Latest Article Alert from BMC Public Health

The latest articles from BMC Public Health, published between 16-Dec-2012 and 23-Dec-2012

For articles which have only just been published, you will see a ‘provisional PDF’ corresponding to the accepted manuscript.
A fully formatted PDF and full text (HTML) version will be made available soon.

Indigenous populations health protection: A Canadian perspective
Richardson KL, Driedger MS

Latest Article Alert from Breast Cancer Research

The latest articles from Breast Cancer Research, published between 08-Dec-2012 and 22-Dec-2012

For research articles that have only just been published you will see a ‘provisional PDF’ corresponding to the accepted manuscript. Fully formatted PDF and full-text (HTML) versions will be made available soon.

Hiding in plain view: the potential for commonly used drugs to reduce breast cancer

RCUK & Gold OA: Counting the Needless Doubled Costs

In Gold Open Access: Counting the Costs, Ariadne 70 (2012), Theo Andrew points out some of the prominent problems with Gold OA costs and RCUK policy, but he misses some of the most important ones:

RCUK stated that Gold OA is the preferred mechanism of choice to realise open access for outputs that they have funded and have announced the award of block grants to eligible institutions to achieve this aim. Where a Gold OA option is unavailable, Green OA is also acceptable; however, RCUK have indicated that the decision will be ultimately left up to institutions as to which route to take.

Theo states the policy correctly but fails to point out that as it stands, the policy is self-contradictory:

1. RCUK prefers Gold.

2. Choosing Green is acceptable where Gold is unavailable.

3. Institutions are free to choose Green or Gold.

So is or isn’t the choice of Green unacceptable where Gold is available? Is or isn’t the fundee free to choose Green?

RCUK has since grudgingly conceded, in supplementary statements, that the institution and author are still free to choose Green or Gold even when a journal offers both; but RCUK have still stubbornly refused to fix the official policy wording, which continues to state that Green can only be chosen if the journal does not offer Gold, rather than simply: Fundees may choose Green of Gold. Perhaps this incoherence and ambiguity is left in so as to bias confused authors and institutions toward RCUK’s preferred choice…

There is a general expectation that over time APCs will settle to a reasonable rate and similarly journal subscriptions will lower to reflect the gradual change in business model from subscription fees to APCs.

General expectations, and speculations. (Whose? and on what evidence are they based?) But meanwhile, if the expectations and speculations are wrong then RCUK authors are being pushed toward an unreasonable APC rate and subscriptions will not lower.

APCs and subscriptions are worldwide matters and the UK only produces 6% of worldwide research.

And if the goal of the RCUK policy is Open Access to UK research, rather than to test expectations and speculations with UK research funds, then RCUK need only have mandated Green.

But in any case, UK researchers, if they can see through the RCUK policy’s formal double-talk, can comply by choosing to provide Green OA without paying any APCs. Moreover, the PCs (sic) (publishing costs) are already being paid, in full — by (worldwide) subscriptions.

Much of this transition period to full open access will have to be navigated through uncharted territory, where no one has a clear handle on the costs involved.

Yes, the transition to Gold OA is indeed uncharted; moreover, the destination is a global one. It is not at all evident that the UK is in a position to steer the world on this uncharted course by unilaterally conducting its expensive and heavy-handed experiment — or it is merely needlessly wasting a lot of scarce UK research money to double-pay publishers.

The most likely outcome of the experiment, however, will be that the vast majority of UK researchers choose Green rather than Gold.

And if RCUK does not implement a mechanism for monitoring and ensuring compliance with the Green OA option, the RCUK mandate will not even generate Green OA.

(All compliance considerations are so far focused on how to spend the Gold funds, and what to do when they run out; not a word yet on how to ensure that Green is actually provided, when chosen.)

[E]ven with guaranteed funding from HEFCE, and other funders of research, large research-intensive universities will not be able to pay for all of their research to be published under Gold OA.

And here is an instance of this blinkered focus on how to spend HEFCE Gold: If researchers and their institutions manage to read through the RCUK double-talk, they will see that what they can do if the HEFCE Gold subsidy runs — or even while the HEFCE funds are still available to double-pay publishers — is to choose to provide Green OA, at no extra cost in APCs.

