Molecular/cellular biology textbook to consolidate what I know about molecular/cell biology I'm a medical student (who is halfway through med school) looking for a textbook that will consolidate some of the biology I already know. While I've read a lot of books that go into great detail about genetics, immunology and cell signaling, I've not found many books that focus on clear insights.

After recently having perused a very well-written nanotechnology book geared towards bionanotechnology ("Bionanotechnology: lessons from nature," by Goodsell), I found many cell biology topics very well explained. For example, it states simply that "lipids are used for infrastructure [in the body]", and that "polysaccharides are used in specialized structural roles". Such sentences I've personally never really come across in any of the "standard" molecular biology texts (Alberts, Cooper, etc); I found that they focus far too much on detailing exactly the components of the DNA polymerase, or the ribosome (which are very important, but also something I'd like to go "beyond".)

Clarification on what type of book I seek:

A book within cell or molecular biology
Scope of book; a book that covers any of the following: biochemistry, genetics (replication, translation, transcription, gene expression and its regulation, epigenetics, heredity, genetic engineering), developmental biology, cell biology (cell structure, organelles, cellular processes, cell signaling) and molecular biology (techniques such as high-throughput biology; concepts such as enhancers, repressors) and molecular evolution.
Level of the book doesn't matter, although I have completed all the subjects above at an undergraduate (bachelor) level - the book could thus be directed towards graduate/masters students.

Any books/texts that will hone one's knowledge on the subjects mentioned will be warmly received!

Campbell's Biology is, I quote my biology teacher, "the Bible of AP Biology". I know you're a medical student and therefore far past that introductory college level, but Campbell's does quite a good and thorough job of explaining a plethora of biology topics. It's a fairly reliable textbook, I think you might like it. It also gives a good deal of examples for the various concepts and avoids such abstract statements as those you quoted from your textbook. I would suggest skimming through the book at a local bookstore if you can and seeing if it fits your criteria.


Queller's 1985 version of Hamilton's rule Queller 1985 ("Kinship, reciprocity and synergism in the evolution of social behavior") provides a generalization of Hamilton's rule that allows for non-additivity. To accomplish that, Queller writes the fitness of an individual as
\begin{align}
  W = W_{0} - CP + BP' + DPP'
\end{align}
where $W_0$ is the baseline fitness; $P$ is the phenotypic value (1 for altruist or 0 for nonaltruist); $P'$ is the phenotypic value of the interacting individual; $C$ is fitness cost if $P=1$; $B$ is the fitness
benefit if $P'=1$; $D$ is the deviation from additivity of $C$ and $B$ if
both were altruistic (i.e., $PP' = 1$).

Queller then substitutes this equation into Price's equation $\Delta G = Cov (G, W)$, where $G$ is the frequency of altruism allele in the focal individual($0$, $1/2$ or $1$). The resulting equation is:
\begin{equation}
  - \bar c + \bar b \frac{Cov(G,P')}{Cov(G,P)} + \bar d \frac{ Cov(G,PP') }{Cov(G,P)} > 0
\end{equation}
where $\bar c$, $\bar b$, and $\bar d$ are the sample means of $C$, $B$, and $D$.

My question is: how did Queller arrive at the sample means $\bar c$, $\bar b$, and $\bar d$? I understand that $Cov(aX,Y) = a\, Cov(X,Y)$, provided that $a$ is a constant. But what Queller is doing here is different; he seems to be saying that $Cov(AX,Y) = E(A)\, Cov(X,Y)$.

It is just worded a little wierdly in my opinion. The key line in the paper is: 'Fitness components are also defined for all individuals, for example, $C$ is defined, even for a non-altruist, as the cost it would incur if were altruistic.'

Essentially, if it doesn't matter what individual you are you always pay the same cost, then $C$ is a constant. This is pretty much the definition of a constant! The expectation of a constant is just the constant, $E(C) = C$.

The reason it works is that to find whether or not the cost is realised, Queller simply multiplies by the focal individual's phenotype value $P$, which is either 0 or 1. So either the individual pays the cost or it doesn't.


Does cell phone radiation promote longevity? This preprint presents results from a 2-year National Toxicology Program study on the effects of cell-phone radiation in rats. On page 8 of the PDF, survival results are presented. The presentation of the results is complicated by the fact that some treatment groups experienced significantly different effects when compared to the control group, while in other groups the effect was small but not significant. However, the gist is that rats treated with phone radiation lived longer, and that the effect is stronger in male rats.

I was confused by the fact that this result is presented in the "Results" section on page 8, while the seemingly less significant finding - that treated rats had higher rates of cancer or tumors - was presented in the "Summary" section on page 4. Obviously the study was funded to address concerns we have about observed relationships between cell-phone use and cancer, but when an effect on longevity was discovered, shouldn't this have become the primary result?

The plots on page 11 (Figure 3) and 12 (Figure 4) show some more interesting relationships between the survival of the various groups. Figure 4A shows the high-dose (6W/kg) CDMA male group overtaking the control males only towards the end of the study. With the GSM males (Figure 3A), as well as the low-dose CDMA males, the control group does worse almost from the beginning.

I'm curious to know why more people haven't commented on this result in news outlets. My opinion is that controlled experiments in animals aren't perfect, but they're much better than cheap "longitudinal" studies in humans. As far as I can tell, this is the best evidence we have to date, and it says that cell phone radiation promotes longevity. So why aren't we being required to sleep with phones next to our heads?

If you read the discussion, and also the full contents of the PDF which include some reviewer comments, there is concern about the control group:

  The survival of the control group of male rats in the current study (28%) was relatively low
  compared to other recent NTP studies in Hsd:Sprague Dawley® SD® (Harlan) rats (average 47%, range 24-72%).

Specifically, the control group had an abnormally high mortality rate for that strain of rat. There is no increase in longevity if you compare to historical data.


Is there any biological reason that professional swimming is dominated by white people? I suppose that the question should be turned around to "Why is it extremely rare to see black people competing in professional swimming?" because it is the absence of this phenotype while watching the Olympics that caused me to ask this question.

So,

why are there very few black people competing at world class level swimming?

While I'm here I may as well ask the question:

Why are black people faster sprinters than white people when it comes to world class level?

And of course I want biological reasons.

It's not biological, it's simply an education issue, and googling would give you:

Just under 70% of African-American children surveyed said they had no or low ability to swim. Low ability merely meant they were able to splash around in the shallow end. A further 12% said they could swim but had "taught themselves".

http://www.bbc.co.uk/news/world-us-canada-11172054

Unlike the UK, where learning to swim is enshrined in the national curriculum except in Scotland, the ultimate responsibility in the US often lies with parents.


ECG detection using minimal number of electrodes Disclaimer: Hello, I'm someone from an electrical engineering background, so this question may sound dumb.

I wish to make a wearable ECG monitoring device for arrhythmia detection. Since the device is to be wearable, it has to be small and should not obstruct normal behavior (kind of like those ECG patch monitors).

My question is, which lead should I monitor for arrhythmia detection. I read that I do not need all 12 leads for this purpose. The leads should preferably involve electrodes close as possible to reduce area of contact with the body.

You could try to dig into the specs of the new/upcoming Withings ECG smartwatch for some insights https://www.withings.com/uk/en/move-ecg


How to decide if genes are linked in an unordered mapping problem? From what I understand, if the tetrads resulting from a cross exhibit the same number of parental ditypes as there are nonparental ditypes, then the genes under consideration are said to be unlinked.

For example, say I cross two gametes containing $ab^+$ and $a^+b$, respectively, and get 170 tetrads exhibiting parental ditype (all offspring are $ab^+$ or $a^+b$), 165 exhibiting nonparental ditype (offspring are $a^+b^+$ or $ab$), and 30 exhibiting tetratype (offspring one of $a^+b^+$, $a^+b$, $ab^+$ or $ab$).

I'm not sure whether to classify these genes as linked or unlinked. I want to say yes, they are indeed linked, but 170 and 165 seem like close enough numbers to suggest they may be unlinked.

I would think the ratio of parental to nonparental ditype has to be considered close enough to 1, but how do we decide a threshold for that?

I'd use a chi-squared test.  You calculate what you expect to see if your hypothesis is true, and you take what you do see, and the chi-squared result tells you how likely it is that your results are different enough from what's expected to indicate that your hypothesis is incorrect.


How does a brain distinguish stimuli? If all the brain ever "sees" is action potentials, how do we know that one set of action potentials denotes a flash of light, another one signifies a loud sound, etc ?

The fundamental way in which this works is by geography: signals triggered by different stimuli travel by different pathways to different regions of the brain that are specialised for dealing with the sorts of information they contain.

For example, visual signals from the retina pass down the optic nerve and (after a few interesting twists and turns that, inter alia, send the left and right halves of each visual field to different brain hemispheres) wind up in the visual cortex, which contains neuronal networks adapted for recognising different structures and regularities in the image. Whereas sound information from the ears, after an even more tortuous sequence of processing steps, winds up in the auditory cortex.

