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What is the fibre axis in the Watson and Crick paper?
I was reading Watson and Crick’s original article on DNA structure in Nature 171, 737–738 (1953). The accompanying diagram (shown below) has something called the “fibre axis” going through the DNA. This axis isn’t shown in modern models of DNA, so what is it?

As this question quotes a paper written in British English, a language acceptable on this list, changing the spelling to US English was neither accurate or necessary. I have corrected the quotation.

Short answer:
The term fiber axis is not in reference to the DNA model, it comes from the experiments that Watson and Crick referenced to guess their model (performed by Rosalind Franklin).   The fiber axis is the direction along the DNA strand.
Longer:
Watson and Crick created their model of DNA based on the esoteric experiment called X-ray fiber diffraction.  To collect fiber diffraction data ( gathered by Rosalind Franklin actually) DNA is pulled out of a cell lysate and washed with buffer.  It looks like a clear, liquid, string of snot (a technical term that is).  Its stringy though because the long DNA molecules pull out and create viscous fluid where the DNA is pulled along the length of the snot fiber.  Because the DNA is ordered in this one dimension, if you shoot a beam of X-rays through it, it creates a pattern on film that looks like this:

As you can see its got a nice X-shaped pattern.  The DNA in the fiber is mostly aligned along the fiber, in the up and down direction.  Because this is so, the spacings between the different layers is due to the spacings between the DNA bases and the x-pattern comes from the fact that DNA forms a double helix.
Some misc details - you have to use X-rays because their wavelength is about the size of an atomic bond and this is the scale of model Watson and Crick and Franklin and Wilkinson were trying to find.
The fiber axis is along the y axis (top to bottom) because the trail of DNA snot hangs down - it will sag if you hold it an angle.
Rosalind Franklin was a great experimentalist and she realized that the DNA snot trail dries out over time as the experiment would go on for days.  She set up a moist stream of hydrogen gas blowing over the DNA strand during the X-ray experiment and so was the only experimentalist who obtained what we now know to be the true result - double helical DNA.  As it dries out, DNA interconverts to the Z-DNA form I believe, which does not have the x-pattern and also confuses things because the result is a smear of the DNA helix converting from one form to another.
Francis Crick had actually predicted the X-pattern for helices.  The structure actually required these two to come together to get the answer while the American genius Linus Pauling was working hard in California on the structure as well and would have won too if he understood how to keep his snot properly damp.
The reference for nearly all of this is Watson's somewhat self-centered but historically accurate book "The Double Helix".
After some surprisingly difficult Googling, I can't found a picture of DNA fiber... picture below. You can make some yourself from the protocol listed here and some saliva, soap and other common household items.

Your statement "For their experiment (and for Rosalind Franklin who was also doing Fiber diffraction) " implies that W & C were actually doing experiments, but of course they weren't - they relied entirely upon Rosalind Franklin's data, supplied to them by Maurice Wilkins who shared the Nobel prize with W & C.

I adjusted the wording, but didn't feel the need to get into every detail of the story - link to the book is provided.

The obituary of the person who took the key photograph has just appeared in The Guardian "...Freda Collier [was]...part of the core team of Maurice Wilkins, John Randall and Rosalind Franklin (plus Franklin's PhD student, Raymond Gosling) working at King's College London on the structure of DNA. Freda...headed the photographic laboratory at King's that produced the famous "photo 51" seen by James Watson from Cambridge University. Watson immediately realised that the molecule revealed was a double helix."

@AlanBoyd what was your opinion of Maurice Wilkins?  It seems to that Franklin had little or no discussion with him - whether right or wrong - about the work.  I know he's on the paper, but what was his contribution really?  Did he train her in fiber work?  I've not found an answer to that question and certainly sometimes it does not really seem he helped.  I know it was his lab and all, but I mean intellectually or in terms of direct work...

At this date I don’t expect an answer, but why do you term X-ray diffraction of fibres esoteric?  Mainstream molecular biology at the time. That’s how the structures of hair and silk fibres were determined.

Why is Fiber Diffraction esoteric?  relatively few biological molecules are so long.   You are aligning the molecules by pulling snot or a fiber into a string.  In so doing the molecules have to line up.  Hair, spider silk, horn, some kinds of very long virus families (e.g. tobacco mosaic virus) and DNA qualify.  Also the results are often quite low resolution.  Now Electron Microscopy can look at many thousands of particles of arbitrary shape and get low to even medium resolution structures.  A much more useful approach.


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What are the benefits of elucidating the three-dimensional structure of a protein?
I have spent months as a student working on trying to form a tricky protein crystal. But I have never actually had explained to me why the structure will be useful. Once elucidated, what can we potentially learn from the structure in terms of biological significance?
Are there examples of drugs, or treatments that have only been made possible because of a known crystal structure?
Generally speaking, why do people spend so much money on synchrotrons, laboratories, robots and so on, for a protein structure?

Out of curiosity, what is the protein/what does it do?  If you don't mind me asking...

Protein structures, which can be obtained from protein crystals or from concentrated solutions of pure protein via NMR, are arguably the primary source of knowledge that we have about how genes perform their function on the molecular level.
RCSB.org is the protein structure repository in the US. They write up a story on an important protein structure monthly - its a great way to pick up some fascinating stories.
The precise atomic positions from a protein structure are indispensible for several reasons.  Since biological processes are all fundamentally chemical ones.  The specific positions of the atoms reveal how proteins, nucleotides, lipids, drugs and other biological molecules specifically interact.
Examples:

Protein structures broke the ground in biological inheritance (Watson / Crick / Franklin's DNA structure)
Protein structures of lysozyme and proteases were the first to show exactly how proteins bind their substrates and enzymatically catalyze chemical reactions.
Protein structure of hemoglobin in both oxy- and deoxy- forms (i.e. with and without oxygen bound). showed that proteins change their spatial arrangement to modulate their function.

This list goes on to more recent breakthroughs in how signals and molecules interact with the cell through the membrane.  There is literally no topic in cellular biology which has not substantially benefitted from having a protein structure revealed.
The advantages of working with protein crystals are that they can be larger proteins and certain kinds of difference experiments an be more easily performed when a protein crystal is obtained.  For instance if you have a crystal of a 100 kDa (~900 amino acid) protein, you can often find the binding pocket of the enzyme without a tremendous amount of work.
The disadvantage of working with protein crystals, as you probably know well is that getting crystals is often a quixotic effort soaking up months or years, often with little or no results.  Pretty demoralizing until you hit the target.
If you're astounded to think that proteins, which are often hundreds or thousands of times larger than a salt or mineral you usually find in crystals...you are dead on.  The crystals are often very tiny - a decent sized crystal measures about a millimeter on one side, but often are only a fraction of that size.  That's why protein crystals often are taken to synchrotrons, linear accellerators or other free electron X-ray sources which are millions (?) of times more intense than a dental x-ray. I would guess that most protein crystal structures are obtained using special beamlines created especially for biological crystallography.
That sort of tells you the funding priority science is willing to put into x-ray protein crystal structures.  Simply the idea that protein crystals might be easier to grow in microgravity (along with the low weight of the experiment) justified over a decade of protein crystal growth experiments on the shuttle and ISS.
Interesting note: The Guardian (which is based in the UK where crystallography, protein or otherwise started out) has posted a short video outlining highlights of crystallography's contributions over the past 100 years.  If you watch assiduously you will see protein crystallography cropping up with a litany of nobel prizes.
New thoughts:
There are signs that crystal structures are coming to an end.  Using an electron micrograph to simply take a picture of many thousands of individual proteins laying about can be digitally averaged to create low resolution structures they are gradually becoming higher resolution and are a lot less work than preparing and making a protein crystal - and it works well on larger proteins and protein complexes!

The method to stabilize the crystals since the early 90s has been to freeze the crystals with a stream of nitrogen at about liquid N2 temperatures.  Since then, its been a lot easier to get good diffraction data.  The hard part is still getting crystals in many cases tho.

I always wondered this myself, but the structure of a protein  can end up being quite important for a number of reasons.  Most relate to the fact that protein function often depends on specific domains, and while a protein may have multiple functional domains it is important for all domains to be properly aligned and constructed in three-dimensional space.  Misfolded proteins often have negative phenotypes, so being able to visualize the improperly folded areas can be enlightening.  Perhaps more commonly, these techniques can be used to validate an artificially produced protein before approving it for therapy.
Additionally, while we can know the sequence of amino acids in a protein very easily we don't necessarily know which ones are useful.  A region oriented toward the outside of a protein may partake in a biological function.  If a specific protein domain is imbedded inside the center of the protein, it is not very available for function, either by the protein or for other targets such as antibodies.  For example, one of the big projects in HIV research now is to get very good and very fine structure of viral proteins on the envelope of the virus; knowing which regions are readily accessible would make for potential good drug/cell/antibody targets.
Finally, the structure itself can give some insight as to function.  Proteins may not have homology by amino acid sequence, but similarly-structured proteins can have similar functions.  People smarter than me can recognize those features and can learn quite a bit about a protein just from its shape.

Here's a fun little anecdote I conveniently just came upon.  It's a quote from Your Inner Fish by Neil Shubin (© 2008) about two researchers, Linda Buck and Richard Axel, who in 1991 discovered a family of genes that allow us to smell.

