Guest post Research integrity

The Perennial Northern Blot of Lopez-Otin

Cancer researcher Carlos López-Otín published the same Northern blot no less than 23 times in 23 publications, between 1994 and 2006. Eventually Lopez-Otin et al even stopped caring what order of samples that original loading control had.

On the Iberian peninsula, there seems to be a tradition to give well-connected scientists suspected (or even convinced) of data fudging an award. In Spain, Carlos López-Otín, Professor of Biochemistry and Molecular Biology at the University of Oviedo, was given a Mentoring Award from the elite journal Nature, on recommendation from Spanish academia and despite evidence of data irregularities in his papers. This prompted my readers, in particular the famous pseudonymous data integrity sleuth Clare Francis, to comment on on PubPeer and on my site (as “Zebedee”) with additional evidence, which made Lopez-Otin’s scientific credibility look progressively worse and worse, with each new post.

Eventually, an image of a Northern blot (showing expression of mRNAs which code for proteins) was found to appear recurrently across several papers from that Oviedo lab, where the authors pretended it was a newly produced analysis. In reality, it was a “library” loading control reused so the authors could re-run same RNA gel of human tissue lysates over the years and never check ever again what they have actually loaded on their gels. Eventually Lopez-Otin et al even stopped caring what order of samples that original loading control had.

Clare Francis was soon joined on his quest for the Perennial Northern Blot of Oviedo by Elisabeth Bik, famous microbiology blogger and image duplication detective, and my regular contributor (also pseudonymous) Smut Clyde, who now presents you the findings of no less than 23 appearances of that same northern blot in 23 publications from Lopez-Otin’s lab in the guest post below. It is just as convincing as if the Spanish actor Antonio Banderas appeared in 23 different films still dressed in same costume from his 1995 hit Desperado, carrying same guitar case. Incidentally, also Lopez-Otin’s Perennial Northern Blot made its first appearance at around that year.

screenshot-vimeo.com-2018-05-04-12-18-38
Celebrity friends. Still from a 2017 video by Fundació Princesa de Girona

The cancer researcher Lopez-Otin is an actual real-life celebrity in Spain. On 29 June 2017, he helped the King of Spain open the Princess of Girona Foundation Awards ceremony, together with another Spanish celebrity of the creative art of the pretend, Antonio Banderas. The Princess Foundation wrote about their 2017 gala host:

“Carlos Lopez-Otín is an academician of the European Academy and the Royal Academy of Sciences of Spain, and Doctor Honoris Causa by several Spanish and foreign universities. Throughout his scientific career he has received several awards such as the European FEBS Prize for Biochemistry, the DuPont Award for Life Sciences, the “Carmen and Severo Ochoa” Award, the Mexico Prize for Science and Technology, King Jaime I Prize Research and the National Research Award “Santiago Ramón y Cajal”

That multiple award winning research star is also EMBO member, just like some other of his Spain-based colleagues of questionable research integrity are: Maria Pia Cosma and Pura Munoz-Canoves. These two also regularly receive juicy research grants and recognition: Munoz-Canoves’ most recent was the “Vanguardia de la Ciencia” award, while Cosma was given in 2016 “Ciutat de Barcelona” award. Another Spanish researcher with shady data in his papers is Manel Esteller, he also gets awarded regularly, in 2016 it was the Catalonia International Prize from (now fugitive) President Puigdemont. In Portugal, Esteller’s former PhD student and now zombie scientist Sonia Melo was given a Prémio FAZ Ciência award from Fundação AstraZeneca, only two months ago. There are surely more of such questionable Iberic awardees, readers are welcome to salute these stars of Photoshop in the comment section.

Lopez-Otin’s data integrity issues involve also such obviously manipulated gels like this Northern Blot in Llano et al Cancer Research 1999. What was it the authors didn’t like that they had to duplicative parts of this gel and introduce other digital “modifications”?