Along the way, the signals will typically be split up across many neurons and reintegrated into new signals that pick out different kinds of information. So a particular stimulus will result in a complex spatio-temporal pattern of action potentials firing across many regions of the brain.

Conceptually, the further along this process you go, the more abstracted the signal probably becomes, so that it stands for a collection of events and ideas and thoughts rather than for excited photoreceptors or vibrating hair cells. But exactly how this parsing of the sensory content eventually turns into perception and conscious recognition is essentially unknown.


What is the identity of this spider from India? I came across this strange guy today at my classroom in Tamil Nadu, India. It is a spider which is not very much bigger than an ant but with an artistic body. He has 8 legs, but the two on the front are raised above his head, just like a crab does. Can anyone identify this little guy?

Anyone identify this little guy?

That is a Siler semiglaucus, which is a type of jumping spider. It has the nickname of "metallic jumper", and can be found all throughout India, Indonesia, Philippines, and Thailand.

  He has 8 legs, but the two on the front is raised above his head, just like a crab does.

Here is a wonderful collection of more images, which also includes locations of discovery.


Why is egg white alkaline? According to Tiefenbacher,

Egg white is naturally alkaline with an initial pH of 7.6–7.9 but in storage the loss of carbon dioxide by diffusion through the shell
increases the pH of the egg white up to about 9.7 with age.

The loss of $\ce{CO2}$ means loss of $\ce{H2CO3}$, an acid with pKa of 6.3. This reduces acid and in a neutral solution pH would approach 7. Since it goes up towards 9-10, what is the base? Albumin is a buffer in biological systems but I don't think it is that strong a base. What is the alkali causing pH of around 9-10?

In the terms of the question, this can be regarded as calcium hydroxide, with the carbonate being in the form of calcium carbonate. Calcium hydroxide is a stronger base (pH of aqueous solution at 1mm = 11.27) than carbonic acid is an acid (pH of aqueous solution at 1mm = 4.68), so that 1mm calcium carbonate has a pH of 9.91. (Values from Aquion)
Calcium carbonate is, of course, the constituent of eggshell, which crystallizes out of solution when it is deposited in the uterus. Its presence within the egg white is presumably a consequence of this.
–––––––––––––
I would add that one does not generally regard there being a particular base balancing the carbonic acid: when the hydrogen ions are removed there is an increase in the free hydroxyl ions and hence an increase in pH. The way the question is formulated only really makes sense if one assumes that the egg white acquired extra carbonic acid to reduce the alkalinity resulting from the calcium carbonate/hydroxide.


Where’s the flaw in my proposed TB Treatment? Ten years ago, I emailed a prominent lung specialist with my suggestion for a treatment for Tuberculosis. His lack of response led me to believe that the idea had no merit whatsoever – but I had no idea what the failings might be. I still don’t and I’m hoping someone will enlighten me as to why this is not worth exploring.

The idea is based upon the fact that Mycobacterium Tuberculosis is aerobic – in fact Wikipedia states it “requires high levels of oxygen”. I’d heard that the TB “Sanatoriums” used to practice the treatment of breaking ribs on one side to collapse that lung and “rest” it. It seemed to me that this resting was actually starving the bacterium of Oxygen and killing the infestation.

My suggestion is that we take advantage of having two lungs by inserting a pair of breathing tubes into the respiratory tract and into the head of the two bronchi: it may be necessary to use ultrasound or other imaging to accurately position the tubes.

We feed pure Nitrogen into one tube, and 40/60 Oxygen/Nitrogen into the other – double Oxygen concentration. The patient therefore receives all their Oxygen requirements through one lung. After some period of time, when we judge that the bacteria in the “starved” lung are all dead, we switch the supplies to the 2 tubes and treat the other lung.

Can anyone see why this idea is so flawed?

High oxygen concentration can be deleterious; it can induce oxidative
damage.
The systemic blood circulation would supply oxygen to the
"oxygen-deprived" lung.
Moreover, Mycobacteria can survive in anaerobic conditions.

And what if both lungs are infected? There are many flaws in the proposed therapy.

Adding this point from one of the comments below:

There are several cases of extrapulmonary tuberculosis and in these cases treating just the lung would not make sense.


Why has the human eye evolved to become sensitive only to the visible light? The human eye has evolved to become sensitive only to visible part of the electromagnetic spectrum. Why? Why is infrared vision disfavoured for us by evolution but not for some other animals? I am not an expert of biology but curious.

Actually, it's got nothing to do with evolution or even human biology.

Why?

  What’s in a name? That which we call a rose,
  By any other name would still smell as sweet. William Shakespeare.

First, try to define visible yourself. Next look at the definition of it in various respected dictionaries; in our context it means

  that can be seen

Consider the case of Goffin's cuckatoo, they can see as far up to as ultra-violet spectrum. They don't speak English (or Portuguese for that matter) but for them visible would mean "what they can see".

So, coming back to your question, even if we had capability to see, say, infrared spectrum, visible would have meant: VIBGYOR + infra. And then we'd have complained about not being able to see bacteria with naked eye :P


Why are not both alleles knocked out at the same time in knock out mouse? I was reading this little 'article' about homologous recombination and knockout mouse. According to this article you first remove embryonic stem cells from a gray-fur blastocyst, then insert the construct and place them back into the blastocyst. Further the text states:

  A knockout mouse has had both alleles of a particular gene replaced
  with an inactive allele. This is usually accomplished by using
  homologous recombination to replace one allele followed by two or more
  generations of selective breeding until an breeding pair are isolated
  that have both alleles of the targeted gene inactivated or knocked
  out.

However what I don't get here is that we have cells from an embryo, and thus have cells with both alleles. Hence, the regions surrounding these alleles will be homologous, so why would this step result in heterozygous (and thus require selective breeding afterwards) instead of homozygous mouse direcly?

It is a simple matter of probability. If the probability of replacing one allele is p then the probability of two alleles getting replaced would be p2 (note that the latter will be smaller because probabilities are less than one).

If you have a selectable marker such as GFP then you'll end up selecting both heterozygotes and homozygotes but the frequency of the former will be much higher especially when you consider the fact that the probability of homologous recombination mediated knock-out/in is very low in mammalian cells (10-7 – 10-5). Therefore, inbreeding is an easier way to obtain homozygotes than screening the ESCs. Moreover, selective breeding is inevitable because in the first round will just produce chimeras (not all ESCs are replaced with the modified ones).

Technologies like CRISPR are now being used to accelerate the rate of gene replacement.


What is the meaning of the "d(...)2" notation when writing a DNA sequence? When the sequence of a DNA oligo is written as d(CGCTAGCG)2 what is the meaning of the d(...)2?  Why would it not simply be written as CGCTAGCG?

I recognize this sequence is the complement of itself.  Is that what this notation indicates?

Assuming that you were referring to this specific usage of d(CGCTAGCG)2, the image provided for the crystal structure clearly shows that the structure refers to the fact that two strands of deoxy-ribonucleotide oligos were dimerised to each other.

Had the same structure been formed by double-stranded RNA instead, the resultant dsRNA duplex helix would be referred to as r(CGCTAGCG)2


Do "non-human" animal like cat, dog, bird or fish think about future while sleeping? I don't think "non-human" animal like cat, dog, bird or fish think about future while sleeping.

I think when sleeping, the "non-human" animal will feel rather think about anything. I think when sleeping, the "non-human" animal will feel  their breath just like when we are meditating. So, when we meditate we will feel our breath like "non-human" animal that are sleeping.

Do "non-human" animal like cat, dog, bird or fish think about future while sleeping?

Issue with your question

This question is full of terms that don't have a proper definition in Biology. I don't think there is any clear definition in the verbs "feel" and "think". Also, I don't fully understand what the differences between feeling or thinking (whatever that means) when sleeping matter for the question of whether some animals "think" (and its variants) about future while sleeping. I am not sure either what "thinking about future" really means. One doesn't know the future, he can imagine it and in some cases it is kinda complicated to really know whether a set of thoughts are encompassed within the concept of "thinking about the future". I vote to close for primarily-opinion based. Finally, your question might eventually be a better fit on CognitiveScience.SE.

Theory of Mind

You might be interested in the Theory of Mind (ToM). Having the ToM (I know it is weird formulation, ToM is not a theory per se) means having the ability to 1) be aware (might have various definitions for "aware") of its own existence and 2) be aware that others also think and have intentions and 3) more importantly be aware that others might be aware that you think and have intentions.

It is pretty hard to investigate whether an animal has the ToM. Here is a list of species (and lineages) where ToM has been found (or thought to exist at some level). The list is probably not exhaustive and the difficulty to accurately define ToM and awareness make those pretty arbitrary.