Experiments showed that odor receptors have a characteristic structure with a number of molecular loops that help them convey information across a cell.  This was a big clue, because Buck and Axel could then search the genome of a mouse for every gene that makes this structure.

Expanding on something Amory said:
They are very beneficial in drug discovery. This is because it is absolutely essential that you have a structure to do any sort of molecular dynamic simulation. In the early phases of drug discovery it is cheap and easy to do these types of experiments on a computer, rather than setting up an assay for different potential therapeutics. You just take the crystal stucture of the protein, and a structure of your compound, and a program will simulate how they will interact with each other. From this you can see if the compound is able to enter the active site of the protein, the orientation it would be in, etc. Using a supercomputer you can do this with hundreds of compounds in a matter of hours. Molecular dynamics has other useful purposes, drug discovery is just one example.

Why study protein structure?

“What is the secret of life?’ I asked. ‘I forget,’ said
Sandra. ‘Protein,’ the bartender declared. ‘They found something
out about protein.‘ ‘Yeah,’ said Sandra, ‘that’s it.”

[Kurt Vonnegut, Cat’s Cradle]
Proteins are essential molecules in living organisms serving a range of intriguing different functions. Determining their individual structures is essential to understand how they perform these functions. So, quite simply, we study them out of scientific curiosity.
Proteins and medical science
As implied above, the basic reason most scientists study proteins is scientific curiosity, and an answer to the question in the title could be “a greater understanding of life”. But of course, it goes without saying that they realize that the resulting understanding provides the intellectual framework for much of modern medicine, and many proteins are chosen for study because of their physiological or pathological relevence. However, only a small part of the medical application of our knowledge of proteins is on drug design, and this generally does not involve the scientists who determine proteins structures but the pharmaceutical companies that have the resources and expertise for the long and expensive process of drug development.
Proteins and Drug Design
Nevertheless, drug design is frequently given as an example when explaining the medical relevence of research to the general public, so I think it is quite reasonable for the poster to ask:

“Are there examples of drugs, or treatments that have only been made
possible because of a known crystal structure?”

As this part of the question has not been addressed in any of the answers I present some examples below. It will be evident that the drugs listed have only been licensed over the last 20 years, whereas the first protein structure (myoglobin) was determined in 1958.

Drug
Target Protein
Organism/Disease
Year approved
Drug Company

Zanamivir/Relenza
neuroamidase
influenza
1999 (FDA)
Glaxo

Imatinib/Glivac
bcr-abl kinase
leukaemia
2001 (FDA)
Novartis

Aliskiren/Tekturna*
renin
hypertension
2007 (FDA)
Novartis

Raltegravir/Isentress
integrase
HIV
2009 (EU)
Merck

Vemurafenib/Zelboraf
B-Raf kinase
melanoma
2011 (FDA)
Plexxikon/Roche

Avibactam
β-lactamase
resistant bacteria
2015 (FDA)
Actavis/AstraZenica

Erdafitinib/Balversa
FGFR
various cancers
2019 (FDA)
Janssen

SPR720
DNA gyrase
M.tuberculosis
2020 (clinical trial)
Spero Therapeutics

*Marketing terminated 2012 due to contraindications
References
These examples are taken from the following reviews, in which details of their discovery and other examples may be found:
Nero et al. (2018) Protein structure and computational drug discovery
Maveyraud and Mourey (2020) Protein X-ray Crystallography and Drug Discovery
Staker et al. (2015) Recent contributions of structure-based drug design to the development of antibacterial compounds

As for generating a table in posts - instructions are available from the edit bar.

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Recycling and storage of nitrogen from breakdown of macromolecules?
If nitrogen is so important (it's a constituent of both proteins and nucleic acids), why are animals still throwing them out, and needing to eat it again? Is it true that in almost a billion years of evolution, life still haven't found a way to recycle nitrogen inside the cells or inside the body of multi-cellular organisms? Why does this seem so hard to achieve? Or are there animals that don't need to excrete nitrogen compounds (like ammonia, urea and uric acid), and instead reuse them?

Ammonia, urea, and uric acid are toxic to the body; why would we want to keep them around? Asking why didn't "x" evolve to happen when what actually has happened is working fairly to extremely well is fairly pointless.

Also the necessary nitrogen-containing compounds seem to be in more than adequate supply in the diet, so that eating enough calories, proteins, &c provides more than enough nitrogen.  What to do with the excess, except excrete it?

@anongoodnurse yes they are toxic, but they are created as a by-product. Why not recycle them back into protein and nucleic acids? Then there would be no toxic residuals asking to be excreted.

@jamesqf we store fat and glycogen for energy, but we must eat nitrogen to replace what was excreted. I guess we could pass more time without eating if we were able to recycle nitrogen. This could be an advantage in lots of animal groups, but as far as I know, all animal groups have nitrogen excretion mechanisms. This makes me think nitrogen recycling is somehow very hard for animals to do. The question is: why?

@tomd - Yes, and in nature (before all this population) we used to return that fixed nitrogen to plants which could use them (whereas we can't). Benefits all around. I have two dogs who have not yet learned to use the toilet. You should see my back yard...

@tomd - Chill, man...

@Rodrigo: I admit I'm no expert, but what I do know about physiology suggests that you are utterly wrong.  First, because we don't use nitrogen, we use nitrogen-containing compounds, mostly proteins.  (Simplistically) in digestion these are broken down into amino acids, which are either used to build/repair tissue, or are further broken down for energy.  End products of this process are fats & glycogen, which are stored, and various nitrogen-containing waste products, which are excreted.  Bottom line is that there's an excess of nitrogen in the diet.

I have reworded the title to remove any implication of volition in evolution. I think it important always to say an organism or a pathway has evoved or not.

It would be helpful if you could mention the biochemical pathway — absent from multicellular organisms — by which unicellular organisms recycle nitrogen (as implied in your title).

@jamesqf By nitrogen I mean any molecule containing it, which we convert in the forms useful to us (or any other organism, by the way). And I tend to agree with you, the answer probably lies in that there's an excess of nitrogen in any animal diet.

@David Thanks for the edit. The title is much better now. About unicellular organisms, I was actually thinking about the nitrogen assimilation process that happens mostly (only?) in plants. Confused it with the nitrogen fixation process...

Possible duplicate of Why do some bad traits evolve, and good ones don't?

@BryanKrause I edit the title of the question, because it's more specific than that.

The premise of the question is incorrect. Mammalian organisms do recycle nitrogen. They only excrete excess nitrogen.
Ammonia from deamination of amino acids can be incorporated into glutamate and glutamine:

Transamination can then transfer the amino group from glutamate, for example, to other ketoacids for the synthesis of other amino acids.

The capacity for recycling nitrogen is presumably determined by requirement. If there is excess to requirement, then there is no evolutionary advantage in retaining the excess and instead a mechanism has evolved to neutralize it and then excrete it.
Addendum: Recycling, yes, but why not also storage?
Although nitrogen from the degradation of amino acids is recycled, the excess is excreted, rather than stored in some form. Why has no storage form (analogous to glycogen or triglyceride) evolved? I will consider this from two inter-related  viewpoints.

Yes, nitrogen is important for the proteins required for growth and maintenance of organisms, but the effects of depravation are only seen in the long-term. Carbon is of more immediate importance, i.e. the supply of carbohydrates to provide energy. Indeed, in extreme starvation of mammals metabolism treats muscle protein as expendable, breaking it down for the carbon skeleton of the amino acids. Thus, the selective advantage the evolution of a nitrogen storage system might give to an organism is not so clear.
If there were a nitrogen storage system one needs to consider what form it might take. Obviously not as ammonia, because of its toxicity, but it could be condensed into a neutral form. However a small metabolite, such as glutamate (above), would disrupt the metabolic balance, and a dedicated small molecule such as urea would be excluded because of the effect on osmosis and general water balance. So we are thinking of a macromolecule — a conventional  protein like ovalbumin (which may, in fact, be a storage protein), or some special ‘new’ branched protein. The trouble with this method of storing nitrogen is that involves tying up large amounts of carbon — a price, as I argued in 1, that the organism cannot afford to pay.

I wonder who downvoted that and why?

@Rodrigo — Don't worry. I don't any more.  I actually plan to add some ideas on why the excess nitrogen is excreted rather than stored, which I hope will improve the answer further.

Well, it will be great if you do that, because it's really interesting.

You might want to add that this process does not offer a way of long-term storage of nitrogen and is only for immediate usage of released ammonia due to side effects of its products and requirement of substrates in other metabolic activities. See my answer.

@another'Homosapien' — I didn’t wish to get into a discussion about your answer, but "ammonia is too toxic to be stored" seems to me a red herring. The toxicity of ammonia is only relevant if it is not recycled because it is surplus. Then, if it cannot be released into the environment (as in fish) it has to be converted to a neutral form until it is excreted in the urine. Your reproduction of the urea cycle deflects the reader such as me from the valid points in your answer.

@another'Homosapien' — Not that I can think of at the moment. Busy week ahead and am away at the weekend, so low profile until next week.

