Research integrity

No Time Toulouse!

These 3 molecular biologists from Toulouse should really consider to stop. In fact, one of them already switched to psychiatry, probably to forget the Photoshopped science he published.

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:

“Tubulin band in A contains four repeated lanes. It also overlaps with the tubulin in B, after a 180-deg rotation.”

“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

file

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.


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19 comments on “No Time Toulouse!

  1. One interpretation of French Republican values (Liberté, égalité, fraternité) is that French citizens should engage with other citizens and be accountable. The French aristocracy came to a sticky end because it was alleged that it was not accountable and shielded from the public gaze.

    This debate seems to be a current one in the Republic, but let’s see how the authorities in Toulouse live up to Republican values.

    Like

  2. “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 “.

    Figure 5A.

    Hoya Camphorifolia has noticed unexpected symmetry of the ERK1-Myc-His panel (orange rectangle).

    https://pubpeer.com/publications/5EF0D7091A93960CC4C9783DCBB868#8

    There also seems to be unexpected symmetry in the Gab1-Myc panel (yellow rectangle).

    Like

  3. WB should be abolished in my opinion

    Liked by 1 person

    • “WB should be abolished in my opinion”.

      I understand the sentiment, but western blot is useful because it provides images which can be scrutinized.

      Like

  4. Smut Clyde

    Raynal is now deep into psychopathology, and describes himself as a “volunteer clinical psychologist”.

    A Lacanian psychologist, perhaps? Because some of these blots can be explained by Lacan’s Mirror Stage.
    https://en.wikipedia.org/wiki/Mirror_stage

    Like

  5. “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”

    Thomas Edouard and Armelle Yart turn up here:

    Blood. 2019 Sep 27. pii: blood.2019001543.

    Figure 5E.

    Full citation:

    Blood. 2019 Sep 27. pii: blood.2019001543. doi: 10.1182/blood.2019001543. [Epub ahead of print]
    1 comment on PubPeer (by: Tiliqua Nigrolutea)

    Catalytic dysregulation of SHP2 leading to Noonan syndromes impacts on platelet signaling and functions.
    Bellio M1, Garcia C2, Edouard T3, Voisin S4, Neel BG5, Cabou C6, Valet P7, Mori J8, Mazharian A9, Senis YA10, Yart A7, Payrastre B11, Severin S12.
    Author information
    1
    Inserm U1048 I2MC, France.
    2
    Laboratoire d’hématologie, CHU Toulouse, France.
    3
    Endocrinoloy, Bone diseases, and Genetics unit, Children Hospital, Toulouse University Hospital, France.
    4
    Laboratoire Hématologie, Centre Hospitalier Universitaire Toulouse, France.
    5
    Perlmutter Cancer Center, NYU Langone Medical Center, United States.
    6
    UMR1048, INSERM, France.
    7
    UMR 1048 Inserm-UPS, France.
    8
    University of Birmingham, United Kingdom.
    9
    The Medical School, Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom.
    10
    Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom.
    11
    Platelet production and function, signaling and phosphoinositides, INSERM, France.
    12
    INSERM U1048 I2MC, France sonia.severin@inserm.fr.

    Like

  6. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4257-62. doi: 10.1073/pnas.1119803109. Epub 2012 Feb 27.
    Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature.
    De Rocca Serra-Nédélec A1, Edouard T, Tréguer K, Tajan M, Araki T, Dance M, Mus M, Montagner A, Tauber M, Salles JP, Valet P, Neel BG, Raynal P, Yart A.
    Author information
    1
    Institut National de la Santé et de la Recherche Médicale U1048 and Université Paul Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires, F-31432 Toulouse, France.

    Figure 4C. Unexpected symmetry.

    Like

  7. “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”

    Pubpeer comments: https://pubpeer.com/publications/D60ECE15A418E7B5E809BC2732CE59

    Figure 7A. Unexpected symmetry.

    Like

  8. “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 in Yart et al JBC 2002.”

    J Biol Chem. 2002 Jun 14;277(24):21167-78.
    Figure 4C. Much more similar after horizontal stretching than you would expect, yet the treatments are different.

    Like

  9. I really believe if you were to remove 1.) old, beyond retirement age deadwood faculty, and 2.) serious cheaters, out of any academic institution, 1/2 the faculty would be gone. My conclusion: academic-grant sponsored research is an unbelievably wasteful system; Its wasteful in money and human resources. Think about of all of the tons of money these schools get to do research, and how little of it goes to supporting the creation of reproducible data–these are the people you want to support, but in the end there is little money for, and its not a steady job. And republicans in the USA think that cheap labor and capitalism solves all problems!

    Like

  10. For your consideration: A letter from faculty to students in his lab explaining that they must work at least 60 hours a week, because it is a “learning environment. ” Funny. I’ve never learned much of anything from faculty; Ive learned what I know through doing a lot of experiments, and the errors and problems that come about from them.

    This is exactly why revolutions occur: idiot leaders who expect more from their charges than they can possibly provide in return.

    http://www.chemistry-blog.com/wp-content/uploads/2010/06/Gassman-and-Meyers.pdf

    Like

    • alfricabos

      “Eminent investigators are not spellbound or overly impressed by the work of their predecessors and mentors but instead observe and question.” Santiago Jamon y Cajal.

      Like

    • “if you fulfill the requirements spelled out above, you can expect me to go all out in support of you” how about a decent salary for minimum 60hours per week, without taking a part-time job in washing dishes? Is this letter supposed to be a joke? 12 hours per working day? 10 hours per week just to read? Ask anyone working in a lab to have even 1 hour per week to read!!

      Like

  11. “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”

    Figure 3A. Unexpected symmetry.

    Like

  12. A few years ago there was a young woman at Columbia U carrying around a mattress to call attention to rape on campus. I’m thinking of throwing my recently obtained -80 freezer from a lab busted for fraud, putting on a cart, with the doors of the freezer open, and pushing in down hallways at my esteemed R1 research university to call attention to fraud. It is halloween, so maybe I can wear a blue blazer and don an English accent to pretend I’m Richard Marias, and I can start yelling into other labs, to call attention to buyllying. I can get my redhead ex girlfriend to follow me around to be Caroline Springer. LOX all the way. What fun.

    Liked by 1 person

  13. Given a system that rewards authors on impact factor, we have, for the Nth time, further examples that ‘never mind the data, just feel the hugeness of my IF’ becomes the driver for many, some out of desperation, others because corruption is a way to an easy 5 course meal.

    Like

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