immunology - Do you know of any disease where HLA / MHC association discovery has led to better treatment or management?

If we discover an association between a disease and a particular HLA type (MHC class I or class II molecule) then it may provide us with some insight into the disease in a very basic way. However, will it provide us with a therapeutic target? Or second best, will it provide us with information that is useful for diagnosis or management? I am looking for examples. Do you know of any?

The most obvious is in transplantation where one would use HLA typing to match donor to recipient but that is not the same as using knowledge of an HLA type to target, treat, diagnose, prognosticate.

gel electrophoresis - What is the DNA/protein charge ratio?

This is really sounds like a guideline, a starting place, not necessarily your best protocol.

In practice its hard to be more specific as MS says. The pH of the buffer will affect the charge of the protein, and to a lesser extent the DNA.

Also the protein may have an ideal pH for binding which you could guess is in the range of 7.0-7.4, but might find that the strongest binding depends on unexpected pH and salt concentrations, or the addition of a small molecule.

The affinity of araC for instance is greatly increased by the presence of arabinose in sufficient concentration.

lac Repressor, in contrast releases itself from DNA in the presence of IPTG or lactose.

evolution - Could an organism theoretically produce a metamaterial-like structure?

I'm curious to know if this is physically feasible because during my reading up on synthetic biology and just general research i realise that life is capable of producing some exquisitely complex materials and biological structures and wondered if they could potentially recreate artficial materials that aren't found in nature well not yet anyway. Could such a structure evolve naturally or would it have to be designed or directed via synthetic biology techniques?

Thank you for your time.

eyes - Are rods/cones rejuvenated periodically?

Pretty much what the title states.

Some cells/structures in the human body undergo rejuvenation periodically by flushing away older cells and growth of new ones.
E.g Skin, Blood

Does this (for want of a better word) 'rejuvenation' apply to Rods/Cones within the eye too? If so, how are the old cells flushed out - or do the old cells become part of the local humour?

bioinformatics - What is the significance and method behind Ramachandran plots?

Ramachandran plots show the relationship between the phi and psi angles of a protein referring to dihedral angles between the N and the C-alpha and the C-alpha and the C-beta. As an aside, the omega angle between the C-beta and the N tends to be fixed due to pi-pi interactions.

Dihedral Angles

There are limits to possible distributions of phi and psi angles due to steric clashes between the side chains. Furthermore other limitations from higher order structure will result in the adoption of defined phi-psi angles. Using data from solved crystal structures, it can be seen that the dihedral angles will adopt specific conformations in a protein.

RAMACHANDRAN PLOT from Lovell et al.

Furthermore, it can be noted that some of these conformations relate to specific secondary structures. As seen above, peptides in alpha-helices and beta-sheets adopt a even more limited set of phi-psi angles. Certain amino acids like glycine and proline, which differ from from canonical amino acids have an unique Ramachandran plot.

The angles from a Ramachandran plot are useful not only for determining a amino acids' role in secondary structure but can also be used to verify the solution to a crystal structure. Furthermore, it assists with constraining structure prediction simulations and helps with defining energy functions.

homework - Does Human Female Meiosis II occur after fertilization with sperm?

Meiosis, as you know, have two stages, Meiosis I and II. The oocyte is arrested during metaphase II of MEOISIS II. This arrest is facilitated by a complex called "Cytostatic Factor" (CSF).

After fertilization, the sperm induces a rise in intracellular calcium ion which activates and enzyme, Calmodulin Kinase II. This complex, through a series of phosphorylation and ubiquitination, degrades the CSF comples and in turn, activates APC (Anaphase Promoting Complex). APC will then degrades cyclins, securins and this will promotes the completion of Meiois II.

Sperm must ignite some process in female that puts female meiosis II going on before sperm can fuse with egg.

I think the statement is a bit incorrect. The sperm will ignite (I prefer induce) the above changes and fuse at the same time. Because, what starts all the process above is part of the sperm's cytoplasm that need to be assimilated into the oocyte's cytoplasm.

I hope this clears it all up. Or if you are interested, I can provide the long list of signalling pathways that leads to zygotic development.

genomics - Which functional annotations could be useful?

Analyzing a genome, for a generic gene, which functional annotations (e.g from Gene Ontology) can help understanding its meaning/function or, at least, provide helpful informations?

• Annotations of that gene


• Annotations of orthologous genes (?)


• Annotations of paralogous genes (?)


• Co-expressed genes (given a biological condition) (?)


• What else?

Thank you.

evolution - Did animals evolve from plants?

See this paper "Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi" for information on the divergence estimates (I'm not sure if there are more recent papers discussing this).

Plants, animals and fungi are eukaryotes, distinct from eubacteria and archaebacteria, which are prokaryotes. The difference being in the composition of the cell, particularly a nucleus contained within a membrane for eukaryotes, along with other membrane bound organelles, e.g. chloroplasts. They all share a common ancestor, according to this paper, that split 1.576 Bya (billion years ago) +/- 88 Mya (although it states the relationships are unresolved - it is often difficult to resolve relationships so deep in a tree). They form distinct groups known as Kingdoms under Linnaean based biological classification; the Fungi, Plantae and Animalia. Thus, in answer to your question, no, animals did not evolve from plants.

