I was listening yesterday to an interview with Madeleine Albright, former secretary of state, on KGNU, an online radio station based in Colorado.

While plugging her new book, she said that the job of secretary of state is more complex than when she had it. The reason? The position now requires more science savvy: the next secretary of state, she said is going to have to know about climate change, energy and public health.

So it’s not just a bunch of geeks thinking all this science stuff is getting more important. So-and yes I keep bringing this up-Madame Secretary, are you prepared to add your name to a call for a Science Debate?

Posted by Charlotte Schubert at 11:52 AM | Permalink | Comments (2)

Speaking of mammals (see the end of my previous entry), not even rats and mice always cut it when it comes to providing good models of human disease. Take, for example, cystic fibrosis. There are a couple of mouse models of the disease (we have published at least one of them), but the community does not seem to be satisfied with them. It is therefore great to see a pair of papers in the JCI reporting on two new attempts at generating the ideal model of cystic fibrosis.

The two of studies are very similar. In the first one, Xingshen Sun and colleagues report the first description of genetically engineered ferrets. They started by targetting the CFTR gene (the gene affected in the disease) in fibroblasts using an adeno-associated viral (AAV) construct, and then used a nuclear transfer protocol to obtain cloned ferrets heterozygous for the CFTR mutation. In the second one, Christopher Rogers and colleagues employed a similar strategy in pigs to obtain heterozygous piglets carrying the CFTR mutation.

The next steps will be to establish how much these models truly recapitulate human disease, and then use them to learn new biology about the disease and/or for preclinical drug-discovery work.

The figures, taken from the papers, show the cloned CFTR ferrets and a non-cloned albino at different ages, and the first CFTR heterozygous pig at one day of age.

Posted by Juan Carlos Lopez at 03:40 PM | Permalink | Comments (5)

People with acne will find this JCI paper of interest. 13-cis retinoic acid can be used to treat acne, as it can kill human sebaceous-gland cells by apoptosis. The molecule is teratogenic, though, making it necessary to look for alternatives. As the mechanism of action of 13-cis retinoic acid is unknown, Amanda Nelson and her colleagues tried to elucidate it, hoping to identify new targets for the treatment of the bothersome skin condition. Using transcriptional profiling of skin cells from people with acne and cultured sebaceous glands, they found that lipocalin-2 was distinctively upregulated by treatment with 13-cis retinoic acid. They also found that the apoptotic effect of 13-cis retinoic acid indeed depended on the expression of neutrophil gelatinase–associated lipocalin (NGAL), the protein encoded by lipocalin-2; by using siRNA to lipocalin-2, they blocked the apoptotic effect, and by adding recombinant NGAL, they promoted it. It is therefore conceivable that manipulating NGAL expression could lead to a new way to fight acne.

A more serious pathology with a connection to retinoids is Matthew-Wood syndrome, a fatal disease characterized by multisystem developmental malformations that has been linked to mutations in STRA6. STRA6 interacts with retinol-binding protein 4 (RBP4), which is, in turn, a carrier of retinoids (vitamin A and its derivatives). A paper published in Cell Metabolism establishes that the biochemical interaction between STRA6 and RBP4 is indeed functionally relevant. Studying zebrafish embryos, Andrea Isken and colleagues found that Stra6 deficiency allows more Rbp4 to remain free and to carry an excess amount of retinoids to several embryonic tissues, including bone, heart and eye. In fact, reducing the levels of Rbp4 prevented these effects. The findings provide a nice molecular account of Matthew-Wood syndrome, although I cannot help but wish that the authors had done the in vivo experiments in a mammal. I must confess that, when we evaluate papers at Nature Medicine, we're seldom enthused by data from zebrafish, Drosophila or C. elegans, as the relevance of these models to human physiology tends to be harder to ascertain. Nothing personal against the fish or the invertebrates, though.

Posted by Juan Carlos Lopez at 01:27 PM | Permalink | Comments (0)

Pretty interesting report in Nature a week ago about the NIH's proposal to revamp its peer-review process. We plan to discuss the proposal in more detail at a later date, but I cannot help but refer to the graph that accompanied the story:

What I wanna know is who the one investigator with 11 NIH grants is. Truly remarkable! I'm willing to bet that this person has no strong criticisms of the quality of peer review at the NIH.

Anyway, this graph also reminded me of those plots you see of wealth distribution in New York or London, in which a few people have a lot of money, making those cities a lot less affordable for the rest of us.

Posted by Juan Carlos Lopez at 02:09 PM | Permalink | Comments (0)

Clearly, John McCain does not read this blog.

He blundered into Nature Medicine territory this week, saying that there was “strong evidence” for a link between autism and vaccines (there is not, a point we have driven home before).

Reminds me of a stumble McCain had last year with a reporter on another of our pet issues, HIV and condoms:

Q: “So no contraception, no counseling on contraception. Just abstinence. Do you think contraceptives help stop the spread of HIV?”
A: Mr. McCain: (Long pause) “You’ve stumped me.”

