I've been getting down to business writing my PHYS3900 pop science article on the contributions of physics to fluorescence microscopy (following on from my last post about nanodiamonds). Whilst reading about quantum dots I came across a `review' from Science Magazine and thought it was such a nice informative piece that I should post it here. It is quite readable and interesting without drowning in technical details (although there is a time and place for technicality!).
Quite briefly, quantum dots are small semiconductor structures which support delocalised electronic excitations, meaning that they can be fluorescent. The delocalisation ensures that the energy levels are determined by the size of the dot, rather than the atomic energy levels, so emitted light can take on a wide range of colours (no two dots are quite the same yet because they are self-assembled). They are attractive as fluorescent markers because of this property.
Drawbacks include cytotoxicity (ranging from severe to negligible, depending on the materials) and blinking (intermittent loss of fluorescence activity due to electron trapping).
I also found out that it is possible to make blue fluorescent nanodiamonds by coating them with a hydrophobic film.
My completed article will be posted soon!
Thursday, 8 September 2011
Thursday, 1 September 2011
Consequences of the R^4 term in Hagen-Poiseuille relation
I seem to recall from last weeks class discussion that we found dividing a metabolic system into subsystems had an associated cost (a result of the B=kM^3/4 scaling law.) Implicit in this scaling law (as we saw in BIPH2000) are the properties of the circulatory system. In Chapter 5, Nelson uses the Hagen-Poiseuille relation of show that while two pipes with the same cross-sectional area doubles the flow of a single pipe (no surprise there), a single pipe with double the cross-sectional area has 4 times the flow, due to the R^4 term. Thus the relative about of energy needed to "drive" the flow (i.e. establish the pressure differential) will be less for larger pipes. This is perhaps the underlying physical cause for the cost of dividing a metabolic system.
[Not a fully formed idea but I thought I'd put it out there for discussion.]
[Not a fully formed idea but I thought I'd put it out there for discussion.]
Sugar Abuse
It's the wee hours of the morning and ScienceDaily has caught my eye yet again. What a treasure trove of weird and wonderful articles.
Asa Mackenzie is an associate professor of neuroscience at Appsala University who recently led a study on mice with inactive VGLUT (Glumate transporters), sugar and cocaine. Imagine that - mice doing blow.
As we all know, the brain has it's own way of rewarding us when we do exercise or if we eat something delicious etc - it gives us a good feeling. This good feeling is associated with the release of the neurotransmitter, dopamine. Illicit drugs can take advantage of this system and that's why (theoretically) is feels good to take drugs - "get high". Howoever, in comparison to the brain's rewards, cocaine etc, has effects which are too strong, and this gives rise to addiction.
Dopamine has been observed to co-signal with glutamate (which is transported via VGLUT). As previously mentioned, mice which didn't have VGLUT (as well as the usual control group) were put on nutritious diet of sugar and cocaine. The study yeilded the following results: the mice with inactive VGLUT ate more (sugar and cociane, that is), and their memory show a huge increase in regards to places in the study environment associated with getting the sugar and cocaine. The non-VGLUT mice also showed hypersensativity (to the stimulants(?)) and their levels of dopamine showed a decrease.
The research is significant in opening the door to future studies between VGLUT and its relationship with addiction. (Mackenzie, 2011)
It occurred to me while reading this that the part about the mice remembering where to get their goods made complete sense - obviously crack addicts know where to go get their fixes, otherwise they wouldn't have, and ergo, wouldn't be crack addicts. Furthermore, I'm interested to know how mice in general would react to stimulants such as cocaine and amphetamines - simultaneously cruel and hilarious. No mention of sugar-only, cocaine-only test groups were apparent in the source.
I read a book quite a while ago on sugar metabolism in the human body. While there are regulatory mechanisms to regulate the amount of fats and carbohydrates ingested, no such system exists to monitor sugar intake, as sugar (in the form we know it today, table sugar) in nature appears in such small concentrations, and is therefore supposed to comprise a minuscule portion of our diet. Could this absence of a regulatory mechanism possibly contribute to enabling an addiction to sugar?