I personally have a theory that in this way the system of Iberian academia announces who is untouchable, in order to intimidate critics of research misconduct in their own ranks. Probably a pathetic left-over from the fascist past of Spain and Portugal. The subliminal message is: yes, we all know what these award-winners did to create those big papers and we don’t mind at all. The award-giving farce shows who the role models are and what Spanish and Portuguese scientists are expected to do with their silly notions of research integrity: shove it, start making big papers whatever it takes, or lose your job. In fact, not even the arch-zombie scientist Susana Gonzalez had to suffer unemployment, unlike masses of honest young Spanish scientists.


A Perennial Northern Blot, by Smut Clyde

The title of this post refers to the famously picaresque Western blot belonging to a Brazilian diabetes researcher. sinbt0jIn its protean versatility, Mario Saad‘s pentadecaplicating blot could transform itself into any protein — tubulin, actin, GLUT4, IRS1 — from any combination of source conditions. It thereby appeared in at least 15 versions, spread across 10 papers in “an intricate publishing web“, serving as the loading control in that many different experiments (that is, as a measure of the total level of extracted protein, for normalising the measurements of the protein of interest). In my imagination it spoke with the voice of Robin Williams. This site forwarded a report on the Wandering Western… the ensuing saga included editorial Expressions of Concern, lawsuits, an investigation by Saad’s university that saw no evidence of misconduct, and 13 retractions so far (RetractionWatch are keeping score).

The present case also concerns re-use of a loading control, but this time featuring a Northern blot. The compass-point tradition for naming gel-electrophoresis techniques began with Sir Edwin Southern, pioneer of Southern blotting, for this is how humor works in molecular biology. It has been explained to me that Northern blots do not directly measure the popularity of a protein in the cellular economy; instead, mRNA (encoding for a protein) is the chemical species, extracted from various sources (lanes), and spread out into bands according to molecular weight. Then transferred (blotted) from the electrophoresis gel to a filter for stability, and detected by inducing the mRNA to bind to a matching and radiotracing DNA probe.

So in this case, a team of researchers have a bank of 28 “cell smoothies”: two sets of eight tissue types, one set of eight cancer-cell lines, and four fetal-tissue samples. In a series of papers published over a decade, the team have characterised numerous proteins from within the self-organising complexity of the human cell — sequencing the DNA for each protein and specifying its chromosomal location, describing its role within that complexity, and checking which tissues express it (which depends on which genes remained active in each lineage of cells that differentiated and specialised and became a tissue). That is to say, the Northern Blots were just one aspect of the papers, and they are all outside my comfort grade and above my pay zone.

the future

Each study took a few drops from the stored samples, blotted it (“Filters containing about 2 µg of polyadenylated RNAs from the indicated human tissues”), and probed for the mRNA of choice. But there are limits to the precision that a pipette can provide — even in the hands of a trained gene-modified laboratory monkey — so the final stage is to wash the probe DNA out of the filter and probe it again for Actin (a background “housekeeping” protein, required by cells to maintain their architecture, unless they are dead) to correct for the actual aliquots that were used. Thus papers in this sequence typically include a phrase along these lines:

“Filters were subsequently hybridized with a human actin probe to ascertain differences in RNA loading”.

It is conceivable, however, that this phrase was repeated from the first paper, along with the loading blot itself. Comparing 23 papers, there appears to be one original blot for each bank: four blots, which are variously compressed and clipped according to the exigencies of publication, and varying also in exposure, rather than a separate measurement after each separate exercise in tissue localisation. The sources are ‘Zebedee’, commenting on threads at this site; anonymous contributors to PubPeer threads; Elisabeth Bik; and myself.

northern1-5

This comes to our notice because a 23-fold replication beats the 15-fold record of the Brazilian wanderer. Crucially, though the possible copies are consistently identified as Actin, and the authors have tried to label the sources of the lanes consistently. The reuse of a ‘loading library’ is deprecated, but this does not begin to approach the problematic level of the Brazilian Western: there was no attempt to mislead (other than the claim that the control in each study was specific to it, made subsequently to the data to be controlled). It is a perennial blot, always in the same place, rather than a wanderer or vagrant.

northern6-10

northern11-15

Regrettably, the labelling of lanes was not as consistent as was intended. In a 2003 appearance of the fetal-tissue blot, it was flipped horizontally relative to the lane labels, as marked with a red box in the Figures. Note that in some publications the lanes are listed in reverse order — from Leucocytes to Heart rather than vice versa — and in the Figures I have flipped each band and labels in such cases, to keep a single sequence of tissue types (hence the mirror-image text in places).

