Blog Archive

Wednesday, 17 June 2009

A fertility network

Cell signalling: A fertility network
Nature Reviews Molecular Cell Biology, advance online publication 17 Jun 2009; doi:10.1038/nrm2721

Mammalian fertility depends on luteinizing hormone (LH)-induced changes in ovarian follicular growth. A new study now reveals some of the signalling components that effect these changes.

As oocytes mature and follicles grow, the somatic granulosa cells (GCs) in the ovarian follicle terminally differentiate into luteal cells, constituting the corpus luteum that forms after ovulation. LH induces the expression of epidermal growth factor (EGF)-like proteins, but the roles of the EGF network in LH-induced follicular changes remain undefined.

To investigate, Fan et al. created a mouse model in which the network components extracellular signal-regulated kinase 1 (ERK1) and ERK2 were depleted in GCs. These Erk1/2gc–/– mice were infertile because ovulation and the differentiation of GCs failed, although expression of positive cell cycle regulators and proliferation of GCs continued. Furthermore, whereas serum oestradiol levels rose in these mice, progesterone levels did not, because corpora lutea could not form. Therefore, GC fate decisions depend on the activation of ERK1 and ERK2 by LH and the EGF-like factors.

Of the 563 LH target genes identified in GCs of ovulating follicles, the effects of 77% were impaired in Erk1/2gc–/– cells, including those that regulate oestradiol biosynthesis. Mice with GCs that lack C/EBPβhave an ovarian phenotype similar to Erk1/2gc–/– mice, and point mutations show that C/EBPβ is a substrate of ERK1 and ERK2. These components therefore form a key signalling network in GCs, in which LH-induced signalling through EGF-like proteins activates ERK1 and ERK2 and their substrates, leading to reprogramming and terminal differentiation.

ORIGINAL RESEARCH PAPER Fan, H.-Y. et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for fermale fertility. Science 324, 938–941 (2009)
Article

Saturday, 13 June 2009

Here I Go Again...

...but not on my own.

RIGHT, I'm off on another adventure, albeit shorter and more rigorously budgeted than the last one. Rachel and I are heading to New South Wales and Western Australia for the next little while. I plan to blog from faraway fields and tell tales of experiences and local history, as you have come to expect from my gibberings.

While I fly across the globe and assemble my thoughts, I have dredged up below an assortment of blogs, comments and pictures from my previous expedition. Please do take a look if you've never seen this content before, as I cannot guarantee the quality of what is to follow!