(Please recall that the UK and the rest of the world are still paying for publication costs, in full, via subscriptions; and that those subscriptions cannot be cancelled until and unless that journal content is accessible by another means: That other means is Green OA.)

“[There is] a positive correlation between APCs and impact factor

And a moment’s reflection will show that the causality underlying that correlation cannot possibly be that paying more money for APCs raises articles’ citation counts! Obviously the journals with the higher impact factors are charging higher APCs.

[P]ublication in hybrid journals (n=185) was significantly more popular than publishing in full OA journals (n=75). This may be due to the fact that there are more hybrid journals to publish in?. the average APC cost for hybrid journals was £1,989.79 compared to £1,128.02 for full OA journals ? a difference of £861.77.

Of course there are more established journals that have offered hybrid Gold OA as an option (cost-free double-earners for them, super-easy to offer) than there are new start-up Gold OA journals. And of course it is the established journals that have the track-record for quality, rather than new start-ups.

And obviously a track-record for quality is more “popular” with authors than a pig-in-a-poke.

What’s not obvious is why any author would prefer to pay their journal-of-choice for hybrid Gold OA, when they can provide Green OA at no cost.

But that is precisely the practice that the RCUK OA policy was meant to have remedied, by mandating Green (with effective compliance ensurance) rather than throwing money needlessly and pre-emptively at Gold while PCs (sic) are still being paid, in full — by (worldwide) subscriptions.

Research-intensive institutions are likely to be hit twice; since they publish more articles and more frequently in higher-impact journals, their share of Gold OA bills is likely to be disproportionally larger.

This is Theo’s biggest oversight: Productive institutions are being hit thrice, not twice!

Not only do they (1) publish more articles, (2) in higher-quality (hence higher-APC journals) but, by far the most important of all, they are still (3) paying in full for PCs, via subscriptions, over and above any APCs they are paying for Gold (whether hybrid or “pure”). Indeed all institutions that produce any research at all are double-paying for whatever OA they buy via Gold APCs, high or low.

In a nut-shell: paying pre-emptively for Gold OA today is unnecessary, premature, and a waste of scarce research funds, while subscriptions are still paying (in full) for publication costs.

It is only if and when mandatory Green OA becomes universal worldwide, and makes it possible to cancel subscriptions by offering an alternative way of accessing all published research, that journals will need to convert to Gold OA — and institutions can then use their annual windfall subscriptions savings to pay the APCs.

And those post-Green APCs will be far lower than today’s Gold APCs; hence they will be affordable and sustainable (rather than bloated, arbitrary double-payments, as now). Why? Because the cancelation pressure from global Green OA will force publishers to cut obsolete goods and services and their costs (like the print edition and the publisher PDF) and to offload all access-provision and archiving functions onto the global network of Green OA institutional repositories, leaving nothing to charge APCs for but the management of the peer review (which the peers do, as always, pro bono).

Moreover, the APCs for the post-Green Gold OA peer-review management will be “no-fault“, which means this it will be charged uniformly for each actual round of refereeing, for all submitted articles — regardless of whether the outcome is acceptance, revision/resubmission or acceptance — rather than bundling the APCs for refereeing the rejected articles into the APC of each accepted article.

Journals will not earn more by trying to charge a higher APC for refereeing: they will earn more by establishing higher quality standards for evaluation (and those may indeed be worth a higher refereeing price). But in any case, refereeing prices will be so low, compared to the windfall subscription cancelation savings, that affordability will no longer be the life/death matter that it is for journal subscription PCs today.

This is all hypothetical, of course (just like RCUK’s “general expectations and speculations”). But the fact that Green OA is already paid for in full by subscriptions today — and hence can provide OA cost-free — is not.

The causes of significantly higher APC costs for high impact factor and hybrid journals are hard to identify and the suggestions made here are purely speculative…

The principal reason higher quality journals (which are often, but not always, higher-impact-factor journals) can and do charge higher APCs is obviously that they are the journals that are more in demand, and hence can name their price.

As to the other potential factors:

“[Possible causes of higher APC coats:] Higher rejection rates

Yes, higher-quality journals reject more articles. Hence, in a pre-Green Gold APC system, they bundle the costs of the costs of rejected articles into the costs of accepted ones.

Post-Green this will no longer be necessary; and meanwhile, pre-Green, it is not necessary to pay Gold APCs for OA: Green OA will provide OA at no extra cost.

