Nature-Asia Publishing Index

Nature Asia-Pacific has just launched the Nature-Asia Publishing Index, which analyses the papers published in all of the Nature group of journals by researchers working at institutions in the Asia-Pacific region, including India and Australasia. The data is interesting, because the Nature journals are very important primary research journals, so they give some idea of the spread of high-quality basic research in the region, both by country and by institution. It’s not surprising that Japan is still top, by a significant margin, but Singapore does very well for its size, and China is moving up rapidly.

The other interesting thing here is the value of this to the Nature group. Because the index undeniably does have value, policy-makers in the region are likely to use it. That means that moving up the index is likely to directly benefit institutions. And that means that, all else being equal, researchers at those institutions are going to submit to a Nature journal, rather than one that isn’t in the index. In other words, it should give the Nature journals a slight edge over journals of comparable Impact Factor in the competition for the best papers from the Asia-Pacific region. I do wonder how much that drove the decision making. The commercial benefit is likely to be minimal; the journals are already important enough that no serious institution could manage without a subscription. However, the prestige benefit could be quite important.

Incidentally, five of the top ten institutions in the region are Japanese. The University of Tokyo, Kyoto University, Osaka University, RIKEN, and Tohoku University. Kyushu and Keio are at eleven and twelve.

The data did immediately make me wonder what a global version of the index would look like. The USA would dominate in much the way that Japan dominates this one, but the lower places would be more interesting. I wonder whether the rest of the Nature group is thinking about doing something similar.

Natural Helper Cells

All animals have some way to fight off infections by bacteria, viruses, and parasites. If they didn’t, they would soon die. In mammals, this system is quite complex, and includes two main branches. One, the adaptive immune system, learns about infections the first time they are encountered, and then can deal with them quickly if they come back. This is the system that is used in vaccination. The other system, the innate immune system, has a fixed set of responses, and deals with things that look like they might be dangerous, even though the body has never encountered them before. Today’s paper, by a team led by Kazuyo Moro and Shigeo Koyasu at Keio Medical School, reports more discoveries about the innate immune system.

The immune system includes cells called helper T-cells, which secrete substances, called cytokines, that provoke strong immune responses. If these cells respond to the wrong sort of thing, it can cause serious allergies, and an over-reaction can be fatal, leading to a so-called cytokine storm. There are two main types of helper T-cells, as far as I can tell from this article, TH1 and TH2. However, in the years since they were discovered, many cell types have been found to perform a similar function to TH2 cells, so that the name is now being used to refer to a function, rather than a cell type.

This paper reports the discovery of a new group of TH2-type cells, fat-associated lymphocyte clusters (FALCs), which are clusters of fat cells and natural helper cells, a kind of lymphocyte, found along blood vessels near the intestines. The cells seem to be involved in, at least, responding to parasitic infections of the gut, provoking other cells to react in a way that clears the parasites out of the gut. The authors call them natural helper cells, as they have none of the characteristics of T cells.

So, why is this important? Well, an entirely new class of immune cells is a significant discovery. It’s important to understand the immune system as a whole, and in order to do that we need to know what cells make it up. The better we understand the immune system, the better we can handle it when treating infections and the like. Of course, as the cells have only just been discovered, their full importance is not yet known, so the ultimate significance of this discovery is still uncertain. Science is often like that.

Natural helper cells (Editor’s summary)

Immunology: The expanding TH2 universe (News and Views article: Nature 463, 434-435 (28 January 2010) | doi:10.1038/463434a; Published online 27 January 2010)

Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells (Original paper: Nature 463, 540-544 (28 January 2010) | doi:10.1038/nature08636; Received 6 October 2009; Accepted 5 November 2009; Published online 20 December 2009)

Fossil Viruses in the Human Genome

There is a commonly-heard idea that Japanese science is not creative, although they are very good at refining other people’s ideas. This idea is commonly heard even in Japan; I’ve had to disabuse quite a few of my students of the idea. Including some of the ones working as research scientists. It is true that Japan has yet to produce a Newton, Darwin, or Einstein, but then there really haven’t been very many of them in history. Japan does produce high-quality original research, so I’m going to introduce a bit of it on my blog.

My standard is simple: I will introduce articles published in Nature, with an accompanying News and Views analysis, that were produced by researchers working in Japan, possibly in collaboration with other nations. Because I don’t have time to check every article’s origin, there is, at least for now, another practical requirement: the first author needs to have a Japanese-looking name, or the News and Views article needs to mention where the research was done. This would be bad if I was trying to be systematic, but I’m not.