Opera By Night


Simon Says...: Bumpy on the Bay of Bengal
Flying to Singapore; expectations; Today's Best Mix
Simon Says...: A Lizard Watched Me In The Shower!
The remarkable story of Thomas Stamford Bingley Raffles; exploring Singapore; Fire Toast
Simon Says...: Welcome to Paradise
Pulau Ubin and Chek Jawa
Simon Says...: The War The World Forgot
Changi Prison and Museum; reflections on war
Simon Says...: A Day In International Territory
How not to spend ten hours in Changi airport
Simon Says...: I'm a Natural Blue
To the Great Barrier Reef; big fish, little fish and 'Rotund' fish, apparently
Simon Says...: Never Smile At A Crocodile (ya flamin' galah!)
Conservation Volunteers Australia (CVA); Claude the Cassowary
Simon Says...: Imposter! / Interlude
Rachel fills us for me as I have lots of fun in the rainforest; notes on the Stinging Tree (the Gympie Gympie)
Simon Says...: In The Jungle, The Mighty Jungle
Cloudland Nature Refuge with CVA; teaching Koreans words like 'onomatopoeia'
Simon Says...: Steve
A man called Steve: friend of the Aborigines, discoverer of dinosaurs and guru of megafauna; safety advice for Englishmen
Simon Says...: Senoritas y Margaritas
Cape Tribulation; the discovery of Australia; Captain Cook
Simon Says...: In Memory of Kirsty
Week 2 at CVA: tree planting at Mission Beach; bush bashing with machetes; the man who liked shrimp
Simon Says...: Johnstone River Crocodile Farm
OzExperience begins; Davo the galah; a severe rant about a crocodile farm
Simon Says...: A Pinker Shade of Tanned
All at sea; sailing around the Whitsunday Islands; swimming with turtles
Simon Says...: A Fringe Of Leaves
Aborigines and Europeans; Eliza Fraser and her island
Simon Says...: What A Beauty!
Visiting Australia Zoo (Steve Irwin's zoo); wombats on leads and marvellous monotremes
Simon Says...: It's A Small World (After All)
Arriving in Sydney; run-ins with the police; coincidental meetings with school friends; a statue of a pig; chocolate by the bald man; Julia
Simon Says...: Kookaburra Sits In The Old Gum Tree
The Blue Mountains; Blaxland, Lawson and Wentworth; the story of the Three Sisters; a terrifying little train
Simon Says...: Australian Capital Territory
Arriving in Batmania (or, as we know it now, Melbourne) via the nation's capital, Canberra
Simon Says...: The Great Divide
Wandering around Melbourne; Melbourne vs. Sydney
Simon Says...: Go! Go! Go!
The Australian Grand Prix (minus racing cars, grandstands, television crews and people)
Simon Says...: Another Multicoloured Blog
Rachel fills in for me while I have a Very Nice Time
Simon Says...: Not With A Bang But A Whimper
The plight of the Tasmanian Devil
Simon Says...: Sunrise to Sunset
Reflections on the beautiful continent of Australia; onwards to New Zealand
Simon Says...: In Treebeard's Domain
Six days in New Zealand, and already I'm exhausted
Simon Says...: And In The Darkness...
Horse riding, like the riders of Rohan; Queenstown/Lothlórien
Simon Says...: Paikea
Kaikoura to Rotorua; Whale Rider
Simon Says...: Waewae takahia kia kino*
A Maori Marae and hangi feast
Simon Says...: Where Poets Speak Their Hearts
Climbing One Tree Hill with Catherine Holley; on to Fiji
Simon Says...: If You Pick A Raw Paw
The Hurricane
Simon Says...: Fifty Nifty United States
On landing three hours after taking off (eighteen hours ago); Washington DC
Simon Says...: A Is For Parrot, Which We Can Plainly See
New York in two days
Simon Says...: Perfect to Stay
The Boston Tea Party, live from Boston; coming home

GeoffSo you think you know what life is all about?I shall call him Clive
A Colony of BatfishThe shot factoryCapitol Christmas
All at seaPrettyView From The Otherside


Scorched Blue


A few follow-up posts and further stories I wanted to tell at the time:

Simon Says...: A is for Parrot (Again)
John Lennon's poem
Simon Says...: Dear Anonymous
In defence of my views on the Johnstone River Crocodile Farm
Simon Says...: Re: Not With A Bang But A Whimper
Hope for the Tasmanian Devil
Simon Says...: Sai yau levu na lotu keina lomavinaka...
A lost story from Fiji: island life on Waya Lailai; my friend Sau; "Jesus is strong in Fiji"

All images taken by me, published here.

Friday, 12 June 2009

Ah, unemployment

SO that's it. Yesterday was my last day. I am now unemployed, and will be for the next four years.

Things are now very hectic. I move out of my house today, I am going to a wedding tomorrow, and then I get on a plane to Sydney on Sunday. That means many threads I've started here will have to be put on hold. I had intended to make reference to the Jared Diamond libel case, and I had some interesting stories to share about Nikolai Vavilov and the Kazakh Beatles. It will all have to wait.

I won't be abandoning it all, however: thanks to my colleagues I have in my posession Trick or Treatment?: Alternative Medicine on Trial, a book by Edzard Ernst and, you guessed it, Simon Singh, which I will be taking on the plane.

See you on the other side.