“[Possible causes of higher APC coats:] Reprints: various publishers have commented that they maximise their income streams by selling commercial reprints. A fully open licence (for example Creative Commons Attribution CC-BY) would remove this as users are free to distribute and reuse without further payment.

These days most authors respond to reprint requests with eprints, not hard-copy.

But just as pre-emptive Gold is neither urgent nor necessary, CC-BY is neither urgent nor necessary — in most fields. Some fields may indeed need CC-BY more than others, but all fields need free online access, it’s much easier and cheaper to provide (and mandate), yet we do not have even that yet.

And most uses already come with the territory, with Green (Gratis) OA.

“[Possible causes of higher APC coats:] Value: Related to the issue of brand, there is a commonly held view that having high costs for publishing articles in high impact journals is justified as this is a valued service for which researchers are willing to pay a premium.

The value of a journal comes from its track-record for quality, which in turn comes from its peer review standards. Higher quality journals are in higher demand, by both authors and users, so when they double-charge for hybrid Gold, pre-Green, they can ask for higher APCs.

Gold OA APCs post-Green for peer review alone will be so much lower that any price differences will be negligible.

(I also think it will be the lower-quality journals that will charge more, for faster, lower-standard refereeing.)

“[Possible causes of higher APC coats:] Commercial publishers may seek to set the APCs at a price point which they think the market can bear.

But pubishers would have more trouble doing this if it were not for RCUK’s double-talk about author choice: It would certainly keep pre-Green Gold prices down if RCUK fundees had a clear idea that if they did not wish to pay (or could not), they could always provide Green,

In theory, researchers can choose exactly where to publish and are free to publish elsewhere if they don’t like the prices.

Better still, they can provide Green and not pay any price at all (if they can see their way through the RCUK red tape obscuring this fact.)

[W]ith an inelastic market – researchers are unlikely to shop around – and where the costs are sheltered – central funds mean that researchers are not exposed directly to costs – the APCs would remain high because normal market forces would not drive costs down.

If RCUK authors have sense, they will not waste scarce research money on double-paying publishers for Gold OA at all while subscriptions are still being paid: They will simply provide Green.

Hybrid journals seem to be more popular venues for Open Access publication

This was already explained earlier: Established journals are likely to be hybrid Gold rather than pure-Gold start-ups, and they are also likely to be (rightly) in greater demand. — But there’s also need to double-pay them for hybrid Gold. RCUK fundees can simply choose Green.

Hybrid journals generally charge more than full OA journals independent of journal impact factor

That’s probably because unlike pure-Gold OA journals, hybrids still provide a print edition, and if they publish N articles per year, they probably charge somewhere around 1/Nth of their total annual subscription revenue for each hybrid Gold double-payment.

There is a positive correlation between APC cost and impact factor for both hybrid and full OA journals.

Supply and demand. High quality/impact journals are in greater demand, allowing them to get away with a higher price.

Open Access policies require rigorous compliance monitoring to be successful, and seem to be more effective when punitive sanctions are imposed.

“Punitive” is overstating it. Mandate effectiveness needs both carrots and sticks, but RCUK has so far only specified how it will monitor Gold compliance. For Green, RCUK would do well to look to the Belgian model.

Research-intensive institutions are likely to be hit by a cost ?double whammy?; they not only publish more articles, but they also publish them more frequently in high-impact-factor journals.

Triple whammy: They also have to keep paying subscriptions.

Stevan Harnad

Open Access Explored! A conversation with Jorge Cham of PhD Comics, live from UC San Francisco

2012 was a milestone year in the transition of Open Access into a mainstream issue, within both academia and the public at large.  Conversations about the future of academic publishing filled pages from the Economist to the New York Times and even reached YouTube, where PhD Comics’ video, “Open Access Explained!” saw over 100,000 views in its first few weeks.

“Open Access Explained!” has been shared thousands of times and sparked countless conversations as an introduction to the issue; however, it is just a starting point.

Join us online or in person on Thursday, January 17th at 12:00pm PST (3:00pm EST) at the University of California, San Francisco’s Pottruck Auditorium for a conversation with Jorge Cham, the animator behind PhD Comics.  Jorge, who started PhD Comics while completing his PhD at Stanford, will discuss his evolving view of Open Access, how it changed while making “Open Access Explained!”, and explore lingering questions with Heather Joseph, Executive Director of SPARC, and Jonathan Eisen, an evolutionary biologist at UC Davis and chair of the PLoS Biology Advisory Board.

