Publishing with eLife: “more a process of a collaboration than an exam you need to pass”

In our paper “Knockout of cyclin-dependent kinases 8 and 19 leads to depletion of cyclin C and suppresses spermatogenesis and male fertility in mice” we showed that deletion of both CDK8 and CDK19 suppresses male fertility, through lowering of production of testosterone by Leydig cells, and arrest of spermatocytes in pachytene of Meiosis I.

Overall, this is the first time a role of CDK8/19 was demonstrated in spermatogenesis and testosterone production. This is a fascinating result for two reasons – first of all, single knockouts of CDK8 and CDK19 don’t exhibit a major phenotype in adult animals (although CDK8 deletion is lethal embryogenesis).

For a long time it was theorized that CDK8 can be replaced by CDK19 and vice versa, and this is why we don’t see major phenotypes from single knockouts, and this is indeed what we saw in our model. Previously a similar effect was shown in Dannappel et al., where double KO of CDK8 and CDK19 in the intestine partially inhibited secretory cell differentiation, and we also confirmed this effect in our mice. But interestingly the effects of CDK8 and CDK19 deletion in spermatogenesis were not present (or previously reported) in mice treated with CDK8/19 inhibitors.

Which leads to the second reason why this is an unexpected outcome – most phenotypes of CDK8 and CDK19 are kinase dependent, although several papers also reported kinase-independent phenotypes in cells. Previously several papers, including one from us, showed that CDK8 or CDK19 are needed to stabilize their partner cyclin C, which may have functions of its own (at least it was demonstrated in yeast), and here we also saw that cyclin C was absent in DKO. So this may be a kinase-dependent phenotype of CDK8/19, but to prove this we will need to study mice with the kinase-dead variant of CDK8. Alternatively we don’t see this phenotype in drug-treated mice because we can’t achieve full and continuous inhibition of CDK8/19, which we see in KO mice, although the same concentrations are enough for the anti-cancer effects of these inhibitors.

”Most of all we liked that the Editor accepts the paper, and then the review process begins.”

We were not fully aware of the eLife model at the time of submission, but when we understood the process we decided that we liked it.

Most of all we liked that the Editor accepts the paper, and then the review process begins. This really lessens the stress that the paper would be ultimately rejected after a lot of work done after revisions. It was also great that the reviewers coordinated their reviews, so we wouldn’t be pulled apart by conflicting suggestions. We liked that every part of the review was open to everyone. The rating/assessment system was a bit hard to understand at first, but after we read more about it we liked that it gives you more information about the paper.

Editor’s note: you can learn more about eLife Assessments here.

... scientific publishing should not be dependent on for-profit rating agencies…

Our only reservation about the process was would the article be indexed by WoS/Scopus (the dispute was ongoing at the time). The grant system in our country requires a certain amount of WoS indexed papers published per year, and so it is critical for us to have the paper indexed by these organizations. We totally agree with eLife's position that scientific publishing should not be dependent on for-profit rating agencies, but unfortunately this is the position of our grant agencies.

[publishing with eLife] felt more a process of collaboration than an exam you need to pass to get your paper published.

We liked the reviews, they were very constructive and really helped to improve the article. At the same time we felt at ease that we didn’t need to do the experiments which we couldn’t perform because of different constraints.

This is especially valuable for people from developing countries or labs which do not have the resources of bigger centers. While in the traditional model that would mean that we would need to risk a rejection or spend a lot of time and resources to perform the experiments, delaying the publication, here we could focus on things that we thought were important, and simultaneously doable in our hands.

Overall it felt more a process of a collaboration than an exam you need to pass to get your paper published. Maybe with more adverse reviewers we would feel differently, but this was one of most not only pleasant, but useful peer-review experiences.

The assessment is an interesting system and we liked it – it provides more information about the article, and can give an indication for readers about the most important articles. We think that it would be useful if editors and reviewers would be more transparent about why the ratings change during reviews and what suggestions can improve the rating.

On the one hand this can lead to trying to game the scores, on the other hand we saw changes in both ratings going up and down after each round of the review, and it would be great to understand the logic of these decisions. Overall we were happy with our scores, and I think if we would submit another article to eLife we would be much more comfortable.

Try it! It takes a bit getting used to, but it’s a fresh take on the peer-review system and you have much more control over the process. In the end it’s still a tweak of the usual system.

VT: Personally it is often a stressful and disappointing experience. The landscape is understandably heavily tilted towards well funded and glamorous places in the West, and it’s hard to compete with them.

First of all, publishing costs are too high. Even an APC of 2000 USD is a substantial sum for us, and if you need to pay more it’s very hard on limited budgets. While you can ask for a discount or waiver of APC this is again not a happy experience, which feels like begging and also harder for many people culturally.

Then reviewers often ask for experiments that we cannot perform because of lack of funds, time constraint or because some reagent is not available for us. This is again totally understandable – we want the best experiments to answer the questions of the paper – but if this means that the paper would be rejected then no information from it will be available to anybody.

I personally think that we would often benefit from an option of more rapid and informal discussions with the editors and reviewers about experiments for revised versions – what is easier for us to do, can we try an alternative approach etc.

The last big problem is scientific agencies in our own country, which is shared in many places in the developing countries – as science is a very prestigious endeavour, countries want to have as many papers published, in the most prestigious journals possible. So they require a certain number of papers published per year for grant funding, require papers in top 25% cited journals (Q1) and incentivise publishing in high impact factor journals by awarding premiums for IFs. This of course leads to a lot of bad practices, such as prioritizing fast and less scrupulous journals, slicing data for several publications and outright research misconduct.

Just want to thank the eLife staff and reviewers! It was a long process, but all our interactions were helpful and friendly.

“The pragmatic reason [for choosing eLife] is that funding for this project was essentially at an end. The referee mindset of demanding more and more has spread to journals at almost all levels of perceived importance…”
– Mark Boothby

“This model has many benefits in my mind. But one of the biggest advantages is that the authors have a lot of control in the publication process.”
– Meike van der Heijden

“... we liked the idea of having an open ‘conversation’ with the reviewers...without the threat of rejection.”
– Patrick Allard

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What is an eLife Assessment?
What happens after you submit your research?

We are a relatively new lab of Molecular Oncobiology formed in 2019 in the Institute of Gene Biology.

Victor Tatarskiy (senior author) graduated from Moscow State University and did his PhD in Blokhin Memorial Cancer Center in Moscow.

Alexandra Bruter (first co-author) graduated from Moscow Institute of Physics and Technology, and completed her PhD in Institute of Molecular Biology.

Katerina Varlamova (first co-author) is a graduate of Moscow State University of Fine Chemical Technologies, and is currently finishing her PhD in our lab.