Chimpanzee
Orang-outan
elephants
dolphins
corvids
some parrots
bee-eater

Btw, your list of lineages is funny by the fact that you seem to weight equally two relatively closely related domestic species (cat and dogs) and two gigantic taxa that are fishes (fishes do not represent a monophyletic group) and birds


Is the autonomic nervous system only activated by internal stimuli? My professor claims that the autonomic nervous system is only activated by stimuli from organs but I really feel like I've read that it can be activated by outside stimuli, although I'm not sure what receptors that would be.

Is my professor right?

Short answer
External stimuli can drive autonomic responses.

Background
The autonomic nervous system is a visceral sensory and motor system. The viscera are the internal organs. Virtually all visceral reflexes are mediated by local circuits in the brain stem or spinal cord (Fig. 1). It is one of two major subdivisions of the nervous system; the other being the somatic (or voluntary) nervous system. The main distinction between the two is that the latter is involved in voluntary and conscious actions (e.g., movement, perception and cognition), while the autonomic nervous system is engaged in involuntary processes, such as regulating heart rate, breathing and bowel function (Fig. 1).

Fig. 1. Autonomic nervous system. Source: Austin Community College

Although by far most stimuli driving autonomous responses come from within (think muscle movements driving bowel movements, increased heart rates during physical exercise), outside stimuli do directly impinge on the autonomous system.

For example, the cilliary muscle in the iris is under the control of light coming into the retina. The pupillary light reflex test is based on this principle, and is routinely used to diagnose damage to the visual system. Also, production of saliva is controlled by external stimuli (smell and taste of food and see the striking example below from @anongoodnurse). And technically, the entire digestive tract can be considered to be outside the body, as it is continuous with the skin and lining of the mouth. Hence, the mechanical stimuli impinging on the intestines by a moving bolus of food that drives the waves of peristaltic movements can, arguably, be considered to be caused by external stimuli too. Lastly, the fight-flight-fright response involving the hypothalamic-pituitary-adrenal gland (HPA) axis is often initiated by external stimuli (loud sudden noises etc.).

The most important characteristic of the autonomic nervous system, as said, is that the autonomous responses are not voluntarily controlled. While you can decide to look or track a visual stimulus, you cannot decide to move the bolus of food back up to your stomach, or voluntarily constrict your pupil. The way the input is received may not be the best way to distinguish it from the voluntary nervous system.

Didactic answer
If you are left with questions, the first place to go to is your professor.

Reference
- Kandel et al. Principles of Neural Science 4th ed. (2000). Ch.49 The autonomic nervous system and hypothalamus. p.960-81


When life first formed in earth's ocean, was it salty yet? Do we have any tangible proof, e.g. by studying fossils of primitive life forms, that during their time the ocean was already salty, and at roughly similar levels to today's, or on the contrary, that water has no or very low salinity?
Did life had to adapt to dramatic changes in sea water salinity, as it has (I believe) for changes in air composition?

Current estimates suggest that last universal common ancestor of life on earth lived in hydrothermal vents 3.8–3.5 billion years ago.1  Petrologic examination of quartz formed near these vents during that time suggests that seawater had a higher salinity compared to current oceans 2 --

Our data are in agreement with six other data sets—from the 3.75 Ga Isua Greenstone Belt (W. Greenland), the 3.24 Ga Pilbara region (W. Australia), the ∼3.2 Ga Barberton Greenstone Belt (South Africa; 2), the ∼2.7 Ga Matagami area (Abitibi Greenstone Belt, Canada), and the Proterozoic (∼2.2 Ga) Ongeluk Formation (South Africa). The consistency of fluid inclusion data suggests that Archean and early Proterozoic seawater may have been more saline, and potentially stratified, compared to modern seawater.

Note: Ga (for gigaannum) – a unit of time equal to 109 years.

Weiss, M., Sousa, F., Mrnjavac, N. et al. The physiology and habitat of the last universal common ancestor. Nat Microbiol 1, 16116 (2016).
Weiershäuser, L., Spooner, E.T.C. Seafloor hydrothermal fluids, Ben Nevis area, Abitibi Greenstone Belt: Implications for Archean (∼2.7Ga) seawater properties. Precambrian Research, Volume 138, Issues 1–2, 2005, Pages 89-123.


What impacts penetrance of Huntington's disease? From Principles of Life by H. Craig Heller, David E. Sadava, Mary V. Price:

From what I understand, Huntington's disease exhibits varying degrees of penetrance depending on how many times the mutation is found in the person's genome. Penetrance is nearly complete if the incorrect base pair sequence is found over a certain number of times.

My question is what affects penetrance? Is it exclusively environmental?

Penetrance describes the frequency of a gene's expression:

  Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. (Genetics Home Reference nih.gov)

More specifically:

  [P]enetrance is defined as the percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype. For example, an organism may have a particular genotype but may not express the corresponding phenotype, because of modifiers, epistatic genes, or suppressors in the rest of the genome or because of a modifying effect of the environment.

Note that the environment is only one factor affecting the expression of an allele.

Retinoblastoma and achondroplasia are often referred to in discussions about penetrance.

Retinoblastoma is caused by mutations in the Rb gene. Not all people who carry this mutation suffer from retinoblastoma (about 90% do). There are numerous inherited diseases (including cancers) in which the same mutation is not expressed in all the individuals who carry it. Achondroplasia, on the other hand, has 100% penetrance: every person with the specific point mutation in the fibroblast growth factor receptor 3 gene always has abnormal bone growth and dwarfism.

Huntingtons is a little different in that patients with 36 to 41 HD CAG repeats exhibit reduced penetrance; that is, some may not develop HD in their lifetime; however 100% of those with the mutation produce the abnormal/polyQ/polyglutamine-enlarged huntingtin. The age of onset is dependent on number of repeats but is affected by other modifiers (both genetic and environmental); this becomes less obvious in individuals with higher repeats sizes (e.g. greater than 44).

Huntington's is not a genotype affected only by environment.

 Genetics in Medicine
 A new model for prediction of the age of onset and penetrance for Huntington’s disease based on CAG length


Shortest strings not present in the human genome What length are the shortest strings of DNA not present in any known person's genome, and what are they?

And is there a database online by which I could find this out?

The human genome contains less than 416 base pairs, so, even after including a factor of 2 for the two strands and another to allow for some genetic variation, there must certainly exist some 17-base string not found in either strand of the genome.

Now, 417 bits is two gigabytes, which fits easily within the memory of a typical desktop computer these days, so a simple and efficient algorithm for finding such a string would be to set up an array of 417 bits, initialize them all to zero, and then simply iterate over the entire genome (including all known variations), taking each 17-base subsequence (and its complement), mapping them to base-4 integers and setting the bits in the array at the positions given by those integers to one.

Once you're done, any remaining zero bits will correspond to strings not found in the genome.  More to the point, the longest consecutive block of zero bits will give you the shortest base string not present in the genome.


Where are newly discovered medicines tested When a medicine is prepared by a biologist,then where does he first test on? And how does he know that this is the exact combination for a disease to get cured? Does he test that medicine on a human or specific sample of blood? I'm an engineering student but still I'm curious to know.

This is a very broad question, so I won't attempt to answer it fully. Instead, I'd recommend starting out by reading the Drug Development and Drug Discovery articles on Wikipedia, and if you have more specific questions after that then feel free to ask them here.

Basically, new drugs (either small-molecule "chemicals" or large-molecule "biologicals") are discovered in myriad ways, from pure accidents (see Penicillin) to specifically-targeted research. Once a lead compound is identified, it is put through a series of biochemical assays to determine, for example, if it inhibits certain enzymes of interest. From there, it moves into testing by cell-based assays using both normal cells and disease-specific models. All the while, investigators are looking for high specific activity (potency), low toxicity, and minimal off-target effects.

If a compound or group of them looks promising in these in vitro assays, experiments then move into animal models. The goals are similar here - high activity, low toxicity, and few (if any) side effects. The experiments get progressively more complex, with different endpoints depending on the exact aspect being studied.

It is only after extensive animal testing that a compound will be tested in humans. There are different phases of testing, each with different criteria, dosing patterns, number of patients, and reporting rules. The link I just gave explains each phase briefly.

Hopefully this is enough to get you started. Like I said earlier, if you have more specific questions after reading through all the references, please let us know.


Does cooking ginger reduce its anti-nausea effect? There seems to be strong evidence to support the hypothesis that eating ginger helps reduce nausea e.g. during pregnancy (e.g. Vutyavanich et al.).  It seems that gingerol is the active ingredient in preventing nausea (cf. Qian et al.).  Wikipedia writes: "Cooking ginger transforms gingerol into zingerone...".  Presumably, zingerone does not affect nausea.

Question: Does cooking ginger reduce its anti-nausea effect?

