Tuesday 27 May 2008

genetics - What are Haplogroups?

I understand haplogroup as the group of people that share the same given haplotype for a region of the genome.
A haplotype is the readout of the DNA sequence for a part of the genome in one of the two copies that diploid organisms have. If you start reading the DNA sequence for a given point in the genome from one of your copies and someone else's copies, it will coincide up until a point where there is a change. It is more probable to have longer identical haplotypes if the two people that are compared are related. The closest the relation, the longer their haplotypes will be identical. What breaks haplotype identity are recombination events that happen in the germinal line in the previous generation, and mutations that happen both in the germinal line and the soma (the rest of your body) along time.

Monday 26 May 2008

biochemistry - Can a living organism run on electricity?

No; the problem is, as you pointed out, that no organism will manage to multiply, grow or even sustain itself without absorbing matter to create new cells and fill metabolic losses.



Even photoautotrophic organisms which get energy from light (which is in fact an E-M wave, so pretty close to electricity) collect matter from the environment -- plants for instance seem to grow out of nothing, but in fact gather significant part of their mass from atmospheric CO_2.

immunology - How is duration of efficacy estimated for vaccines?

Duration of efficacy is typically determined by tracking the antibody titers of a cohort of subjects who have gotten the vaccine, and estimating based on the trajectory of those titers where they will eventually cross the threshold to the point where the vaccine no longer confers immune resistance.



These estimates do get revised and estimated as time goes on - you will occasionally see new recommendations for a second or third "booster" dose of a vaccine, which is meant to extend the duration of immunity beyond the duration of the original vaccine.



Two major types of studies track this over time. Phase IV clinical trials, which are clinical trials required post-licensure, and observational epidemiology trials, which tend to be performed when disease transmission starts to occur in supposedly vaccinated populations.




Mechanical snail has raised the issue of viral evolution, so I'll touch on it briefly. The duration of efficacy discussed above is based on how long a patient's body can mount an immune response to a particular challenge. That's a concern for all vaccines.



For some vaccines, there's a secondary process that's of concern - that of the virus evolving in such a way that the antigens targeted by the vaccine are no longer those on the virus itself. This is only a concern for some viruses, notably those that are particularly fast-evolving, like influenza or HIV, and less of an issue for say, measles and HPV.



But that's typically not what people are talking about when they say "duration of efficacy" because it's inherently unpredictable, and less a function of the vaccine and more a function of the virus.

Friday 23 May 2008

biochemistry - Are there any plants that fix their own nitrogen?

As far as I know, all biotic nitrogen fixation is performed by prokaryotic organisms such as Rhizobium. I don't know of any plants which can carry out this function on their own.



Plants can't use atmospheric N2 because it is held essentially inert by the nitrogen triple bond. The process of reducing N2 to NH3 which is usable by plants can be summarized:



N2 + 8e- + 8 H+ + 16 ATP -> 2 NH3 + H2 + 16 ADP + 16 Pi



(where Pi is a phosphate group)



Nitrogenase catalyses the reaction reducing N2 to NH3 by adding H+ and electrons. The whole process requires 8 ATP and is therefore energy intense.



In order to perform this coversion, bacteria require sufficent carbohydrates from decaying matter or plant vascular tissues (this is how Rhizobium derives energy from the host plant).



However, I should add that bacteria often have a mutualistic relation with the plant to perform this function, so in this sense you could say that plants can fix their own nitrogen.



There are also "free living" ammonifying bacteria in soils.



Ref



Science and the Garden, eds. Ingram, D.S., Gregory, P.J., Blackwell, 2008

bioinformatics - What value type would a chromosome position be in a database or form?

Since it sounds like you are the one designing the database, you can make this a number of ways. The simplest is probably to reduce it to two variables, likely two decimals.



See this hemoglobin example for a chromosomal locus example.



  • There are N chromosomes (23 for humans, if you like, sex chromosomes can be treated as a pair).

  • There are 2 chromatids per chromosome.

  • The part of the chromatid is either p or q (short or long arm).

  • Then there is the location on the portion of the chromatid (eg, 15.5).

Chromatid can be easily represented as a decimal, where the integer portion is the chromosome number, and the decimal portion corresponds to the chromatid and arm.