Wednesday, 10 June 2009

Icons

TO mark its centenary, the Science Museum in London has launched a campaign to decide the greatest icon of science within its collection. The shortlist of inventions, innovations and discoveries is:

The steam engine
Stephenson's Rocket
The electric telegraph
The X-ray machine
The Model T Ford
The discovery of penicillin
The V2 rocket engine
The Pilot ACE computer
The discovery of the structure of DNA
and the Apollo 10 capsule

There are many inventions that cannot be displayed, such as the Internet, and are therefore not part of the vote. It's an interesting list to chew over, and hints at massive changes in lifestyle over the past few hundred years. The steam engine (1712) revolutionized mining and industry. Penicillin (1928) and the discovery of antibiotics transformed medicine and saved the lives of countless people. The V2 rocket (1944) threatened to change the face of history as, in the hands of the Nazis, it was pointed at us with the fuse smouldering; but it also took us into space, and without satellites many of our computer systems and communication networks would become obsolete. If so, we'd have to go back to using the electric telegraph (1837), which began to make the world a smaller place, as people no longer needed to wait months to receive messages from hundreds of miles away.

As a biologist I greatly respect the discovery of the structure of DNA (1953) by Watson, Crick, Franklin and Wilkins (albeit in a world where Franklin did all the work and received very little of the credit). It has certainly changed the landscape of modern molecular biology - it is the foundation of it all. But can elucidating the logic of a structure compare to the genius required to engineer and build Stephenson's Rocket (1829) or the first computer capable of processing more than one thing (1950)?

I simply cannot decide. Any thoughts?

Tuesday, 9 June 2009

90 minutes of pure indulgence


COURTESY of the BBC:

Keep on Running: 50 Years of Island Records

featuring pretty much every great band ever

Sunday, 7 June 2009

Nerds rejoice!

Previous posts on Simon Singh:


Hurrah! Simon Singh has decided to appeal.

Consequently, Sense About Science have launched a campaign, targeted at the UK Government, to fight the ability to use libel to silence scientific discussion. "We the undersigned believe that it is inappropriate to use the English libel laws to silence critical discussion of medical practice and scientific evidence" begins the statement. This was initially signed by 100 notable people from the worlds of science, journalism, publishing, entertainment, literature and law, including MPs from the three major political parties in the UK, the Astronomer Royal and the Poet Laureate, the UK's former Chief Scientific Advisor, and the likes of Stephen Fry, Professor Richard Dawkins FRS, professors and eminent scientists from around the world, and, brilliantly, Derren Brown. Oh, and my boss.

The campaign has allowed the story to break into the mainstream media. Articles have now appeared in New Scientist, Nature News, The Times, The Independent and The Observer. As Jack of Kent points out, however, Singh's decision to appeal is not an automatic right and may not be accepted. The increased publicity can only be a good thing, however, whether it is too late for Singh or not.

Frustratingly, reading blogs and comments around the Internet, there are many who still do not understand this case. Particularly, chiropractors and practitioners of other alternative medicines have kicked up an almighty fuss, and understandably so. But this is no longer an attack on them. We are not protesting their professions. Chiropractic, homeopathy, aromatherapy et al. work for many, and long may they be allowed to do so*. What was initially protested was their right to make claims with reference to health (particularly children's health) without evidence. The general public can be misled, dangerously, by this. This has now become a protest of free speech - Simon Singh pointed out the lack of evidence, and instead of producing it (which would have been a more than acceptable reponse) the British Chiropractic Association (BCA) sued him for libel. They bullied him into silence. If there is evidence, then they should produce it - it is as simple as that. Furthermore, we are not asking for the abolition of libel - people do make defamatory remarks and there must be a system to hold them accountable. It just shouldn't be a bent law that is widely abused and globally infamous. Chiropractors have protested that they are not being allowed to speak freely... which is odd, because that's exactly what we are asking them to do.
"The libel laws discourage argument and debate and merely encourage the use of the courts to silence critics.

The English law of libel has no place in scientific disputes about evidence; the BCA should discuss the evidence outside of a courtroom. Moreover, the BCA v Singh case shows a wider problem: we urgently need a full review of the way that English libel law affects discussions about scientific and medical evidence."