A Google search will reveal numerous suggestions for giving ginger tea to pregnant women to help with morning sickness.  But boiling the ginger could conceivably defeat the purpose of taking the ginger in the first place (and any effects are primarily due to the placebo).

There's an article (Basirat et al.) which describes an experiment in which biscuits with ginger were given to patients (instead of ginger tablets), although their results alone have not convinced me one way or the other.  The authors conclude that their results indicate an anti-nausea effect, but some of their tests do not match that conclusion (i.e. a placebo was comparably effective).  Also, the group given the ginger biscuits started off with worse conditions on average.

Good news! Some Australians have published on the stability of aqueous gingerol at elevated temperatures: http://onlinelibrary.wiley.com/doi/10.1002/jps.1116/full

Gingerol turns out to be stable enough to make a cup of tea with at neutral pH. They also note that gingerol and its primary decomposition product form a 50-50 mixture that doesn't degrade further over shortish time periods, and that the decomposition product is probably restored to gingerol in the stomach's acidic pH -- so you're good to make your tea, and probably to hold on to it for at least a few days.


How do animals end up in remote areas? I was thinking specifically about random marshy water holes on farmers fields. It seems that you can visit just about any one of these and you will find frogs if you look hard enough.

They usually don't seem to be connected to each other. If it were any other land animal I would figure they walk from one spot to another, but in the case of frogs, I don't imagine their range is very vast. But often these marshy spots can be separated by fairly large distances to a frog.

So this brings me to my question: how do each of these spots end up with frogs in them?  I don't imagine a frog is going to go hopping over a hill to get to a marsh on the other side, is it?

I don't imagine a frog is going to go hopping over a hill to get to a marsh on the other side, is it?

Why not? In wet weather, the conditions would be just fine for an enterprising amphibian to go exploring, perhaps driven by predators or lack of available resources, not to mention Ro Siv's comment about wind-borne dispersal of animals. Birds of prey may also pick up small animals, fly away with them, then drop them for whatever reason.

You are also neglecting the fact that these organisms have existed for millions of years, and the landscape has changed tremendously in that time, with glacial periods interspersed with interglacials every 20-50,000 years or so. As glaciers melt, large lakes form, and as those dried the organisms were dispersed across the land into smaller bodies of water. Streams and rivers form, transporting aquatic life forms, and may dry out and form isolated ponds, or they may be blocked for any number of reasons (mudslides, earthquakes, volcanic eruptions, beaver dams, fallen trees, etc.). As erosion and landscape remodeling occur, all traces of the original body of water may be erased, except for the wide distribution of similar organisms.


Relationship of the DNA of a eukaryotic gene to the 5'-UTR of its mRNA In eukaryote pre-mRNA I am having a little trouble grasping exactly what the 5 prime untranslated region is defined as.

It seems that it could be defined as the difference in pre-mRNA between the transcription and translation, is that right?

If so, does the transcription begin immediately after the end of the promoter sequence? Immediately after the promoter region on the DNA ends, does the next nucleotide become part of the 5'UTR?

Concise Answer

The 5′-UTR region of a eukaryotic mRNA is derived from the RNA transcript of the region of a gene between the transcription start site and the DNA corresponding to the translational initiation codon. It differs from that region of the initial transcript in most cases by having a modified guanosine nucleotide added at the 5′-end in a ‘cap’ structure, and in some cases by lacking an intron present in the former.

The Transcriptional Start Site (TSS) and the Promoter

This answer is in terms of the TSS rather than ‘promoter region’ or ‘promoter sequence’, favoured by the questioner because in eukaryotes, at least, there is no simple and easily definable promoter sequence. A 2012 review of metazoan promoters begins with the definition: “Gene promoters are the loci overlapping transcription start sites (TSSs), at which the total regulatory input of a gene is integrated into the rate of transcriptional initiation. The immediate role of the promoter is to bind and correctly position the transcription initiation complex…”.

A simplified diagram of some components of human promoters (adapted from an earlier review by Hahn) is shown below. The position of ‘Inr’ — the Initiator box which contains the TSS — varies with respect to the TATA box (usually from –25 to –30 in humans),  as does its sequence. Hence, even ignoring the alternative TSSs mentioned by @Luke it is not possible to identify the TSS unequivocally by inspection of the DNA sequence of a gene in the way the questioner would apparently wish.

The Translational Initiation Codon

It should be mentioned that it also not possible to identify the mRNA translational initiation codon unequivocally by inspection of the DNA sequence of a gene. Although 90% or more cases follow Kozak’s rule, so that it corresponds to the first ATG, in some cases it may correspond to the second ATG, and in a small minority — where internal initiation occurs — to some distal ATG. There are also a very few examples of initiation of translation at codons other than AUG.

Introns in 5′-UTR regions of pre-mRNA

A common rationalization of the intron/exon nature of eukaryotic pre-mRNA is in terms of alternative splicing to produce different protein sequences. Perhaps because of this, the presence of introns in the primary transcript containing the 5′- and 3′-UTRs is often ignored (see Bicknell et al. for a review). In fact, approximately 35% of 5′-UTR precursors contain introns, not present in the mature mRNA.

5′-capping of eukaryotic mRNA

The vast majority of eukaryotic mRNAs have a cap at their 5′-end, produced by the addition of a guanosine nucleotide in a 5′-5′ pyrophosphate linkage to the 5′-residue (usually A) of the pre-mRNA. This is subsequently methylated at carbon-7; and 2′-O-methylation of the ribose of the subsequent one or two nucleotides may also occur.

Footnote

Although “DNA makes RNA makes Protein”, I do think it important to describe features of information molecules in terms of their actual composition. Thus, the 5′-UTR has to be defined in terms of mRNA, not promoters or exons. If one makes reference to the information content of DNA or RNA than I think a form of words should be used to make that clear. Muddled forms of words can easily lead to muddled thinking.


The fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%? I would appreciate help in understanding the meaning, logic, and, in particular, how to interpret the phrase:

The fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%

I could ask numerous question regarding the biology (including what happens to the rest of the genome, and positive selection) and formal logic of this statement, but maybe I could impose, and just leave it to whomever kindly replies.
This remark comes from the abstract of Grauer & al. "On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE"
And the Abstract itself:
A recent slew of ENCyclopedia Of DNA Elements (ENCODE) Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 - 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these "functional" regions or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly by employing the seldom used "causal role" definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as "affirming the consequent," by failing to appreciate the crucial difference between "junk DNA" and "garbage DNA," by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and by emphasizing statistical significance rather than the magnitude of the effect. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten.
Thanks

I will try to tackle the terminology first

Conserved: That remains identical (or at least very similar) across species.

Purifying selection: Is one of the possible forces that lead to conservation of important sequences of DNA, by removing deleterious alleles.

So, the phrase simply means that the proportion of the genome that is very similar in sequence with the genome of other species (i.e. evolutionarily conserved) is less than 10%.
This is the answer to you question. Then, I just want to add that I share David's view on the abstract.


Why does immunity from the flu vaccine appear only after two weeks? It is said that immunity from a flu vaccine appears after about two weeks. However, from experience, the flu usually lasts only a few days.

If sufficient antibodies appear only after two weeks shouldn't the flu also last that long? Or is there a difference between how the body reacts to the actual flu virus as opposed to the dead one in the flu vaccine (like maybe there being more viral particles in an actual infection or something)?

Most information here can be found broadly in Cellular and Molecular Immunology, 8th Ed.

Here's how the flu vaccine works: Scientists forecast months in advance which strains they think stand to cause the most problems. The vaccine is often trivalent, protecting against three different strains on flu: Two influenza A and one influenza B. You can read about the process directly from the CDC.

The two major viral receptors are neuraminidase and hemeagglutinin. They determine the serotype of the virus, such as H1N1. They serve as peptide antigens for immune recognition. Where influenza infects a cell, it starts to produce proteins essential to it's replication in the host cytoplasm.

The innate immunue system, upon realizing there's an infection, does quite a bit to try and mitigate things but it's a messy job. Looking at the link, lots of inflammation, damage and dead tissue. At that, there will be no memory of the same infection, and the same process happens over and over unless there's a better way to take care of things.

This is really where your adaptive immune system comes in, T/B cell, antibodies, etc. A wild type influenza virus stimulates the same adaptive response as the strains in a flu vaccine: Proteins such as the neuraminidase are picked up by macrophages or dendritic cells, and they enter transport to the closest lymph node. On the way, they chop up the viral protein into peptide antigens and load them onto MHC-II molecules, and export the complex to the cell surface, becoming antigen-presenting cells or APCs. T cells expressing CD4 coreceptor can interact with the MHC-II on APCs in a cascade of events that lead to effector T-helper (Th) cells. Th cells, in concert with follicular dendritic cells and recognition of cognate antigen by naive B cell can result in proliferation and differentiation of B cells to plasma cells that secrete antibodies specific to the viral antigen that was initially recognized.

