrease renal perfusion
  because of the lack of blood proteins (proteins found inside the
  blood vessels that keep water in the blood vessels via osmosis)
  holding fluids in the intravascular space and having them escape into
  the extra-vascular (outside the blood vessels but still outside the
  cells of the body) space. Again, to maintain adequate blood pressure the renal artery is constricted.


• burns, also because of loss of blood proteins--> leakage of intravascular fluid to extravascular space--> decreased blood volume and increased sympathetic nervous system output--> reduction of renal blood flow... same as for cirrhosis

In addition to reduction of salt in the diet, diuretics (ex. loop and thiazide) can help the body excrete even more sodium into the urine than what your body can do on it's own.

this article describes the renal handling of excess salt in the diet:
http://booksite.elsevier.com/brochures/thekidney/PDFs/TheKidneyCh36_P088488.pdf

entomology - How do ants sense imminent rainfall?

This article claims that ants do sense approaching rain and modify their activities in preparation. The claim is not sourced. This weather site also speaks of ant mound-building before a rain but frankly places it in the "some folks say" category. The AntBlog is associated with AntWeb, a large multi-university-affiliated database. The author of the linked blog states that ants can sense humidity with their antennae, which strikes me as a plausible means of anticipating rain.

That ants might sense changes in barometric pressure is an intriguing idea but has not to my knowledge been demonstrated.

A 2010 article in Journal of Neurophysiology reports an almost unbelievable sensitivity to temperature in ant antennae, allowing them in principle to sense minute temperature changes ($0.005^o$C) over a wide range of temperatures and over 0.2 second time intervals (5Hz). This is said to assist them in orientation in their microenvironment but I think it goes a long way to accounting for an ability to detect looming weather fronts. Humans can sometimes 'smell' rain and we can detect gross temperature changes that almost always accompany rain, but to be able to detect humidity and micro-scale temperature changes would give the ants a real advantage in forecasting. After all, not all rainstorms are preceded by a dramatic drop in temperature but probably the majority are preceded by minute step-wise drops in temperature that evidently the ants can sense.

So while I think the building activity may be anecdotal (and probably true for some species) the ability to sense humidity changes and micro-scale temperature changes accounts for their ability to sense rain ahead of time.

Ants are very well-studied and it's hard to rule out that one has missed something. There are a few "ask the expert" questions on this topic online and no one seemed sure.

zoology - Polymorphism in cnidarians?

It seems like your question might contain two separate and linked issues, both of which are perhaps equally confusing and equally interesting. They're both really discussion questions in a sense, but they've also both been dealt with in the literature in thoughtful ways, so here's a stab at an "answer".

Issue One: how does your species concept deal with polymorphism?

This may depend on which species concept you're using. And, to some extent, the choice of which species concept you use depends on what kind of organism you're dealing with (for instance, organisms that reproduce asexually have a whole different set of issues and challenge several species concepts).

Various papers by Kevin de Queiroz deal very well with species concepts. In 'The General Lineage Concept of Species' (which is also summarized on this page), he argues that although there are many different species concepts that can be better applied to different situations, they all share the basic tenet of defining a "segment of a population-level lineage". In other words, each concept is attempting to put a continuum into slightly different categorical bins, but they all recognize the existence of the same continuum (the lineage). (Also see his 'Species Concepts and Species Delimitation'.)

I think most species concepts have no trouble dealing with polymorphism because the different morphs are all part of the same lineage, that is, "a series of entities forming a single line of direct ancestry and descent" (de Queiroz 1999).

---

Issue Two: how does your concept of the individual organism deal with colonialism?

In 'Does Biology Need an Organism Concept?' Pepper and Herron make a similar point to that of de Queiroz. They argue that multiple definitions (concepts) exist, and that these concepts all attempt to categorically bin what is in fact a continuum. Like de Quieroz, they argue that most definitions recognize the same underlying continuum, and that the difference is in the categorical bins.

In the case of the organism concept, this continuum is based on two criteria: increasing genetic homogeneity, and increasing physiological integration.

So, for instance you could have two organism concepts (in the picture below, lighter yellow and darker yellow) that agree that Physalia falls in the same location along these axes, but disagree on exactly where to draw the boundary between their "multiple organisms / colony" zone (yellow), and their "individual organism" zone (white).

I'll finally get to my point, paraphrasing both de Queiroz and Pepper and Herron. For both concepts of the species and of the organism, arguing about whether one concept is better than another is endless (especially on a site that aims at answers rather than discussion). However, recognizing that there are different concepts, understanding that what these concepts do is to bin the same continuum in different ways, and being clear about which concept you decide to use is very useful.

biochemistry - Conversion rate of topical Retinol to Retinoic Acid (Tretinoin)?