This case is important. 10,000 signatories agree. Please sign the petition here, and tell everyone you know to do the same.


*Whether they are scientific or not.

The Incredible Human Journey... goes on

THERE has been a lot of great programming from the BBC recently. A few weeks back Bill Bailey took us on his Remarkable Guide to the Orchestra in his typical abstract style, including a hilarious rendition of The Swan from the Carnival of the Animals on alpine cow bells, and the William Tell Overture, Cockney style*.

Next came South Pacific, a natural history documentary covering the wildlife, geography and anthropology of the islands in the world's largest ocean, from Macquarie Island south of New Zealand up to the equator and beyond. The programme is beautifully shot, with slow motion images from inside waves, panning shots of penguin-infested beaches (the elephant seals weren't very happy about that) and images of tame eels, leaping out of freshwater pools to eat scraps provided by Solomon Island villagers. It is a little repetitive, but doesn't suffer from an overly slow pace, like I always felt Blue Planet did. Besides, it is presented by a man called Benedict Cummerbund (sorry, Cummerbatch), which can never be a bad thing.

And then they went to Anuta.

Meanwhile, straight after South Pacific in the listings is The Incredible Human Journey, in which "Dr Alice Roberts, medical doctor and anthropologist" follows and investigates the possible route of human migration out of Africa, following "in the footsteps of our ancestors". Each episode teaching a little of what we know about the ancestry of our species throughout evolution and the possible ways in which we inhabitated every corner of the planet.

The Incredible Human Journey is a good programme, for what it is trying to achieve, but it is very easy to criticize. Not least because it is the television programme that I always wanted to make. For a long time I have wanted to travel this route, investigating and telling the tale of humankind along the way and experiencing some of the hurdles that we as a species would have experienced. My journey would have started somethere like Hadar in Ethiopia, where Lucy, the fossil of an Australopithecus afarensis, was found. I'd have seen some of the major African sites for anthropology, including Lake Turkana in Kenya, the Ethiopian Omo Valley (the Omo flows into Lake Turkana) and the Olduvai Gorge in Tanzania, home of the Laetoli footprints, and then proceeded north. (Dr Alice Roberts, medical doctor and anthropologist, starts her journey at Omo Kibish in the Omo Valley, where the oldest primitive human remains have been found, dating to - possibly - 195,000 years ago.) I hadn't really worked out how I would cope with passing through modern day Sudan, and how I would cope beyond Arabia when some populations proceeded into Europe and others populated Asia. What I knew for sure, however, was that I was definitely going to go to Teshik-Tash in Uzbekistan, the supposed Eastern boundary of Neanderthal migration. However, Dr Alice Roberts, medical doctor and anthropologist, and the BBC beat me to it, although promisingly she doesn't seem to be actually doing the journey itself, but popping up at key sites along the way, and there's a lot she has missed out. Nonetheless, she does get to travel the world, the lucky thing.

So, given that I wanted desperately to make this programme, I watched episode one in a somewhat cynical frame of mind.

Her journey starts in "one of the most remote parts of the continent". She says this while driving a car. On a road. Later in the programme she spends a night in the bush to portray the dangers of how primitive humans would have lived. But she doesn't have a night vision camera, so all we see is her illuminated face, and all we hear is her complaining about the noises of the night:

"Did you hear that? I'm scared now! Is that a lion? Is that a leopard? Is that a hyena? Oh I don't like that. That's really spooky."

There's a lot of padding in this programme. It is also a little bit predictable: in the Australia programme, I knew she was heading to Mungo before she'd even said it. The science isn't brilliant too - in fact it is entirely lacking: we hear the conclusions only, the programme makers apparently concerned that telling us the theory behind the truth would be off-putting, but I find the opposite. It is wrong to just accept conclusions without understanding where they come from, and this form of presenting is patronising. "Geneticists working for this programme have been able to calculate..." Yes, but how?

