Thursday, 31 May 2007

Your brain is weird

If you thought quantum mechanics was weird, you haven't seen weird yet.

It's common knowledge that the human brain is probably the most complex system that evolution has produced to date. For (as far as we can tell) the first time in evolutionary history, life is able to turn its curiosity right back at itself and ask the most ridiculous questions ever asked on this planet: "How did I get here?", "How can I make green pigs?", and most importantly, "Why am I even asking questions?". The very endeavour seems almost paradoxical; we are trying to use brains to figure out how brains work.

Absurdity aside, the weirdness goes far beyond just boring philosophy, and well into the realm of useful things (i.e. science). Neuroscientists have been peering into the brains of unsuspecting mice, monkeys, and even humans, and as with pretty much any hard scientific problem, all they have come up with is just more and harder questions. Here are some of the weird things going on inside your brain:

  • There are an estimated 10,000 different types (or sub-types) of neuron. We, of course, have no clue how the diversity arises, but our best guess is that the mechanism is something analogous to the V(D)J mechanism in antigen receptor diversity of the immune system. Also, there appears to be some sort of selection mechanism, once again much like in the immune system, whose function we have very little clue about.
  • Your brain is a mosaic of euploid and aneuploid neurons (aneuploid cells have more or less chromosomes than the "normal" 23 pairs). Depending on the region of the brain, aneuploidy varies from 10% up to 50%. Aneuploidy has generally been associated with diseases such as Down's syndrome and cri-du-chat syndrome, but since studies on mice brains in 2001 by Rehen et al., all evidence has shown that there are aneuploid neurons in healthy mammalian brains. Only vague speculation is provided as to why this is the case, and it is generally that differential levels of gene expression between cells increases the complexity of the brain, contributing to behavioural variability.

  • LINE-1 retrotransposons seem to play a significant role in neuronal differentiation. L1 activity is kept at bay in neural stem cells by Sox2, but its downregulation seems to trigger several events that bring about differentiation. Subsequently, L1 insertion sites seem to be most commonly found near or in genes related to neuronal function, even though insertions are generally uncommon. This suggests that L1 insertion may be regulated and that neuronal development may lean heavily on insertion events.

These are just a few of the extremely unusual properties of brain cells. You can read about the above in more detail and discover even more neuronal weirdness in Muotri & Gage (2006). We still, of course, have no clue whatsoever where that bloody engram is.

Wednesday, 30 May 2007

'Green-turning-red spots' movie- world premiere

Once upon a time scientists didn't know how proteins where trafficked and changed along the Golgi apparatus. Some argued they were transported in vesicles from one type of cisterna to the other, where they were differently altered by different resident proteins. Others argued that the cisternae themselves were mobile and could become the next cisterna in sequence by the retrograde trafficking of the required enzymes... There was much pain and confusion, and the scientists were not happy. Until one day one group of scientists decided to see if little green dots on cells could become red. And they could. Everyone was happy, and they lived happily ever after...

--> The moment of truth- when green becomes red- and our understanding of life, the universe and everything changes...

As Dr Gareth Evans has put it, on the email that kindly provided the link to this movie:

'You can then get the popcorn in and enjoy the show! (obviously you'll also enjoy the fantastic educational benefits of a green spot changing to a red spot) '
For all of you poor children who have not been in his lectures (or who may have fallen asleep):
Basically a protein specific of cis cisterna (Man-6-P receptor) was labelled with GFP while one from trans cisterna (ARF proteins) was labelled with dsRed. The fact that a single cisterna changes colour indicates that are the enzymes that trafick between cisterna changing proteins, rather than proteins to be changed that trafick to different cisterna.

The original reference: Losev et al., (2006). Golgi maturation visualized in living yeast, Nature, 441. 1002-6

Tuesday, 29 May 2007

What is an ORF?

An open reading frame (ORF) is the DNA sequence between a start codon (ATG) and a stop codon (TAA, TGA and TAG). A long ORF suggests it could be a protein coding gene. In prokaryotes, like everyone’s fav bacteria E. coli, they are usually 1000base pairs so making a protein of about 350 amino acids. Many short ORFs are present and even some long ones may not make a protein. Even when quiet positive that an ORF makes a protein (codon bias is correct etc) we may not know what it does. It could only be expressed in a situation that cannot be replicated in the lab. Of course everything becomes more complicated in eukaryotes like us! Our ORFs are interrupted by introns so between the start and stop codon extra start and stop codons may be present in the intron so finding genes are a lot more difficult. So sequencing cDNAs (mRNA made into DNA) can show us where genes are in the genome. We can match up sequences from cDNAs (like ESTs) to the genome and find genes. This could show up pseudogenes so we need to check the gene is expressible.

So this blog is a place for us to talk about allsorts but all we know anything is about is biology so I suppose it will be mainly about that. It is an ‘open’ place to talk about it (get the pun, open…yeah I know I’m funny).

Osteoclasts are cool

Right, so this blog was needing a post... but as I should be writing an essay rather than playing with the computer it is a small one. Basically in a tutorial last week one of the guys talked about osteoclasts and ostebolasts. As you clever folks probably know, the osteoblasts are responsible by forming the bone while the osteoclasts eat it up. An equilibrium between the two is required, as excess of osteoclasts means less bone and an excess of osteoblasts means an extra-calcified bone- in any case, the bone becames brittle and more easily breaks. Any therapy to prevent osteoporosis is complicated by the fact that they normally tend to target osteoclasts... which besides eating up the bone also secreted components that promote osteoblast development, in order to guarantee the normal equilibrium (that allows bone renovation).

Really interesting, however, are the photographs below.

In this photo you can actually see the contact between an osteoclast. Osteoclasts produce hydrogen ions that acidify and dissolve the bone surface, as well as hydrolytic enzymes

My favourite one, which I cheesily baptized of osteoclast at breakfast, basically shows an osteoclast with some similarities to a snail- leaving behind not a trail of mucus but rather of eaten bone.

Finally, there is a movie of an osteoclast. Not extremelly interesting (it cannot beat the green-turning-to-red spots of Gareth Evans) but at least it shows that osteoclasts are motile (note that it has been speed up 100 times) and have multiple nuclei: