Researchers continue to add to the diagnostic alphabet of saliva by identifying the presence of at least 50 microRNAs that could aid in the detection of oral cancer, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research.
"It is a Holy Grail of cancer detection to be able to measure the presence of a cancer without a biopsy, so it is very appealing to think that we could detect a cancer-specific marker in a patient's saliva," said Jennifer Grandis, M.D., professor of otolaryngology and pharmacology at the University of Pittsburgh School of Medicine and Cancer Institute and a senior editor of Clinical Cancer Research.
MicroRNAs are molecules produced in cells that have the ability to simultaneously control activity and assess the behavior of multiple genes. They are a thriving research topic right now, and researchers believe they could hold the key to early detection of cancer. The emergence of a microRNA profile in saliva represents a major step forward in the early detection of oral cancer.
"The oral cavity is a mirror to systemic health, and many diseases that develop in other parts of the body have an oral manifestation," said David T. Wong, D.M.D., D.M.Sc., Felix and Mildred Yip Endowed Professor at the University of California, Los Angeles School of Dentistry.
Wong and colleagues measured microRNA levels in the saliva of 50 patients with oral squamous cell carcinoma and 50 healthy control patients. They detected approximately 50 microRNAs.
Two specific microRNAs, miR-125a and miR-200a, were present at significantly lower levels in patients with oral cancer than in the healthier controls.
Wong said that the findings of this study would have to be confirmed by a larger and longer analysis.
Peptide Delivers Anti-Cancer Compounds to Where They Can Do the Most Good
Researchers at Burnham Institute for Medical Research at University of California, Santa Barbara have identified a peptide (a chain of amino acids) that specifically recognizes and penetrates cancerous tumors but not normal tissues. The peptide was also shown to deliver diagnostic particles and medicines into the tumor. This new peptide, called iRGD, could dramatically enhance both cancer detection and treatment. The work is being published December 8 in the journal Cancer Cell.
Led by Erkki Ruoslahti, M.D., Ph.D., distinguished Burnham professor at UCSB, this research was built on Dr. Ruoslahti’s previous discovery of “vascular zip codes,” which showed that blood vessels in different tissues (including diseased tissues) have different signatures. These signatures can be detected and used to dock drugs onto vessels inside the diseased tissue. In addition to homing in on tumor vessels, the new iRGD peptide penetrates them to bind inside the tumor. Previous peptides have been shown to recognize and bind to tumors, but were unable to go beyond the tumor blood vessels.
“This peptide has extraordinary tumor-penetrating properties, and I hope that it will make possible substantial improvements in cancer treatment,” says Dr. Ruoslahti. “In our animal studies, the iRGD peptide has increased the efficacy of a number of anti-cancer drugs without increasing their side effects. If these animal experiments translate into human cancers, we would be able to treat cancer more effectively than before, while greatly reducing the side effects the patient would suffer.”
The novel iRGD peptide, identified by using phage display for a peptide that binds to the blood vessels of pancreatic and bone tumors, was tested to determine its ability to penetrate tumors. Researchers injected fluorescent-labeled iRGD into tumor-bearing mice and found that the peptide accumulated in a variety of tumors, including prostate, breast, pancreatic, brain and other types. In addition, the peptide only targeted the tumors and did not accumulate in normal tissue.
Iron oxide nanoworms, which can be visualized by magnetic resonance imaging, were coupled to the peptide and shown to penetrate the tumors, whereas uncoupled nanoworms could not. This demonstrates that iRGD can deliver diagnostics to tumors. The anti-cancer drug Abraxane was also shown to target, penetrate and spread more within tumor tissue when coupled to iRGD than with other formulations.
Soft and synthetic red-blood-cell-like particles carry oxygen, drugs, and more…
Santa Barbara, California, December 14, 2009—Scientists at UC Santa Barbara, in collaboration with scientists at University of Michigan, have developed synthetic particles that closely mimic the characteristics and key functions of natural red blood cells, including softness, flexibility, and the ability to carry oxygen.