Short answer: This is because the most common form of nitrogen found in multicellular organisms (not incorporated into any other compound) i.e. ammonia is too toxic to be stored or recycled.
Background: Ammonia, the product of deamination of amino acids, is basic in nature ($NH_3~+~H_2O \rightarrow NH_4OH \rightleftharpoons NH_4^+ + OH^-$) and thus disturbs intracellular pH (Ohmori et al, 1986). Though the mechanisms through which ammonia exerts its toxic effects are not known, hyperammonemia is known to alter several amino acid pathways and neurotransmitter systems, cerebral energy metabolism, nitric oxide synthesis, oxidative stress and signal transduction pathways, leading to irreversible damage to the developing central nervous system: cortical atrophy, ventricular enlargement and demyelination; causing cognitive impairment, seizures and cerebral palsy (Braissant et al, 2013).
Talking about how it is produced (just for information, skip this part if you are aware of urea cycle): Amino acids are deaminated for storage since the carbon skeleton of these amino acids can be easily converted to glucose or fatty acids for storage. This reaction yields ammonia which, in liver, is converted to urea (via urea cycle) which is not only less toxic, but also requires lesser water for excretion. See this page for more information and the diagram below.

Talking about why it is not recycled, there has always been a constant supply of amino acids to organisms (through nitrogen fixation or food). Indeed, amino acids are deaminated for storage i.e. we already have more than enough of it. Also, storing urea is also not easy since it is toxic too (it is just less toxic than ammonia). And since these products are so much harmful, it seems difficult for an organism to evolve itself so that it can store toxins rather than just throwing it away so that it can later be ingested in a useful form (amino acids from plants or herbivores). Finally, evolution works as decent with modification, meaning if something is a better alternative of current situation, it is not necessary that organisms will evolve towards that (unless there is strong selection pressure for it). In short, evolving to recycle nitrogen is (most likely) just not worth it.
P.S. you might be interested in this question to know more about evolution. Another answer here talks about storing excess nitrogen by adding ammonia into amino acids, yielding glutamate and glutamine. However, this process can be used only to a limited extent due to limited amount of substrate ($\alpha$-keto glutaric acid and glutamate) in the body. Also, excess glutamine in the body can have many major and minor side effects like skin rash, vomiting, etc. (see here for full list). Also, excess glutamate has much more pronounced effects. Since glutamate is a neurotransmitter, its excess causes cellular damage. This is what makes it an excitotoxin (see this for more details). Apart from this, the substrate ($\alpha$-keto glutaric acid) is an intermediate of Krebs cycle and is important in many other cellular activities (see here for details). So, its deficiency (caused due to conversion into glutamate) can easily affect many crucial metabolic activities. Thus, though this process seems an effective way of recycling nitrogen, it has many side-effects and is not much reliable i.e. can only be seen as an immediate solution. This is why when glutamate and glutamine build up in body, they are converted back to $\alpha$-keto glutaric acid and glutamate and the ammonia released via urea cycle.

Thank you! I know how evolution works, just thought that, in the huge variability of animal kingdom, there might be some animal able to recycle nitrogen. I disagree that it seems difficult for an organism to evolve itself so that it can store toxins. What about all the venom stored in snakes, wasps, scorpions, spiders, rays...?

@rodrigo venoms are specific to some special proteins (see this), and their effect can thus be prevented by storing them in structures lacking those proteins. Since ammonia disrupts as basic cellular properties as pH, it doesn't seem easy to store it inside a cell/tissue/organ. Yet, there might be organisms who can do so, about whom we don't know yet...

@Rodrigo: But for animals, the problem is not storing nitrogen, but getting rid of the excess.  It's rather like asking why we haven't evolved to store carbon dioxide :-)

@another'Homosapien' Right. But we can convert ammonia into urea and store urea (or uric acid, for the animals who use that). Maybe we could convert urea (or uric acid) back into a form of nitrogen that we could use to build more proteins, instead of throwing it out. But it seems there's really an excess of nitrogen in animal diets.

@Rodrigo, if you want to go in that direction, you might ask why we don't just store it in the form of protein (the same way we store fat). I guess you could argue that muscles are in fact big stores of protein :)

@VictorChubukov Very nice. But muscles require one to eat more to keep them (since they use lots of energy), so this is kind of problematic, isn't it?

@Rodrigo Converting urea and nitrogen back into protein or storing it would take calories, quite a bit since they are in low energy states.  More calories than just digesting more nitrogen in an available form which is happening anyway to get calories for everything else. Most biological process come down to a cost/benefit question, there is a solid cost and no substantial benefit since organisms are taking in protein whenever they eat anything.

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Where can I find clinical trial data published in JAMA?
Data in the paper:
http://jama.jamanetwork.com/article.aspx?articleid=336799
is cited in the statistical analysis in the book Clinical Trial Data Analysis using R. Can anyone help me find it?

Are trying to access the paper (question answered by @BenWelborn) or are you trying to get the data (spreadsheet;question I tried to answer to) used for this paper?

The full article: Effects of Treatment on Morbidity in Hypertension.

Data, spreadsheet would be nice.

Can you give a more precise pointer to where (chapter/section/page number) in the book they're discussed?  I couldn't find it in a quick skim through the Google books version ...

page 33, chapter 3 "treatment comparisons in clinical trials"

which edition? In the preview on Amazon, p. 33 is in section 1.6.1 - 1.6.2 ??

Is this data something that is not already given in the article? I think the author of the book must have compiled the data given in the tables in the form of an excel sheet (or other modern formats) and re-analysed them.

I'm kind of stumped -- I've searched through the available previews of all three editions on Amazon and can't find the section you're referring to ...

Raw data is not in the article.

I have edited your question so that the title gives a reader an idea of what "this" is, and the question can be read independently of the title. Please try to emulate this style in any future questions you may ask.

Online repository
Today, most journals (although t may depend on the field) require author to upload their data. The paper you are interested in was published in 1967 (internet was invented in 1969). It is very likely that the data have not been uploaded. It is also possible that the data have never been compiled numerically but is only on paper.
Ask the authors
Your best chance is to contact the authors directly and politely ask if they can give you their data. The author might be hard to contact as well as they may have changed university, be retired or even dead.
Possible loss of data
If you can contact the authors, then it is not unlikely that the data have just been lost. The loss might be due to a flood, to a technical issue or just because they don't know where it was placed.

alternatively you could try contacting the book authors. Sometimes data used in a book are available from a web page associated with the book, but this is the only associated web page I could find, and it doesn't appear to have any associated supplementary materials.  You could also try asking on http://opendata.stackexchange.com/ , although I don't think your chances are very good.


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How do messenger RNAs regulate each other's expression levels?
I know that researchers learn gene regulatory networks from microarray experiments that measure the mRNA expression levels. However, I do not understand how mRNAs regulate each other's levels. Do they affect the transcription step or the translation step? I know that there are transcription factors which affect the transcription step, but those are not mRNAs but proteins. How does an mRNA (the product before translation) affect another mRNA's expression level? Is this regulation process very similar to the regulation by microRNAs?

You say that "researchers learn gene regulatory networks from microarray experiments". I do not believe this is true. Microarray experiments just indicate which mRNAs increase or decrease in expression in a given situation. I suggest you either cite a paper to support your contention, delete the first sentence of your question or change the question to "How do microarray experiments show..." (to which I would say the answer is that they don't).

@David: We can argue about whether folks actually learn gene regulatory networks from these experiments, but they definitely claim to!

Yes, they claim to, that is what I mean. Bu the first sentence is not really the point here. We can even completely delete that sentence if that is confusing. What I am wondering is whether mRNAs have any regulatory role on gene transcription before they are translated to proteins.

Typically, these experimenters aren't thinking that the mRNAs directly regulate each others' expression levels, but rather that the proteins they code for affect expression. They're just mRNA as a proxy for the corresponding protein.

Thanks! Don't the mRNAs regulate gene expression at all while they are mRNAs (before being translated to proteins)? Maybe there are mRNAs transcribed but that are not translated at all, and have some function in gene regulation? Do you have any ideas?

I am a beginner and I liked your question. As @Daniel Weissman pointed out, proteins are coded by mRNAs, so the proxy is such a powerful analogy here. A coding error (horror), as it seems.


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Definition and example of Gene Variant
Could someone clearly define what a gene variant is with an example. I am totally confusing myself with SNPs, alleles, variants and how the major and minor allele are defined. An example with gene names would be really helpful.

I have condensed your title so that only the key features remain, making it easier for people scanning the list to see what it's about. You don't need "Could someone..." in a title. Trust this is OK.