I'm wondering if someone out there has more information than me. Retinoids have well known metabolic pathways in vivo, and it's usually something like: Retinyl Palmitate --> Retinol --> Retinaldehyde (Retinal) --> Retinoic Acid (Tretinoin) which is the biologically active form of the Retinoids.

Retinoids are used in cosmetics all the time, and while Retinol is available OTC, Retinoic Acid (Tretinoin - a.k.a. "Retin-A" by brand) is available by prescription only since it is a 'stronger' version of Retinol. It's not difficult to find 1% Retinol creams or higher, but Retinoic Acid treatments top out at 0.1%.

However, I can't help but wonder 'why'? One study I was able to dig up was here: Retinoic Acid Biosynthesis and Metabolism PDF. The table on page 5 shows Physiological Concentrations - starting at 50 microM for Retinol and ending at "<50nM?" suggesting an ultimate conversion rate of a little less than 10% which would make the 1% Retinol treatments roughly equivalent to a 0.1% Retinoic Acid treatment (and a 2% Retinol treatment to a 0.2% Retinoic Acid treatment - double what's available by prescription).

Do other studies/other evidence support the rate of conversion of Retinol to Retinoic Acid to be roughly 10% or suggest than a 1% Retinol topical treatment is equivalent to a 0.1% Retinoic Acid topical treatment? Or are there some other interfering factors that reduce the utilization of Retinol to Retinoic Acid that I'm missing?

genetics - Drosophila reference genome

That was surprisingly buried.

I found this in a paper describing genome build 3 - See "Materials and Methods". I imagine that this is consistent through to the current build. In any case it should get you started.

"Sequencing templates were made from P1, BAC and WGS DNA libraries using the D. melanogaster strain yellow (y1); cinnabar (cn1) brown (bw1) speck (sp1)."

physiology - What are potential side effects of myostatin inhibitors?

Myostatin inhibitors, which are being developed to treat muscle wasting diseases like muscular dystrophy, are likely to be abused by athletes. What are the potential long-term side-effects of taking a myostatin inhibitor? Will it have different side-effects for patients compared to healthy athletes (especially young athletes that are still developing)? Could there be adverse drug interactions with other common performance enhancing drugs like EPO, hGH, and anabolic steroids?

Sources I've explored (StackExchange is only allowing me to insert two hyperlinks):

• New Muscle Drugs Could Be The Next Big Thing In Sports Doping - NPR story by Jon Hamilton


• Wikipedia entry on myostatin


• Wyeth found one of its drugs to be safe in a clinical trial, but it stopped development because the drug was ineffective at increasing muscle mass.


• An internet search mainly brings up dieting and body building forums, which I do not trust.


• According to a review by Breitbart et al. 2011, myostatin inhibition does not have negative effects on cardiac tissue.


• According to a review by Allen et al. 2012, the increase in muscle mass caused by myostatin inhibition leads to be metabolic health (e.g. lower glucose levels and higher insulin sensitivity).

dna - There are linear and rotary molecular motors in the cells. Do any of them have a fixed or stable frequency or speed?

These molecular motors' response maybe dynamic and nonlinear. But it entirely dependent on the external influence and also the characteristics of the motor itself including number of active motors involved in operation. As it is microscopic, it will not possible to analyse by assumptions and say they have some random frequency. They do have certain frequency of operation (I do not know whether they are controlled by biological clock or some master clock but they are controlled by nucleus of the cell) and "Modeling molecular motors" explains how motors act on the filament inside the cell. It mainly talks about the influence of external force on the operation of motor and also speed(v) of the motor. The following excerpt from that paper talks about the external force on motor.

The action of the motor is induced by generalized forces, which for
the motor/filament system may be identified as the mechanical force
fext applied to the motor, and the chemical potential difference
Dm, which measures the free-energy change per consumed ‘‘fuel’’
molecule. The force fext describes external forces, for example of
optical tweezers, microneedles, or the viscous load of an object that
is carried. fext could also include viscous friction forces between
the motor and the surrounding solvent if the latter is considered as
‘‘external.’’ The chemical potential difference Dm is for the
process of the hydrolysis of Adenosinetriphosphate (ATP) to
Adenosinediphosphate(ADP) and phosphate (P).

The frequency of molecular motor according to "Biophysics of Molecular Motor" has been classified into two categories:

1. Density controlled: In the density-controlled model, it is assumed that the depolymerization rate is proportional to the motor density at the terminal site of the microtubule. Here the frequency of motor is dependent on density of the motor.




2. Flux controlled: Filament depolymerization is determined by the flux of motors
   to the end. Here the frequency is dependent on the flux of the motor.

In both the above cases the length of the filament on which motor is acting is also important. These models have been analysed and plotted on a graph to give a clear picture of it.

