No Time Toulouse!

Recently, the pseudonymous image integrity sleuth Clare Francis alerted me to an interesting trio of molecular biologists working at the Toulouse seat of the French National Institute of Health and Medical Research (INSERM) and the University of Toulouse III. Patrick Raynal (at Toulouse Mind & Brain Institute), as well as Christophe Heymes and Frank Lezoualc’h (at Institute for Cardiology and Metabolic Diseases, I2MC) truly have no time to lose for doing science properly.

Why should they, if their respective labs’ most important scientific technology seems to be The Photoshop. This is why things like this get published.

T Edouard, JP Combier, A Nedelec, S Bel-Vialar, M Metrich, F Conte-Auriol, S Lyonnet, B Parfait, M Tauber, JP Salles, F Lezoualc’h, A Yart, P Raynal Functional effects of PTPN11 (SHP2) mutations causing LEOPARD syndrome on epidermal growth factor-induced phosphoinositide 3-kinase/AKT/glycogen synthase kinase 3beta signaling Molecular and Cellular Biology (2010) doi: 10.1128/mcb.00646-09 

Such gel band duplication is unlikely to be a mistake of oversight, and this is just one example from this paper. One more example is this:

This is not just a gel image horizontally flipped and reused for a different experiment. This is in fact a physically different exposure film, but of the exactly same western blot, this is why the images look somewhat different.

Update 4.11.2019. There are more image manipulations in that paper, but Raynal himself sees nothing serious, as he explained on PubPeer:

“Obviously I did not pay enough attention to the images that were used as control for gel loading in this manuscript, but on a daily basis, controlling gel loading was a priority for me. And thus the main outcome of these experiments cannot be reconsidered.”

The Raynal lab seems to have been trolling scientific journals and the community, testing how far they can go before someone says something. There is no other way to explain the following publication.

M Dance, A Montagner, A Yart, B Masri, Y Audigier, B Perret, JP Salles, P Raynal The adaptor protein Gab1 couples the stimulation of vascular endothelial growth factor receptor-2 to the activation of phosphoinositide 3-kinase Journal of Biological Chemistry (2006) doi: 10.1074/jbc.m600987200 

The Myc immunoblot is hilariously unreal. First of all, the last 4 bands are for some inexplicable reason mirrored horizontally on themselves, and the other three bands of same gel were most obviously cut-and-pasted from somewhere else (the boxed edges are a clear give-away). Why did the authors do it? Was there some kind of Photoshop competition going on, back then in the Golden Age of Biological Imaging?

Another gel band is a vertical mirror image of itself. Why?

There are of course also other spliced and cloned gel bands in that paper, do have a look. But how to explain what happened to the pAKT gel band here, the first one from left:

Is the pAKT band really drawn with a felt-tip pen? If so, couldn’t they at leats try to draw it more convincingly, or was that actually the whole point?

The Raynal lab has more to offer, in fact a kind of psychological warfare on biomedical science. This is why Raynal is now deep into psychopathology, and describes himself as a “volunteer clinical psychologist”.

A Yart, M Laffargue, P Mayeux, S Chretien, C Peres, N Tonks, S Roche, B Payrastre, H Chap, P Raynal A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor Journal of Biological Chemistry (2001) doi: 10.1074/jbc.m006966200

Here, the first two and the last two bands of the Erk2 western blot are the same, only stretched. Which is probably an innocent mistake of oversight by some student who is no longer in the lab and those are loading control anyway and you can’t seriously expect us to still be storing original data from a paper which is 18 years old?

There are more problems in that paper, for example a lighter exposure of the same Erk2 loading control western blot decided to make a second appearance one year later, in a different set of experiments and in another JBC paper:

A Yart , S Roche, R Wetzker, M Laffargue, N Tonks, P Mayeux, H Chap, P Raynal A function for phosphoinositide 3-kinase beta lipid products in coupling beta gamma to Ras activation in response to lysophosphatidic acid The Journal of biological chemistry (2002) doi: 10.1074/jbc.m110411200 

Update 4.11.2019. Raynal explained on PubPeer what went wrong here:

“Indeed the same blot for controling Erk expresssion has probably been used in these 2 figures. I guess this is for convenient reasons. I apologize for this. Please note that this does not change the major outcome of each figure, as the images shown are representative of several experiments with similar results.“

The INSERM professor added:

Indeed, there seems to be an issue with the images controlling gel loading in this particular experiment shown in this figure. Please note that the particular images shown in this figure are representative of several expriments with similar results in terms of Gab1 and Sos association, and all of them have been controlled for gel loading, even though perfect images are not always obtained when one performs westerm blotting.”