One blogger offers a charitable—and probably accurate—explanation for the autism statement:

The vast expansion of the state means that we expect our representatives to have opinions on everything from missile defense to flame-retardant pajamas. No one could possibly learn about every subject we expect them to know, even if he were not spending sixteen hours a day doing the grip-and-grin with voters, lobbyists, donors, and other politicians.

It would be interesting to hear more about the views of McCain and the other candidates on HIV prevention, contraception and even vaccination (another reason for a science debate). But at least he’s got the scientific consensus right when it comes to global warming.

Posted by Charlotte Schubert at 01:00 AM | Permalink | Comments (2)

Three papers published this past Sunday touch upon different aspects of the aging problem. The first one appeared in Nature and is authored by Rui Yi and colleagues, who found that microRNA-203 promotes the differentiation of skin stem cells by repressing "stemness". In stratified epithelia, stem cells located basally are crucial for self renewal. As these cells leave the basal zone, they differentiate and cease to behave like stem cells. What the authors found is that microRNA-203 is crucial for this differentiation process, leading the stem cells to exit the cell cycle. Mechanistically, this effect depends on repression of p63 expression, a molecule that had previously been shown to regulate stem-cell maintenance in epithelia.

The second one is on one of my favorite topics -- progeria. Writing in Nature Cell Biology, Paola Scaffidi and Tom Misteli report that expression of mutant lamin-A, the molecule that causes Hutchinson-Gilford Progeria Syndrome (HGPS), interferes with the function of human mesenchymal stem cells (hMSCs) by promoting the activation of downstream
effectors of Notch, affecting the differentiation potential of hMSCs. The in vivo relevance of these results to HGPS and to normal aging remains to be established, but the possibility is indeed tantalizing.

The third one is a Brief Communication in Nature Genetics. In it, Marc Vermulst and his colleagues establish a link between mitochondrial DNA (mtDNA) deletions and aging in the so-called Polga mice, which harbor a proofreading-deficient copy of polymerase gamma and are characterized by premature aging. They found that the rate at which different tissues accumulate mtDNA mutations before they reach phenotypic expression differs profoundly -- brain, heart and gut are among the most affected parts of the body. The question remains, though, if these mtDNA mutations are also relevant during normal aging in wild-type mice and, of course, in humans.

Posted by Juan Carlos Lopez at 04:01 PM | Permalink | Comments (1)

I saw this amusing paper in the latest issue of EMBO reports.

The article's title is "Six senses in the literature. The bleak sensory landscape of biomedical texts", and its authors -- Raul Rodriguez-Esteban and Andrey Rzhetsky -- argue that "scientific texts have a reputation for being factual, rational and 'dry" in contrast to other prose that is designed to evoke emotional responses". They therefore set out to obtain evidence that "the sensory-deprived writing style that dominates the biomedical literature impedes text comprehension and numbs the reader's senses and mind".

To that end, they measured the frequency of use of "sensory" words (terms related to the perception of color, smell, taste, touch, sound and time) in 250,000 articles from 78 biomedical journals and compared it to their frequency in news reports from Reuters, in articles in Wikipedia, and in the complete collected works of Poe, Shakespeare and Whitman. They found (surprise, surprise!) that articles and news reports were a lot "bleaker" in comparison to the works of literature. The figure below is some sort of homunculus that gives you an idea of the "sensory" characteristics of the different works they looked at. It shows the balance of "sensory" terms in the different bodies of work they compared, together with the average -- the face in the center.

The authors speculate that reading texts with the characteristic of a biomedical article "is similar to the effect of a long journey through a colourless flat terrain devoid of prominent features: a numbing of the senses", and suggest that "cognitively bleak biomedical texts can and should be transformed into perceptually richer prose".

All of this is well and good, but I must confess that, when I read scientific papers, I have very little patience for metaphors and analogies, which some authors, alas, love to use. Some of them are so gratuitous that it makes you wonder if their use of imagery and metaphor is itself, in fact, an attempt to "numb the reader's senses and mind".

Back when I was the Editor of Nature Reviews Neuroscience, I remember that a couple of my colleagues and I created something we dubbed "Analogy-watch" to record the most ridiculous analogies that we could find in scientific texts. (I regret to say that many of them were penned by some of our own in-house Editors.) Maybe as a result of that experience I've always tried to be careful and separate literature from science. I hope that prospective Nature Medicine authors don't rush to follow the authors' advice and instead use "sensory words" in moderation. Trust me, you don't wanna end up being part of our Analogy-watch file.

To close, I cannot help but pointing out that Calvin (of Calvin & Hobbes fame) had already observed an effect somewhat related to the one reported by Rodriguez-Esteban and Rzhetsky. I didn't see Calvin cited in the reference list, which is why I thought I would include the relevant "report" down here. (Note, you may have to save the image on your desktop, as it appears truncated in the blog page.)

Posted by Juan Carlos Lopez at 04:10 PM | Permalink | Comments (1)