One hopes not to see seedy crack smoking mice wobbling out of dark alley ways, noses bleeding with bags of table sugar in hand.
As we all know, the brain has it's own way of rewarding us when we do exercise or if we eat something delicious etc - it gives us a good feeling. This good feeling is associated with the release of the neurotransmitter, dopamine. Illicit drugs can take advantage of this system and that's why (theoretically) is feels good to take drugs - "get high". Howoever, in comparison to the brain's rewards, cocaine etc, has effects which are too strong, and this gives rise to addiction.
The research is significant in opening the door to future studies between VGLUT and its relationship with addiction. (Mackenzie, 2011)
 |
| Cocaine |
 |
| Sucrose - table sugar |
One hopes not to see seedy crack smoking mice wobbling out of dark alley ways, noses bleeding with bags of table sugar in hand.
Moves aside St.John's Wort
I came across this recently and thought it tied in nicely to a discussion we had in a BIPH meeting a few weeks ago, while Seth was absent, regarding mind-altering drugs for the treatment of depression/anxiety/ADHD.
 |
| Lactobacillus rhamnosus |
Canadian researchers from the Alimentary Pharmabiotic Centre in University College Cork, and the Brain-Body Institute at McMaster University have recently uncovered from their clinical studies of feeding mice probiotic bacteria, Lactobacillus rhamnosus JB-1 (which is found as a preservative in many yoghurt products and has a high immunity against strong acids found in the gut), that levels of the hormone corticosterone, which is stress induced, were notably lower than those of mice in the placebo group.
 |
It was also found that the stress-related and anxiety and depression-related behaviours were reduced in the trial group. Other results included noticeable changes in the GABA neurotransmitter receptors when mice were fed the probiotics on a regular basis. ( Bravo & Cryan, 2011)
The findings highlight pathways of communication between the gastrointestinal tract and the brain, and is significant in possible developments of microbial treatments of anxiety or depression (Cryan, 2011) The changes in GABA neurotransmitter receptor expression is significant in highlight the direct influence of the probiotics on brain chemistry.
The communication between the microbes, the gastrointestinal tract and the brain is referred to as microbiome-gut-brain axis. Future studies on this network may open the door for probiotic treatment of more psychiatric illnesses and disorders. (ScienceDaily, 2011)
.svg) |
| Serotonin |
I found this very interesting, considering the nature of current treatments for anxiety and depression, such as SSRIs (selective serotonin re-uptake inhibitors) or SNRIs (Serotonin Norepinepherin Re-uptake Inhibitors), which essentially inhibit the re-uptake of serotonin (or norepinepherin) resulting in a higher extracellular concentrations of the either neurotransmitter, so more is actually in the synapse to be able to bind to the postsynaptic receptors.
So the concept of using the microbiome-gut-brain axis for treatment effectively means that the receptors will be altered instead of the neurotransmitter concentrations.
Wednesday, 31 August 2011
Nanodiamonds for Biological Imaging
This week I am away because I am attending the IQEC CLEO Pacific Rim conference in Sydney (international laser physics, optics and quantum optics conference). This morning I went along to a talk (by one Varun Sreenivasan) about imaging within live cells using colour centres in nanodiamonds, and thought it was rather interesting and neat. The basic concept is to replace organic dyes and fluorescent proteins with luminescent diamonds!
Diamonds naturally contain some concentration of impurity atoms which are captured during formation of the crystal. For artificial diamonds, usually synthesised by methane vapour deposition or detonation of an explosive compound, the principle impurity is nitrogen. If the crystal is irradiated with ionising radiation (gamma or alpha particles in particular) carbon atoms are displaced from the crystal, leaving vacancies: at high temperatures these are able to diffuse. If a vacancy is `captured' by a nitrogen impurity (which are covalently incorporated into the crystal) the new compound entity is referred to as a NV centre.
