Journal of Biology - Latest Comments

Response to comment by Professor James Till

Arthur D Lander — 2009-09-29T10:33:02Z

I believe that the question being asked is, "how does the model presented in Figure 1 bear on published results in which purified hematopoietic stem cells have been studied in reconstitution assays, and particularly in those studies in which quantitative analysis of engraftment efficiency over time has been measured?" This is an interesting question. Benveniste et al. (2003), for example, provide evidence that purified hematopoietic stem cells (HSCs) engraft with near 100% efficiency, but then clones are subsequently lost; this was taken as evidence in favor of the model of stochastic renewal (and extinction) of HSCs originally developed by Till and colleagues. This interpretation is not challenged by the possibility of feedback regulation of renewal probability (my Figure 1). What feedback regulation does is make renewal (and extinction) probabilities variable, rather than constant. For example, in the bone marrow of an irradiated host, in which mature hematopoietic cells are depleted, one might expect renewal probabilities of HSCs to be high shortly after transplantation, falling as restoration of normal mature cell numbers is achieved. This could contribute to the observation that short-term clonal engraftment efficiencies are so high (near 100%) at the outset, falling a great deal later on. It is certainly possible to build stochastic models of lineages that incorporate feedback, but to make precise predictions one would need to know the degrees to which feedback regulation is achieved through changes in the proportion of divisions that are asymmetric, the proportion of symmetric divisions that are renewal divisions, or both. It would also be necessary to know whether there are feedback effects on cell cycle speed as well. At the moment we don’t have this information for HSCs (in part because we don’t know with certainty what the feedback molecules are). Interestingly, a paper published a few months ago by Marciniak-Czochra et al. (Stem Cells and Development 18(3), 377-385 doi: 10.1089/scd.2008.0143) argues, based solely on the dynamics of hematopoietic repopulation following bone marrow transplantation, that feedback regulation just like that in my Figure 1 must occur in the HSC system (I apologize for not citing this paper in my piece; I only just learned of its existence).

Thanks, Professor Till for your interesting comment.

What about purified stem cells?

James Till — 2009-09-29T10:28:57Z

The model shown in Figure 1 is an interesting one. It would have been helpful if the author had included comments about the particular context where purified stem cells have been studied. See, for example, the publications on purified hematopoietic stem cells by Spangrude, Heimfeld and Weissman, 1988 and Benveniste, Cantin, Hyam and Iscove, 2003.

The author reflects on comments received

Virginia Walbot — 2009-03-17T10:30:18Z

It has been rewarding to receive gracious e-mails and posted comments about how to better train young scientists as thoughtful reviewers. Of course, I also heard from pit bull owners in defense of their pets. I stand by the analogy, however, because a good owner trains the dog to be a safe companion, while a bad owner can incite vicious and dangerous behavior – and the pit bull’s jaws are strong enough to sever your arm! Furthermore, it’s easier to train than retrain a dog, or a person. This is exactly the point of training graduate students and postdocs: we need to use class time for this excerise and also explicitly discuss our own reviewing habits with our lab groups to reap future benefits of thorough and reasonable criticism.

Several commentators also pointed out related essays that interested parties may wish to consult: http://www.healingtherapies.info/Objective%20Science.htm and http://jcs.biologists.org/cgi/reprint/113/24/4373

Finally, I think it’s important to evaluate how the recent changes in the Journal of Biology reviewing policies play out over time. Can journals mitigate the angst felt by authors by tweaking the reviewing system? Will reviewers become more thoughtful if they receive fewer “rewrites” of nearly ready to publish manuscripts and can hence concentrate much of their review on the list of required alterations that authors can readily achieve without subsequent outside reviewer approval? Should we maintain the cloak of anonymity in our current system? These are all issues ripe for the community comment.

The solution for 'manuscript-savaging reviewers'

Colin Anderson — 2009-03-16T18:17:17Z

The article by Virginia Walbot is an excellent primer for reviewers. However, it is surprising that the simplest solution to the "manuscript-savaging reviewer" problem was not considered. The solution is to encourage or even demand that reviewer’s identities are not hidden. Non-anonymous reviewers are much less likely to make spurious claims or demands. Instead, due to the accountability that comes with open reviewing, the reviewers restrict their criticisms to those they are quite certain of. The usual argument against open peer review (e.g. as practiced by the journal Biology Direct) suggests that the critiques will not be sufficiently rigorous. This should not be seen as a strong argument against open review, as the reviewer’s reputation is in fact much more on the line in opening reviewing. There will be much more pressure to catch the fatal flaws and ignore the subjective gut responses, responses that are all too frequent in rapidly done anonymous reviews. Given the time demands we all face, I would surmise that the true origin of resistance to open review lies in reviewers not wanting to have to take the time that the accountability of open review demands. The primer for reviewers (and editors) should at least include an encouragement to sign reviews.

A paper's own merits

Mark Gijzen — 2009-03-16T18:16:51Z

There definitely seems to be a rise in excessively critical and disingenuous reviews. But there is also poor handling of manuscripts by editors, who often show bias or misunderstanding of the subject. My feeling is that much of this arises from our current over-obsession with journal prestige and impact factor. Perhaps open access models will help to put more emphasis on judging papers based on their own merits, rather than the title of the periodical it is published in.

