Like science?

April 30, 2013

Like science and the progress and prosperity it brings the UK? Then sign the pants off this bad boy. http://ow.ly/kyyQ7 #sivpoint8


POP QUIZ – What’s this?

April 16, 2013
Erm...

What the hell is this thing?

A little game – What the hell is this thing? Take a guess in the comments below – the red blobs are me deleting labels that might have given it away.

The prize is kudos, the admiration of your peers, and a life time subscription to this blog. šŸ˜‰


#QEDcon 2013 ISS passes

April 9, 2013

Information shamelessly lifted from meteorwatch.orgĀ and metcheck.com.

Friday Night (12th)

  • 21:43-21:48 – “Incredibly Bright” – cloud cover 23%

Saturday Night (13th)

  • 20:52-20:59 – “Incredibly Bright” – cloud cover 99% šŸ˜¦
  • 22:29-22:32 – “Incredibly Bright / Short pass” – cloud cover 100% šŸ˜¦

Sunday Night (14th) (forĀ theĀ stragglers)

  • 21:39-21:44 – “Incredibly Bright” – cloud cover 94% šŸ˜¦

So… Friday night it is then, caveats about weather forecasting notwithstanding. If we can drag ourselves out of the bar for 5 minutes.


[Journal Club] – “Identification of a central role for complement in osteoarthritis”

April 3, 2013

In a little experiment, I’m going to do a journal club style blog post. I’m going to look at a paper, explain why I like it, and how I think it could be improved. If you like it, “like it” and I may do more.Ā 


The paper I am going to look at is “Identification of a central role for complement in osteoarthritis” by Wang et al, published in Nature Medicine in December 2011. [PUBMED|PDF|F1000] I chose this because it is a pretty big paper in myĀ field, and it is a damn good paper (but it is not without flaws).

The paper explores the hypothesis that the complement immune system is involved in the development of osteoarthritis (OA) (a degenerative disease of our joints).

The authors show that the presence of markers of complement activation in samples from (human) patients, such as “C3a des arg” and “C5b-9” (the membrane attack complex), correlate with osteoarthritis (fig1 b&c).

The membrane attack complex (or MAC) is the final step of the complement immune cascade, and is a complex of proteins that in high levels punches holes in cells and kills them.

They also show that patients with osteoarthritis make more complement activating proteins and less complement inhibiting protein in the synovium of their joints when compared to healthy patients (fig1 e).

Having demonstrated a correlation between complement activation and osteoarthritis in human samples, WangĀ et al go on to explore this in mouse models of arthritis.

They show that if you knockout the genes for complement components C5 and C6 in mice (preventing the formation of the MAC), these mice develop less severe arthritis (as measured by cartilageĀ degradation) in surgically-induced arthritisĀ (fig2).

The also show that in mice lacking CD59, a natural inhibitor of complement, cartilageĀ degradationĀ is more severe.

These genetic models support the authors’ hypothesis that complement activation might enhance osteoarthritis progression/severity.

ā€¢Mice that canā€™t ACTIVATE MAC have LESS cartilage damage in OA models
ā€¢Mice that canā€™t REGULATE MAC have MORE cartilage damage in OA models

They then show in human chondrocytes (cartilage producing cells)(in cell culture) that extracts of arthritic cartilage or certain proteins (such as fibromodulin) known to be over-produced in arthritis can induce the production of the MAC.

And they show that low (“sub-lytic”) levels of MAC can make normal chondrocytes (but not C5 deficient chondrocytes) produce proteins known to degrade cartilage, such as ADAMTS-4 and -5, but also some Matrix MetalloProteases (MMPs).

Again, this observation supports the hypothesis that complement activation (that culminates in MAC formation) can induce osteoarthritis.

All in all, a very comprehensive paper, and a fantastic piece of work, and I’ve deliberately ignored some parts of the paper to simplify the story.

There are however, a few chinks in the armour.

1) All mice models of arthritis were surgical models – i.e surgery was performed on the mice that caused them to develop arthritis. No “sham-surgery” controls were performed (or if they were, they weren’t mentioned, which seems odd).

Given that it is known that surgery can induce complement activation, this control absolutely should have been done.

Other models of arthritis (such as proteoglycan induced arthritis) were not explored.

2) They should have looked for the products of ADAMTS induced cartilage degradation in the arthritis mice. Antibodies that recognise the breakdown products (so-calledĀ “NITEGE”) are available and could be used in immuno-histochemistry to see if/where ADAMTS-mediated cartilage damage isĀ occurring. (H/T to Jen in our lab who pointed this out).

3) None of the subjective cartilage degradation scoring was blinded. This is a potential source of bias.

I still think that the hypothesis explored in this paper is a good one, and that complement activation is almost certainly part of the complicated puzzle of osteoarthritis pathology, but ideally I’d like to see a follow-up paper that included some of these extra experiments.


[PODCAST] – Me on Dessert Lionel Discs

March 21, 2013
Damn good coffee, and hot!

Damn good coffee, and hot! (Photo credit: photojenni)

Self promotion, dead ahead!


I have been fortunate enough to have been interviewed by @AstrondrewĀ ofĀ Ā Sound of ScienceĀ for episode 5 of the Dessert Lionel Discs podcast šŸ˜€

In it I talk about how I got into science, who inspired me to do science, and what exactly I do as part of my day job. I also talk Pink Floyd, Crystals, Twin Peaks and damn fine coffee.

Please listen, and I hope you enjoy!


Ice crystal forest.

March 18, 2013

image


[TALK] Studying Life at a Molecular Level!

March 3, 2013
Caffeine. One of nature's many triumphs.

Caffeine. One of nature’s many triumphs.

ATTENTION GOOD PEOPLE OF LIVERPOOL!

I am talking about how we understand what we understand about the molecular nature of life!

It will be just like “Wonders of Life” but with less silhouettedĀ  pointing up a mountain, and more pictures of molecules and crystals and me.

The talk is on Tuesday 12th March, 2013 at the Hope Street Hotel, on Hope Street, in Liverpool – doors open at 730pm.

There is a facebook event page here. See you there.