The problem, is that this process takes time to ramp up plasma cells numbers and antibody production. The average time often denoted by literature is about 2 weeks.

Furthermore, with adaptive immunity you get memory cells that will remember a given infection and quickly resolve it with antibodies should you ever catch the same bug.

The difference between our wild type influenza and the ones in the vaccine is attenuation. The point of the wild type influenza people often catch is it's really good at infecting humans, and upon infection it causes a lot of damage. We can attenuate influenza's pathogenicity by growing the flu strains in tissue that is not human. Over a few generations, the virus adapts: it becomes more pathogenic/virulent in non-human tissue, but harmless to humans. You then remove the harmful parts of the hemeagglutinin and neuraminidase genes from a wild type strain to get inert HA and NA (so that you get the wild type immunogenicity), combine them with structural proteins from the attenuated strain, and combine them to form a new, live-attenuated vaccine strain that can be grown in the non-human tissue (see image below).

So also keep in mind that just because your infection resolved in under 2 weeks that the antibodies you produced wont help you from getting the same bug again. During flu season it tends to come at your from all sides and the antibodies that evetually get produced help a lot.


Does sleep in humans re-structure based on the expected sleep time? I've read about anecdotal evidence that human brain has a fairly good internal clock that can be used to judge the amount of time that has passed. I'm wandering if there are any mechanisms in the human brain by which the brain can make adjustments to biological processes, based on the expectation of getting so many hours of sleep in the upcoming night. In this case, an alarm clock is not used.

For example, a person typically sleeps for 8 hours a night. On one day, that person realizes that he/she will sleep for only 5 hours that night, has there been any studies that demonstrate that the person's sleep would be "different" from the regular sleep? Will the person's sleep on that night be just a "cut short" version of regular sleep, or will the sleep be restructured to accomodate sleep time restriction?

For example a person's normal sleep cycle is 90 minutes long, so in 8 hours there would be about 5 complete cycles. Would there be any observable adjustments to the sleep cycle length or the amount of deep/REM sleep within the cycle, if a person expects to sleep only 5-6 hours or 10+ hours?

Thank you for your input!

I haven't heard of studies like the one you're proposing, but you can test this hypothesis on yourself with this app.

Knowing you need to sleep less than your usual amount will probably affect the quantity and quality of your sleep, but not because of an "internal clock". Most likely, whatever you need to wake up early for will cause you some anxiety, which will affect both sleep duration and quality.


Could AI be applied to protein folding? Two years later, there is a follow up question to the one asked here: How do we know if the folding@home project results are right?
Since we are quite sure F@H is working right and following this article's statement:

  Similar techniques could be applied to protein folding, reducing energy consumption, or searching for revolutionary new drugs and materials.

...I would like to ask if AI stuff, like deep learning, neural networks and the rest of today's buzz words could be applied to molecular dynamics, especially in the protein folding field?

Yes, and no :-)

In the meantime many protein structures can be predicted quite accurately - even those for which no reference fold had been known before.

In this case the important buzz word is "big data": co-mutations (of charged amino acids) that can be found when sequencing many independent genomes. (... which indirectly bypasses the emphasis on dynamics for protein folding)

Editorial: 2017, Science: http://www.sciencemag.org/news/2017/01/hundreds-elusive-protein-structures-pinned-down-genome-data

Perspective: Soding et al. , 2017, Science ( http://science.sciencemag.org/content/355/6322/248 )

Research article: Ovchinnikov et al. 2017, Science ( https://www.bakerlab.org/wp-content/uploads/2017/01/ovchinnikov_science_2017.pdf )


Insertion of an additional base at start codon make the protein still functional? So the question is if:

a deletion of a codon for the amino acid lysine (AAG) is more or less likely to cause nonfunctionality of the protein than:

Insertion of an additional base (C) within the start codon for this protein
Mutation of the stop codon (TAG) to an arginine codon (CGC)

My attempt at an answer:

Not more likely. Since the insertion of the “C” base is done at the very start, the reading frame could be shifted and the sequence would remain the same after the first base. Since the most common start codon is “ATG”, the “C” would not affect it and the “reading” of the sequence would start after the “C” and at “ATG”
More severe as the stop codon is what signals that the translation of the sequence has ended, so if the stop codon got modified then the sequence would continue into the untranslated region. More peptides would be added to the sequence which would only stop when the next stop codon is reached. If the next stop codon is relatively close and the length if similar to a normal protein then it would still be functioning. But most cases it would continue for a considerable length and cause it to be non-functional

I think the question is fairly confusingly worded, so good job on your attempt based on that.

If a C is inserted within the start codon, I presume that is referring to making a sequence that was originally ATGXXX and making it either ACTGXXX or ATCGXXX. Either insertion means the start codon will be missing completely. This is going to either cause no protein to be made whatsoever, or for the beginning of the protein to be severely truncated or completely frameshifted if there is another open reading frame created downstream. This is going to be magnitudes more serious than a deletion of 3 bases corresponding to a lysine.
I think your answer here is fine - lots can happen with a missing stop codon. If there happens to be another stop codon in the same reading frame shortly downstream, then the effect could be not that severe, but if not it could result in a substantial additional peptide chain added to the end of the protein, which could cause all sorts of issues with folding, and the mRNA may not even be functional and be degraded.

Again, this question isn't worded in the best way, but I think the general principle it is trying to convey is that whole missing codons do a lot less damage to the structure of a protein than mutations that affect the reading frame or the stop/start codons, because they affect only a single amino acid. Of course, it could turn out that that amino acid is crucial to the structure of the protein, but the question is about what is most "likely."


Can pulmonary infarction be asymptomatic? I think it can because there are many parts in lungs.
Like for some COPD patients.
However, I am not sure if COPD patients can have infarction.

Lungs have parallel circulation.
Red infarct is possible there.
Blood can flow there.
One symptom should be at least pain.
So now, I think no asymptomatic possible.
But still, I am not sure.

Can pulmonary infarction be asymptomatic?

No. Based on experience. Lungs are very active organs.


Struggling to make sense of Km So I have two substrates for one enzyme and I measured the product formation-> michaelis menten kinetics. The Vmax for both substrates is the same, the Km however is higher on substrate number 2.  What can I conclude from this in terms of enzyme-substrate interaction?

The situation you described is entirely normal. $V_{max}$ is the same, so when described with a graph of initial reaction rate vs. substrate concentration, both curves will asymptotically approach the same maximum level. $K_M$ is higher in one than the other, so the exact shape of the curve as it goes from 0 to $V_{max}$ is different. As you may know, you can interpret $K_M$ as the substrate concentration that causes the initial reaction rate to be half of $V_{max}$. This means the substrate with the higher $K_M$ will have a shallower first half of the curve.

You can read more about these parameters and initial enzyme kinetics in Berg biochemistry or at khanacademy.


advantages of shivering in cold environments When we feel cold, our the muscle tries to generate heat by shivering and the brown adipose tissue tries to generate heat by non-shivering methods. The muscle generates heat but also spends energy on movement whereas the adipose tissue produces heat directly. This feels like muscle is not as efficient as BAT in generating heat.

What makes the muscle cause shivering? Isn't it sort of unnecessary movement which wastes energy which could otherwise have been used to directly produce heat?

Firstly, movement by shuddering or shivering, in simplicity, effects the conversion of potential energy into kinetic energy. This is achieved by expending ATP in muscular tissue, causing rapid bursts of contraction.

Brown adipose tissue, although located within most mammals ranging from infants to elderly, is predominantly found in infants differing from white adipocytes insofar as brown adipose tissue has a greater capillary network. Due to the higher surface area to volume ratio of the infant comparative to adults, the rate of heat loss is appreciably greater than a human adult. Thus a more efficient means of thermogenesis is required, namely, when the BAT detects body temperature below the homeostatic norm, the hormone norepinephrine is released, reacting with lipases to form triglyceride. This may subsequently decomposed further, to be converted into heat energy around the body (there are of course various intermediate stages).

Additionally, located primarily in brown adipose tissue is a protein named UCP-1. This allows the cells respectively to undergo 'non-shivering thermogenesis', heat generation without shivering by uncoupling the respiratory cycle in the mitochondria to oxidise more rapidly the substrate. As a consequence, fewer molecules of ATP are produced but heat production is increased.

Therefore, the differences may be rested on 1) the required efficiency of heat generation between infants and adults; 2) the act of shivering per unit of muscle area generates more heat.

You can find further information regarding the UCP-1 uncoupling mechanism in BAT from, https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7350


Why do we have to exhale (or inhale) in order to speak? Every time we speak, sing, or make any other kind of advanced noise with our throats, we exhale, or to put it that way, blow air through our throats. Why is this required? After all, speakers do not need any air blowing through them, they simply vibrate the air and create the vibrations (sounds) they're supposed to.