Now, before moving on to the other two colleagues from Toulouse, one more psycho bombshell in the attrition war which the biochemist Raynal used to wage on molecular biology before he became a clinical psychologist. A certain Hoya camphorifolia decided to help Clare Francis tackling this monster.

C Sampaio, M Dance, A Montagner, T Edouard, N Malet, B Perret, A Yart, JP Salles , P Raynal Signal strength dictates phosphoinositide 3-kinase contribution to Ras/extracellular signal-regulated kinase 1 and 2 activation via differential Gab1/Shp2 recruitment: consequences for resistance to epidermal growth factor receptor inhibition Molecular and Cellular Biology (2008) doi: 10.1128/mcb.01318-07 

Gel bands copy-pasted, flipped and mirrored wherever you cast your eye. Those were just some examples from that Raynal lab paper.

Now Journal of Biological Chemistry, and to a degree Molecular and Cellular Biology, are dangerous journals to mess with, one can easily end up with a retraction for data manipualtion, regardless how old the paper is. American Heart Association (AHA) journals like Circulation or Circulation Research on the other hand are a relatively safe heaven for Photoshop enthusiasts. Luckily, both Heymes and his younger I2MC colleague Lezoualc’h are into cardiology.

M Métrich, A Lucas, M Gastineau, JL Samuel, C Heymes, E Morel, F Lezoualc’h Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy Circulation Research (2008) doi: 10.1161/circresaha.107.164947

The cardiology editors definitely won’t lift a finger about this 11 year old paper, also because it’s just some western blot loading controls which are irrelevant anyway. Same probably for this paper from Heymes lab:

X Loyer, AM Gómez, P Milliez, M Fernandez-Velasco, P Vangheluwe, L Vinet, D Charue, E Vaudin, W Zhang, Y Sainte-Marie, E Robidel, I Marty, B Mayer, F Jaisser, JJ Mercadier, S Richard, AM Shah, JP Bénitah, JL Samuel, C Heymes Cardiomyocyte overexpression of neuronal nitric oxide synthase delays transition toward heart failure in response to pressure overload by preserving calcium cycling Circulation (2008) doi: 10.1161/circulationaha.107.741702

However, the next Heymes-Lezoualc’h paper is rather new and the authors might at least get asked if they still happen to have any raw data. To which the authors will probably reply, unfortunately not, but the results were perfectly verified elsewhere, and no editorial action necessary will be needed.

M Bisserier, M Berthouze-Duquesnes, M Breckler, F Tortosa, L Fazal, A De Régibus, AC Laurent, A Varin, A Lucas, M Branchereau, P Marck, JN Schickel, C Deloménie, O Cazorla, P Soulas-Sprauel, B Crozatier, E Morel, C Heymes, F Lezoualc’h Carabin Protects Against Cardiac Hypertrophy by Blocking Calcineurin, Ras, and Ca 2+ /Calmodulin-Dependent Protein Kinase II Signaling Circulation (2015) doi: 10.1161/circulationaha.114.010686 

So what that theHDAC4 bands are obviously duplicated? Do you really think the conclusions are affected? Of course not, hence not even correction will be necessary!

This following paper appeared just this year. Someone felt so hilariously safe after all those years of Photoshop artistry that they really stopped giving a flying toss.

X Loyer, C Dubroca, M Branchereau, G Griffith, L Garcia, C Heymes Neuronal NO synthase mediates plenylephrine induced cardiomyocyte hypertrophy through facilitation of NFAT-dependent transcriptional activity Biochemistry and Biophysics Reports (2019) doi: 10.1016/j.bbrep.2019.100620 

The University of Toulouse had a serious fraud case just two years ago, in plant sciences, as it was reported on my site. The INRA-CNRS group leader Susana Rivas is not listed on INRA institutional website anymore, her lab profile was deleted sometime in 2018. INSERM already is dealing with the case of Patrick Legembre in Rennes, which involves accusations of bullying and now also data manipulation.

And now INSERM can enjoy going through the growing PubPeer records of Patrick Raynal, Christophe Heymes and Frank Lezoualc’h.

---