Open Access Explored is presented by the Right to Research Coalition, and co-sponsored by SPARC, the Public Library of Science, and the University of California, San Francisco Library.

Registration for both the webcast and in-person event is free but required.

? Click here to register for the webcast of Open Access Explored!  After registering, you will receive a confirmation email.  Details on how to login to the webcast will be sent to you 3 days prior to the event.

? Click here to join us in person at UCSF’s Pottruck Auditorium.  Space is limited, so please be sure you can attend before registering.  There will be a light reception following the event.  Pottruck Auditorium is located within Rock Hall on UCSF’s Mission Bay campus at 1550 4th St, San Francisco, CA 94158.

About our speakers:

Jorge Cham is the animator behind PhD Comics.  He received his PhD in Mechanical Engineering from Stanford University and was a full-time Instructor and researcher at the California Institute of Technology (Caltech) from 2003-2005.  ”Piled Higher and Deeper” the comic strip has appeared in The Stanford Daily, MIT, Carnegie Mellon University and Caltech newspapers among over 50 others.  The strip has appeared or been featured in the journal Nature, Science Magazine the Chronicle of Higher Education, IEEE Potentials magazine, Math Horizons magazine, Stanford Magazine and Canada’s The Peer Review magazine among others, and has been linked to by USA Today’s, The NY Times and The Washington Post’s websites.

Heather Joseph serves as the Executive Director of the Scholarly Publishing and Academic Resources Coalition (SPARC), an international coalition of over 800 libraries working to enable a more open system of scholarly communication. As SPARC’s Director, she has focused on supporting the development of new publishing strategies and business models, and advocating for national and international policies that encourage the adoption of Open Access as a central principle of research and scholarship. Prior to joining SPARC, she spent 15 years as a publishing executive in both commercial and not-for-profit publishing organizations.

Jonathan A. Eisen was born in Brookline, MA and grew up in Bethesda, MD. He went to Harvard College where he majored in Biology and then attended graduate school at Stanford University and earned a PhD in Biological Sciences. He was on the faculty at The Institute for Genomic Research (TIGR) for eight years before moving to the University of California, Davis. At UC Davis he is a Professor with appointments in the Department of Evolution and Ecology, the Department of Medical Microbiology and Immunology and the UC Davis Genome Center. He is the author of over 200 scientific publications, a member of the American Academy of Microbiology, is actively involved in the movement for increased openness in science, and serves as chair of the PLoS Biology Advisory Board.

PLOS ONE News and Blog Round-Up: 2012 in Review

In this round-up, we would like to share with you some of the PLOS ONE articles covered by the media in 2012. Over one thousand papers published in PLOS ONE were covered in the news! Exciting as it is to see the wide coverage all these papers received, this made it difficult to narrow down the list below to just a few. Some of the papers the media found newsworthy are listed below (in no particular order).

The study “The Impact of Climate Change on Indigenous Arabica Coffee (Coffea arabica): Predicting Future Trends and Identifying Priorities” suggests that climate change threatens the growing conditions for wild coffee varieties, and could potentially damage the global production of coffee within the next century. Read coverage of this research in the French Tribune, Scientific American or BBC News as you sip your next precious cup.

In November, three papers reported on different aspects of children’s health. The study, “Fetal Alcohol Exposure and IQ at Age 8: Evidence from a Population-Based Birth-Cohort Study” , covered by New Scientist and Wired, reports that consuming even small amounts of alcohol while pregnant can reduce a child’s IQ. Yawning in the womb at 24-36 weeks of age may be a sign of healthy fetal development, according to the study “Development of Fetal Yawn Compared with Non-Yawn Mouth Openings from 24–36 Weeks Gestation”, which received coverage from the Guardian, Fox News and io9. Researchers describe a test to estimate a newborn’s risk for childhood obesity in the paper “Estimation of Newborn Risk for Child or Adolescent Obesity: Lessons from Longitudinal Birth Cohorts”. The Boston Globe, TIME and Mother Nature Network reported on this study.