Why can't humans create (intelligible) sound just by having an organ that vibrates the air around us? Also, are there any animals that can? (None that I can think of at least). Would it be an evolutionary gain, or just rather pointless?

PS:
Obvoiusly we can clap out hands and the like, but that's not what I'm talking about.

Edit: The question is not about exhaling/inhaling, but rather why we need airflow in the first place; why we cannot use a mechanism similar to that of speakers.

As part of your question, you ask if other animals can create sound without continuous airflow. Many insects (e.g. cicadas and moths) do exactly this by using tymbals. A tymbal/timbal is an external membrane organ that is controlled by muscles or wing movements, that cause the membrane to flip back and forth, creating clicks or other sounds. So in many ways it produces sound in a similar way as loudspeakers, by creating sounds using a vibrating membrane.

One example can be found in this clip, which nicely shows how the organ functions:
Moth Making Sonar Jamming Sounds (youtube)

On this page (in Swedish) you can also listen to slowed-down butterfly sounds from four species.


how does one apply for masters in genetics abroad? Please can some one give me step wise instructions for applying for a masters degree in genetics or biological sciences?

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How to derive the Equilibrium value $\hat F$ equation In population genetics, there is a relationship between $\hat F$ and $Nm$.

$\hat F=\frac{1}{1+4Nm}$

In population genetics textbook, (i.e. Hartl, D. L., and A. G. Clark. 2007. Principles of population genetics. Fourth edition. Sinauer Associates Incorporated, Sunderland, Massachusetts.) it reads that using the equation below:

$F_t= \bigg(\frac{1}{2N}\bigg)(1-m)^2+\bigg(1-\frac{1}{2N}\bigg)(1-m)^2F_{t-1}$

  Set $\hat F = F_t = F_{t-1}$. After expanding the squared terms on the right-hand side, and assuming
  that $m$ is small enough and $N$ large enough, and that terms  in
  $m^2$ and $m/N$ can be ignored, some rearrangement leads to:

  $\hat F=\frac{1}{1+4Nm}$

I tried redoing it algebraically, without success. So do you know how to get to "$\hat F=\frac{1}{1+4Nm}$"

$(1-m)^2 = 1-2m+m^2$

$F_t= \bigg(\frac{1}{2N}\bigg)(1-2m+m^2)+\bigg(1-\frac{1}{2N}\bigg)(1-2m+m^2)F_{t}$

$F_t-\bigg((1-2m+m^2)-\frac{(1-2m+m^2)}{2N}\bigg)F_{t}= \frac{(1-2m+m^2)}{2N}$

$F_t(1-(1-2m+m^2)-\frac{(1-2m+m^2)}{2N})= \frac{(1-2m+m^2)}{2N}$

$F_t(-2m+m^2-\frac{(1-2m+m^2)}{2N})= \frac{(1-2m+m^2)}{2N}$

$F_t(\frac{2N(-2m+m^2)}{2N}-\frac{(1-2m+m^2)}{2N})= \frac{(1-2m+m^2)}{2N}$

$F_t(\frac{2N(-2m+m^2)-(1-2m+m^2)}{2N})= \frac{(1-2m+m^2)}{2N}$

$F_t= \frac{(1-2m+m^2)}{2N} * (\frac{2N}{2N(-2m+m^2)-(1-2m+m^2)})$

$F_t= \frac{1-2m+m^2}{(-4Nm+2Nm^2)-1+2m-m^2}$

Then $m^2= 0$

$F_t= \frac{1-2m}{(-4Nm)-1+2m}$

$F_t= \frac{1}{(-4Nm)-1+2m} -\frac{2m}{(-4Nm)-1+2m}$

??

$F_t= \frac{1}{(-4Nm)-1+2m}$

Magic

$\hat F=\frac{1}{1+4Nm}$

Sign problem

When you go from

$F_t(1-(1-2m+m^2)-\frac{(1-2m+m^2)}{2N})$

to

$F_t(-2m+m^2-\frac{(1-2m+m^2)}{2N})$

You make a mistake in the sign. It should be

$F_t(2m-m^2-\frac{(1-2m+m^2)}{2N})$

Approximations

I will assume this error of sign propagate to inverse your end result. You hence should get

$F_t= \frac{1}{4Nm+1-2m} -\frac{2m}{(-4Nm)-1+2m}$

$\frac{2m}{4Nm+1+2m}$ is negligible compared to $\frac{1}{4Nm+1+2m}$, so you can indeed remove it. You get

$F_t= \frac{1}{4Nm+1-2m}$

Also, $2m$ is negligible compared to $4Nm$, so again you can remove it. You end up with

$F_t= \frac{1}{4Nm+1}$

Tadaa!


why dna polymerase 3 requires a primer for replication Why DNA polymerase 3 needs a primer to star replication.And whats happens when there is no AUG sequence on entire DNA.

You are confused among DNA replication, DNA transcrption, and RNA translation.

First, DNA replication happens during cell division, it create two exactly same daughter DNA.

Second, DNA transcription transcribes DNA sequence into RNA sequence, this RNA sequence may be used to synthesize protein, or RNA itself as signal, etc.

Third, RNA translation is the RNA sequence (codon) recognized by tRNA, and then synthesize protein sequence.

AUG is a codon in the RNA, the is recognized by tRNA, and then start translation. And please remember, DNA use A, G, C, T, but RNA use A, G, C, U, there is no U in DNA.

For DNA synthesis, why does it need primer? I have another answer for solving your question: https://biology.stackexchange.com/a/40954/17473


Which information can be extracted from time course RNA-Seq Data? So I am very new to the area of biology so I am sorry if this is a stupid question.

I have RNA-Seq data carried out over a span of 100 days and I have gene expression data in the following format. Each expression value is the mean of
3 replicates.

           Day 1         Day 10     Day50     Day 100
Gene 1      12             42         35       12
Gene 2      50             53         23       100
.           .              .          .        .
.           .              .          .        .
.           .              .          .        .

so on, the above data is just something I came up with, but can you tell me what information I can extract from this type of data ? Such as differential gene expression. Thank you very much

It can be complicated because RNA-seq data is looking at gene expression, in the form of mRNA. But there are thousands of housekeeping genes that are expressed constantly, as long as an organism is alive. So the real interesting genes in a time course are those that are differentially expressed. So gene 1, in your example is not that interesting. Gene 2 however shoes a 4-fold increase between day 50 and day 100. Still, that is not that huge. You need computer programs to sort all this out. But what you want is to be able to associate a huge change in mRNA (gene expression) that can be distinguished from background.


what are some examples of how evolution's limitations prevented species from climbing to the absolute highest peak on the fitness scale? In this answer, the author argued that plants are green instead of red or any other color because of some  limitations of the evolutionary process. what are other examples in which the physical and functional characteristics of an organism were a direct result of limitations of evolution?

The "limitations" of evolution is somewhat subjective, I suppose, but a couple of the important ones include random mutations, lack of foresight, and environment. Evolution is a complex process by which mutations occur which either benefit an organism, making it more fit, harming the organism, leading (usually) to death, or to no noticeable change. Over time, these mutations bring about significant phenotypic changes. There's no goal, no purpose to it. In your example of plants, chlorophyll could certainly have evolved a structure that absorbed light in different wavelengths.

Another example is the difference between the vertebrate eye vs the octopus eye. For mammalian eyes, the optic nerve covers part of the retina. This is commonly known as the "Blind spot". For Cephalopods, on the other hand, the optic nerve is located behind the retina, so they have no bind spot.

Both of these examples are the result of random mutations coinciding with ideal (or non-ideal) environmental situations. The author of the post you cited is accurate to say that evolution is not an engineer, working towards a goal. The only goal of evolution is "What maintains life?" It's merely millennia of trial and error, and occasionally calamities occur, causing extinctions and loss of genetic potential.

I really think ANY characteristic of any species you care to name could be considered a result of evolution's limitations.


Comparison of gene expression time series in vitro and in vivo I have to analyse two datasets consisting of time-series measurements of gene expression. One set are in vivo data from the expression profiles obtained between a few days before birth to several days post-partum. The second data set was obtained in a C2C12 cell line, where t = 0 was defined as the day in which 100% confluence was reached.

Is there an optimal way to align the two time series? Simply aligning the two series using the two t= 0 samples as starting point seems arbitrary.

Direct comparison of the course would be difficult between tissues and cultured cells. In stead of time scale, you might want to use markers.
For example, Kislinger et al. show the expression peak of SIX1 is 2 days after differentiation; SMAD3, 4 days. I am not a right person who can tell which markers are good, but I believe you could find more information by literature search.

http://www.mcponline.org/content/4/7/887.full


Gibson assembley for small fragments? I am new to the Gibson assembly, I know how I need my plasmid but main problem is I don't have short tags and linker so I wanted to do Gibson assembly?
5'-TCACTCTCGGCATGGACGAGCTGTACAAGcagcggcagcgaaaccccgggcaccagcgaaagcgcgaccccggaaagcgaaaacctgtactttcagtccgactacaaggaccacgacggtg

Capital letters - my plasmid backbone
Italics - 3xtag
Bold - TEV site

I have plasmid backbone but I dont have 3xtag and TEV site so how can I design the primer so that i can do Gibson assembly to incorporate the sequence?