The chromosomal locus can be another decimal, such as 15.5 for the example above.



This is of course one way, and there are many other ways you could do this.

Saturday 17 May 2008

How does Yeast-two-hybrid detect interactions between several proteins in one experiment?

I am trying to understand the Y2H screening method. I can understand how we can check if two specific proteins interact with each other. For example, if we want to check whether protein A and protein B interact, we fuse A with the Activation Domain (AD) of a transcription factor and B with the Binding Domain (BD) of another transcription factor. When the two fusion proteins are transfected into a yeast cell, the reporter gene is expressed only if the AD and the BD get together and form a complete transcription factor and that happens only if proteins A and B interact with each other.



However, I have seen claims that Y2H is a high throughput system, i.e., it can be used to detect several interactions at once. But most articles online that attempt to describe it, seem vague to me.



For example, suppose I fuse the "bait" protein to the BD and several different cDNA's to the AD and let the yeast grow. Next, I observe that the reporter gene is expressed. Doesn't this observation only imply that there exists some protein from the cDNA library that interacts with our bait protein? How do we know exactly which of the target proteins have interacted with the bait and resulted in the expression of the reporter gene?

Friday 16 May 2008

biochemistry - Is there an enzyme for the transformation of the hydroxyl group?

It is possible to search for enzymes or a series of enzymes that will take similar reactants to similar products.



ReBIT allows you to query enzymes by your molecular structures of interest using their SMILES code. Unfortunately, a quick search using coumarin didn't produce any results but searches for phenol and phenolate gave some hits.



If you're seeking to do a more extensive search, I would suggest BRENDA. There you can search for reaction substrates and reaction products and even both. Both strategies may provide you with an enzyme that does the transformation chemistry that you're looking for.



Lastly there is always ENZYME, The Enzyme Data Bank. There you can search for chemical compounds. I did a search of coumarin and there are a few hits but they are for methyl-transferases and hydrolases. A more extensive search may give you a few leads.



Most of the concepts that I just suggested are explained in the following review: De novo biosynthetic pathways: rational design of microbial chemical factories.

Tuesday 13 May 2008

dna - Abiogenesis: Beyond the research journals as a lead in to discussions on evolution

I just came across this abstract:




Aminoacyl-tRNA synthetases (aaRSs) are responsible for creating the pool of correctly charged aminoacyl-tRNAs that are
necessary for the translation of genetic information (mRNA) by the ribosome. Each aaRS belongs to either one of only two
classes with two different mechanisms of aminoacylation, making use of either the 29OH (Class I) or the 39OH (Class II) of the
terminal A76 of the tRNA and approaching the tRNA either from the minor groove (29OH) or the major groove (39OH). Here,
an asymmetric pattern typical of differentiation is uncovered in the partition of the codon repertoire, as defined by the
mechanism of aminoacylation of each corresponding tRNA. This pattern can be reproduced in a unique cascade of successive
binary decisions that progressively reduces codon ambiguity. The deduced order of differentiation is manifestly driven by the
reduction of translation errors. A simple rule can be defined, decoding each codon sequence in its binary class, thereby
providing both the code and the key to decode it. Assuming that the partition into two mechanisms of tRNA aminoacylation is
a relic that dates back to the invention of the genetic code in the RNA World, a model for the assignment of amino acids in the
codon table can be derived. The model implies that the stop codon was always there, as the codon whose tRNA cannot be
charged with any amino acid, and makes the prediction of an ultimate differentiation step, which is found to correspond to the
codon assignment of the 22nd amino acid pyrrolysine in archaebacteria.




Granted, this is a few years old, but I often find myself having to admit that "I don't know" when at the root of discussions on evolution. That is, once abiogenesis has occurred, we can go on and explain the rich diversity of life, but sadly we really don't know much before that critical step. Generally, those satisfied with "magic" as an answer posit their myths and fables, whereas I'd rather try to actually find out what happened. Sadly, as the abstract shows, you actually need a level of education to understand papers such as this that is generally well beyond those who would deny the reality of evolution.



Does anyone have a collection of papers on abiogenesis that are more accessible and understandable to laypeople?

Saturday 10 May 2008

evolution - Why do plants have green leaves and not red?

There are several parts to my answer.