The other two conditions are meaningful. Nature is the most influential science journal in the world, just about beating Science, the main competition. This means that any articles published in it are important research. The News and Views articles are written about a small proportion of the articles (normally called “letters”, for historical reasons), with the editors choosing the ones of most general interest and importance. Thus, getting an article in Nature, with a News and Views commentary, means that your research is of the highest normal global quality. Realistically, this is the best you can aim for.

I will link to the articles on the Nature site, but while the editorial summary can be read for free, the actual articles need a paid-for subscription. If you’re at a university, your university probably has one; otherwise, you need a personal subscription to Nature. If you’re interested in science, I think it’s well worth it, but it’s not cheap.

Obviously, these articles will be a bit irregular, depending on when appropriate papers appear in Nature.

Anyway, on to this time’s paper. The research was mainly done by a group at BIKEN, in Osaka, by Masayuki Horie and Tomoyuki Honda, with assistance from a lot of people (the author list is in the freely-accessible information).

It is well-known to biologists that a large proportion of the human genome (about 8%) comes from viruses. Bits of the viral genome get incorporated in chromosomes, and then reproduced with the rest of human DNA. All the previously known examples were from retroviruses. Retroviruses are so-called because they reproduce by first converting their RNA genome into DNA, and then using the machinery of the infected cell to make more RNA from the DNA template. Integration of this DNA into the host genome is relatively common, and may, actually, be a normal part of the process; as this article isn’t about retroviruses I’m working from memory.

This paper reports the discovery of DNA elements derived from Borna viruses, a different class. These viruses have RNA genomes, but do not normally integrate any DNA into the host genome. However, they do carry out their entire life cycle within the cell nucleus, the part that contains the host DNA. Further, they naturally infect neurons, cells that do not normally die, and so the infection can be extremely persistent.

The researchers started by searching the databases of genome sequences for sections that matched sequences from the Borna virus genome. They found plenty. There were several in humans, some of which appear to still function as genes; that is, the DNA could be transcribed to messenger RNA and then made into proteins, and in one case there is already evidence that it is. Most of the insertions, however, have lost bits over time, and can no longer be used to make proteins; these are called pseudogenes or fossil genes. By looking at the presence of similar sequences in related primates, the authors determine that the virus must have been integrated into the genome about 40 million years ago, because it is in all the primates that split off from the lineage that leads to humans after that time, but not in the ones that split off before that.

They also found evidence for the virus genes in other animals, with varying dates for integration.

For the viral genes to be inherited, they have to be incorporated in the germ line; that is, in the eggs and sperm that go on to make the next generation. Since the virus normally infects neurons, a different class of cells, this might be relatively rare, so the authors looked to see whether the viral genes get incorporated into the DNA of neurons. It turns out that they do, and that this seems to be quite frequent.

The incorporation of the DNA is blamed on so-called L1 elements, elements of DNA found in mammalian genomes that reproduce themselves throughout the genome. Their machinery seems prone to picking up a particular gene from Borna viruses, and incorporating it instead. (All of the insertions were derived from one of the Borna virus genes, a gene for the protein shell that encapsulates the virus when it leaves the cell.)

So, what’s the significance of this?

From a pure science perspective, it’s the first evidence for contributions from a virus other than a retrovirus to the human genome, which is interesting in itself.

The 40 million year age is also interesting, because so-called RNA clock methods for measuring the age of Borna viruses suggest that they are much younger than that. (An RNA clock works by measuring the rate of mutation in the genome, and then looking at changes, or at how long the virus could be stable.) This suggests that the RNA clock doesn’t work very well for viruses.

Finally, incorporating bits of DNA into the genome in random places can disrupt the cell’s function. It can cause cancer, but also have other effects. There is, apparently, some (disputed) evidence associating Borna-virus infection with mental illness, and this provides a mechanism by which the virus could have that effect. Disruptions to neural functioning could, of course, cause mental illness of various kinds.

Viral ‘fossils’ in the genome (Editor’s summary)

Virology: Bornavirus enters the genome (News and Views article: Nature 463, 39-40 (7 January 2010) | doi:10.1038/463039a; Published online 6 January 2010)

Endogenous non-retroviral RNA virus elements in mammalian genomes (Original paper: Nature 463, 84-87 (7 January 2010) | doi:10.1038/nature08695)