Plants have chloroplasts in their cells, which provide the ability to produce energy via photosynthesis. It is thought that the chloroplast resulted from a symbiotic relationship between early plants and a cyanobacteria in that they both relied on each other for survival and so coevolved. Animals don't contain chloroplasts and instead contain an organelle called the mitochondria (although most plants also have mitochondria), which is also thought to have been a bacterial endosymbiont, probably related to rikettsias.

Protists also contain chloroplasts. The protists are intermediate between all three groups and have been notoriously difficult to classify, being placed into a fourth Kingdom, the Protozoa, although this grouping has been contested. The current Cavalier-Smith system was proposed in 2004 and classifies life into 6 Kingdoms.

Chloroplasts are thought to have evolved from a single endosymbiotic event in Archaeplastida, although there are evidence to suggest some secondary endosymbiotic events. Check out this paper for more information; figure 1 shows the relationships between the different groups and the endosymbiotic events. The Opisthokonts are the origin of the Fungi and Animalia kingdoms.

human biology - Why Does Salt Water Help Sore Throats?

Salt water may have anti-septic properties due to the effect it has on water potential. Pure water has a water potential (Ψ) of zero. A concentrated salt solution has a lower (more-negative) water potential. The water potential of the salt solution is likely to be more negative than that of the pathogen's cytoplasm; the salt solution is therefore referred to as hypertonic. Therefore water osmoses out of the cell (osmosis being the net movement of water from a higher water potential to a lower water potential across a semi-permeable membrane). The loss of water from the pathogenic cells causes osmotic crenation - the cell becomes shrivelled and dies.

A hypotonic solution (for example cells placed into pure water) would cause the opposite effect - osmotic lysis. This is the bursting of the cell due to the movement of water into the cell. The bacterial cell wall would first have to be damaged (e.g. by penicillin). This would not be the process by which a salt solution has effect, however.

The fact that the salt water is warm in order to improve solubility may also have the side-effect of causing vasodilation around the infection, increasing the rate at which white blood cells can arrive at the infection site.

It has been more difficult to find a theory as to why a salt solution would have analgesic properties, see the comments below & previous versions of this answer.

genomics - Is it possible to trace of the ancestry of a person by only using his/her genetic information?

In short, yes, it is possible. There are companies that sequence part of your genome and then can trace it back to your ancestors. All human family trees can be traced back to their African origin 200 000 years ago, but the companies that sequence your genes do not do that. For example, 23andMe sequences only 1 million of your base pairs (single nucleotide polymorphisms (SNPs)). They trace your most recent heritage, which could lead to Europe, Africa, or Asia. They can basically trace which part of your chromosomes (and thus your ancestry) came from your mom or your dad:

Unlike the sex chromosomes and the mitochondrial DNA, which are inherited as blocks, the 22 biparental chromosomes, known as autosomes, are scrambled during reproduction. Through a process known as recombination, each parent pulls his or her paired set of 22 autosomes into chunks, then reassembles a new single set using half the material from each pair. The two single sets of chromomes from each parent are combined into a new paired set when a sperm fertilizes an egg.

You can read more about 23andMe here. There are other companies that are specialized in tracing your ancestry: Genetic Genealogy, DNA Tribes, and Heirlines.

genetics - Predicting progeny of recessive mutations using recombination

First, the recombination equation is:

cM = recombinants/(recombinants AND parentals) * 100

Let's assign the following genotypes for clarity's sake:

RR = black bristles
Rr = black bristles
rr = red bristles
SS = pebbly eyes
Ss = pebbly eyes
ss = shiny eyes

F1 cross: rrSS x RRss = RrSs (all progeny)
F2 cross: RrSs (F1) x rrss = ?

You would have the following gametes:

Parent 1, RrSs = RS, Rs, rS, rs
Parent 2, rrss = rs, rs, rs, rs

Draw your punnet square and you get the following genotypes of the offspring.

So your GENOTYPES of your F2 cross will be RrSs, Rrss, rrSs, rrss

Let's translate those to phenotypes.

RrSs: black pebbly (parental)
Rrss: black shiny (recombinant)
rrSs: red pebbly (recombinant)
rrss: red shiny (parental)

Now let's look at recombination frequency.

15cM = (recombinants/(recombinants+parentals)*100
recombinants/(parentals+recombinants) = 15/100

This tells you for every 15 recombinants, you have 85 parentals. If you scale this up to 1000, that's 150 recombinants for every 850 parentals.

Your 150 recombinants comes from 75 black/shiny and 75 red/pebbly.

Your 850 parentals ceoms from 425 black/pebbly and 425 red/shiny.

Anyways that was my attempt which appears to be directly opposite to what your answer key says. Did you copy it down correctly?

lab techniques - What effect does vortexing have on a fluid sample that simple mechanical shaking does not?

what specific effect the vortexing has that makes it better than manual shaking

In addition to @bobthejoe's answer about viscous fluids, (manual) mechanical shaking is also less consistent and more tiresome than vortexing.

If the vortexer is always at the same speed and each sample is vortexed for the same amount of time, then the shaking step will be less variable among samples. For example, the vigor of mixing an aqueous soil suspension could potentially affect the amount of aggregate decomposition and release of molecules into the suspension (I don't have a reference for this, but it is good practice to treat replicates the same to minimize any non-treatment effect).

Manual shaking is not only less consistent, it is also tiresome - especially with larger volumes (>=10ml) and large sample sizes.

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.