Saturday, 14 January 2012

Bacteria can sense you're stressed!

Yep, they can! At least there seems to be a link between stress levels and infection.
One of the main hormones that is released in the body under stress is adrenaline. This helps bring about a Fight or Flight response, with effects such as an increase in heart rate, bronchodilation, and that unpleasant sensation of suddenly getting a dry mouth. These effects are due to adrenaline binding to receptors on different target cells (i.e. heart muscle cells, smooth muscle cells in the airways, or salivary glands) and triggering a signalling cascade within those cells, which initiates the responses seen.
Bacteria have been found to have adreceptors too (i.e. receptors that bind adrenaline). This means that invading bacteria should be able to detect adrenaline in the body as a response to stress. The question that poses itself now is: "How does adrenaline influence bacterial behaviour?" Unfortunately for us, they seem to love it! Bacteria use a method called Quorum Sensing to communicate to each other and assess their population density, as well as regulate the expression of virulence genes. It is thought that adrenaline is one of the hormones released by the human body that influences this mechanism by enhancing it and increases the bacteria's ability to replicate at the site of infection.
This is not only important in the field of medicine, where drugs developed to block adrenoceptors in bacteria may provide a way of combatting antibiotic resistance, one example of bacterial virulence, but also in the food industry, where the method of slaughter and animal keeping may play a role in increasing adrenaline levels in the muscle, which would make the meat more susceptable to bacterial colonisation.
This is just one of the many pathways that may be involved in the development of bacterial disease, and icreased susceptability to infection may well be due to the interplay and crosstalk between these pathways. But that's what makes it so fascinating!
So the next time your job gets you stressed or the kids are playing a bit too loudly, think about the bacteria that might be loving your high adrenaline levels ... on second thoughts - don't - that might make you even more stressed! :)

References:


http://www.pnas.org/content/100/15/8951.abstract?ijkey=6ccaada220c61e2c45a5c80d2cb7439e00291a50&keytype2=tf_ipsecsha

Wednesday, 11 January 2012

Use of Foetal Tissue Grafts in Treatment of Parkinson's

Research into Embryonic Stem cells has gone so far that foetal tissue has actually been implanted into Parkinson's patients' brains, the results however, have not been conclusive. The first studies that were conducted transplanting human foetal tissue were started in 1987 (1) and have been continued to this day. The type of implanted tissue has been varied to find the type of foetal tissue that would most efficiently survive in an adult brain as a Dopamine-secreting neuron. The foetal tissue is most often obtained through elective abortions, where mothers who want to have an abortion consent to the foetus being used in the study after abortion has taken place (2,3). I have not found a study that used surplus IVF embryos as tissue graft source.
When I heard of this the first time, I felt like something turned around inside me. I know the principle is similar to organ donation after a person has died. But an embryo cannot "consent" to its tissues being used for research or the treatment of another person's illness. The question that is even more important though is "Where does Human Life begin?" Does it begin at conception, which would be the most logical answer, or at somepoint later on? Maybe once a human form has begun to be visible? The potential to form each one of us was stored up in that single fertilized egg. I don't want to judge the women who have had abortions, no doubt their position is a very difficult one and I only hope to imagine some of the pressures that must be faced by them. I just want to remind us all of the immense value of a human life, be it contained in a fully developed human like you and me, or in an undeveloped human seen in a fertilized egg. 
Please feel free to comment - I would very much like to see your point of view!

References:


(1) Lindval O, Björklund A (2004): "Cell Therapy in Parkinson's Disease" in The American Society for Experimental NeuroTherapeutics 1(4): 382-393 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC534947/

(2) Kordower J H, Freeman T B, Snow B J, Vingerhoets F J G, Mufson E J, Sanberg P R, Hauser R A, Smith D A, Nauert G M, Perl D P, Olanow C W (1995): "Neuropathological Evidence of Graft Survival and Striatal Reinnervation after the Transplantation of Fetal Mesencephalic Tissue in a Patient with Parkinson's Disease" in The New England Journal of Medicine 332: 1118-1124 
http://www.nejm.org/doi/full/10.1056/NEJM199504273321702#ref16=&t=articleMethods

(3) Strömberg I, Almqvist P, Bygdeman M, Finger TE, Gerhardt G, Granholm A, Mahalik TJ, Seiger A, Olson L, Hoffer B (1989): "Human Fetal  Mesencephalic Tissue Grafted to Dopamine-Denervated Striatum of Athymic Rats: Light- and Electron-Microscopical Histochemistry and in viva Chronoamperometric Studies" in The Journal of Neuroscience 9(2): 614-624 

Monday, 9 January 2012

Calcium Signalling - truly marvelous!

I am currently revising for my upcoming exams and one of the topics we have covered this semester is Calcium Signalling. Calcium is a metal ion that is essential for the correct functioning of a huge range of cellular processes.
Maybe the most well-known of these is its importance for muscle function. In this case, Calcium binds to a molecule called troponin, leading to the movement of protein fibres called myosin and actin, creating a contraction of the muscle cell.
Calcium at high levels in the cell is toxic however, as it readily binds phosphate to create nonsoluble Calciumphosphate, the main constituent of kidney stones. So how does the cell generate levels of Calcium that are high enough to initiate the response it needs without endangering itself?
This is where a collection of clever mechansims come into play: The cell's Calcium-control Toolkit, so to speak. There are molecules called Buffering Proteins that bind and effectively mop up any Calcium they come across. Another type of molecule involved is the Plasma Membrane (i.e. Cell Membrane) Calcium ATPase (or pump). This uses energy to pump Calcium out of the cell. Another such pump, the SERCA, pumps Calcium from the cytoplasm (the inner environment of the cell) into the ER or SR (these are a type of organelle, i.e. membrane-bound compartment, found in any normal cell and specifically in muscle cells, respectively), where the Calcium is stored.
These two organelles play an important role in the control of Calcium Signalling. When a certain type of hormone binds onto a receptor on the cell surface, a signalling cascade (involving the Phosphoinositol pathway) takes place that releases the molecule IP3. And tata tata - the ER (i.e. the afore mentioned organelle that stores Calcium) has a receptor for IP3! Binding triggers the release of the stored Calcium. Now comes the really clever part: some signalling pathways rely on large Calcium waves sweeping through the cell, instead of only local increases in Calcium. Once Calcium has been released by the ER, that Calcium itself can then initiate further release from the ER, which can initiate further release, which initiates further release, which ... you get the picture. It's awesome! :) Once the cell realises there is much too much Calcium in the cell, the release stops and the Toolkit come into play again to decrease the Calcium level to resting state.
This Calcium wave is central to the fertilization of an egg cell: once the first sperm enters the egg, a Calcium wave like this is triggered and the increase in Calcium across the whole cell initiates the formation of a protective protein envelope around the fertilized egg, preventing any more sperm from entering. It also starts off the fertilized egg on the route of development! Isn't it amazing that each one of us started developing from a single fertilized egg cell into who we are today because of this amazing mechanism involving a humble metal ion???!!

References


Berridge MJ, Lipp P, Bootman MD (2000): "The Versality and Universality of Calcium Signalling", Nat Rev Mol Cell Bio 1: 11-21