biochemistry - Does GFAJ-1 use Adenosine triarsenate as its energy currency?

This is a cool topic/question.

To answer your question. The hypothesis was based on the conjecture that there was so little phosphorus in the culture medium that phosphorous would have been replaced by arsenic in all its roles in the cell. IF they had found arsenate DNA, it would have been derived from NTAs (nucleotide tri-arsenates) or a hybrid Phosphorous/Arsenic analog of the compound as DNA polymerase consumes NTPs to create DNA. If there were only NTAs to drive DNA biosynthesis, then the cell's energy cycle would also have had to use ATA.

BUT

The primary evidence was that the mono lake strain grew in a fermentor (culture) with lots of arsenic (which is impressive) and very little phosphorous. how little? 3 micromolar. The investigators say that they did add a little phosphorus (3-5 micromolar), which, after some more careful accounting, appears to be enough to keep the bacteria growing at the observed rate without using arsenate nucleotides (submitted to Science).

This is not completely surprising as the original publication in 2010 of a preliminary finding in Science Express which only had x-ray abosorbtion fine edge spectroscopy work consistant with an arsenate like that found in a phosphorus backbone. Given that they did not produce a more direct reading of the compounds such as mass spec or an NMR experiment, this looked pretty iffy in the first place.

You an see why arsenic life was so improbable - a dozen (or more) vital pathways in the cell would have to adapt to use NTAs - pretty much all at once. If they had I suspect Mono lake would be full of those suckers.

Its sort of a bummer, for those of us who want to discover new forms of life, but you can't find what isn't there.

cell biology - Intrinsic apoptosis in erythrocytes

Red blood cells (RBCs) don't have nuclei in mammals, so they are usually considered to be pretty inert compared to other cells.

They do have some biochemical activity, and evidently there is some mechanism for cell death in RBCs when they are induced to degrade or infected by pathogens. I found this reference that shows caspases -8 and -3 are evident in mature RBCs. Several other components of the cell death pathway are not evident.

At this time the authors speculate that they don't activate to induce cell death.

It seems that over the broad field of disease research 'apoptosis' and 'cell death' are used equivalently even when the well known apoptosis pathway is not involved.

nutrition - Human Body "Fat" Equilibrium

I'm not quite sure what you mean by

regardless of x and y being out of balance.

Surely it would make more sense to assume you gain 0 weight if x and y are balanced? The prime reason why people get obese is probably because x and y are not balanced for them (there are other reasons though, as well as reasons why people can have it imbalanced and still not gain weight).

1. Even if you consume exactly as many calories as you expend in a day, you may gain weight depending on how (ratio of protein/fats/carbohydrates) and especially when you consume the calories. The body may for example store consumed amounts as fat after eating and then use carbohydrate storage from liver and muscle when starving, so long term you would still gain weight.



2. Adipose (fatty) tissue requires energy too. If you consume in the same manner after as before cutting a large amount of it away, you may just regain it until x=y again.




3. Also consider: if people ate just half an apple a day more than the exact amount of energy they need, they should gain more than a kilo on average every year. But they don't, and you can hardly assume that people manage on average to consume the exact amount their body needs.

The reason for that is probably leptin. It is a hormone produced by adipocytes (fat cells) and essentially indirectly reduces food uptake and increases expenditure, among others by decreasing your appetite. This has been regarded as a sort of "adipostat"; your leptin system creates a genetically determined level of body fat that you will tend to obtain. Dieting or cutting away fat will cause a drift to return to the previous weight because of a lower level of leptin (due to reduced fat cells). Of course it's not as simple as that though, so it's also possible that you will actually long-term reduce weight through those methods. E.g. exercise seems likely to be an exception somehow.

biochemistry - How to compute properties of peptides ?

I have been tasked with writing a program for computing properties of a give set of peptides. These peptides are given as 1-letter amino acid sequences and I need to compute the following :

• Length of peptide


• Number of Each Amino Acid


• Percent composition of each amino acid


• Molecular weight


• Net charge of peptide


• Positive charge


• Negative charge


• Isoelectric point (pI)


• Hydropathicity


• Percent polar amino acids


• Percent positive amino acids


• Percent negative amino acids


• Percent hydrophobic amino acids


• Hydrophobicity


• Lipophilicity


• Amphiphilicity


• Water-Octanol Partition Coefficient


• Steric Bulk


• Side chain bulk


• Net donated hydrogen bonds


• Percent alpha helix


• Percent random coil


• Percent beta sheet

While some of these properties are self explanatory ( eg. size, num. of amino acids, percentage of amino acids. ) and easy to compute. Other properties ( like Molecular weight, Net. charge, Positive charge, Hydorphobicity etc ) have been difficult for me.