Gibson Assembly is not ideal for short fragments; chances are that the T5 Exonuclease will digest your entire fragment before it has the chance to hybridize with the backbone. For fragments shorter than 200 bp NEB recommends a 5-fold excess to compensate for this, but in your case the fragment would only be around 130 bp long. It might work, but efficiency will be very low.
Either way, based on my understanding that you don't have the 3xtag-TEV sequence available as PCR template, what you would need is two long primers designed such that they overlap by 20-25 nt at their 3' ends (orange), and with the backbone at their 5' ends (blue) as shown below:

You would then run PCR cycles with the primers alone to generate your double-stranded fragment, which you can then use in the Gibson Assembly reaction.
If you're not using a commercial Gibson Assembly kit, but instead add the enzymes yourself, you can also try an alternative method called TEDA cloning. The procedure is practically the same as that of Gibson Assembly, but TEDA uses only T5 Exonuclease. Instead of relying on (very expensive!) Phusion DNA Polymerase and Taq DNA Ligase for sealing the plasmid, plasmid repair in TEDA happens after transformation into bacteria, taking advantage of E. coli's own DNA repair machinery.
In your case, the advantage with TEDA is that you can try different incubation times with T5 Exonuclease to find a short enough incubation time such that single-stranded 5' homology ends are generated without digesting your entire fragment; or even incubate your backbone first and add your short fragment later in the TEDA reaction. As an extra bonus, TEDA cloning costs a fraction of the price of a Gibson Assembly reaction.


Meaning of red blood cell volume expansion In the scientific papers about EPO I read RBC volume (mL) expansion. What is it? The volume of a single cell or the volume expansion (=that is the increase of the number of cells) caused by the EPO?

Thank you in advance.

EDIT: see fig.1 page 3 please http://s000.tinyupload.com/index.php?file_id=08669957844938542361

Red blood cell volume is the percent of blood taken up by red blood cells (also known as the hematocrit), and is expressed as a percentage (so, normally, RBCs should comprise x% of blood by volume.) It says nothing of the size of the red blood cells.

That needs to be done by measuring the mean corpustular volume either by special machine or by looking at a slide of cells. So if the MCV is not mentioned, you can assume that expansion is referring to increased number of RBCs.

Smaller than normal RBC's are called microcytes, larger than normal are called macrocytes.

Recombinant EPO just increases the production of RBCs (and, unfortunately, it has some other effects as well.) It should not affect the size of the final erythrocyte.


How does a test like the Natera Panorama distinguish the child's genome from the mother? Blood tests on an expectant mother, like the Natera Panorama, are now being used regularly to screen fetuses for chromosome abnormalities. At my wife's recent prenatal visit, she wasn't really even asked if she wanted the test; apparently it's standard in that office. I understand some of the science of how such a test could be performed. When the placenta implants, some of the fetal cells get into the mother's bloodstream, and even though the chromosomes from those cells are breaking down, these pieces can be scanned for the markers for genetic disorders and gender. But I don't understand how the fetus's maternal chromosomes can be identified against the background of the mother's genome.

For example, one of the things that they can rule out with pretty high certainty is Monosomy X: only one X chromosome and no Y. I can see that after determining the mother's genome, it could be determined if there was no evidence of an X or Y from the father. But how would they know if an X was not contributed by the mother. If they are looking through decomposing pieces of DNA in the mother's bloodstream, are they not guaranteed to find each of her X chromosomes, whether or not the fetus has a copy of either one? How can they determine that any piece of a maternal fetal chromosome really came from the fetus rather than from the mother?

Disclaimer: I do not endorse Natera over any of their competitors. I mention them by name only because they are the only ones I am familiar with.

As you correctly discerned, distinguishing the fetal cell free DNA from the mothers cell free DNA in the blood stream is one of the major challenges in this type of diagnostics.

Consequently, the results that can be directly linked to the paternal DNA are the most reliable.

In the case of the example you give, the high accuracy stems from the fact that in case of Monosomy X, there is no indication of neither a paternal Y nor a paternal X chromosome. While the Y chromosome is the most easily discerned, a paternal X chromosome could also be detected because in that case the cell free DNA would contain fragments of three distinct X chromosomes.

This publication summarizes the issue nicely:

  Once the cell-free DNA fragments have been purified, small differences
  between the fetal and maternal DNA sequences are exploited in order to
  make a specific fetal diagnosis. To date, the majority of studies have
  focused on the detection of paternally inherited sequences that are
  entirely absent from the maternal genotype, such as those on the Y
  chromosome of male fetuses. This target is particularly attractive as it
  comprises a large portion of DNA which is not otherwise present in
  women.

  Variable regions of repeated DNA (short tandem repeats or
  STRs) can be used to identify paternally inherited sequences, by comparing
  the number of repeats present with the paternal and maternal sequences.
  Paternal alleles on the autosomal chromosomes can also be detected, if
  they are known to be absent in the maternal genome, but this requires
  detailed sequence knowledge of the paternal genotype of interest, as
  well as detection methods that can distinguish DNA sequences that
  might only differ by a single nucleotide. Importantly, all these methods
  rely upon the fetus inheriting a uniquely paternal sequence that is conveniently
  located for a particular diagnosis.

The reliability of these tests can apparently be improved by enriching the fetal cell free DNA:

  Selective enrichment of fetal DNA, based on a difference in the
  average physical length of fetal and maternal DNA fragments, which
  can be exploited to increase the relative amount of cffDNA. Fetally
  derived DNA fragments are generally smaller than those that are
  maternally derived, being predominantly ,313 base-pairs in length
  (Chan et al., 2004). Therefore, by using standard size fractionation
  to select only DNA fragments ,300 base-pairs, circulating cffDNA
  can be enriched such that it comprises around 70% of the total cellfree
  DNA (Li et al., 2004b), prior to detection and identification by
  either PCR (Li et al., 2005) or mass spectrometry (Li et al., 2006).


What is the most recent well-attested common ancestor of chimpanzees and humans? Humans and chimpanzees are related and thus have a most recent common ancestor. Of course pinning down this precise point is essentially impossible, so I'm interested in close ancestors of this most recent common ancestor. Also, I'd like to know things about it -- how it compares to common chimpanzees, bonobos, and humans in various ways -- so species known only from fragmentary evidence are less interesting to me. Ideally I'd ask for something with at least one near-complete skeleton and a separate (perhaps less complete) find, but as a non-expert I'd be happy to settle for whatever is considered to be well-attested.

So, what is the most recent well-attested common ancestor of chimpanzees and humans?

Two reasonably close relatives of the most recent chimpanzee-human ancestor (CHA) are Sahelanthropus tchadensis and Orrorin tugenensis, but both are poorly attested.

One better candidate is Ardipithecus ramidus, which has a fairly-complete skeleton ("Ardi") among other fossils. It's a bit young (4.4 Ma), perhaps, to be a CHA but should be a close relative.

Another reasonable candidate is Oreopithecus bambolii. It is very well-attested. The trouble is that no one seems to know how it's related to humans; 'best guess' is that it's not actually an ancestor but a sister taxon.

(I'm not an evolutionary biologist, nor even a scientist, but I thought I'd leave what information I collected here as there is no better answer at this time.)


What does orbital mean in orbital frontal cortex? Orbital frontal cortex is where decisions are made.

What does the word orbital there mean?

I looked around in wikipedia and never find it.

Orbitofrontal cortex: the area of the cerebral cortex located at the base of the frontal lobes above the orbits (or eye sockets), involved especially in social and emotional behaviour.


Correlation between genome size and mutation rate? Martin Nowak in his book "Evolutionary Dynamics" talks about a given correlation between genome size and mutation rate.

What correlation does exactly exist between these two concepts?

Is it a linear correlation?
What is the coefficient of correlation?
Does this correlation exist in many different taxa?

One will need to make whether we talk about mutation rate per base per generation or for the whole genome.

Some references to accompany claims are welcome!

Bradwell et al. report RNA viruses with the smallest genome may have particularly high mutation rates. A particular bug was shown to have about 1.4 x $10^{-4}$ substitutions per nucleotide per round of copying (high for viruses generally) and the authors suggest this is to optimize adaptibility. Correlation Between Mutation Rate and Genome Size in Riboviruses: Mutation Rate of Bacteriophage $Q \beta$, Genetics, vol.195 no. 1 243-51 (2013).