The primary function of natural red blood cells is to carry oxygen, and the synthetic red blood cells (sRBCs) do that very well, retaining 90% of their oxygen-binding capacity after a week. The sRBCs also, however, have been shown to deliver therapeutic drugs effectively and with controlled release, and to carry well-distributed contrast agents for enhanced resolution in diagnostic imaging.
"This ability to create flexible biomimetic carriers for therapeutic and diagnostic agents really opens up a whole new realm of possibilities in drug delivery and similar applications," noted UCSB chemical engineering Samir Mitragotri. "We know that we can further engineer sRBCs to carry additional therapeutic agents, both encapsulated in the sRBC and on its surface."
Professor Mitragotri, his research group, and their collaborators from the University of Michigan succeeded in synthesizing the particles by creating a polymer doughnut-shaped template, coating the template with up to nine layers of hemoglobin and other proteins, then removing the core template. The resulting particles have the same size and flexibility, and can carry as much oxygen, as natural red blood cells. The flexibility, absent in "conventional" polymer-based biomaterials developed as carriers for therapeutic and diagnostic agents, gives the sRBCs the ability to flow through channels smaller than their resting diameter, stretching in response to flow and regaining their discoidal shape upon exiting the capillary, just as their natural counterparts do.
In addition to synthesizing particles that mimic the shape and properties of healthy RBCs, the technique described in the paper can also be used to develop particles that mimic the shape and properties of diseased cells, such as those found in sickle-cell anemia and hereditary eliptocytosis. The availability of such synthetic diseased cells is expected to lead to greater understanding of how those diseases and others affect RBCs.
A group of scientists has succeeded in creating the first transistor made from a single molecule. The team, which includes researchers from Yale University and the Gwangju Institute of Science and Technology in South Korea, published their findings in the December 24 issue of the journal Nature.
The team, including Mark Reed, the Harold Hodgkinson Professor of Engineering & Applied Science at Yale, showed that a benzene molecule attached to gold contacts could behave just like a silicon transistor.
The researchers were able to manipulate the molecule's different energy states depending on the voltage they applied to it through the contacts. By manipulating the energy states, they were able to control the current passing through the molecule.
"It's like rolling a ball up and over a hill, where the ball represents electrical current and the height of the hill represents the molecule's different energy states," Reed said. "We were able to adjust the height of the hill, allowing current to get through when it was low, and stopping the current when it was high." In this way, the team was able to use the molecule in much the same way as regular transistors are used.
The work builds on previous research Reed did in the 1990s, which demonstrated that individual molecules could be trapped between electrical contacts. Since then, he and Takhee Lee, a former Yale postdoctoral associate and now a professor at the Gwangju Institute of Science and Technology, developed additional techniques over the years that allowed them to "see" what was happening at the molecular level.
Being able to fabricate the electrical contacts on such small scales, identifying the ideal molecules to use, and figuring out where to place them and how to connect them to the contacts were also key components of the discovery. "There were a lot of technological advances and understanding we built up over many years to make this happen," Reed said.
There is a lot of interest in using molecules in computer circuits because traditional transistors are not feasible at such small scales. But Reed stressed that this is strictly a scientific breakthrough and that practical applications such as smaller and faster "molecular computers" -- if possible at all -- are many decades away.
"We're not about to create the next generation of integrated circuits," he said. "But after many years of work gearing up to this, we have fulfilled a decade-long quest and shown that molecules can act as transistors."
Denmark is a big shame.
The sea is stained in red and it’s not because of the climate effects of nature.
It's because of the cruelty that the human beings (civilised human) kill hundreds of the famous and intelligent Calderon dolphins.
his happens every year in Feroe iland in Denmark . In this slaughter the main participants are young teens. WHY?
To show that they are adults and mature.... BULLLLsh
In this big celebration, nothing is missing for the fun. Everyone is participating in one way or the other, killing or looking at the cruelty “supporting like a spectator”
Is it necessary to mention that the dolphin calderon, like all the other species of dolphins, it’s near instinction and they get near men to play and interact in a way of PURE friendship
They don’t die instantly; they are cut 1, 2 or 3 times with thick hocks. And at that time the dolphins produce a grim extremely compatible with the cry of a new born child.
