Life of a Lab Rat

If you're a scientist then you've probably heard of Nature Precedings,

a place for researchers to share pre-publication research, unpublished manuscripts, presentations, posters, white papers, technical papers, supplementary findings, and other scientific documents. Submissions are screened by our professional curation team for relevance and quality, but are not subjected to peer review. We welcome high-quality contributions from biology, medicine (except clinical trials), chemistry and the earth sciences.

Turns out, from a comment made by Hilary Spencer over at Jennifer Rohn's weblog, that pre-publication research includes stuff that didn't work.

I am eyeing my thesis, curiously and thoughtfully.

One of the great things to come out of the internet phenomenon is RSS. If you don't know what RSS is by now, you've probably got someone to print this off for you so I'm not going to bother explaining.

As I've mentioned previously, RSS makes it ever so simple to keep up to date with my favourite journals.

I realized that Trends in Biochemical Sciences, a review journal that I remember fondly from my graduate days, is not in my feed. So I tootle off to Google, find the website (spit, Elsevier) at ScienceDirect and click on the Article feed button:

Which leads directly to a custom 404 page saying Feed? What feed?

Come on people. It's two thousand and bloody eight. This isn't, never was, rocket science.

Thank goodness for BaRf.

We know that most scientists can't write to save their lives. The root of the problem is deep-seated.

But when you get missives from the University (or its agents) saying things like

Date sensitive computer applications such as calendars will be impacted during the period between the new and original transition dates. Therefore, all systems need to be adjusted to reduce the impact of the 2008 transitions and eliminate issues in future years.

you might be forgiven for throwing up your hands and in the towel.

Here's a clue. Colons get impacted, as do wisdom teeth.

Read on, for the full horror, but be warned: Your inner editor will die.

I do most of my literature reading via the built-in RSS aggregator in Safari. It looks something like this:

I find it convenient and useful. However, I have noticed a disturbing trend.

Whenever I see the word 'Retraction' in that list, I have an almost irresistible urge to click on it. I don't care about the scientific field or the content, nor even the authors or institute:

Retraction — click.

It's almost Freudian. Help me, please.

Yes, I've been away, so this isn't exactly timely, but seeing as I previously drew your attention to a minor furore over citation indices, I should probably also link to the open source free alternative.

Declan Butler writes in detail about the SJR on the Nature website, although he forgets to actually link to it. Which is a bit suss, but hey.

And from this bit of news you may now calculate that I'm 20 days behind my reading (at least according to my RSS reader). Considering I was only away for 15 that's pretty good going. Ahem.

The Journal of Cell Biology has a scathing editorial on the reliability (and utility, actually) of impact factors.

This database appeared to have been assembled in an ad hoc manner to create a facsimile of the published data that might appease us. It did not.

And the killer?

Just as scientists would not accept the findings in a scientific paper without seeing the primary data, so should they not rely on Thomson Scientific's impact factor, which is based on hidden data [...] we hope that people will begin to develop their own metrics for assessing scientific quality rather than rely on an ill-defined and manifestly unscientific number.

There is a somewhat unsatisfactory response by Thomson, that completely misses several points, not least those of transparency and reproducibility.

We all knew that impact factors were crap anyway. Now we just have to convince the funding bodies.

Here's a fantastic Christmas present:

The Journal of Cell Science is making its entire scanned archive freely available online. One hundred and fifty years of cell biology.

Lots of holiday reading there. Some interesting factoids in Fiona's editorial, too:

One eminent director of The Company of Biologists suggested we should simply call the new incarnation Cell – rightly, this was deemed an inappropriate title for a serious academic journal.

Har har — it's a laugh a minute in this business.

You've probably heard how Jimmy Wales is talking up Wikipedia, the encyclopaedia where any— no, we've done that joke already.

Wikipedia has introduced a system of peer review, as if this solves anything. The problem is with the word 'peer'. If articles were guaranteed to be edited by people who know what they're talking about, then it would be fine. But you have no such guarantee, and in esoteric subjects (much of science, for example *cough*) you can not be sure that another student (a 'peer'), for example, is not deliberately falsifying entries to steal a march on the competition. Paranoid, moi?

You betcha.

As my friend Mark puts it:

I am not in favour of citing Wikipedia as an "authority", if by this we mean using it as a means of establishing points without any further discussion. I encourage my students, who are preparing for examinations at the moment, to engage critically with a range of secondary sources, one of which may indeed sometimes be Wikipedia.

