I found the past two online installments of Nature to be particularly strong.

Sunday's issue had two papers showing that activation of the aryl hydrocarbon receptor (AHR) -- a ligand-dependent transcription factor that mediates the action of environmental toxins such as dioxin -- plays a role in the pathophysiology of EAE, the commonly used animal model of multiple sclerosis.

Marc Veldhoen et al. and Francisco Quintana et al. found that AHR exacerbated EAE by promoting the differentiation of Th17 cells and the production of IL-22. Remarkably, Quintana and his colleagues went on to show that the effect of AHR depended on the agonist they used; whereas one agonist promoted EAE, a different agonist suppressed the pathology by inducing regulatory T cells. The authors don't go too far downstream to nail down the transcriptional pathways that are responsible and account for the dual effect of AHR (which is in and of itself not unprecedented), but the possibility that environmental toxins might use this receptor to modify the course of multiple sclerosis in people is very interesting.

Then, on today's edition of the journal, there are two RNA-related papers that are also very interesting. The first one is a proof-of-principle study by Joacim Elmén et al., showing that it is possible to silence microRNAs in non-human primates. Although therapeutic effects of blocking microRNAs in rodents have been published, there has been scepticism about translating the approach to the clinic. Elmén and his colleagues now show that it is possible to silence a liver microRNA in the green monkey by delivering a locked-nucleic-acid-modified "antimiR". Moreover, this silencing approach had a functional readout -- decreased plasma cholesterol -- and no obvious toxicity. This is a reassuring finding for those interested in targeting microRNAs in humans with therapeutic purposes.

The second RNA-related paper reports a somewhat unexpected finding. There are reports that you can use siRNA to target proangiogenic molecules like VEGF or its receptor, and block pathological angiogenesis in patients with neovascularization linked to age-related macular degeneration. Now, Mark Kleinman and his colleagues show that it doesn't quite matter what molecule you target because a large number of siRNAs (even if some that target non-genomic sequences or antiangiogenic genes) have the same antiangiogenic effect. As long as the siRNA is 21-nucleotides or longer, it will exert an anti-angiogenic effect mediated by the TLR3 signaling cascade. This "class effect" implies that generic siRNAs might be therapeutic agents, and that siRNAs might have unanticipated actions on the vascular and immune systems.

Posted by Juan Carlos Lopez at 01:25 PM | Permalink | Comments (0)

Today is the 10th anniversary of the FDA's approval of sildenafil nitrate for the treatment of erectile dysfunction. A decade and over 30 million users later, there's very little left to say about Viagra that hasn't been said before. Maybe that's why the media coverage of the anniversary has been somewhat modest. I nevertheless found this pretty neat graphic in the Spanish newspaper El Mundo. It's, of course, in Spanish, but I hope you get the gist of it.

After this anniversary, Pfizer probably won't be looking forward to future ones; their patent on the drug is set to "go limp" between 2011 and 2013.

Image by n3wjack's world in pixels

Posted by Juan Carlos Lopez at 09:59 AM | Permalink | Comments (1)

Today's announcement that the British Prime Minister is ready to compromise and have a free vote on parts of his government's embryo research proposal is disappointing.

Britain has traditionally taken a much broader view of stem-cell research than, say, the US. So, for Gordon Brown to yield under the pressure from Catholic MPs, who had threatened to step down if a vote was not held, is nothing short of a step backwards.

One of the most controversial aspects of the Bill has to do with the generation of "cybrids" or "admix" embryos generated by injecting a human nucleus into an animal egg. Critics of the Bill cite ethical concerns. For example, Cardinal Keith O'Brien (Roman Catholic Archbishop of St Andrews and Edinburgh) stated that "It is difficult to imagine a single piece of legislation which more comprehensively attacks the sanctity and dignity of human life than this particular bill", and that the Bill could lead to experiments of "Frankenstein proportions".

Needeless to say, supporters of the Bill have urged the Catholic church to become more familiar with the facts before making such strong statements. In fact, if you look at what a cybrid really is and realize that it's something that may or may not even be successful, the alarms set off by opponents of the Bill seem rather out of proportion. (See this correspondence from MIT's Richard Hynes that we published some time ago, in which he clarifies the terminology and dismisses some of the most erroneous concerns about the generation of chimeras, hybrids and cybrids.)

Clearly, the Prime Minister's decision to compromise is political, and he sounds confident that the Bill will pass as intended despite the objections from the rebel MPs. Hopefully his gamble is correct, and we don't have to live through another case of science taking a backseat to religion.

Posted by Juan Carlos Lopez at 11:01 AM | Permalink | Comments (0)

I'm in the middle of preparing a talk that I'm scheduled to give in Madrid in a few days. The talk is called "Myths and realities of publishing in the Nature journals", and its goal, at least in part, is to dispel the myth that our journals discriminate against, say, Spanish-speaking countries or developing nations, and that we favor countries like the USA and Britain.

Thinking about the comments I've heard from people, this myth can be divided into at least four parts:

1. The fame myth -- "to publish in the Nature journals, you have to be a big name."

2. The friends myth -- "to publish in the Nature journals, you have to be a friend of the journal, and you have to be on first-name terms with everyone in the field so that you always draw positive reviewers."

3. The language myth -- "to publish in the Nature journals, you have to have the Queen's English, or the editors won't even read your paper."

4. The surname myth -- "to publish in the Nature journals, it's better if you are Dr. White and not Dr. Blanco. In fact, if I were to change the names of the authors in my paper to anglosaxon names, I'm sure you would have sent it out for external review at least."

Each of these myths can be rebutted, and part of my talk will consist of data proving that this is not the way we operate. For example, you don't need to be famous to publish in Nature Medicine. Just flicking through the last four issues of the journal (including April 2008), I found that 75% of the articles we published were authored by people I didn't know about before their submission.

That being said, I'm most interested in any evidence you may have in support of the myths. I want to make sure that my perception of the fairness of our processes is a legitimate one. So, if you know of any specific instance of discrimination, please send it over. I may even include it in the talk.

Posted by Juan Carlos Lopez at 10:25 AM | Permalink | Comments (2)