At the other end of the age spectrum, the study “High Phobic Anxiety Is Related to Lower Leukocyte Telomere Length in Women” reported on the effects of anxiety on the ageing process. The researchers report that women who suffer from a chronic psychological distress called phobic anxiety have shorter telomeres in their blood cells, a change in DNA structure that is linked to faster ageing. This study received coverage from the Scientific American blogs, Huffington Post and CBS News.

Several other papers that reveal how we (and our bodies) respond to stress grabbed media attention also. In the study, “Overtime Work as a Predictor of Major Depressive Episode: A 5-Year Follow-Up of the Whitehall II Study” , researchers found that people who work over 11 hours a day had double the risk of depression compared to employees who worked 7-8 hours per day. Read the coverage of this study from the Herald Sun and the New York Times blogs. Spending too much time online can lead to internet addiction disorder (IAD) in teenagers, and this was linked to changes in the structure of the brain in the paper “Abnormal White Matter Integrity in Adolescents with Internet Addiction Disorder: A Tract-Based Spatial Statistics Study”. The Wall Street Journal, Mashable and other media outlets covered this research.

Results of the study “When Math Hurts: Math Anxiety Predicts Pain Network Activation in Anticipation of Doing Math” suggest that the anticipation of math problems can be physically painful to those who suffer from math anxiety. The study was covered by several news outlets including National Geographic, ArsTechnica and The Atlantic. And all this stress may affect how we perceive the other sex. Stressed-out men are likely to find larger women more attractive physically, reports the paper “The Impact of Psychological Stress on Men’s Judgements of Female Body Size”. This research was covered by The Daily Show, Le Monde and Jezebel.

Is this blog post getting too stressful? Relax with these cute puppies! As it turns out, viewing cute images like this one can improve concentration as reported in the paper “The Power of Kawaii: Viewing Cute Images Promotes a Careful Behavior and Narrows Attentional Focus” . This research had media outlets including Forbes, the LA Times and Cosmopolitan reaching to publish the cutest animal photos with their reports.

And if you’re still looking for cute animals, look no further. Three new animal species described in PLOS ONE papers this year have your adorable animal needs covered. The lesula, a new monkey species was described in the study “Lesula: A New Species of Cercopithecus Monkey Endemic to the Democratic Republic of Congo and Implications for Conservation of Congo’s Central Basin”, four new species of chameleons small enough to fit on a fingernail were discovered in Madagascar, according to “Rivaling the World’s Smallest Reptiles: Discovery of Miniaturized and Microendemic New Species of Leaf Chameleons (Brookesia) from Northern Madagascar” and a study published in January leads this menagerie of adorable animals, as it reports on the world’s tiniest frog. _ is small enough to fit on a nickel CK, and is described in the paper “Ecological Guild Evolution and the Discovery of the World’s Smallest Vertebrate”.  Hundreds of media outlets across the world featured stories about these new species, including the New York Times, Reuters, Science Now and even The Onion.

To round things off, researchers watching animals from space identified new colonies of emperor penguins in the Antarctic. Their results were published in the study “An Emperor Penguin Population Estimate: The First Global, Synoptic Survey of a Species from Space”, which was covered by The Scientist, Christian Science Monitor and USA Today.

These papers are only a small fraction of more than a thousand that were covered by the media. Visit our Media Tracking Project to see the full list of over 7000 news stories that reported on PLOS ONE research published in 2012.  Or follow us on YouTube, SoundCloud and Twitter to keep track of some of the great science multimedia we’ve published this year!

Images: Coffee by kaakati on Flickr, puppies by pellaea on Flickr, all others from PLOS ONE papers




#opencontentmining MASSIVE step forward. Come and join us in the UK!

The UK government has now given the go-ahead to the major reforms proposed by the Hargreaves committee. . The message is now very simple:



Business Secretary, Vince Cable said:

“Making the intellectual property framework fit for the 21st century is not only common sense but good business sense. Bringing the law into line with ordinary people’s reasonable expectations will boost respect for copyright, on which our creative industries rely.

“We feel we have struck the right balance between improving the way consumers benefit from copyright works they have legitimately paid for, boosting business opportunities and protecting the rights of creators.”