A fairly easy-to-understand example is that of the ABO blood group system. In this case, there is a single gene involved - ABO, which codes for an enzyme that modifies sugar groups on the surface of red blood cells. This ABO gene has three variants or alleles — i, IA, and IB. i (coding for Type O blood) is recessive, which means that its phenotype can only be observed if there are two copies of it – ii – one from the mother and one from the father. IA and IB are co-dominant, meaning that both can be expressed at the same time, and their phenotypes can be observed even if there is only one copy of that allele — for example, IAi would give Type A blood (as would IAIA), IAIB would give Type AB, and so on.
Major and minor alleles (at least in my mind) simply refer to the frequency with which an allele is found in a given population: a minor allele is one that is expressed less-often than a major one. The term minor allele frequency is sometimes used as a numerical representation of expression — a certain allele is only expressed in 3% of the population, for example.
These terms are all from classical genetics — talking about genes and variants without really knowing (or needing to know) what exactly the gene was made up of. Of course, we now know that genes are composed of sequences of DNA nucleotide base pairs (A, T, C, and G), which are then translated by 3bp-codons into proteins, where each codon corresponds to one of 20 amino acids, plus START and STOP sequences. It is in this context of DNA sequence analysis that terms like SNP or Single Nucleotide Polymorphism are used. If you were to compare two alleles, say IA and IB, any single-nucleotide difference between the two could be termed a SNP. Frequently, SNPs are often notated based on the changes the difference would bring to the translated protein sequence — for example, a AAG codon codes for the amino acid lysine, while GAG encodes glutamatic acid. In other cases, a SNP would make no difference to the protein sequence — for example, TTA, TTG, CTC, CTA, CTG, and CTT all encode leucine. You can find the DNA codon table here.
You should keep in mind that SNPs are not the only source of variation in genetic sequences — deletions, translocations, repetitions, inversions, frame shifts, and other mechanisms can all alter the DNA sequence at a particular locus or site. Taken together, all of these differences are often referred to as mutations, which simply means "changes."
I hope this was helpful, please let us know if you still have questions.


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Introductory biology text for an outsider
I'm a maths major and I have an interest in learning biology. I know very, very little; I know how babies are made and that's about it. Could anyone recommend a stimulating text to read for its own sake and also to use to learn biology?

What aspect of biology do you wish to learn? (Human biology, plant biology or Zoology? I'm guessing you are interested in human biology from your e-mail). For example are you looking to explore mathematical applications within biology?-e.g. mathematical biology or you just want to study biology in your leisure.

I'm being deliberately vague here; I just want very basic biology and not specific at all. I am deliberately NOT looking for a mathematical perspective, however I would like a generally insightful and interesting view on the topic.

I think Helena Curtis Biology is a quite interesting book. It was written many years ago and so does not involve really recent research but it is really insightful. Another book I would recommend is Campbell - it is both recently written and thought provoking. You should also read magazines like Scientific American to get insight into latest happenings.

I found the Campbell Biology textbook to be quite comprehensive and approachable. I think many introductory biology courses use it.
http://www.amazon.com/Campbell-Biology-Edition-Jane-Reece/dp/0321558235

Yes.  This one. By the time I graduated, I think I had 4 editions.

There are tons of books and it is quite hard to find one that gives such a broad overview. Campbell Biology is a book that basically covered the first year of my Bachelor degree in biology. I am not sure it would be very stimulating though! If there is a specific branch of biology that interests you, let us know we'll be able to give you a better advice.
As a math Major you might enjoy some fields of biology that are highly mathematized. For example, system biology or theoretical evolutionary biology. For the latter, you might like to read Evolutionary Dynamics: Exploring the Equations of Life book from Martin Nowak. But I am afraid it might not be a nice idea to directly jump into some specific subject before having a good overview of the life sciences.
Otherwise you might appreciate some books of popular (but good level) science such as the Extended Phenotype from Richard Dawkins. This book is very stimulating and I think it starts with some basic definitions of biological concepts such those of "alleles" or "phenotype".
I gave you two examples of books from the field of theoretical evolutionary biology. For more recommendations in this field, please have a look at Books on population or evolutionary genetics?.
Hope this helps a bit!

Could you list the book title that you linked to?  The link is now dead but I'd be interested in checking out the book.

@Addem Thanks for highlighting my broken links. It was a link for the Campbell. The same one as suggested in xuanji's answer. See edit.

You should check out Richard Dawkins' book The Greatest Show on Earth: The Evidence for Evolution
It does focus heavily on evolution but it is an amazing book on biology in general.  He covers a wide rage of other topics, from how birds flock so elegantly to dating fossils using dendrochronology.  The chapter on embryology is fascinating.

@xuanji offers a good choice with Campbell Biology  if you want a text solid biology textbook. I've got a copy in my library. I would suggest buying a previous edition if you're trying to save money. However, the book could be a bit dry. Reading semi-popular books on topics you are interested about would probably be better approach.
Both @ebrohman and @Remi.b provide good suggestions with Dawkins. I also like Ernst Mayr's What is evolution on the topic of evolution.
For ecology, check out books by E.O. Wilson or Jared Diamond.
If you want to learn more about environmental toxicology, Rachel Carson's Silent Spring is a good book to start off with.
If you're looking for a mathematical biology book, Linda Allen has two biomath text books, one on deterministic models the other on stochastic models. Murry's also produced some classical mathematical biology books. Most people would consider these books dry, but as a mathematician, you might like them.
James Watson can be controversial but he's written some interesting books. His Double Helix is a good read.
If you provide what specific type of biology and mathematics you are interested in, I will provide more suggestions.

The Bible of biology is the Alberts' Molecular Biology of the Cell:

http://www.ncbi.nlm.nih.gov/books/NBK21054/

The Campbell is also pretty good and maybe easier to read..

Campell would provide a better overview if the OP wants to learn about more than molecular biology.


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Can someone identify these eggs?
They were attached to a tree in a black-water inundated forest (igapó) near Manaus, Amazonas, Brazil. The photo was taken in mid June, the water level was already high, and the eggs were about one metre above the water (not sure if they had been or would be under water at some point). It's been many years now, but I think the whole group was about 5 to 10 cm long (about 2–4 inches).

That's an apple snail egg cluster. They're freshwater snails, and by placing their egg clutches above the water line they protect them from predation.
We actually have an issue with apple snails in Florida, because while the Florida applesnail Pomacea paludosa is native, three different invasive species have been introduced that are eating through native vegetation without many predators (1).
Different species produce different colors of egg mass, and a good example of the green egg masses includes Pomacea haustrum, the titan applesnail, which is present in the continental US, but actually native to Bolivia, Brazil and Peru (2, 3). Since other species also produce green eggs, it's difficult to tell exactly what snail produced those, however.

Could you provide more support/info for this answer? Thanks

@theforestecologist what sort of information would make this answer more helpful? I will add a couple neat facts, but those eggs are very distinct.

What characteristics should the OP or others be looking for for a positive ID? (in other words, how did you know they were distinctly apple snail eggs)? Also discussing their range and other interesting facts is always nice :). A picture is helpful for people visiting this post in the future, as well.

Thanks for the answer. So it's most probably an Ampullariidae, though it will be harder to know the genus for sure, since it could be native, introduced, or even something new...

@Rodrigo I'm no expert, but many apple snails are native to S. America. The only catch is many species that may be native may also produce green eggs.

Yes. If I knew the genus would be good enough. But to know the family is already much better than the state I was before (not even sure if it was Mollusca).


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Terms and abbreviations in Hapmap files
For a project I've been working on, I've been looking at the HapMap Project, and the associated online files. The README file states that for each legend file for each chromosome/region, there is an rs id, an allele coded 0, 1, and a base pair position.
I presume that base pair position means where each nucleotide is located along the genetic sequence. Is this correct?
But what do "rs id" and the other terms mean?
Here's the link to the README file, and in the same directory are the files about the participants, only including SNPs.
HapMap Project README file link
HapMap Project sequence data link (phase 2)

rs id is reference SNP cluster ID see here. It's basically a unique identifier.
This table is taken from your link:
rs              position        0       1
rs11089130      14431347        C       G
rs738829        14432618        A       G
rs915674        14433624        A       G

The allele codes are the 3rd and 4th columns. An SNP is  site where a different base is found in different versions of the same gene (different versions of genes are alleles). For a given SNP the different alleles are referred to as the 0 or the 1 allele. So in the table the first SNP, rs11089130,  has two alleles: allele 0 has a C at the SNP position (14431347) whereas  allele 1 has a G at that position. The allele code does not imply any biological significance.
I'm not sure what would happen if there were three alleles at an SNP, but presumably there would then also be an SNP coded as 2.
Edit:
Allele 0 is the residue from the reference genome. Allele 1 is the residue being studied, the SNP.

so 0 is the standard allele and 1 is the mutated allele?

@higgs241 0 is the residue found in the reference genome and 1 is the residue found in others. Please don't refer to "mutated alleles" variation is the norm...

@terdon is the reference genome the same for every registered SNP? I mean, if you took the 0 allele at every SNP registered with a rsID, would you end up with the genetic profile of one specific individual?
It seems not: I read in http://en.wikipedia.org/wiki/Reference_genome that "the Genome Reference Consortium human genome (build 37) is derived from thirteen anonymous volunteers from Buffalo, New York". Is that the genome used as a reference for 0/1 labelling of SNPs? And what to do when there is polymorphism in this group of people? Maybe I could make a new question...

@bli It seems pretty clear from the WP page that you link to that the reference genome is a curation construct and so does not correspond to one individual. in fact the page includes this sentence: "The ABO blood group system differs among humans, but the human reference genome contains only an O allele (although the other alleles are annotated)."

@Alan Boyd Yes, I should have read the page further. So there is this "GRC human genome (build 37)" which is an artificial haploid reference. Is this the reference for all registered SNP? It could be but I have no certainty. One reason for my doubts is the following: Can it happen that a new SNP is identified in a portion of the genome not yet present in this reference genome? I suspect this is becoming rare, but when this reference was in earlier stages of construction, may be it could have happened.