Red boxes were also necessary in some cases where the cancer-cell blot was flipped relative to its lane labels, and for the #2 array of tissue cells in the 1999 paper. In addition, that blot was rotated through 180° from 2001 onwards (so that the Actin background for Thymus cells becomes that of Colon cells, and vice versa, while Testes and Ovary change places, and Spleen with Leucocytes). This is marked with orange boxes. One can only hope that these pictorial labelling issues did not extend into the measurements of Actin from the blots, as used in the quantitative results.

northern16-20

Finally, two blue arrows mark the omission of ‘Pancreas’ and ‘Skeletal muscle’ from one study each, with the loading band spliced to remove that lane.

I am going to play ‘good cop’ here, and propose that the corner-cutting absence of study-specific controls probably made little difference to the results. Corrigenda to the paper acknowledging the use of archival controls would be appropriate (along with correction of any flipped and rotated bands). Other issues have been raised about other figures in some of the papers, but I do not address those here.

Details of the 23 publications follow. We are still hopeful of finding a few more examples of the Perennial Northern Blot.

  1. 1994. “Human cathepsin O. Molecular cloning from a breast carcinoma, production of the active enzyme in Escherichia coli, and expression analysis in human tissues“, Velasco et al; J Biol Chem., 269(43):27136-42.
  2. 1995. “Cloning and expression analysis of a novel human serine hydrolase with sequence similarity to prokaryotic enzymes involved in the degradation of aromatic compounds“, Puente & López-Otín; Journal of Biological Chemistry 270, 12926-12932. DOI 10.1074/jbc.270.21.12926 Figure 5.
  3. 1996. “Cloning and Expression Analysis of Human Bleomycin Hydrolase, a Cysteine Proteinase Involved in Chemotherapy Resistance“, Ferrando et al.; Cancer Research 56: 1746-1750. PMID: 8620487
  4. 1996. “Molecular Cloning of a Novel Membrane-type Matrix Metalloproteinase from a Human Breast Carcinoma“, Puente et al; Cancer Research 56:944-949.
  5. 1997. “Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location, and tissue distribution“, Pendás et al; J Biol Chem. 272(7):4281-6. doi: 10.1074/jbc.272.7.4281 Figure 7.
  6. 1998. “Cathepsin L2, a Novel Human Cysteine Proteinase Produced by Breast and Colorectal Carcinomas“, Santamaría et al; Cancer Res. 58(8):1624-30.
  7. 1998. “Cathepsin Z, a novel human cysteine proteinase with a short propeptide domain and a unique chromosomal location“, Santamaría et al; J Biol Chem. 273(27):16816-23. doi: 10.1074/jbc.273.27.16816 Figure 5.
  8. 1999. “Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members“, Velasco et al; J Biol Chem. 274(8):4570-6. doi: 10.1074/jbc.274.8.4570 Figure 6.
  9. 1999. “Molecular cloning and structural and functional characterization of human cathepsin F, a new cysteine proteinase of the papain family with a long propeptide domain“, Santamaría et al; J Biol Chem. 274(20):13800-9. doi: 10.1074/jbc.274.20.13800 Figure 6.
  10. 1999. “Identification and Chromosomal Location of Two Human Genes Encoding Enzymes Potentially Involved in Proteolytic Maturation of Farnesylated Proteins“, Freije et al; Genomics 58, 270–280. DOI: 10.1006/geno.1999.5834
  11. 2000. “Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors“, Velasco et al; Cancer Research 60, 877–882. pubmed: 10706098
  12. 2001. “Identification, Characterization, and Intracellular Processing of ADAM-TS12, a Novel Human Disintegrin with a Complex Structural Organization Involving Multiple Thrombospondin-1 Repeats“, Cal et al; Journal of Biological Chemistry 276, 17932-17940. doi: 10.1074/jbc.M100534200 Figure 5.