I donot have Chemistry or Biology background and hence have found these difficult to compute. I would be appreciative if someone could point me in the correct direction ( I have already been through Wikipedia ) containing methods to compute the above mentioned properties or to a standard text which would explain the above mentioned properties and also provide methods to compute them. Thank you all.

abiogenesis - Why are amino acids in biology homochiral?

I know that you are referring to the commonly ribosome-translated L-proteins, but I can't help but add that there are some peptides, called nonribosomal peptides, which are not dependent on the mRNA and can incorporate D-amino acids. They have very important pharmaceutical properties. I recommend this (1) review article if you are interested in the subject. It is also worth mentioning that D-alanine and D-glutamine are incorporated into the peptidoglycane of bacteria.

I read several papers (2, 3, 4) that discuss the problem of chirality but all of them conclude that there is no apparent reason why we live in the L-world. The L-amino acids should not have chemical advantages over the D-amino acids, as biocs already pointed out.

Reasons for the occurrence of the twenty coded protein amino acids (2) has an informative and interesting outline. This is the paragraph on the topic of chirality:

This is related to the question of the origin of optical
activity in living organisms on which there is a very
large literature (Bonner 1972; Norden 1978; Brack and
Spack 1980). We do not propose to deal with this
question here, except to note that arguments presented
in this paper would apply to organisms constructed from
either D or L amino acids.

It might be possible that both L and D lives were present (L/D-amino acids, L/D-enzymes recognizing L/D-substrates), but, by random chance the L-world outcompeted the D-world.

I also found the same question in a forum where one of the answers seems intriguing. I cannot comment on the reliability of the answer, but hopefully someone will have the expertise to do so:

One, our galaxy has a chiral spin and a magnetic orientation, which causes cosmic dust particles to polarize starlight as circularly polarized in one direction only. This circularly polarized light degrades D enantiomers of amino acids more than L enantiomers, and this effect is clear when analyzing the amino acids found on comets and meteors. This explains why, at least in the milky way, L enantiomers are preferred.

Two, although gravity, electromagnetism, and the strong nuclear force are achiral, the weak nuclear force (radioactive decay) is chiral. During beta decay, the emitted electrons preferentially favor one kind of spin. That's right, the parity of the universe is not conserved in nuclear decay. These chiral electrons once again preferrentially degrade D amino acids vs. L amino acids.

Thus due to the chirality of sunlight and the chirality of nuclear radiation, L amino acids are the more stable enantiomers and therefore are favored for abiogenesis.

1. BIOSYNTHESIS OF NONRIBOSOMAL PEPTIDES




2. Reasons for the occurrence of the twenty coded protein amino acids




3. Molecular Basis for Chiral Selection in RNA Aminoacylation




4. How nature deals with stereoisomers




5. The adaptation of diastereomeric S-prolyl dipeptide derivatives to the quantitative estimation of R- and S-leucine enantiomers. Bonner WA, 1972




6. The asymmetry of life. Nordén B, 1978




7. Beta-Structures of polypeptides with L- and D-residues. Part III. Experimental evidences for enrichment in enantiomer. Brack A, Spach G, 1980

visualization - How to typeset gene regulatory networks

I have a relatively simply gene regulatory network I would like to visualize, complete with the common arrow and bar symbols used to show, respectively, which genes enhance or repress with other genes. Is there a way to typeset a gene regulatory network using something like LaTeX or Graphviz?

For very simple networks, I guess something like Photoshop or Illustrator would probably be the quickest solution, but these programs become very tedious as the size of the network grows even a little bit. What do people typically use for this type of task?

cell biology - Regarding TIMP and MMP enzymes

For your first question

Both enzymes, are components of Epidermal growth factor receptor (EGFR) signalling pathway.

MMP is a matrix metalloproteinase, that triggers EGFR signalling, this can be done by a mechanism called transactivation

So, A signal from G-coupled receptor, or cytokine receptor could activate the cleavage of MMP, then MMP converts to a ligand for EGFR activation

For example Angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) which are GPCR, there are evidence for crosstalk with EGFR, look for this paper. This could be linked with hypertension or inflamation. Also cancer, could trigger EGFR receptors by NMP's.

And finally tissue inhibitors of metalloproteinases (TIMPs) are the negative regulator of MMP's

This are only an overview of the whole biological process involving MMP, so I think there is no single answer to your question, but you can delimit the topic for a specific disease, and look for papers at google scholar.