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Is a single cell "irreducibly complex"?
(sorry if the title seems like flame-bait - but it's a real question).
I'm trying to understand what could have come before the first cell (What are the "minimum requirements" for a single cell?)
From what I've seen, the presented chemical evolution (aka abiogenesis) process centers around self-replicating RNA that gets trapped inside a lipid-based protocell and then somehow turns into a functioning cell.  But it seems like a giant leap to go from that situation to the most basic cell we know about.
Instead of starting from basic molecule and trying to get more complex, what if we take a simple cell (which is actually really complicated) and try to get more simple - try to take out some of the pieces. Work our way backwards. The problem is, I don't know what pieces you can take out. It seems there are several molecular systems that need to be functioning for cell to be viable.  Once you start to imagine a cell without them, it seems the cell will not be able to survive or replicate.
My question is, what would the step just before a "minimum cell" look like?  Are there pieces we can take away and it would still be able to survive and replicate?
** Edit **
Based on some of the discussions in the comments, I wanted to clarify what I'm asking. This is a bit long - but hopefully it will help.
Evolution is a process in which replicating systems transfer beneficial permutations to 'offspring'.  Usually the term is applied to "biological evolution) (meaning something living - from a cell to more complex organism) but I've also heard people refer to "chemical evolution" which is the process in which atoms combine to make molecules and amino acids and the amino acids combine to make RNA which can replicate.  Or fatty molecules combine to make a lipid membrane, etc.
In this process to get to something more complex, you have to have gone through a simpler stage.  To arrive at RNA, you had to have a system that would first produce nucleic acids.  If the first life was in the oceans, you needed something that could survive in and out of water before you now have creatures on dry land.  Each stage has to have a predecessor.
Generally question of the origin of life start at the raw materials and work their way towards the more complicated.  Most of the discussion I've seen basically end with RNA in lipid cells + billions of years = a prokaryote.  The difference between RNA in a protocell and a working basic cell is vast and I haven't seen an explanation on how to bridge that gap.
I'm approaching the question from the opposite direction.  If we take the most basic, simple prokaryote cell - what came before it? Even such a simple cell is in actually very very complicated (semi-permeable membrane, nucleoid, ribosomes, cytoplasm, etc..) There are so many interconnected pieces that it seems are only valuable when working as a whole. Eg, could I have had a cell without ribosomes and then some how it mutated to have ribosomes?  It seem not, because a cell without ribosomes would never have survived/replicated.  The same with other components.. if I have some precursors without that piece, it would never have survived long enough to mutate to now have that component.
So my question is what could the predecessor to a basic cell have been, considering its complexity and the seeming interdependence on the pieces for the cells survival?
I hope that helps explain the question better - thanks for any insight you can provide!

Comments are not for extended discussion; this conversation has been moved to chat.

ribosomes are made of RNA, Ribozymes are strands of RNA that act like enzymes ribosomes among them. So you have a smoother transition from RNA that catalyzes itself to RNA that catalyzes other strands of RNA, to RNA that translates other RNA into proteins.  The human classification systems get in the way of your imagination, at the chemical level there is very little difference between many "essential" molecules many are in fact the same just arranged in slightly different ways.

This is not a question in terms of SE Biology, but an attempt to start a discussion.  This explains the latest rant it has provoked (Nov 2019). Surprised? Just vote to close.

Part of the issue you are having is cell is not the simplest thing that can reproduce, replication does not require a cell. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943892/

This question has too many false assumptions to be clear.

@David and others - this is absolutely a real question and the fact that someone started a "rant" has nothing to do with it.  Unless you want to revive the beliefs of the Church and unquestionable dogma - we are allowed to ask questions about how the process works and we can ask hard questions.  This is physics and chemistry, not magic.  If we started with RNA and end with a complete cell, there have to be steps in the middle.

@John - I understand that other things can replicate.  I say it in my question.  The problem is that an RNA molecule has no other dependencies - it just is.  If you have it, it can replicate and make more of the same thing.  But a simple cell is so much more complicated and multiple dependent systems (as I understand it).

I encourage people unclear about this question to read https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926753/ to understand that it is a valid question.  If people have specific criticism of the question other than inferences about my motives or vague issues ("This question has too many false assumptions to be clear"), please let me know and I'll be happy to try to answer.

@Yehosef sure but they survive better with more complex things like the ability to sequester material and protect them selves from other RNA (cell membrane) or with a way to store the information in RNA in a way that is not so easy to degrade/mutate, (DNA)  the fact that all these things are produced by RNA or the direct product of RNA (proteins) means there is no missing step. Even in modern cells RNA is the basis of basically every process. A simple step up would be a an RNA that catalyses itself but also makes a protein that breaks down other RNA.

the source list for this video will provide a plethora of papers about modeling the origin of life. https://www.youtube.com/watch?v=KvGdllx9pJU also the simplest cell lack many of the things you mentioned, https://pubmed.ncbi.nlm.nih.gov/27013737/ try these out so you can ask a better question.

"try to take out some of the pieces. Work our way backwards."
Backwards in what, time? Does what you're doing work for any other natural system? No, it doesn't. That is not how scientists infer the history of any process given snapshots, transitional forms, etc. To discover history, they apply validated physical models and processes to the snapshots, they don't remove arbitrary parts.
"The problem is, I don't know what pieces you can take out."
No, the problem is the method you're using is invalid. I'm pretty sure it was a religious fundamentalist that seeded your idea in the first place. You're using a complexity/function-based "reverse-evolution" which may seem reasonable but never worked anywhere else, in any other part of science, for any natural process. How would you apply your method successfully to stellar evolution?
Both complexity and function are not measured, they are assessed subjectively and depend on the size of the system of interest and surrounding environment. They are philosophical concepts and are not good guides or a valid basis for inferring the history of a natural process. They are useful for communication between biologists or as a guide for planning experiments, but have no simple quantifiable relationship to any natural system.
Complexity is superficially related but entirely irrelevant to existence of a particular form of life or anything else. What's relevant, says the laws of physics, is prior conditions, surrounding environment and natural laws that act on those conditions.
To say whether something is functional one must know the environment it exists in. Even if you identify a function relevant to life, it still has other functions. Everything is made of atoms which function as the building blocks for both life and non-life, therefore there is no such thing as objective or fundamental function.
Irreducible complexity (IC) isn't even a coherent philosophical concept let alone a scientifically valid concept. It's a philosophical thought-experiment with no empirical, scientific or observational justification. Basically, IC does the following:
1) Breaks something into parts[1], philosophically, inside the mind.
2) Remove one of those parts [2].
3) Assert with no supporting evidence that the incomplete thing in step #2:
a) actually existed at some time in the past, and
b) was part of some chain of modifications or changes that led to the complete thing in step #1.
4) Assert without evidence that since the incomplete object had no obvious purpose or function [3], then it couldn't have been a step in evolution because evolution requires all parts to be functional[4].
One key blunder and reason why IC fails is step (3). In order for IC to be valid and relevant to this universe, or anything in it including evolution, step 3 must be supported by empirical evidence.
One can't just randomly choose some arbitrary division an object, however relevant to biology it may seem, then choose a random part, remove that part and claim the incomplete object once existed in the real universe. One must demonstrate with evidence that it really existed.
Another key blunder is step #4 that is just plain wrong, evolution allows for non-functional and even functions that hurt survival.
Part 3b is actually another straw-man or misrepresentation of evolution because evolution does not say that the incomplete object in step #2 ever existed or must have existed.
It is a false assumption to think that any combination of parts an object is made of, minus one part, must have existed or been an actual step in the formation process. That doesn't even hold true for designed things.
For example, take a house. Remove its roof. (By the way a house without a roof still functions as a barrier suitable for keeping non-flying and bad-at-climbing things outside the house.) It is a false assumption to say that the house without a roof must have existed at sometime in the past.
It might happen that the typical order for building a house is bottom to top; foundation, walls, roof. But that is not the necessary order. You could easily build the house from left to right using scaffolding, instead of bottom to top. This is how additions or extensions of completed homes are done.
Another false assumption of IC is that removal of one part of something completely destroys ALL functions relevant to survival. See footnote [4] for more details.
[1] Breaking something into parts is completely subjective because there are always multiple ways to do that, and multiple sub-parts in each part down to sub-atomic particles. Even if you somehow had something with indivisible parts, there are still many ways to do that.
[2] The part removed is chosen carefully by the creationist to achieve the conclusion of the argument they want. It is not based on any empirical observation or scientific evidence. There is no evidence that the removed part was once not part of the whole object at sometime in history.
[3] Purpose and function is again subjective and depends on the person assessing the thing in question. If the person sees no obvious purpose or function, that does not mean there is none.
[4] This is false. Evolution does not require all parts being functional. There can be non-functional parts and even parts that hurt survival. What matters is the TOTAL survival ability of the individual, species, or greater group as a whole, not just the function of one part.

Welcome to Biology.SE! This is an impressive rant, but an ideal answer will contain supporting references. ——— You may also want to take the [tour] and then go through the help pages starting with [Answer] questions effectively on this site and edit your post accordingly. Thanks!