In his review of intellectual property and growth, Professor Hargreaves made the case for the UK making greater use of these exceptions, which are allowed under EU law. In response to a consultation earlier this year, the Government will make changes to:


  • Data analytics for non-commercial research – to allow non-commercial researchers to use computers to study published research results and other data without copyright law interfering;


These changes could contribute at least £500m to the UK economy over 10 years, and perhaps much more from reduced costs, increased competition and by making copyright works more valuable.

In addition the Government will introduce a new, non-statutory system for clarifying areas where there is confusion or misunderstanding on the scope and application of copyright law. Copyright notices will issued by the Intellectual Property Office. These notices are intended to clarify, but not make new law.

It makes it clear that publishers cannot set licence terms that override this.

New measures include provisions to allow copying of works for individuals’ own personal use, parody and for the purposes of quotation. They allow people to use copyright works for a variety of valuable purposes without permission from the copyright owners. They will also bring up to date existing exceptions for education, research and the preservation of materials.

We can start content-mining today (and we shall).

Copyright is complex and some of the questions are not easy to answer. So there is a provision for copyright-holders to appeal to the Secretary of State if they don’t like it. If publishers can convince Vince Cable that my activities are a threat to the health of the UK economy I’ll stop.

So everyone should adopt the principle:

If you have a right to the content you have a right to mine it

You DON’T have to ask permission.

What about non-UK people? Just come and visit us here! You will then be governed by the law of the UK. And we’d love to see you.



ChemistryOpen‘s Final 2012 Issue is Live!

ChemistryOpen Issue 5ChemistryOpen’s sixth Issue is now online and free to read, download and share.
This last issue in 2012 covers topics ranging from bibliometrics and oxidative rearrangements to molecular recognition in glycoaldehyde.

R. Martínez-Mánez and co-workers present their work on detecting finasteride, a steroid used in sports for doping. To do so, they use mesoporous silica nanoparticles that are functionalized with a finasteride derivative. They then load the nanoparticles with the fluorescent dye, rhodamine B, and cap them with an anti-finasteride antibody. The dye is trapped inside the mesopores and is only released when surrounding finasteride competes for binding to the antibodies, which then leads to decapping of the mesopores and release of the detectable fluorescent dye.

K. Breuker and B. Ganisl (University of Innsbruck, Austria) report on their findings towards the question whether electron capture dissociation cleaves protein disulfide bonds. They discuss their results on electron capture dissociation measurements of disulfide-bonded proteins, ecotin, trypsin inhibitor, insulin, aprotinin, and peptides K8- and R8-vasopressin, and conclude that it is nearly impossible to predict whether and to what extent disulfide bonds are preserved during collisionally activated dissociation (CAD), electron capture dissociation (ECD), or electron transfer dissociation (ETD).

Submit your next article to ChemistryOpen!

Ecology and Evolution Publishes the Final Issue of 2012

ECE 2 12The latest issue of Ecology and Evolution is now live! Over 20 excellent articles free to read, download and share. The cover image is taken from Permeability of the landscape matrix between amphibian breeding sites by Josh Van Buskirk. This is the final issue in what has been another fantastic volume for Ecology and Evolution.

Below are the editors’ highlights from this issue:

 Diversity of birds in eastern North America shifts north with global warming by Kenneth W. McDonald, Christopher J. W. McClure, Brian W. Rolek and Geoffrey E. Hill
Summary: Here, we report that bird diversity in North America increased and shifted northward between 1966 and 2010. This change in the relationship of diversity to the latitudinal gradient is, likely, primarily influenced by range expansions of species that winter in the eastern United States as opposed to species which migrate to this area from wintering grounds in the tropics. This increase in diversity and its northward expansion is best explained by an increase in regional prebreeding season temperature over the past 44 years.

 Evidence of stable genetic structure across a remote island archipelago through self-recruitment in a widely dispersed coral reef fish by Mark A. Priest, Andrew R. Halford and Jennifer L. McIlwain
Summary: For the majority of marine organisms a pelagic larval stage provides the primary mechanism for dispersal amongst often spatially fragmented habitat patches. The degree to which larvae disperse and populations are subsequently connected may have a profound influence on the population dynamics of a species. We used microsatellite markers to assess the population genetic structure of the scribbled rabbitfish Siganus spinus in the western Pacific. This species is a culturally important food fish in the Mariana Archipelago and subject to high fishing pressure. Our results confirm the relative isolation of the southern Mariana Islands population and highlight how local processes can act to isolate populations that, by virtue of their broad-scale distribution, have been subject to traditionally high gene flows.