But, these are probably minor quibbles amplified by my jealousy of Dr Alice Roberts, medical doctor and, you guessed it, anthropologist. In truth it is a good programme, and I learnt a lot from it. It has been a few years since my human evolution teaching and quite some time since reading Humankind Emerging, and there are great gaps in my knowledge, gaps that this programme was able to fill, at least in part. Such gaps include the Africa-Israel vs. Africa-Yemen debate. So, overall, well done the BBC, although grrr, and indeed, arg.

But at the start of her quest to find Omo Kibish, Dr Alice Roberts, insert qualifications here, wanders into the local village, and enlists the help of the Nyangatom.

And here we find my concern.

Both the Nyangatom and the residents of Anuta have been the subject of the BBC programme Tribe, one of my favourite shows, in which Bruce Parry spends a month with indigenous communities to learn and experience their culture first hand. He lives with a family in these communities and does everything that they do. At those times, unless I have been fooled by TV magicland, these tribes were remote, and relatively unused to western influence and presence. It therefore concerns me when a new film crew visits these people to record again. Roberts just waltzes straight in and asks to borrow two guides (Parry had to ask for permission to even enter the village). South Pacific showed new footage of the same topics that Tribe's Anuta programme covered - so why not use the old footage? Instead, a new crew, however small, visited Anuta. Even with the best intentions, these new visits will slowly have negative impacts on the traditional way of life. Repeated contact is bad for the preservation of society. It might not be immediately devastating, but in my view it is sufficiently bad. This saddens me, because I would love to follow in the footsteps of people like Parry. The BBC are not to be held accountable for this, as I am sure many other crews have visited similar places and had similar effects. My point is, the appearance of a television crew cannot be allowed to become something ordinary and familiar to these people.





*including "Have a Banana!"

Saturday, 6 June 2009

Bricks and mortar

AND then the sun came out, if only for a while, scorching the land and catching the majority of folk off guard. The Underground had to play recorded warning messages about carrying water and having a sit down if feeling unwell; sun lotion went flying off pharmacy shelves; and high street shops emptied as people flocked to the parks.

A couple of weekends ago I was up in Birmingham for Rachel’s belated birthday celebrations, an extended weekend of good food, lots of time in the park and the excellent new Star Trek film. On the Saturday, as various friends went back to Selly Oak on the train, Rachel’s sister, her boyfriend Gary and I opted instead to walk back along the canal. It was a glorious day, and the canal is a good way to cut through the city but remain away from the bustle of a bank holiday city centre.

The canal follows the train line, past the Botanic Gardens and through leafy Edgbaston, past the university halls of residence and then the university itself before reaching Selly Oak. If you were to stay with the canal it would head past Selly Oak hospital, which resembles Shawshank prison, and then directly to the Cadbury factory in Bournville. Where it goes beyond that I can only wonder.

We started our walk at Gas Street Basin, formerly a junction between the Worcester and Birmingham Canal and the Birmingham Canal. Nowadays the barrier between the two no longer exists and the intermediary toll gates have also been removed. Gary knows the basin well, having finished here after one of his many walks in the past. He had to admit, however, that the sight of the basin, the biggest canal basin in Birmingham but still not much to shout about, was somewhat of an anticlimax after hours of counting down the milestones promoting this mythical end of the line. Nonetheless, just seconds from Broad Street and minutes from the city centre, the change in pace down by the water is worth savouring, no matter how small the basin is. From here we were off to the Mailbox, now home to fashionable shops, restaurants and overpriced inner city apartments, aesthetically unpleasing with their numerous, postmodern and pointless appendages and trendy colour contrasts. I find the Mailbox a bewildering place, as it oozes wealth and yet is bordered by derelict car parks and decaying office blocks. The contrast continues elsewhere: Gary has walked the canals out to Solihull, where he tells me the canal path has been repaved and the waterside environment modernized, but it remains in the shadow of dilapidated warehouses.

As we left the ultra-modern we returned to the classic canal landscape, all brick with vegetation creeping through cracks. A weed with a tumorous growth; specimens of the plant that bloke on the telly said is better than dock leaves at soothing nettle stings; and longboat captains dipping their hats in salute to the passer by.