I see you didn't even take the time to read my answer, or you would not be classifying it as a "rant". As I explained, the OP's question is due to a philosophical misunderstanding, not any real empirical, scientific, substantial facts. The entire enterprise of philosophically breaking into parts, removing a part, and pretending that object existed is bogus. I responded to philosophy with philosophy. The experts on this site should have immediately identified it as such. How do you expect me to give supporting references for basic logical errors?

Thanks, I was just trying to address the topic in the most philosophically complete and detailed manner. I will add that irreducible complexity exists for one singular purpose: to stifle, retard, and even halt scientific progress that has been utterly devastating to religion in the last 400 years. IC was designed solely for that purpose by fundamentalist lawyers and philosophers at the ultra-conservative christian think-tank, the discovery institute. Micheal Behe is their pawn.

I think you comprehensive answer suffers due to the numerous problems in the question.

@user6552 - thanks for the strawman argument!  I pointed out at the beginning of my question that I was using a loaded, flame-baity title.  Maybe a bad idea - I thought this was a place that rational adults could look past it and focus on the content of the question.  You basically took the "bait", unfortunately, - and built an entire argument refuting my question by trying to refute "irreducible complexity".  Maybe you should look at this article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2926753/ and let me know how it's different from what they are trying to solve.

"I thought this was a place that rational adult" Why would a rational adult use a word to describe an approach, then do something completely different? Did you mean "let me know how [irreducible complexity is] different from what NIH is trying to solve"? IC is completely different from that article, which is not a thought experiment and doesn't assert or conclude that something is philosophically non-functional, therefore can't exist by natural mechanisms. Again, your entire approach is bogus. Guessing a part to remove based on complexity or function will not yield any insight into history.

"what could the predecessor to a basic cell have been" is a valid question. "considering its complexity and the seeming interdependence on the pieces for the cell's survival" is NOT a valid approach to answering it. Complexity and function are subjective and superficially related but irrelevant to existence. The proper approach is to apply a validated scientific model on reasonably certain prior conditions. I disagree with everyone here who says my response is a straw man or rant (it is a valid philosophical argument against IC), but agree that IC should not appear in any scientific context.

"Again, your entire approach is bogus. Guessing a part to remove based on complexity or function will not yield any insight into history". It's nice that you've decided what's valid science or not.  Try searching for "reverse engineering biology" - I have no idea what is unscientific about this approach.

I wrote, "considering its complexity and the seeming interdependence on the pieces for the cell's survival" and you said this "is NOT a valid approach to answering it." It was never meant to be a valid approach - It's just framing the difficulty of the question.  Asking hard questions is a part of science - ignoring them or trying to label them as religious and anti-science is itself anti-science.

I didn't decide it was invalid, I proved it. Neither complexity nor function are scientifically measurable or have anything to do with existence. Asking philosophical questions is a part of pre-science, before you can even start doing science, which is executing the hypothesis/test/refine process of the scientific method. Nothing was ignored. You presented your philosophical method , I proved it isn't even testable. My question of how your method can be applied anywhere else, like in stellar evolution, was 100% serious. I'm genuinely interested if you can give any successful example.

Searching for "reverse engineering biology" I got this: http://philsci-archive.pitt.edu/12168/1/Can%20biological%20complexity%20be%20reverse%20engineered.pdf published in Studies in History and Philosophy of Biological and Biomedical Sciences. It's all perfectly good philosophy of mind, that may lead somewhere in the far future, once we have empirical substance to back up the imaginary reverse engineered system. But right now there is nothing reliable or scientific about IC or reverse engineering to discover history. Prior states determine history. Complexity and function does not.

@user6552 you are correct about IC. however, 1) simply leaving out "I'm pretty sure it was a religious fundamentalist that seeded your idea in the first place" could have made this much more cordial and productive. 2) OP probably meant to validly ask "what could the predecessor to a basic cell have been" as you said, yet you provided no answer to that.

“Irreducible complexity” is, as you seem to realise, a weasel term used to imply that a thing (like a cell) cannot have arisen from something simpler (or at least “different”). In that sense the answer to the question in the title is a clear “no”, unless we accept supernatural explanations for the origin of life.
You go on to state that the heart of your question is “what could the predecessor to a basic cell have been, given its complexity...”. I can strongly recommend the classic text of A.I. Oparin, “Origin of Life”, published in an English translation  in 1938(!).
This remarkable book contains a general exposition of the notion that living cells were preceded by “a gradual evolution of carbon and nitrogen compounds”, to quote the blurb of my personal copy.
The book is all the more remarkable in that its insights preceded the modern understanding of the nature of RNA and DNA - the type of “inheritance” with which the book is primarily concerned is not one of nucleic acid replication, but the relative abundance of specific chemical reactions - specifically, the so-called coacervates (spelt "coazervates" in the referenced book) and other manifestations of colloidal chemistry.

Eg, could I have had a cell without ribosomes and then some how it mutated to have ribosomes? It seem not, because a cell without ribosomes would never have survived/replicated.

The premise in the chain of reasoning that "we could hypothetically remove parts until we reach the bare minimum, but we can't so the cell came to be in its entirety is flawed". As populations evolve the organisms can gain and lose components. As an analogy consider the question of how humans can develop mouths. Our diet consists of chewing food which gives us energy to build structures like teeth and jaws, but we need teeth and jaws to chew food. A similar paradox. But of course we develop in the womb with an umbilical cord that we used to draw nutrients from our mothers that bypasses the mouth. This structure is not present in us after birth so we can't tell from looking at an adult human.

My question is, what would the step just before a "minimum cell" look
  like? Are there pieces we can take away and it would still be able to
  survive and replicate?

A very interesting question I think, but I also don't think it can be answered by looking at a modern cell and removing parts. The ancestor to cells may have lived through a very different system for example utilizing RNA to both catalyze essential reactions and store replication information as opposed to using proteins and DNA to do the same thing.


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Do all organisms have to die?
I understand (a little) that there are biological clocks and reason that after a certain amount of time organisms die. I'm wondering if that is something inherent in our DNA or in biology/chemistry in general. EG, is it possible that there could be a complex organism that would not die and would just regenerate it's cells In Perpetuam? I'm specifically interested in mammals and even more specifically interested in humans. But, I would be interested in hearing about other organisms like bugs, fish, plant, algae, etc.
I'm not asking if this practical, do we know how to do this, etc.. I just want to know theoretically if living forever is biologically possible, as far as we know. If not, is there an estimated upper limit?

https://en.wikipedia.org/wiki/Biological_immortality

It's definitely not practical. Lets assume an organism had evolved past disease and aging. It would still eventually die because with infinite time, the odds of it eventually falling into a situation where it runs out of food, or gets eaten, or dies in an accident go to 100%. So even an immortal species would still need to reproduce. If birth rates remain normal, but death rates are much slower, the population would explode, leading to many problems with food supplies and space and environmental issues.

@user137 - I'm not considering about practicalities.

Given current world state (lifestyles, climates, environment, food and water resources) and health tech I'd suggest it's in the region of 130-140 years, not sure anyone has lived longer and with billions of people on the planet that's a pretty good sampling effort but then again I'm guessing no one has yet stumbled across the perfect combination of genes and lifestyle so maybe a little longer

This interesting post is very much related

@user137 Might not be practical for the species, but evolution doesn't really care about species survival.

Are you also interested in bacteria and fungi that reproduce clonally? The situation is a bit different compared to higher animals.

@fileunderwater - no - I'm interested in the possible immortality of a single organism.  There may be similarities in how they deal with the Hayflick limit, but I'm not sure.

@Yehosef "single organism" isn't that easy to define though. Do you consider aspen clones a single organism or not? They are considered as one of the oldest living organisms, and should be relevant to your question, even though they are in one sense a multicellular plant analog to bacterial clonal growth.

@fileunderwater - fair enough.. I'm more interested in animals, but it's interesting to see other examples like you mention.

According to Agent Smith (The Matrix series): Everything that has a beginning has an end, Neo...

@jwg assuming the organism developed immortality over a long time the birth rates would have time to adjust as well. But as human life spans have increased over the last century and infant mortality has been greatly reduced, birth rates tended to remain high for several years, leading to a large increase in the number of humans. This is relevant because there are some researchers who think they can develop immortality for humans. Which, if possible, would happen over a short time scale, and birth rates wouldn't adjust.

possible duplicate of http://biology.stackexchange.com/questions/8176/do-immortal-organisms-exist?rq=1

related http://biology.stackexchange.com/questions/7010/is-there-any-kind-of-immortality-in-plants?lq=1, http://biology.stackexchange.com/questions/6884/why-is-the-hydra-biologically-immortal

The immortal jellyfish can revert back to its immature polyp stage after reaching maturity, then mature again, over and over. You can read more on the wikipedia page, but this ability means it can potentially avoid senescence altogether.

It too will die when the sun becomes a red giant.

@Joshua Technically, it will be boiled. But I can say this with certainty that it will surely die when you will disintegrate it into atomic particles. :P

@Joshua naturally, but it will fry, not senesce, and that's what the question is asking about ;)

The cited wiki page cites one iffy reference, but the other is good, and available online: http://www.biolbull.org/content/190/3/302.full.pdf+html  The authers of this article indeed claim that Turritopsis may be immortal (!!). Thanks for this great answer.