But he suffers and there’s no compassion till this sweet being slowly dies in its own blood.
Its enough! We will send this mail until this email arrives in any association defending the animals, we won’t only read.
1.Yes, 70 lakhs crores rupees of India are lying in Switzerland banks. This is the highest amount lying outside any country, from amongst 180 countries of the world, as if India is the champion of Black Money.
2.Swiss Government has officially written to Indian Government that they are willing to inform the details of holders of 70 lakh crore rupees in their Banks, if Indian Government officially asks them.
3.On 22-5-08, this news has already been published in The Times of India and other Newspapers based on Swiss Government's official letter to Indian Government.
4.But the Indian Government has not sent any official enquiry to Switzerland for details of money which has been sent outside India between 1947 to 2008.. The opposition party is also equally not interested in doing so because most of the amount is owned by politicians and it is every Indian's money.
5.This money belongs to our country. From these funds we can repay 13 times of our country's foreign debt. The interest alone can take care of the Center s yearly budget. People need not pay any taxes and we can pay Rs. 1 lakh to each of 45 crore poor families.
6.Let us imagine, if Swiss Bank is holding Rs. 70 lakh Crores, then how much money is lying in other 69 Banks? How much they have deprived the Indian people? Just think, if the Account holder dies, the bank becomes the owner of the funds in his account.
7.Are these people totally ignorant about the philosophy of Karma? What will this ill-gotten wealth do to them and their families when they own/use such money, generated out of corruption and exploitation?
8.Indian people have read and have known about these facts. But the helpless people have neither time nor inclination to do anything in the matter. This is like "a new freedom struggle" and we will have to fight this.
9.This money is the result of our sweat and blood.. The wealth generated and earned after putting in lots of mental and physical efforts by Indian people must be brought back to our country.
Many elements form compounds with hydrogen - referred to as "hydrides". If you plot the boiling points of the hydrides of the Group 4 elements, you find that the boiling points increase as you go down the group.
The increase in boiling point happens because the molecules are getting larger with more electrons, and so van der Waals dispersion forces become greater.
If you repeat this exercise with the hydrides of elements in Groups 5, 6 and 7, something odd happens.
Although for the most part the trend is exactly the same as in group 4 (for exactly the same reasons), the boiling point of the hydride of the first element in each group is abnormally high.
In the cases of NH3, H2O and HF there must be some additional intermolecular forces of attraction, requiring significantly more heat energy to break. These relatively powerful intermolecular forces are described as hydrogen bonds.
The origin of hydrogen bonding
The molecules which have this extra bonding are:
Note: The solid line represents a bond in the plane of the screen or paper. Dotted bonds are going back into the screen or paper away from you, and wedge-shaped ones are coming out towards you.
Notice that in each of these molecules:
The hydrogen is attached directly to one of the most electronegative elements, causing the hydrogen to acquire a significant amount of positive charge.
Each of the elements to which the hydrogen is attached is not only significantly negative, but also has at least one "active" lone pair.
Lone pairs at the 2-level have the electrons contained in a relatively small volume of space which therefore has a high density of negative charge. Lone pairs at higher levels are more diffuse and not so attractive to positive things.
Consider two water molecules coming close together.
The + hydrogen is so strongly attracted to the lone pair that it is almost as if you were beginning to form a co-ordinate (dative covalent) bond. It doesn't go that far, but the attraction is significantly stronger than an ordinary dipole-dipole interaction.
Hydrogen bonds have about a tenth of the strength of an average covalent bond, and are being constantly broken and reformed in liquid water. If you liken the covalent bond between the oxygen and hydrogen to a stable marriage, the hydrogen bond has "just good friends" status. On the same scale, van der Waals attractions represent mere passing acquaintances!
Water as a "perfect" example of hydrogen bonding
Notice that each water molecule can potentially form four hydrogen bonds with surrounding water molecules. There are exactly the right numbers of + hydrogens and lone pairs so that every one of them can be involved in hydrogen bonding.