And of course, with access to a University library, there is no excuse for not critically reviewing the primary literature, and doing your own fact-checking.

One of the things that we are learning in the doing of Science is that, fundamentally, all things are interconnected . Nowhere is this more apparent than in the familiar Central Dogma, the formation of protein from DNA through the intermediation of RNA.

For years the textbooks have viewed this process in three, discrete steps:

1. Transcription (DNA -> pre-mRNA)
2. Processing (pre-mRNA is capped, spliced, tailed and exported from the nucleus)
3. Translation (RNA -> protein)

Although we have long believed that these events happen almost simultaneously to any given 'message' in bacteria, the confounding presence of the nucleus has led us to believe that the same steps in real cells are spatially and temporally distinct. It turns out that this view is untenable.

Not only do bacteria have a nucleoid, the structure of which can influence gene expression in much the same way as eukaryotic chromatin, but the process of transcription-processing-translation in eukaryotes is much more coordinated than was once thought. Capping and splicing seem to be simultaneous with transcription, and export from the nucleus is similarly coupled to transcription and splicing.

Naturally, you only want your ribosomes to see to capped, spliced and polyA-tailed mesenger RNA, which then must be prevented from returning to the nucleus (see Ratcheting mRNA out of the Nucleus by Murray Stewart, and references therein). But how to do this?

The first thing you can do is let everything out of the nucleus, look for stuff that hasn't been correctly spliced &c. and destroy it. A more efficient method, and the one that the cell seems to favour, is to stop incorrectly (or incompletely) processed RNA from getting exported in the first place:

There is a nuclear pore-associated protein called Mlp1 that retains intron-containing RNA, i.e. unprocessed mRNA, at the nuclear pore. This binds to something called Nab2, that in turns binds RNA itself and the mRNA export factor Gfd1 .

Nab2 is potentially a marker for 'mature' (processed and export-ready) mRNA. It has a compact N-terminal domain (i.e., at the start of the protein sequence) that despite looking like a well-characterized RNA-binding domain actually is necessary and sufficient for binding to Mlp1.

By using my NMR structure (left) as a starting point for molecular replacement, Murray was able to solve the phase problem for the 1.8Å dataset obtained from crystals of it. Furthermore, a single mutation in the middle of the domain, that did not negate its binding to Gfd1, completely knackers binding to Mlp1 (much thanks to the yeast people in Atlanta).

So know we have another little piece of the RNA export puzzle. You can read all about it (and what the reviewer said).

Science is supposed to be pretty. Not a lot of point in doing it, otherwise (for a range of values of 'pretty', at least).

So I was first pleased when I saw that an editorial Nature Cell Biology talked about the visual aspects of our work, and then disappointed when there were no accompanying pictures or movies to illustrate the point. Moreover, the link to 'further reading', which I clicked upon with great glee and haste, is empty.

Muppets.

Anyway, I got an email from Laura at the EMBO Journal last night. They are running a cover art competition;

The editors of The EMBO Journal are pleased to announce a new contest to select the best cover image for 2008.

As in the previous years, one winner will be selected from each of the two categories: Best Scientific Cover and Best Non-Scientific Cover. The prize for both winners will be a free one-year print and online subscription to both The EMBO Journal and EMBO reports.

This is a fantastic opportunity to indulge the artistic side of your scientific temperament. It's a shame that no one outside science will probably ever see your work, and the prize is hardly something that will appeal to someone with institutional access, but that's just quibbling. The closing date is 18 January 2008. Get snapping.

My paper was accepted by JMB today. Woohoo!

This is the one about which reviewer #2 said

the work [...] is of premier experimental and conceptual quality and a role model of how to rationally combine structural biology with molecular biology and biochemistry

so I'm just the teeniest bit chuffed.

It's all gone a bit George Smiley.

Peter is concerned about the American Chemical Society (ACS), as well as PRISM, Open Access, and stuff like that. I left a comment on his weblog recently, and from there I think someone at the ACS must have stumbled across the Labrats, because I have a received a second spam email from them, with yours truly in the 'Bcc:' — but this time 'To:' is someone at the NOAA.

My mystery correspondent begins

Dear Colleague and Friend,

Several of you contacted me
about a memo from Judith L. Benham which claimed that the American
Chemical Society is not protesting Open
Access in order to preserve profits and bonuses for the Society's executives.