First, evolution has selected the current system(s) over countless generations through natural selection. Natural selection depends on differences (major or minor) in the efficiency of various solutions (fitness) in the light (ho ho!) of the current environment. Here's where the solar energy spectrum is important as well as local environmental variables such as light absorption by water etc. as pointed out by another responder. After all that, what you have is what you have and that turns out to be (in the case of typical green plants), chlorophylls A and B and the "light" and "dark" reactions.



Second, how does this lead to green plants that appear green? Absorption of light is something that occurs at the atomic and molecular level and usually involves the energy state of particular electrons. The electrons in certain molecules are capable of moving from one energy level to another without leaving the atom or molecule. When energy of a certain level strikes the molecule, that energy is absorbed and one or more electrons move to a higher energy level in the molecule (conservation of energy). Those electrons with higher energy usually return to the "ground state" by emitting or transferring that energy. One way the energy can be emitted is as light in a process called fluorescence. The second law of thermodynamics (which makes it impossible to have perpetual motion machines) leads to the emission of light of lower energy and longer wave length. (n.b. wavelength (lambda) is inversely proportional to energy; long wavelength red light has less energy per photon than does short wavelength violet (ROYGBIV as seen in your ordinary rain bow)).



Anyway, chlorophylls A and B are complex organic molecules (C, H, O, N with a splash of Mg++) with a ring structure. You will find that a lot of organic molecules that absorb light (and fluoresce as well) have a ring structure in which electrons "resonate" by moving around the ring with ease. It is the resonance of the electrons that determine the absorption spectrum of a given molecule (among other things). Consult wikipedia article on chlorophyll for the absorption spectrum of the two chlorphylls. You will note that they absorb best at short wavelengths (blue,indigo,violet) as well as at the long wavelengths (red,orange,yellow) but not in the green. Since they don't absorb the green wavelengths, this is what is left over and this is what your eye perceives as the color of the leaf.



Finally, what happens to the energy from the solar spectrum that has been temporarily absorbed by the electrons of chlorophyll? Since its not part of the original question, I'll keep this short (apologies to plant physiologists out there). In the "light dependent reaction", the energetic electrons get transferred through a number of intermediate molecules to eventually "split" water into Oxygen and Hydrogen and generate energy-rich molecules of ATP and NADPH. The ATP and NADPH then are used to power the "light independent reaction" which takes CO2 and combines it with other molecules to create glucose. Note that this is how you get glucose (at least eventually in some form, vegan or not) to eat and oxygen to breath.



Take a look at what happens when you artificially uncouple the chlorophylls from the transfer system that leads to glucose synthesis. http://en.wikipedia.org/wiki/Chlorophyll_fluorescence Notice the color of the fluorescence under UV light!



Alternatives? Look at photosynthetic bacteria.

Monday 5 May 2008

evolution - How does population stability evolve?

I guess you meant the population size stability.



It is considered that the biosystems will increase their capacity of adaptation when evolving in very fluctuating environments. I believe the population stability is embedded in the adaptability of individuals.



There is a measurement about it, evolvability, when the environment changes, the faster the population adapted to the new environment, the higher evolvability it has. This means that if the population has higher evolvability then the population may be more stable to environmental variation.



Even so, there might be plenty of underlying mechanisms to enable a certain population stability. I recently read a paper about two mechanism: phenotypic switching and sensing machinery, which are common in bacteria and fungi. Please refer to Edo Kussell and Stanislas Leibler's science paper (2005).



As the organism increase its complexity, biosystems invented many more tools to make the individual survival from disasters. Such as human's intelligence. Well it would be an endless issue.

Saturday 3 May 2008

What are the criteria for determining the influence of epigenetic factors?

First of all, the nature of penetrance is almost entirely unknown. Likely it's a combination of epistasis and gene interactions, induced gene regulatory pathways, developmental noise, and other factors. Epigenetics (imprinting, etc) may have little to do with penetrance, while chromatin structure may be a consequence of other things (most now regard histone modifications, etc, as consequence of transcription rather than heritable regulatory mechanism). Currently, the field of epigenetics is undergoing a (long-overdue) reassessment. Until that happens, anyone who wants to make claims of "epigenetics" is free to, so spurious claims are rampant.