Read other top articles in this issue >

Submit your paper to Ecology and Evolution here >

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Latest Article Alert from Harm Reduction Journal

The latest articles from Harm Reduction Journal, published between 05-Dec-2012 and 19-Dec-2012

For articles which have only just been published, you will see a ‘provisional PDF’ corresponding to the accepted manuscript.
A fully formatted PDF and full text (HTML) version will be made available soon.

Understanding the association between injecting and sexual risk behaviors of injecting

Fixing siRNAs by creating an anti-siRNA

Small pieces of RNA in our cells can act like molecular switches that turn genes off by binding to them. These pieces, called small interfering RNAs (siRNAs) are also used by researchers to design experiments to understand what certain genes do.

Scientists can design siRNA molecules aimed at turning off specific genes they are trying to study. Though such siRNA ‘switches’ can be very useful, they are often non-specific, turning off hundreds of genes that they should not have an effect on. As a result, it is difficult for a biologist to conclude whether an experimentally observed effect is due to turning off the gene they meant to turn off or the hundreds that they didn’t (called “off-target effects”).  Eugen Buehler of the  National Center for Advancing Translational Sciences (NCATS), a new center at the NIH, describes an alternate approach to dealing with these off-target effects of siRNAs in his recent PLOS ONE paper. Read on to find out more about this research:

How did you become interested in improving siRNA experiments?

I’ve been working on siRNAs for about the last five years.  When I would talk to my wife (a cell biologist) about my research, I would go on and on about all the problems created by these non-specific effects. Since she uses siRNAs in her research, she would ask, “Well, what should I do to avoid it?”

I didn’t have an answer.  All the methods I had involved a statistical analysis of a large number of results from high-throughput screens, which look at several thousand genes at once. They couldn’t be applied to experiments that only involved one or a few genes, which is what many researchers do.  It frustrated me not being able to help her, and so this question of what to do about off-target effects in small-scale experiments kept nagging me, until I found an answer.

And what was that answer?

As is often the case, the answer involved looking at the problem a different way.  For years, people have been trying to solve the problem by getting rid of the non-specific effects. There are many ways to do this, but they still have a high incidence of these effects.

So, rather than trying to eliminate the off-target activity, we took the opposite approach. We changed three points (bases 9-11) where an siRNA makes contact with its target, so it couldn’t have the effect it was designed for. In this way, we created the C911 version, an anti-siRNA of sorts, which had all the off-target effects but none of the on-target effects.

So if an siRNA has an effect in a cell that is different from what the C911 version of the same siRNA has, we can conclude that the effect is because it silenced the intended target.

Which figure in the manuscript do you think best summarizes your results?

Definitely Figure 3B. Here, we compare siRNAs that appear to have specific effects but don’t (false positives), with ones that do have a specific action on a target gene. We took ten of each kind and created C911 versions for all twenty.

When we compared the two we found that for the false positives, the siRNA and the anti-siRNA had the same effects (left hand panel). But for the siRNAs which really did have an effect on their target, there was a big difference between the siRNA and its C911 version. As it happened, the C911 controls worked perfectly for all twenty siRNAs we had selected for the experiment.

Where do you hope to go from here?

For a tool as well established as siRNA, it will take a while to change the way we design our experiments.  The first step is for there to be a reasonable alternative, and that is what this paper is meant to supply.  The next is to make that alternative easy to choose.  Part of that will involve getting companies that manufacture siRNAs to eventually make negative controls like this, so that negative controls like C911 can be easily and affordably obtained for any siRNA.

My hope is that someday when a researcher orders an siRNA, they won’t even have to ask; they’ll get a tube with their siRNA and a tube with the appropriate negative control by default.

Read about Nobel-winning research on interfering RNAs, and explore more PLOS ONE research about siRNAs here and here

Citation: Buehler E, Chen Y-C, Martin S (2012) C911: A Bench-Level Control for Sequence Specific siRNA Off-Target Effects. PLoS ONE 7(12): e51942. doi:10.1371/journal.pone.0051942

Image: Target by Ivan McClellan on flickr