S/he kindly attached the memo, and continues (I should make explicit that I am quoting from an email. These are the mystery author's opinion and claims, not mine),

Let me assure that I was not involved with last week's memo which is riddled with multiple misdirections typical of a slick political commercial. The most obvious falsehood is this passage: "Our Society's position is also represented by the Association of American Publishers, a non-profit organization whose membership encompasses the major commercial and non-profit scholarly publishers, including ourselves. ACS is not alone among scholarly publishers in reaching out to...."

The statement comes apart once you know the names of the players involved.
The position of the AAP was developed by Brian Crawford, who is chairman of
their scholarly division . Brian Crawford is also head of publishing at ACS. Big surprise.

So what we have are two organizations speaking from the same mouth.

This allows for clever gamesmanship by ACS executives..
Just last year, Rudy Baum wrote his second editorial in Chemical & Engineering
News where he called Open Access "socialized science."[1]

To buttress his argument, Rudy cited--who would have ever guessed!?--the Professional
and Scholarly Publishing Division of the Association of American
Publishers, which "has taken a strong stand" against the Open Access bill.

Rudy also wrote that the AAP's scholarly division had written letters to
senators opposing the bill.. What Rudy forgot to disclose to his
readers is that the letters were signed by the chairman of the AAP's
scholarly division, who is Brian Crawford, also head of publishing at
ACS.[2] Crawford is now apparently Rudy's boss.

Yes, Baum is that ridiculous. But it must be hard for a man to fully inform
readers when his wallet tugs at his conscience. Oh...it gets better.

Brian Crawford holds up his end of the bargain by penning letters against
Open Access on behalf of the AAP, such as the letter last year to the Los Angeles
Times. Brian wrote, "government bureaucracy continues to impede
participation and undermines the successful expansion of information access."
Crawford's byline was credited: "The writer chairs the executive council of the
professional and scholarly publishing division of the Assn. of American Publishers..[3]

I guess that Brian forgot to mention to the Los Angeles Times
that he is also a publishing executive at the American Chemical
Society. He might also have troubled editors with the minor fact that
his bonuses will plummet if ACS publishing profits drop..

So now you see how their political campaign against Open Access works.
First, Crawford creates the policy position at AAP's scholarly division; ACS
executives then point to AAP policy for cover with their members. But it is all a shell game that
quickly falls apart once anyone spends five minutes on Google. Links to the
appropriate information can be found [embedded by BK]. Look for yourself and have a giggle.

And just to prove that we're on the same team, a cheery wave goodbye

I hope everyone has a smashing week! Please keep sending in your emails with links and other bits of information that you find on the internet. And see the wiki for further information. It is only by demanding that ACS leadership becomes more accountable to members that we will see change.

Sincerely,
ACS Insider

No doubt the emails are flying today, because the US is, as I write this, about five hours from waking up, and it's a big day for Open Access over there:

URGENT CALL TO ACTION: Tell your Senator to OPPOSE amendments that strike or change the NIH public access provision in the FY08 Labor/HHS appropriations bill

not that we in the boonies can do anything about it, except maybe tell our friends.

Oh, and naturally, I will continue to report any further developments.

I have a friend who works in the medical communications industry. He has an interesting pharmaceutical perspective on the Open Access debate, which is well worth a read.

Peter has been getting rather agitated about Open Access and a publishing industry response — which demonstrates that it really is all about the money for the publishers.

I was going to weigh in and be scathing and witty, but I have a headache and I see that Alethea has beaten me to it, by linking to a wonderfully surreal piss-take.

I have been whining about Wikipedia, the free encyclopedia where you can write any old rubbish.

The major problem I have with the project is its assumed authority. It is treated as a reliable source by, I guess, most of the population. The problem is that if you're looking something up in an encyclopedia then the chances are you don't actually know much about the subject, and therefore can not tell if your source is correct.

Those of us who have some knowledge about some things are shocked to find that Wikipedia is often wrong about our speciality. And then we become very worried because we have no idea if this failing extends to things we know little, or nothing, about. But it is safe to assume that it does so extend. This is not just restricted to Wikipedia of course: I have read a few stories in newspapers (national and local) where I have had insider knowledge about the reported event. And approximately half of the statements of fact in those stories are just plain wrong.