Cuevas et al. report a phage with 1.0 x $10^{-6}$ mutations per base per round of copying (m/b/r), which conforms (they state) to Drake's rule of 0.003 mutations per genome per round of copying in DNA-based microorganisms. They indicate that DNA-based microorganisms range between $10^{-10}$ to $10^{-6}$ m/b/r. They state that RNA viruses vary between $10^{-6}$ and $10^{-4}$ m/b/r, consistent with the result above. Point Mutation Rate of Bacteriophage $\Phi X174,$ Genetics, vol. 183 no 2 (2009).

Drake's paper often-cited paper (one of them) is available at this link.
He has a remarkable graph on p. 7163 of this paper in which based on his observation of seven microorganisms with a wide range of genome size (bp) he plots the log of the mutation rate per base pair against the log of genome size (bp). The resulting (fitted) line has a slope of roughly negative one.

In a nutshell, Drake shows that over a wide range of genome size, as the genome size climbs exponentially the mutations per base per round of copying drops exponentially. This relationship is roughly log-log linear.

In his discussion he says that the factors influencing mutation rates (in either direction) are so general that they seem to have imposed a small range of variation of mutation rate per genome in microbes that have a large range in genome size and mutation rate per base pair.

As for more complex organisms, I have read very little. There is a recent review article in Nature about a report that a hypothesized inverse correlation between genome size and mutation rates in certain plants (angiosperms) is untrue. Genome size is positively correlated with genome size. Plants with the larger genomes have higher mutation rates than those with smaller than average genomes. I don't have access to this pay-walled article or the methods involved so I am quoting the abstract. Tasci, Nature Reviews Genetics 13, 148 (March 2012).

As usual an expert in this area could correct/expand these few details I've found but it's an interesting question. Drake's paper gives a remarkable result.

As for the question about correlation coefficient, I think that Drake's graph suggests a strong correlation between linearized functions over a certain range.
I suppose we could attach a number to that...


Do humans learn to distinguish different senses? Does a human being learn to differentiate between its senses at some stage in their development? Is there a time when it, for example, cannot tell if an input is a taste or a visual image?

The question came to me because food may taste different when the sense of smell is impaired, although these are two separate senses with their own receptor organs. Is it possible for other senses to be mixed up in a similar way?

Mixing up input from different senses is actually a known neurological phenomenon called synesthesia. Synesthetes (ie. adults experiencing synesthesia) might see numbers in colors for example. Some may even "taste" colors as you say.

Now do all infants have synesthesia before some stage in development is another question. It is actually a rather old hypothesis called "neonatal synesthesia". One piece of evidence comes from this study which tested shape/color association in infants. I do not see any other study concerning this hypothesis though. I guess the main reason might be the difficulty to develop an objective experimental design on small infants who hardly communicate...


Can you force human body to mass produce specific proteins? I've had difficulty finding an answer to this question on Google.

From what I've been taught, DNA is used as a "naive blueprint" to synthesize proteins.

If we can manipulate DNA (Which I hear we can) does this not mean we can force cells to produce specific proteins we want? Purely hypothetically, ethics aside.

I also can't quite understand "what" uses that DNA to create proteins, or does it magically just "replicate itself" and turn into a new cell with the same proteins...

Sorry for the vague last question, but these questions were bothering me for a while now and I wanted to have some more references to read or answers.

Thanks ahead of time.

Yes, using recombinant DNA technology, one can take engineered DNA which has been put in an expression vector, induce it by one of various mechanisms to enter cells grown in culture (they can be from human, mouse, monkey, plant, bacteria, yeast, you name it), and the cells machinery will take over, transcribing and then translating it into protein.

  does this not mean we can force cells to produce specific proteins we want? Purely hypothetically, ethics aside.

Absolutely, and this is done on a regular basis - sometimes at industrial scales, as a matter of fact. Examples of well-known recombinant proteins include insulin, the blood clotting factor VIII, and therapeutic monoclonal antibodies.

  I also can't quite understand "what" uses that DNA to create proteins

This is an extremely broad question, but Wikipedia's Introduction to Genetics may help explain some of these ideas using less technical terms.The quick answer is that it is the cell's transcription and translation machinery mentioned above that do the heavy lifting. Very briefly, DNA is transcribed into messenger RNA or mRNA, which is then targeted to the ribosome for translation in protein. Think of the DNA as the main instructions for the shop, the mRNA as the working templates distributed to many workers, the ribosome as the machinery which takes the template and produces the finished goods, the protein.


Is reproduction intrinsically part of life? If all of the characteristics of life are required for something to be defined as living, how can we account people or other life that can not reproduce?

Every species has the ability to reproduce.  Of course, individuals within a species can be born with a mutation that keeps them from reproducing, or lose the ability to reproduce at some point in life.  However, to say that once these individuals fail to meet that criteria they are no longer forms of life would be a fairly absurd semantics argument.  It might be useful to note in an evolutionary sense that those individuals can no longer pass on their genes, which is could select against whatever it was the resulted in that individual being sterile.

You could probably reword the characteristics of life to stress species instead of individuals, but then theres a problem with microbes which have very poorly, or non-existent species.  But in general, this is not something a biologist is going to lose sleep over.


How does a blunt force stimulate histamine to develop early stages of inflammation? I know that viruses and sharp forces can stimulate mast cells by cut or by a virus infecting them and then release histamine. How can blunt force do this and cause inflammation? It doesn't have the above process. And how will the macrophages, neutrophils and plasma cells  react to this type of inflammation when there is no bacteria or viruses to swallow and create antibodies for?

An brunt force (trauma) may destroy cells and tissues by mechanical action. It simply squashes them.

Cells contain different kinds of chemical substances in specific cellular organelles. The most important in this context are enzymes from lysozyme.

Once enzymes are released (by squashing the cell) they induce irritating reactions to other cells and activate specific receptors found on immunitary system cells. This is how non-infectious inflammation occurs.

Cell components act as inflammatory mediators responsible for the clinical signs of inflammation. Here are some examples  [Wikipedia]:

Lysosome granules from destroyed cells
NO (Nitric oxide) from endothelial cells and some neurons

Other inflammatory mediators are produced by macrophages, neutrophiles and plasma cells, thus leading to a chain reaction, in which immunitary system cells activate one by another.

Macrophages have enough to 'swallow': all the destroyed cells which must be removed from the tissue.

Antibodies are produced because altered cell structures are considered non-self and gain antigen properties.

Source: Wikipedia, Inflammation


How prevalent is sexual dimorphism? I'm writing a lab on sexual dimorphism (sex differences in phenotypic traits) and I want to include a sentence in the abstract that states how prevalent sexual dimorphism is. However, I can't find any figures that pertain to organisms generally (or even for a clade).

How prevalent is sexual dimorphism in nature? How frequent is sexual dimorphism beyond primary sexual traits (gonads, gametes etc.)?

I would say that anisogamy, the different gametes such as sperm and eggs, is itself, a form of sexual dimorphism. However, you've since stipulated that you want to know the prevalence of sexual dimorphism beyond sex organs/gametes.

Sexual dimorphism occurs in a vast plethora of traits, at a variety of levels, and in almost all known dioecious species. It occurs even at the level of gene expression in, for example, mice, birds, mosquitoes, fruit flies, nematode worms, humans, and much more. Sexual dimorphism is prevalent and obvious in morphology such as peafowl, red deer, mallards, humans, guppies, fruit flies, horned flour beetles, and much more. It also occurs in physiology, behaviour, and life history traits (e.g. lifespan, ageing).

Simply put, sexual dimorphism is extremely common. It is hard to put a number on it, any studies of sexual dimorphism are likely to be focussed on sexually dimorphic traits (so a meta analysis will likely suffer from publication bias), and not all traits can be easily measured. However, gene expression is a good place to look because many traits (expression level of each gene is a trait) can be sampled simultaneously. This study found that 18% of genes were significantly sex-biased in any one tissue, while this suggests that at various developmental stages it was between approximately (based on table 1) 13% and 61%. Note again, there's not much literature which actually puts numbers on the general frequency and extent of sexual dimorphism. That is generally because, in the relevant research community, the gonads and gametes are included as sexual dimorphisms.*

Also, despite the frequency of sexual dimorphism, it is thought that the evolution of sexual dimorphism is severely constrained by the sexes working from the same genome (links: 1, 2, 3, 4, 5, 6, 7) and sexually antagonistic selection could readily favour further evolution of sexual dimorphism.

In terms of your report, I don't think you would need firm numbers or a citation; it's a well accepted fact that sexual dimorphism is common.* You would be more than fine to say something along the lines of:

  "Sexual dimorphism is extremely prevalent in nature, found in a
  range of taxa, and found in a variety of traits."

* These points are based on my experience, I did my phd thesis on the evolution of sexual dimorphism so I've read quite a substantial component of the relevant literature.