NV centres are neat because they essentially behave like an atom. By this I mean that they have transitions which are in the optical frequency range, allowing for optical detection of the centres. Specifically, excitation in the green (533nm) gives fluorescence in the red (630nm). They also have an interesting electronic structure in that, instead of singlet ground and excited states with a triplet intermediate, they have triplet ground and excited states with a singlet intermediate. A singlet state involves two electrons with a total spin angular momentum of zero, for a total of one spin projection state, whereas the triplet has net spin one, so has three spin projection states. This means that the NV centre has interesting spin properties which can be exploited for imaging and magnetometry (as it turns out, they might also be useful in nanothermometry and single-spin sensing, or miniaturised NMR/MRI!).
The advantages of NV nanodiamonds over traditional fluorophores are threefold. Firstly, the nanodiamond is very inert chemically and biologically, meaning that they are not cytotoxic or carcinogenic like existing options. Secondly, the surface chemistry of nanodiamonds is flexible, so that there are opportunities to attach specific proteins, functional groups or the like to them. Finally, the nanodiamonds are small, bright and quite photostable: they do not bleach under continued exposure, like a fluorescent protein, or blink (have irregular variations in emission intensity) to the same extent as a quantum dot (it is thought that reduced blinking in NV diamonds is because electronic excitations are localised to the NV site, whereas in a quantum dot the excitation is delocalised across the whole dot).
This presentation concerned labelling nanodiamonds with somatostatin (a regulator which interacts with GPCRs to help drive blood pressure homeostasis) to cause specific cells to endocytose them. The way in which this was done was to use a `lego-like' approach that can be readily extended to other functionalising groups/compounds/regulatory molecules. Rather than rely on covalent attachment or weaker adsorption, a protein-protein interaction was used to attach molecules to the crystal surface. The proteins barstar and barnase interact quite strongly (for a non-ionic, non-covalent bonding interaction) and `clip together', forming the basis of a method allowing attachment of different compounds to the diamond surface. This is quite stable and can be extended relatively easily to a variety of compounds of interest.
When somatostatin binds to the cell membrane of the target and initiates endocytosis the entire diamond is drawn inside (these are 30-40nm in size, although many people are now looking at sizes of 4-5nm) and the three-dimensional position of the crystal can be tracked. In the presence of a magnetic field the spin-field interactions mean that even the orientation can be tracked! Another talk expanded on this... but I will leave that for another time!
As a final comment: I thought it was impressive that the body will actually renally clear these nanodiamonds so long as they are below 8nm in length!
The whole idea is quite interesting and provides a neat quantum/biology interface too. Watch this space!
Diamonds naturally contain some concentration of impurity atoms which are captured during formation of the crystal. For artificial diamonds, usually synthesised by methane vapour deposition or detonation of an explosive compound, the principle impurity is nitrogen. If the crystal is irradiated with ionising radiation (gamma or alpha particles in particular) carbon atoms are displaced from the crystal, leaving vacancies: at high temperatures these are able to diffuse. If a vacancy is `captured' by a nitrogen impurity (which are covalently incorporated into the crystal) the new compound entity is referred to as a NV centre.
NV centres are neat because they essentially behave like an atom. By this I mean that they have transitions which are in the optical frequency range, allowing for optical detection of the centres. Specifically, excitation in the green (533nm) gives fluorescence in the red (630nm). They also have an interesting electronic structure in that, instead of singlet ground and excited states with a triplet intermediate, they have triplet ground and excited states with a singlet intermediate. A singlet state involves two electrons with a total spin angular momentum of zero, for a total of one spin projection state, whereas the triplet has net spin one, so has three spin projection states. This means that the NV centre has interesting spin properties which can be exploited for imaging and magnetometry (as it turns out, they might also be useful in nanothermometry and single-spin sensing, or miniaturised NMR/MRI!).