This is why the boiling point of water is higher than that of ammonia or hydrogen fluoride. In the case of ammonia, the amount of hydrogen bonding is limited by the fact that each nitrogen only has one lone pair. In a group of ammonia molecules, there aren't enough lone pairs to go around to satisfy all the hydrogens.
In hydrogen fluoride, the problem is a shortage of hydrogens. In water, there are exactly the right numbers of each. Water could be considered as the "perfect" hydrogen bonded system.
More complex examples of hydrogen bonding
The hydration of negative ions
When an ionic substance dissolves in water, water molecules cluster around the separated ions. This process is called hydration.
Water frequently attaches to positive ions by co-ordinate (dative covalent) bonds. It bonds to negative ions using hydrogen bonds.
The diagram shows the potential hydrogen bonds formed to a chloride ion, Cl-. Although the lone pairs in the chloride ion are at the 3-level and wouldn't normally be active enough to form hydrogen bonds, in this case they are made more attractive by the full negative charge on the chlorine.
However complicated the negative ion, there will always be lone pairs that the hydrogen atoms from the water molecules can hydrogen bond to.
Hydrogen bonding in alcohols
An alcohol is an organic molecule containing an -O-H group.
Any molecule which has a hydrogen atom attached directly to an oxygen or a nitrogen is capable of hydrogen bonding. Such molecules will always have higher boiling points than similarly sized molecules which don't have an -O-H or an -N-H group. The hydrogen bonding makes the molecules "stickier", and more heat is necessary to separate them.
Ethanol, CH3CH2-O-H, and methoxymethane, CH3-O-CH3, both have the same molecular formula, C2H6O.
They have the same number of electrons, and a similar length to the molecule. The van der Waals attractions (both dispersion forces and dipole-dipole attractions) in each will be much the same.
However, ethanol has a hydrogen atom attached directly to an oxygen - and that oxygen still has exactly the same two lone pairs as in a water molecule. Hydrogen bonding can occur between ethanol molecules, although not as effectively as in water. The hydrogen bonding is limited by the fact that there is only one hydrogen in each ethanol molecule with sufficient + charge.
In methoxymethane, the lone pairs on the oxygen are still there, but the hydrogens aren't sufficiently + for hydrogen bonds to form. Except in some rather unusual cases, the hydrogen atom has to be attached directly to the very electronegative element for hydrogen bonding to occur.
The boiling points of ethanol and methoxymethane show the dramatic effect that the hydrogen bonding has on the stickiness of the ethanol molecules:
ethanol (with hydrogen bonding)
78.5°C
methoxymethane (without hydrogen bonding)
-24.8°C
The hydrogen bonding in the ethanol has lifted its boiling point about 100°C.
It is important to realise that hydrogen bonding exists in addition to van der Waals attractions. For example, all the following molecules contain the same number of electrons, and the first two are much the same length. The higher boiling point of the butan-1-ol is due to the additional hydrogen bonding.
Comparing the two alcohols (containing -OH groups), both boiling points are high because of the additional hydrogen bonding due to the hydrogen attached directly to the oxygen - but they aren't the same.
The boiling point of the 2-methylpropan-1-ol isn't as high as the butan-1-ol because the branching in the molecule makes the van der Waals attractions less effective than in the longer butan-1-ol.
Hydrogen bonding in organic molecules containing nitrogen
Hydrogen bonding also occurs in organic molecules containing N-H groups - in the same sort of way that it occurs in ammonia. Examples range from simple molecules like CH3NH2 (methylamine) to large molecules like proteins and DNA.
The two strands of the famous double helix in DNA are held together by hydrogen bonds between hydrogen atoms attached to nitrogen on one strand, and lone pairs on another nitrogen or an oxygen on the other one.
In chemistry, if you were to draw the structure of a general 2-amino acid, you would probably draw it like this:
However, for drawing the structures of proteins, we usually twist it so that the "R" group sticks out at the side. It is much easier to see what is happening if you do that.
That means that the two simplest amino acids, glycine and alanine, would be shown as:
Peptides and polypeptides
Glycine and alanine can combine together with the elimination of a molecule of water to produce a dipeptide. It is possible for this to happen in one of two different ways - so you might get two different dipeptides.