Never savagery for savagery's sake.

Ian Burgess — 2009-03-16T18:16:15Z

One of the first things I learned as a reviewer is that you should never write something that will not benefit the authors either to improve the manuscript or as a lesson for future writing. I agree that with the introduction of online reviewing it is easy to jump in with documenting flaws without first reading the whole manuscript. However, I also feel that with online submission some authors are sending in their work more hastily than they would once have done had they needed to forward a pile of paper to the editorial office.

Apart from training our students to identify the strengths and weaknesses of others' papers we also need to train them to look critically at everything they write. Many is the manuscript I have seen that clearly has not been reviewed internally either by the author's peers or supervisor or, if it had been, the products of that review show either that the internal reviewers were too close to the trees to see the forest or else they have skimmed over the weaknesses, presumably hoping nobody else would see them. Maybe some of them are too timid to point out the flaws in the work of their supervisees, some are not perceptive enough to identify the issues, and others may fear that a little criticism is not what is required. However, better a mild analytical criticism at home where the issues can be discussed face to face than to be savaged by some unknown using a few short sentences to try to convey points that really need extended discussion. Since a high proportion of manuscripts give acknowledgement to departmental seniors, and even outsiders, for their "helpful" comments on the manuscript I frequently wonder what it must have looked like before it was let out.

Too often I come across vague suggestions as to why a set of results are not as expected but the authors invariably appear to have made no attempt to determine whether their suggestions may be correct, or even state that this line of enquiry is being pursued as a separate investigation. If the results being put forward for publication are preliminary this needs to be said. If the money or time ran out before all the angles could be addressed, why not say so? If you've run out of ideas you should not fear saying "I don't know how to approach this" rather than giving a lot of flim-flam that will only attract vitriol. I know there is considerable pressure to publish rapidly from all sides, but a little quiet reflection about how other people might view what you have written should surely reduce the number of poor manuscripts entering the publications arena.

I really do like reading other people's research. It gives me great pleasure to be able to write that a project was soundly conceived, the results discussed roundly, the conclusions are valid, and a manuscript is well written. Sadly it is something I encounter less and less frequently, so training students to analyse past publications may be working in some fields but doesn't seem to be doing so in mine.

Author response

Robin Weiss — 2009-03-09T16:58:41Z

I thank Burgess for the correction concerning Culex mosquitoes.

I agree that chimpanzees are certainly not exclusive herbivores, but they eat more tree leaves than humans do.

As Burgess points out, humans engaged in fishing and swimming even if they were not an obligate 'aquatic' species.

Robin A Weiss

Authors Reply

Roscoe Stanyon — 2009-02-16T16:23:08Z

Due to space limitations we did not discuss completely the evidence for the hypothesis that Tibetan settlement could well be earlier than that of Japan. We noted that the genetic diversity is much higher, usually considered indicative of earlier settlement, and that the coalescence time of the Tibetan Y chromosome sublineage is older than that of Japan (52,000 vs 37,000). We can add here that Shi et al also noted that the both the Tibetan and Japanese sub-haplogroups have a short-distanced, star-like network structure, typical of founding lineages. Further, the earliest material evidence for modern humans in Japan is at 30,000 year ago while recent archeological data shows modern human presence in Northern Tibet is as least as old if not older (30 to 40,000 year ago). All these data are consistent with an ancient settlement date for Tibet. We cannot judge the detail and the accuracy of the Wikipedia entry, but it is clear that at least some parts of Tibet were apparently hospitable for humans earlier than previously thought. Finally, current research deals mostly with questions of the when and where of modern human migration. The questions of why raised in this comment are not only more challenging, but also more rewarding and certainly will eventually be the subject of future research.

R. Stanyon, M. Sazzini & D. Luiselli

Settlement of Tibet

William Sweet — 2009-02-16T15:51:20Z

Per http://en.wikipedia.org/wiki/W%C3%BCrm_glaciation and the figure "Vegetation types at the last glacial maximum", at roughly the time of the suggested in migration to Tibet, the vegetation was "polar and alpine desert" (if I can correlate the colors correctly). What would push a population (thought to be small?) to such a climate when other areas of southeast Asia have vegetation types that seem to be much more suitable for human occupation?

Parasite risks

Ian Burgess — 2009-02-12T10:48:12Z

I found this overview analysis of great interest. It just goes to show how versatile and resilient most parasites are, considering their otherwise fragile and vulnerable natures.

I found one point of error, Plasmodium vivax is not transmitted by Culex spp mosquitoes. Some of the rodent and bird malarias have culicine vectors but as far as I know none of the human infecting species can form sporocysts in culicines.

Also I think strict herbivory is often not quite the norm in chimpanzees that is implied, they are opportunists that seem to feed on many things given the chance.

Finally, great apes in Africa may not have schistosomes mainly because they are not widely known for their contacts with the relatively open waters likely to harbour the parasites, unlike some of the monkeys. In contrast the fishing, and apparently water loving, humans would have encountered these early on in their move away from dense forest.