The advantages of NV nanodiamonds over traditional fluorophores are threefold. Firstly, the nanodiamond is very inert chemically and biologically, meaning that they are not cytotoxic or carcinogenic like existing options. Secondly, the surface chemistry of nanodiamonds is flexible, so that there are opportunities to attach specific proteins, functional groups or the like to them. Finally, the nanodiamonds are small, bright and quite photostable: they do not bleach under continued exposure, like a fluorescent protein, or blink (have irregular variations in emission intensity) to the same extent as a quantum dot (it is thought that reduced blinking in NV diamonds is because electronic excitations are localised to the NV site, whereas in a quantum dot the excitation is delocalised across the whole dot).
This presentation concerned labelling nanodiamonds with somatostatin (a regulator which interacts with GPCRs to help drive blood pressure homeostasis) to cause specific cells to endocytose them. The way in which this was done was to use a `lego-like' approach that can be readily extended to other functionalising groups/compounds/regulatory molecules. Rather than rely on covalent attachment or weaker adsorption, a protein-protein interaction was used to attach molecules to the crystal surface. The proteins barstar and barnase interact quite strongly (for a non-ionic, non-covalent bonding interaction) and `clip together', forming the basis of a method allowing attachment of different compounds to the diamond surface. This is quite stable and can be extended relatively easily to a variety of compounds of interest.
When somatostatin binds to the cell membrane of the target and initiates endocytosis the entire diamond is drawn inside (these are 30-40nm in size, although many people are now looking at sizes of 4-5nm) and the three-dimensional position of the crystal can be tracked. In the presence of a magnetic field the spin-field interactions mean that even the orientation can be tracked! Another talk expanded on this... but I will leave that for another time!
As a final comment: I thought it was impressive that the body will actually renally clear these nanodiamonds so long as they are below 8nm in length!
The whole idea is quite interesting and provides a neat quantum/biology interface too. Watch this space!
Special Mould
I remember when one of the pipes in the kitchen leaks, I always turn to epoxy to seal the leaking area. Now imagine this being applied in a real human body. A new heat-sensitive gel and glue combo has been introduced in the realm of cardiovascular surgery,. The special mould enables blood vessels to be reconnected without puncturing and sticking a needle and thread into it. The reason behind the creation of this substance is the difficulty to suture minuscule (~ 1 mm wide) blood vessels.
The process of the discovery of the glue is as follows:
"Sutures work by stitching together sides of a blood vessel and then tightening the stitch to pull open the lumen, or the inner part of the vessel, so the blood can flow through. Gluing a vessel together instead would require keeping the lumens open to their full diameter — think of trying to attach two deflated balloons. But dilating the lumen by inserting something inside introduces a wide range of problems, too.
The process of the discovery of the glue is as follows:
"Sutures work by stitching together sides of a blood vessel and then tightening the stitch to pull open the lumen, or the inner part of the vessel, so the blood can flow through. Gluing a vessel together instead would require keeping the lumens open to their full diameter — think of trying to attach two deflated balloons. But dilating the lumen by inserting something inside introduces a wide range of problems, too.
Gurtner initially thought about using ice to fill up the lumen instead, but that meant making the vessels extremely cold, which would be too time-consuming and difficult on the operating table. He approached an engineering professor, Gerald Fuller, about using some kind of biocompatible phase change material, which could easily turn from a liquid to a solid and back again. It turned out Fuller knew of a thermo-reversible polymer, Poloxamer 407, that was already FDA approved for medical use.
Working with materials scientists, the team figured out how to modify the polymer so that it would become solid and elastic when heated warmer than body temperature, and would dissolve into the bloodstream at body temperature. In a study on rat aortas, the team heated it with a halogen lamp, and used the solidified polymer to fill up the lumen, opening it all the way. Then they used an existing bioadhesive to glue the blood vessels back together.
The polymer technique was five times faster than the traditional hand-sewing method, the researchers say. It even worked on superfine blood vessels, just 0.2 millimeters wide, which would not work with a needle and thread. The team monitored test subject rats for up to two years after the polymer suturing, and found no complications."
Based on stem cell research, I don't see why it wouldn't come into this discovery as well.
Source:
http://www.popsci.com/science/article/2011-08/new-gel-glue-method-rejoins-cut-blood-vessels-better-stitches
Subscribe to:
Posts (Atom)