This does not seem to concern the editors of Wikipedia. They are more worried about due process than truth. So if you are looking up something on Wikipedia, your assumption that the author of the article and the editors know anything about what they are talking about is false. All you know is that the article has been written and edited in accordance with some rather arbitrary principles. These arbitrary principles, rather than verifiable truths, are the authority upon which Wikipedia is based.

Now, this would not be a problem, except that increasingly, students and professional scientists are turning to Wikipedia for answers. And people are writing their own websites based on Wikipedia articles. It is a house built upon sand, and we, as publicly-funded scientists, are failing the public if we do nothing about it. Ian points out that it is not worthwhile to write or correct articles, because in some frenzied pomo notion of fairness and equality facts and evidence count for nothing, and the 'wikizombies' (thanks Ian!), with their 'citation needed's and 'balance' and due process 'liberate' (which my thesaurus has as an alternative for 'pillage') scholarship from antiquated notions of 'truth' and 'verifiability'.

Evil triumphs if good people do nothing. So what do we do?

The problem with, say , a 'professional' wiki-type encyclopedia is that the people who we would want to contribute are those who are probably the busiest in their field, doing experiments and writing papers and raising grants and teaching students (who contributes most to Wikipedia? Those with most time on their hands. Hmm). So what we need is some kind of payback to entice scholars to write scholarly articles. Scientists are attracted by the prospect of cold, hard cash, or publications they can put on their CV. The former would mean that any such project would have to cost money to use (let's not even think about advertising revenue), which defeats the purpose of a free resource. We do have something close to this, in HowStuffWorks.com, but again, where is the authority?

So what about a peer-reviewed WikiScipedia? Jenny suggested that contributors should have "a PhD from an accredited university and a current and credible scientific affiliation". That would be a nightmare to organize, and does not get around the quis custodiet ipsos custodes?[0] problem. Peer review works (mostly) for scientific journals, and is where textbooks (eventually) get their authority. Any scientist could contribute; all would be invited to write articles aimed at a reasonably educated (but pre-Bachelor's) adult, but all articles are reviewed by experts in the field. Articles could fall under 'Cutting edge' or 'Established dogma' categories. Maybe there should be two sections; a 'pending review' area where anyone could write/edit and an 'authoritative', peer-reviewed section. And while we're at it, let's at least have pseudonymous if not completely nonymous peer review, so that there is accountability and partisan conflicts can be avoided. And did I say it would be free access?

It would be invaluable to school children, and could also go a long way to increasing the level of scientific literacy in the general population (hey, if you're going to dream, aim high).

It would be hard work to get going, but no more so than any other learned journal. Contributors would be able to cite articles on their CVs, and funding agencies, who are increasingly waking up to the whole communicating with the public idea, should also be happy. We'd need a sponsor to get going, ideally a publishing house already committed to the principle of Open Access, with a competent editorial team that has marketing oomph and a sufficiently large and diverse scientific address book.

Oh, hullo Nature. Doing anything tonight?

Just over a month ago I wrote about Elsevier Reed funding arms fairs. On my return from the lab retreat (very nice, thank you for asking) I find an email saying

Reed Elsevier announced today that it is to exit the defence exhibitions sector. This portfolio of five shows is part of Reed Elsevier’s global Business division and represents around 0.5% of group annual turnover.

Sir Crispin Davis says

[I]t has become increasingly clear that growing numbers of important customers and authors have very real concerns about our involvement in [arms fairs. They] are no longer compatible with Reed Elsevier's position as a leading publisher of scientific, medical, legal and business content

Dear BK,

Anumber: Something really interesting (version 2.0)

I am delighted to advise that we are able to accept your manuscript for
publication. Many thanks for your work on this article.

Your article will pass on to the Production team, who will send you PDF
proofs via email before the article is published online. We will also
notify you when the article is published, and you will then be able to
register for six months complimentary access to the whole of ELS.

On behalf of the ELS editorial team, thank you for your contribution and
interest in ELS.

Kind regards,

Martine

Dr Martine Bernardes Silva
Assistant Editor, Encyclopedia of Life Sciences

You'd have thought that simple questions like "How many genes contain X-type domains?" or even "How many X-type domains are there?" would have been easy to answer, what with the Human Genome Project et al.

Oh hum.

So I'm supposed to be updating an article for the Encyclopedia of Life Sciences. The article is about a certain class of protein domain. After a look through PubMed I googled $PROTEIN_DOMAIN for literary inspiration and realized that $PROTEIN_DOMAIN has a Wikipedia article all to itself.