Either:
Or:
In each case, the linkage shown in blue in the structure of the dipeptide is known as a peptide link. In chemistry, this would also be known as an amide link, but since we are now in the realms of biochemistry and biology, we'll use their terms.
If you joined three amino acids together, you would get a tripeptide. If you joined lots and lots together (as in a protein chain), you get a polypeptide.
A protein chain will have somewhere in the range of 50 to 2000 amino acid residues. You have to use this term because strictly speaking a peptide chain isn't made up of amino acids. When the amino acids combine together, a water molecule is lost. The peptide chain is made up from what is left after the water is lost - in other words, is made up of amino acid residues.
By convention, when you are drawing peptide chains, the -NH2 group which hasn't been converted into a peptide link is written at the left-hand end. The unchanged -COOH group is written at the right-hand end.
The end of the peptide chain with the -NH2 group is known as the N-terminal, and the end with the -COOH group is the C-terminal.
A protein chain (with the N-terminal on the left) will therefore look like this:
The "R" groups come from the 20 amino acids which occur in proteins. The peptide chain is known as the backbone, and the "R" groups are known as side chains.
Note: In the case where the "R" group comes from the amino acid proline, the pattern is broken. In this case, the hydrogen on the nitrogen nearest the "R" group is missing, and the "R" group loops around and is attached to that nitrogen as well as to the carbon atom in the chain.
The primary structure of proteins
Now there's a problem! The term "primary structure" is used in two different ways.
At its simplest, the term is used to describe the order of the amino acids joined together to make the protein. In other words, if you replaced the "R" groups in the last diagram by real groups you would have the primary structure of a particular protein.
This primary structure is usually shown using abbreviations for the amino acid residues. These abbreviations commonly consist of three letters or one letter.
Using three letter abbreviations, a bit of a protein chain might be represented by, for example:
If you look carefully, you will spot the abbreviations for glycine (Gly) and alanine (Ala) amongst the others.
If you followed the protein chain all the way to its left-hand end, you would find an amino acid residue with an unattached -NH2 group. The N-terminal is always written on the left of a diagram for a protein's primary structure - whether you draw it in full or use these abbreviations.
The wider definition of primary structure includes all the features of a protein which are a result of covalent bonds. Obviously, all the peptide links are made of covalent bonds, so that isn't a problem.
But there is an additional feature in proteins which is also covalently bound. It involves the amino acid cysteine.
If two cysteine side chains end up next to each other because of folding in the peptide chain, they can react to form a sulphur bridge. This is another covalent link and so some people count it as a part of the primary structure of the protein.
Because of the way sulphur bridges affect the way the protein folds, other people count this as a part of the tertiary structure (see below). This is obviously a potential source of confusion!
The secondary structure of proteins
Within the long protein chains there are regions in which the chains are organised into regular structures known as alpha-helices (alpha-helixes) and beta-pleated sheets. These are the secondary structures in proteins.
These secondary structures are held together by hydrogen bonds. These form as shown in the diagram between one of the lone pairs on an oxygen atom and the hydrogen attached to a nitrogen atom:
The alpha-helix
In an alpha-helix, the protein chain is coiled like a loosely-coiled spring. The "alpha" means that if you look down the length of the spring, the coiling is happening in a clockwise direction as it goes away from you.
Note: If your visual imagination is as hopeless as mine, the only way to really understand this is to get a bit of wire and coil it into a spring shape. The lead on your computer mouse is fine for doing this!
The next diagram shows how the alpha-helix is held together by hydrogen bonds. This is a very simplified diagram, missing out lots of atoms. We'll talk it through in some detail after you have had a look at it.
What's wrong with the diagram? Two things:
First of all, only the atoms on the parts of the coils facing you are shown. If you try to show all the atoms, the whole thing gets so complicated that it is virtually impossible to understand what is going on.
Secondly, I have made no attempt whatsoever to get the bond angles right. I have deliberately drawn all of the bonds in the backbone of the chain as if they lie along the spiral. In truth they stick out all over the place. Again, if you draw it properly it is virtually impossible to see the spiral.