@Joshua It is considered Biologically immortal, meaning that it will not die as a result of cellular processes... That does not mean that an external agent can't kill it.

@Joshua Well, if someone took such Jellyfish into an aquarium in a spaceship and took it to another solar system, then it could go on living. But of course, any such activity would probably eventually fail.

Won't most bacteria be biologically immortal as well? If food wasn't a limitation.

You have a very interesting question there!
In order to answer, however, we must examine the most widely accepted "reason" for why we age and eventually die. Most scientists agree that it is because of mass cell death. Normally you and I would be able to deal quite well with mass cell death (such as a very large injury), the problem comes in when we are older because we cannot replenish them because we have physically exhausted our own supply of something called stem cells.
Most cells in our bodies actually cannot divide, so they rely on these stem cells (which can divide into any cell; think of them as a wild card) to replenish whatever cells die.
Sounds perfect, right? Not quite, each of us only have a given number of stem cells in our body (even though stem cells can divide into more stem cells, they usually don't). So the reason we age and die is because we "run out", if you will, of these stem cells and our supply of cellular replenishment is slowly cut off.
Back to your question, is it possible to stop this? Well you've probably already come to this conclusion by now, but theoretically if you could somehow supply the body with a constant number of stem cells, theoretically, you could live forever (or at least a really long time). This is evident, as you are aware, in flatworms, who have stem cells constantly circulating their bodies and are practically immortal.

Why do you call "running out of stem cells" the reason we die? It can just as easily be a side effect.

Sorry? Side effect of what?

Death process..

That's what I have found to be the reason for aging in the time that I have studied it.

Oh, I see. I'm only saying that it is one reason for death, not all. Death can be caused by many things.

I know we study a lot of things that are not proven yet. I can remember things from my first biology books that we can laugh about now. That's when I try to bring as much logic in the game as I can. The fact is, we are not born with a fixed amount of stem cells. They grow and multiply rapidly at young age. And then at some point, you can observe a change of direction, instead of increasing, the amount of stem cells starts to decrease. Something causes this.

And I do not profess to know the answer to that, thus why I said it was theoretical. Of all the studies I have done this would most likely be the most mysterious, we know that we stop producing the chemicals needed to stimulate stem cell division as we get older, but beyond that we really don't know. It almost appears to be programmed into us, as if on purpose. I don't know how much Yehosef is wondering about the reason for aging though, and I was just presenting an idea on how to stop it (with a bit of needed scientific background for him to understand the idea of course).

Running out of stem cells seems more like an answer to "how" than to "why".

His question was regarding how immortalization could occur, therefore only a "how" answer was required, therefore that's all I gave.

Interesting - I thought that most cells can divide, its just that https://en.wikipedia.org/wiki/Hayflick_limit that limits how often before the DNA becomes too damaged (see also https://en.wikipedia.org/wiki/Senescence).  Meaning, it seems that the cells stop dividing after a while but new stem cells can take their place and make new cells.  So if you can either stop the DNA damage via expression of telomerase (see lobster longevity) or by generating adult stem cells to regenerate cells that can no longer divide.  Either of these might work.

With many cells that is the case, however the cells I was speaking of are generally those that don't divide, such as nerve cells, brain cells, heart (muscle) cells and blood cells and those cells that rarely divide, such as liver and kidney cells. I suppose that stem cells would replenish those cells that are nearing or have reached the Hayflick limit merely by slowly replacing them with cells that have fresh DNA.


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Is there a command line molecular cloning tool?
There are many software applications such as SnapGene, Geneious, Vector NTI, ApE, Gentle and others for assistance with cloning. Their key functions are:

Making maps of plasmids
Annotating plasmids with common features
Finding restriction sites
Mapping Sanger sequencing reads
Showing sequence, reverse complement of the sequence, translations in different frames
Designing primers for specific applications (such as Gibson cloning)

Is there a tool that does functions such as these, but runs from a command line?

Note: My intent is not so much to get recommendations for what to use, but to get an idea of what software is currently available. Obviously there exist many CLI tools which can be made to serve also these purposes, up to and including general purpose text editors like vi.
I'm interested in what effort has already been made to produce CLI software specifically intended for cloning (by which I mean the functions described above).

Why does it need to be command line? Are you trying to batch these operations? And it would seem like any command line implementation of these would have very complex commands.

I agree with @user137 on this! For protein alignment you have things like Clustal W/Clustal X, which you can find from http://www.clustal.org but for your request it's far too complicated and you might be better off with GUI such as the ones listed. Many, including myself use R for bioinformatics related work and I have came across this (http://www.bioconductor.org/packages/release/bioc/html/ecolitk.html), which can address one of your points but I don't know of any unified CLI for the points you have said. If this answers you question, please let me know so that I can post it as an answer.

@user137 I suspect that I will find the command line to be a more efficient interface for these functions, and it would be much more convenient for integrating the tools into my own scripts.

@Bez I was aware of but not familiar with Bioconductor. If you could explain specifically what parts of the package perform the functions I want, that would be a great answer. Otherwise, I think just mentioning Bioconductor itself is a fair response.

I haven't worked with that specific package itself but if you have R or RStudio, which is my preferred IDE, you simply have to enter the command source("http://bioconductor.org/biocLite.R") command to upload the biocLite package and prepare R for download from the bioconductor database/depository and then execute the command biocLite("ecolitk"). Its mostly for plotting functions to work with circular genomics and can be used with other genomes/plasmids according to the package description http://www.bioconductor.org/packages/release/bioc/manuals/ecolitk/man/ecolitk.pdf

Making maps of plasmids Annotating plasmids with common features

Plasmapper works through commandline

Finding restriction sites

Simple regex searches can do that

Mapping Sanger sequencing reads

BLAST will do it.

Showing sequence, reverse complement of the sequence, translations in
  different frames

EMBOSS has a collection of tools for these things. (getorf is a tool for finding ORFs)

Designing primers for specific applications (such as
  Gibson cloning)

Primer3 works through commandline

You can just download the entire EMBOSS collection. It has many useful tools.

+1 for plasmapper, but the others aren't quite what I'm looking for. They are general tools which, in principle (and with some work) can be adapted for the purposes I mention. They are not a streamlined pipeline explicitly designed for it.

I always used BLAST for aligning Sanger-sequencing reads. You should find a lot of tools in EMBOSS collection (usual stuff like finding ORF, Reverse complement etc). I don't think there is a tool for designing primers for Gibson assembly. BTW plasmapper also annotates common restriction sites.

pydna is a python package designed for cloning. Disclaimer: I am the developer. It can be used in a Jupyter notebook to create executable scripts that result in the sequence of a some genetic construct. Restriction cloning, gibson assembly/homologous recombination are supported.

Welcome to Biology.SE. As written this would be more appropriate as a comment. We're looking for long answers that provide some explanation and context. Please don't post one-line or link-only answers; instead explain why your answer is right, ideally with citations. In this case I personally would preferred the question be closed as opinion based (off-topic), but since it wasn't you could provide a summary of what your package does and how it is an improvement over existing tools. ——— Please take the [tour] and consult the [help] starting with [ask] and [answer] for details.

For protein alignment you have things like Clustal W/Clustal X. Many, including myself use R for bioinformatics related work and I have came across this package which can be found in Bioconductor, which can address one of your points but I don't know of any unified CLI for the points you have said.
I haven't worked with that specific package itself but if you have R or RStudio, which is my preferred IDE, you simply have to enter the command
source("bioconductor.org/biocLite.R")

command to upload the biocLite package and prepare R for download from the bioconductor database/depository and then execute the command
biocLite("ecolitk")

It's mostly for plotting functions to work with circular genomics and can be used with other genomes/plasmids according to the package description.


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Do men have a higher genetic variance than women?
I've heard that with the  distribution of our genome women have less variation on the bell curve than men.
Is there any basis for this? It was my understanding that women have more genetic variation than men due to having two X chromosomes and there being more variation on gene expression within the X chromosomes.
I've also seen a theory that with traits linked to genes on the X-chromosome in women being averaged across the genetic variants found on each of a woman's two X-chromosomes, this would reduce the likelihood of extreme traits (men have just one X-chromosome, precluding this averaging process).
Is there any biological possibility for men to have more genetic variation than women, and if so what would be a potential reason for it?

This question is very interesting and I would love to have a reference to an article that provides such evidence.
Decomposing your question:

Is it true that there is more genetic variance among males than among females (in humans I guess)
If the answer to (1) is yes then: Why is it so?

I am trying to address these two points below
1. Is it true that there is more genetic variance among males than among females ?
There are different ways of understanding your question 1. Do you want to talk about…

Allele richness
Heterozygosity
Polymorphism
Part of the genetic variance in phenotypic variance (heritability). I don't think it is what you meant though!

Therefore, the question is slightly unclear and I don't know of any paper who address any of these questions anyway. So... I don't know!
2. Assuming (1) is true, then Why is it so?
There are many possible explanations for such observation (assuming this pattern has been observed). Below I give some hypothesis I can think of.