Two days later I was on a train, taking the scenic route back to London. The Moor Street to Marylebone line is a hidden gem of England. It is slower than the Virgin line from Euston to New Street but it passes through some of the best countryside on offer: the Chilterns. But at the Birmingham end it is a whole other landscape entirely, as the track weaves through a maze of disused and abandoned train lines, coated with weeds and opportunistic plant life. Old siding tunnels become independent business, but with the rusting train tracks still in place. Old embankments and brick elevations remain, creating isolated pockets of the city beneath, but stop when they reach a major road: nobody has felt the need to dismantle these relics of a bygone age of the train, and yet they now become useless and derelict obstacles to regeneration. It is a captivating world, and one I hope will remain for a long time. Peculiar how we despise decay of that that remains functional, but enjoy the sight of a derelict and abandoned landmark.

***

The story goes on. As you can tell, my spirits are lifted when the weather shows this world in all its glory. Sunshine on my shoulders, as the song goes, makes me happy.

Tuesday, 2 June 2009

First draft

I'M writing a second (and probably final) highlight for Nature Reviews Molecular Cell Biology before I leave - this one based on possibly my least favourite topic in biology. Try as I might, I've never got my head around ovulation! Here's my first draft, based on this reference. Suggestions for improvements and a title would be welcome.

---

Mammalian fertility depends on luteinizing hormone (LH)-induced resumption of oocyte meiosis, ovulation and luteinization. Fan et al. now reveal some of the signalling components that effect these changes.

As oocytes mature and follicles grow, somatic granulosa cells (GCs) in the ovarian follicle differentiate into luteal cells, constituting the corpus lutea that form after ovulation. LH induces the expression of epidermal growth factor (EGF)-like proteins, but the roles of the EGF network in LH-induced follicular changes remain undefined. To investigate, Fan et al. created a mouse model in which the network components extracellular signal-regulated kinase 1 (ERK1) and ERK2 were depleted in granulosa cells. These so-called Erk1/2gc–/– organisms were infertile and ovulation and differentiation of granulosa cells failed - although proliferation of these cells and the expression of positive cell cycle regulators continued. Furthermore, whereas oestrogen levels rose in these mice, progesterone levels did not, because corpus lutea could not form. Therefore, granulosa cell fate decisions depend on ERK1 and ERK2.

How are these effects manifested? Of the 563 LH target genes in mice, the effects of 77% were impaired in Erk1/2gc–/– cells, including those that regulate oestrogen levels. Mice with granulosa cells that lack CCAAT/enhancer-binding protein-β (Cebpb) share an Erk1/2gc–/–-like ovarian phenotype, and point mutations show that CEBPβ is a substrate of ERK1 and ERK2. These components therefore form a key signalling network in granulosa cells, in which LH-induced signalling through EGF-like proteins activates ERK1 and ERK2 and their downstream substrates, leading to reprogramming and terminal differentiation. Further understanding of the roles of ERK1 and ERK2 in ovarian function will aid our knowledge of fertility.

Fan, H.-Y. et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for fermale fertility. Science 324, 938–941 (2009)

Edit 07/06/09 as requested: the DOI link for this paper - doi:10.1126/science.1171396

Friday, 29 May 2009

Comment is free

I HAVE been aware for some time that I never get any comments on the posts that I put up here. But because I have focused so much on what I have been trying to say and on making things look pretty, I never once noticed that this could be because there is no button for you to press to leave a comment.

There should, according to my settings, be a little link at the bottom of every post stating the number of comments and directing you to a commenting page. The peculiar thing is that this DID once exist, because I got a snotty little comment once about my criticisms of the Johnstone River Crocodile Farm, and another snotty comment telling me that the Dutch, not the Portugeuse, first discovered Australia. Criticism is healthy, although positive comments are also appreciated.

After delving into settings I didn't know I had I seem to have rescued the function to add comments, but that little link at the bottom of every post is still missing in action.

So, since comment is free and discussion is marvellous, please do feel free to join in with my adventures as normal service is resumed.