So, what do you need to notice?
Notice that all the "R" groups are sticking out sideways from the main helix.
Notice the regular arrangement of the hydrogen bonds. All the N-H groups are pointing upwards, and all the C=O groups pointing downwards. Each of them is involved in a hydrogen bond.
And finally, although you can't see it from this incomplete diagram, each complete turn of the spiral has 3.6 (approximately) amino acid residues in it.
If you had a whole number of amino acid residues per turn, each group would have an identical group underneath it on the turn below. Hydrogen bonding can't happen under those circumstances.
Each turn has 3 complete amino acid residues and two atoms from the next one. That means that each turn is offset from the ones above and below, such that the N-H and C=O groups are brought into line with each other.
Beta-pleated sheets
In a beta-pleated sheet, the chains are folded so that they lie alongside each other. The next diagram shows what is known as an "anti-parallel" sheet. All that means is that next-door chains are heading in opposite directions. Given the way this particular folding happens, that would seem to be inevitable.
It isn't, in fact, inevitable! It is possible to have some much more complicated folding so that next-door chains are actually heading in the same direction. We are getting well beyond the demands of UK A level chemistry (and its equivalents) now.
The folded chains are again held together by hydrogen bonds involving exactly the same groups as in the alpha-helix.
The tertiary structure of proteins
What is tertiary structure?
The tertiary structure of a protein is a description of the way the whole chain (including the secondary structures) folds itself into its final 3-dimensional shape. This is often simplified into models like the following one for the enzyme dihydrofolate reductase (DHFR). Enzymes are, of course, based on proteins.
Note: This diagram was obtained from the RCSB Protein Data Bank. If you want to find more information about dihydrofolate reductase, their reference number for it is 7DFR.
There is nothing particularly special about this enzyme in terms of structure. I chose it because it contained only a single protein chain and had examples of both types of secondary structure in it.
The model shows the alpha-helices in the secondary structure as coils of "ribbon". The beta-pleated sheets are shown as flat bits of ribbon ending in an arrow head. The bits of the protein chain which are just random coils and loops are shown as bits of "string".
The colour coding in the model helps you to track your way around the structure - going through the spectrum from dark blue to end up at red.
You will also notice that this particular model has two other molecules locked into it (shown as ordinary molecular models). These are the two molecules whose reaction this enzyme catalyses.
What holds a protein into its tertiary structure?
The tertiary structure of a protein is held together by interactions between the the side chains - the "R" groups. There are several ways this can happen.
Ionic interactions
Some amino acids (such as aspartic acid and glutamic acid) contain an extra -COOH group. Some amino acids (such as lysine) contain an extra -NH2 group.
You can get a transfer of a hydrogen ion from the -COOH to the -NH2 group to form zwitterions just as in simple amino acids.
You could obviously get an ionic bond between the negative and the positive group if the chains folded in such a way that they were close to each other.
Hydrogen bonds
Notice that we are now talking about hydrogen bonds between side groups - not between groups actually in the backbone of the chain.
Lots of amino acids contain groups in the side chains which have a hydrogen atom attached to either an oxygen or a nitrogen atom. This is a classic situation where hydrogen bonding can occur.
For example, the amino acid serine contains an -OH group in the side chain. You could have a hydrogen bond set up between two serine residues in different parts of a folded chain.
You could easily imagine similar hydrogen bonding involving -OH groups, or -COOH groups, or -CONH2 groups, or -NH2 groups in various combinations - although you would have to be careful to remember that a -COOH group and an -NH2 group would form a zwitterion and produce stronger ionic bonding instead of hydrogen bonds.
van der Waals dispersion forces
Several amino acids have quite large hydrocarbon groups in their side chains. A few examples are shown below. Temporary fluctuating dipoles in one of these groups could induce opposite dipoles in another group on a nearby folded chain.
The dispersion forces set up would be enough to hold the folded structure together.
Sulphur bridges
Sulphur bridges which form between two cysteine residues have already been discussed under primary structures.