There might have a higher selection (survival differential) among females than males. In a consequence, genetic variance among young females is higher than among older females. In total, genetic variance among females would be lower to that of males.
There might have a very high variance on the Y-chromosom but not on the X-chromosom. This might for example be a consequence of the arrest of recombination that occur on the Y-chromosom. As a consequence of this arrest of recombination, selection hardly purge deleterious mutations (see Muller's Ratchet). See Shigeta's answer for a more detailed overview of this point. See shigeta's answer for more information.
Males might migrate more. If one look at the sex-specific genetic variance in a population (and not on the world-wide metapopulation), this variance might be greater for the sex that migrate more because different genetic background might be brought from other neighbor populations.
Higher selection within mitochondria in females very early in life (in the egg for example) resulting in a decreased mitochondrial genetic variance in females. This is maybe a bit far-fetched.
There might have other hypotheses for species for which sex of an individual is not determined by sex-chromosomes. (see Sex Determination System)
Depending on what you mean in your question, I guess we might find many other hypotheses when thinking of migration, different fitness landscape (different optimum), different selection intensity.
We might as well think of genetic variance of gender-specific gametes (especially for haplon-diplontic species for example)
This evidence (assuming it has been observed) was a False Positive!

Note:
@terdon provided a very good explanation (which was deleted) of why males might cause most of the genetic diversity but as @terdon and I discussed (in the comments that were also deleted) this is not an explanation for greater diversity among males. The reason is that the variation is created via mutation in the testis and the ovary. The fact that most mutations happen in males does not influence the sex-specific diversity because males sire as many male offsprings than female offsprings (so do females!).

what was the explanation that @terdon offered?  I wish it wasn't deleted.  It would seem that if there are more mutations in males (source??), there would be greater genetic variance in males, whether the mutations are in germ or somatic cells.

As @terdon and I agreed after discussion, the argument was flawed (that's why it was deleted). It is not because males transmit more new mutations to their offspring that there will be a greater genetic diversity among males as males make as many males than females make males.

Can it please be retrieved so I can read it?

@sterid High rep users (I don't know how much rep it takes) can see deleted posts. I therefore, copy-pasted this old post into a new answer for you with a very bold warning!

This is an interesting question and we should probably have a statistical geneticist around, so further answers may show up better than this one.  So I'm also assuming the question is: Is the rate of variation on the X,Y and autosomal chromosomes different?  Also assuming XY male heterogamy as humans have - different sex chromosomes will give different results between male/female.
The main distinction being - if males absorb more mutations on X as well as Y, then it would be nigh on impossible to see this phenomenon statistically since those chromosomes get passed on to females immediately.
Its important to remember that some of the X and Y regions do recombine even in men in the pseudoautosomal regions. The Y also maintains itself with a self-recombination event in meiosis.  So the message here applies to the SDR (sex determining regions) of the X and Y chromosomes - other regions are quite possibly not different than the other chromosomes.
Anyway I've found this modeling paper "Patterns of Neutral Genetic Variation on Recombining Sex Chromosomes" which estimates and compares the relative coalescence time for variations on the autosomal, X and Y regions.
In any case the models in the paper says 'yes they are different and Y non-autosomal regions accumulate variants faster'.   The coalescence time is the amount of time for a variation to spread into the general population on one of these 3 types of regions.
In cases where there is neutral selectional pressure "Close to the SDR, expected coalescence times are shorter on Y chromosomes and longer on X chromosomes than for
autosomal sites."
Which is to say speeds for incorporating variations are Y > X > autosomal
Note that the paper goes on to say that when there are more than one competing versions of the Y chromosome in a population (which seems likely to be the case), then the spread of variations on the Y goes to a normal autosomal rate.
So its likely that this effect is small overall.
It has been documented that some Y chromosomes are very competitive though.

WARNING!
This post contains a logical error (see the added section on comments) and the post was deleted by its owner (@terdon). I copy-pasted this deleted post here by request of @sterid who wanted to see it.
Please do not up or down vote!
Yes, this is  actually true. The following is taken from the introduction of the classic human genome paper[1]:

The mutation rate is about twice as high in male as in female meiosis, showing that most mutation occurs in males.

This actually makes a lot of sense from an evolutionary point of view. Primates, like many animals, are species where the male competes for the female. This means that the onus is on the male to convince the female that he is the best father for her offspring. This gives rise to some fascinating and strange behaviors:

Mutations are one of the ways that genetic diversity can be generated. Genetic diversity, in turn, makes it likely that someone or other will manage to impress the female, that some male is born faster, smarter or stronger (or whatever it is the females of his species value) than his peers. Diversity is also important as it increases the chances that a species will survive a catastrophic change in it's environment. The more random stuff you have floating around, the likelier it is that one of them will do just what it is you happen to need at the moment.
Now let's imagine a mutation whose result is a slight increase in the rate of mutation. This will cause in a net gain of diversity. As long as the increase in mutation rate is not great enough to start causing other problems, the increase in diversity will be advantageous and the mutation in question will be selected for. This is a horrible simplification, but I hope you get the general drift.
So, in humans, the males generate greater diversity but it is the females who chose which new traits are favored. In other words, men push evolution but women drive.

Lander et al Nature 409, 860-921 (15 February 2001) | doi:10.1038/35057062;

Discussion between Remi.b and terdon explaining the logical issues of the post
Remi.b: t explains why men create greater genetic diversity. I think the OP was asking if it is true that, among men, the genetic variance is higher than among females. I don't this question got answered. Or maybe I didn't get the link between differential of "diversity creation" between sexes and difference in genetic variance (or diversity?) between the sexes.
terdon: @Remi.b My logic is: men have a higher rate of mutation => more mutations occur in men => men will have more differences in their DNA compared to other men. This means they will have a greater genetic diversity since the higher rate of mutation will result in a more varied group of genotypes.
Remi.b: Yes but mutations occur in the testis when reproducing. And men sire male and female offspring that both carry the same amount of mutations. Therefore the diversity should be the same. What point am I missing in your speech? The only possible explanation to me would imply differential selection early in life in male and in females. The sex that is under stronger selection has a lower genetic variance.
terdon: @Remi.b ah, you make a very good point. Looks like it is my reasoning that is missing something and not your understanding of it :). I will edit my answer as soon as I get the chance.


text:
What exacly happens at chromossome level during fecudation and in the first zygotic division?
I was reading about the viability of animal hybrids and found the following sentence here:

Previously, this idea was not widely accepted, because, in general, different species have different numbers of chromosomes, the structures within cells that contain genes. This difference can prevent the normal development of the embryo, as each chromosome that came from the male parent must be aligned with an equivalent chromosome from the female parent when the fertilized cell divides for the first time. Without this proper alignment, the cell usually cannot divide and, thus, dies.

However, I couldn't find more information about the first zygotic division and this alignment of homologous chromosomes. This bugged me a little since, during mitosis, there's no alignment of that chromosomes.
So, anyone could clarify what exacly happens at chromosome level during fecudation and in the first zygotic division? How can this block the development of an "embryo" formed by two very distant species' gametes?


text:
Are Measles patients infectious until death?
I'm examining a dataset of a measles outbreak, and for each patient I have the date of first appearance of symptoms $t_1$, date of appearance of rash $t_2$, and if applicable, date of death $t_d$. According to the literature, patients are infectious for one day before appearance of symptoms, and up to about 4 days from appearance of rash, so the interval of infectiousness is approximately $\left[t_1 -1, t_2 + 4\right]$. After this, most of the time their symptoms gradually abate and they get better.
However, if a patient dies, presumably they remained sick until they died. If $t_d$ is like, 10 or 15 days after $t_2$, are they infectious during all of this period? Or is it reasonable to conclude that they're infectious for the same length of time as everyone else, and the symptoms that kill them are non-infectious complications?

The characteristic rash of measles is itself an immune response, and is a good marker for progression of the immune response. Patients with immunodeficiency can  have a much more limited or even absent rash. In most patients, if it's been 4 days since the appearance of the rash, and they have improvement in fever, runny nose, and conjunctivitis, without a productive cough, they probably aren't infectious. If you have that data (fever and mucous membrane inflammation), I'd pay attention to that as well as the time since the appearance of the rash. A sick patient with measles should be kept in respiratory isolation regardless, but if you're looking at modeling disease transmission, you can follow the symptom progression.
As far as death is concerned, there are several pathways. Measles can cause a poorly understood immunosuppression and immune dysregulation, which certainly contributes. The most common cause of death is pneumonia (often secondary pneumonia), but early diarrhea can be a major cause in malnourished children. Otherwise immunosuppressed individuals (e.g., HIV, and primary immunodeficiencies) can develop a fatal measles encephalitis (a brain infection). Some deaths result from a fatal post-infectious autoimmune syndrome.
Some of these individuals are probably still shedding virus (diarrhea, primary measles pnuemonitis or encephalitis), many of them aren't (secondary pneumonia and autoimmune cases).
Many texts focus on vaccination and the current epidemiology of measles in developed countries, but Cecil Medicine has a very good chapter (375) on the clinical manifestations of measles. There is an interesting article in Lancet Infectious Diseases about the US army outbreak in 1917-18 that is a good example of the interaction of measles with other respiratory pathogens.