The paper explains the catastrophe frequency, the frequency at which the filament shrinks. Shrinking of of a filament is due to motor. So the paper concludes saying the catastrophe frequency is 0.5 per min for a 8um length of filament.

(Catastrophe = the transition from growing to shrinking of dynamic microtubules).

To summarize, these motors do have speed and frequency of operation but they are not fixed. They vary in a non linear fashion due dynamic environment. But the motor tries to be as much stable and resistant as possible.

evolution - Extraretinal photoreception in mammals?

Its pretty well established that there are photoreceptors in cells besides the cones and rods in the retina of the eye. Humans and most animals have four light receptor genes known (so far). In addition to Rhodopsin - there are the short, med and long wavelength opsin genes.

While they are mostly expressed in the retina of the eye, they can be found in many other tissues as well. The first image from GeneAtlas below shows the relative amount of RNA found for short wavelength opsin in a variety of tissues - its expressed in immune and nerve cells ( cyan and forest green respectively) relatively well too. This might imply that neurons are light reactive. Compare that to that of medium wavelength opsin, which is primarily much more common in the retina.

This is not a psychosomatic effect. Light receptors in the skin are known to help with seasonal affective disorder - shine a bright or blue light behind your knees. These receptors are not connected to optical nerves, and so you don't get any image from them, but the information can affect your biochemistry anyway.

The idea of unconscious receptor inputs from other parts of the body probably applies to many sorts of receptors. This last year there has been a great deal of interest in taste receptors which are expressed in the gut. They can taste sweetness and other flavors a second time and register the gustatory response in the brain. Its not a conscious input, but it registers in the brain in MRI.

Why would evolution do this? It seems to me that this is a new way of looking at the individual life of a cell and makes a good deal of sense. If every cell has all the genes' DNA why wouldn't a little bit of receptor expression be found in any cell which could use the information? The conscious processes of the brain probably only take in a small fraction of the information that is sent in and there maybe hundreds of other such senses from various parts of the body to integrate, only a fraction of which we are aware of.

In addition, there are probably lots of cases where receptor signals are only used locally by cells that are sensing their local environment. It really doesn't make sense that the individual cells must blind themselves. Individual bacteria and fungi have scores of receptors. It makes sense that cells that are part of an organism would have as many or more senses as well.

molecular biology - Why does the hydrolysis of ATP increasing entropy increase the Phosphoryl-­‐transfer Potential?

The phosphoryl transfer potential is one way to think about the free energy available to do useful work when ATP is hydrolysed.

As you can see from the free energy equation below, a positive change in entropy will help to decrease (i.e. make more negative) the free energy change.

This is why an endothermic reaction can still occur spontaneously if the entropy change is big enough to create an entropy term that outweighs the enthalpy term in the Gibbs free energy equation.

ΔG=ΔH - TΔS

where:
T= temperature
G = Gibbs free energy
H = enthalpy
S = entropy

toxicology - Is nicotine toxic to humans?

Nicotine acts as a ligand for nicotinic acetycholine receptors (nAChRs), which are ligand-gated ion channels normally activated by acetylcholine. This family of receptors is expressed in every mammalian cell (Schuller, 2009). A priori, at least to me, I'd suggest that it's a bad idea to chronically introduce a foreign substance that mimics the activity of an essential signaling molecule like acetylcholine.

Directly to your question of toxicity, nicotine appears to be linked to many forms of cancer (Schuller, 2009). Cancer promoting signaling pathways are stimulated as a result of calcium entry through nAChRs. Also, interactions of nAChRs with other signalling systems, such as those based on stress hormones, GABA, and dopamine, can lead to cancer.

Nicotine also has important effects in the brain. Chronic exposure to nicotine induces a homeostatic mechanism that upregulates nAChR expression in the brain to maintain responsiveness to endogenous acetylcholine. This effect partially underlies nicotine addiction (Penton and Lester, 2009). As @Armatus notes, nicotine appears to have some neuroprotective properties against neurodegenerative diseases like Parkinson's (Quik, M., Wonnacott, S., 2011) and Alzheimer's (Mehta et al, 2012).

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Schuller, H.M., 2009. Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nature Reviews Cancer 9, 195–205.

Penton, R.E., Lester, R.A.J., 2009. Cellular events in nicotine addiction. Seminars in Cell & Developmental Biology 20, 418–431.

Quik, M., Wonnacott, S., 2011. α6β2* and α4β2* nicotinic acetylcholine receptors as drug targets for Parkinson’s disease. Pharmacol. Rev. 63, 938–966.

Mehta, M., Adem, A., Kahlon, M.S., Sabbagh, M.N., 2012. The nicotinic acetylcholine receptor: smoking and Alzheimer’s disease revisited. Front Biosci (Elite Ed) 4, 169–180.