Oh dear.

I knew Wikipedia was a bit suspect, and laughed out loud at the spoof published in The Register. But now I'm in a position to actually know something about a Wikipedia entry, I'm shocked. The first two sentences, if not actually wrong, are viciously misleading. The first paragraph concludes with another howler. I gave up at that point, except to note how mercifully short the article is and that the author has written another crappy article and re-used the same figure.

The really disturbing thing is that many, many Google searches come up with a Wikipedia article in the first couple of hits. This has distressing implications. I am moved, therefore, to send a friendly warning to Cagéd readers: I am on the Honours Assessment panel this year. Students in the Cage thinking of using Wikipedia as a reference tool should familiarize themselves with the phrase excretus est ex altitudine. Always, always check your sources.

Mind you, in my quest for inspiration I find that some of the more 'learned' websites make similar errors, which is rather disturbing. I'm sure we've all got examples of textbook howlers: Please feel free to post some in the comments. I think I'm in need of a good laugh.

I read

Organ size is limited by the number of embryonic progenitor cells in the pancreas but not [. . .]

in my RSS aggregator and am desperately, desperately trying to avoid the obvious joke question. Because that would be crass and juvenile and I am a mature, sensible and respectable (if not actually very well respected) scientist.

Ahem. Just who do I think I'm fooling?

The mechanism of alternative splicing in normal and diseased states is perplexing.

Sakharkar et al. In Silico Biology 4, 0020 (2004)

Well, yes. That is exactly why I was looking it up.

<sigh>

I have a confession to make.

My name is Black Knight, and I am an RSS junkie. Ever since most of the journals started using RSS instead of email alerts (there are a couple of honorableannoying exceptions) —

the strangest thing has just happened. I was in the process of checking my facts (I was going to say, Company of Biologists, I'm looking at you) when I stumbled across an RSS aggregator with the rather unsavoury moniker BaRF. And this site aggregates new publications from what looks like most of the journals that are relevant to my research, and provides handy bite-sized RSS feeds (via PubMed, it would appear).

Yes, it is useful to have certain search terms as an RSS feed within PubMed but that is no substitute for at least skimming the titles of articles in each new journal issue. BaRF has just made this a whole lot easier.

You know you've been here too long when your RSS aggregator displays

and your first thought is not 'FLICE-associated huge protein, what a cool name for a protein and I wish I worked on apoptosis', but 'What the hell is Flash doing in PNAS?'

Aw mate. I read the paper and I must say I'm disappointed.

In one of my previous lives I pretended to be a crystallographer.

In other words, I would attempt to persuade concentrated protein solutions to get together and form ordered three-dimensional arrays - crystals - so that I could then shoot X-rays at them. The purpose of this was to determine their structure.

One of the things I was taught when I learned crystallography was to be very, very clean. No dust, human hair, bits of glass or other muck were allowed into the experiment. The most frustrating thing about crystallography is that all proteins are different, and will crystallize (if they crystallize) under different conditions, and there doesn't seem to be any pattern to this at all. The lab's insistence on cleanliness was an attempt to factor out one of the variables in the process. But I soon discovered that this may have been counter-productive. As with a lot of things in research, people disagreed with each other and there was a lot of intuition and opinion without a great deal of solid evidence. I realize that this might come as a surprise to some of you, to those who, perhaps, believe that 'scientists deal with facts'. The truth is that at the frontiers of science we don't know what's going on and we're trying to find out - that's why it's called 'research'. If you want facts, look in a text book (and they all contain mistakes, too).

So as I went on and got more experienced, I began to welcome small amounts of crud in my crystallization experiments. In fact, one recalcitrant protein only ever crystallized once, along what looked like an insect leg. I was never able to repeat that experiment; although I did have gothic fantasies about breeding every different sort of insect I could find and using various bodily insect parts as nucleants. A little too Shelley, perhaps.

Hot from Nature, we have Nature Protocols: Recipes for Researchers.

It's in beta, I'm getting a few 404s and the registration/sign in was weird (stealth login, anyone?) but it could be useful. One of those 'wait and see' projects I feel, and probably in direct competition with the protocols section of the OpenWetWare thing I wrote about last week.

What's interesting to me is that these are peer-reviewed methods, with user comments. So it's almost a Wiki-meets-journal type of thing. Hmm.