  13. 2002. “Matriptase-2, a Membrane-bound Mosaic Serine Proteinase Predominantly Expressed in Human Liver and Showing Degrading Activity against Extracellular Matrix Proteins“, Velasco et al; J Biol Chem. 277(40):37637-46. doi: 10.1074/jbc.M203007200 Figure 8.
  14. 2002Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains“, Cal et al; Gene 283 49-62. doi: 10.1016/S0378-1119(01)00861-7
  15. 2003. “Polyserase-I, a human polyprotease with the ability to generate independent serine protease domains from a single translation product“, Cal et al; PNAS 100(16): 9185–9190. doi: 10.1073/pnas.1633392100 Figure 4.
  16. 2003. “Human Autophagins, a Family of Cysteine Proteinases Potentially Implicated in Cell Degradation by Autophagy“, Mariño et al; Journal of Biological Chemistry 278, 3671-3678. doi: 10.1074/jbc.M208247200 Figure 3.
  17. 2003. “Identification and Characterization of ADAMTS-20 Defines a Novel Subfamily of Metalloproteinases-Disintegrins with Multiple Thrombospondin-1 Repeats and a Unique GON Domain“, Llamazares et al; Journal of Biological Chemistry 278(15):13382-13389. doi: 10.1074/jbc.M211900200 Figure 4.
  18. 2004. “Identification and Characterization of Human and Mouse Ovastacin“, Quesada et al; JBC 279 (25) 26627-26634. doi: 10.1074/jbc.M401588200 Figure 3.
  19. 2004. “Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases“, Queseda et al; Biochemical and Biophysical Research Communications 314, 54-62. doi: 10.1016/j.bbrc.2003.12.050
  20. 2005. “Identification of Human Aminopeptidase O, a Novel Metalloprotease with Structural Similarity to Aminopeptidase B and Leukotriene A4 Hydrolase“, Díaz-Perales et al; Journal of Biological Chemistry 280, 14310-14317. doi: 10.1074/jbc.M413222200 Figure 4.
  21. 2005. “Human Polyserase-2, a Novel Enzyme with Three Tandem Serine Protease Domains in a Single Polypeptide Chain“, Cal et al; JBC 280, 1953-1961. doi: 10.1074/jbc.M409139200 Figure 3.
  22. 2005. “Identification and Characterization of Human Archaemetzincin-1 and -2, Two Novel Members of a Family of Metalloproteases Widely Distributed in Archaea“, Diaz-Perales et al; JBC 280(34):30367-30375. doi: 10.1074/jbc.M504533200 Figure 4.
  23. 2006. “Identification and characterization of human polyserase-3, a novel protein with tandem serine-protease domains in the same polypeptide chain“, Cal et al; BMC Biochemistry. doi: 10.1186/1471-2091-7-9 Figure 7.

Update 7.05.2018. Based on reader comment:

oviedo

 

 

 

 

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99 comments on “The Perennial Northern Blot of Lopez-Otin

  1. I am glad that you discuss this case, which has disturbed me since I noticed all the problematic cases at Pubpeer. I am part of a group of scientist who collected all the evidence, did our own analysis and sent the home institution (University of Oviedo) a Powerpoint report describing the numerous problematic cases in detail.

    The answer from the Research ethics committee of the University of Ovidedo was surprising:

    “After listening to the experts in the field, this Committee has concluded that there are no relevant irregularities in the papers you mentioned and that the research has been performed following the standards established by the different journals.

    The University of Oviedo fully support professor Carlos López Otín and his research group and we are very concerned about the potential consequences of publishing this kind of doubts on the internet.”

    The letter was signed by José Ramón Obeso, Vice-rector of Research.

    When we responded asking for details in the report, especially regarding the Research ethics committee of the University of Ovideo and the “experts in the field” we understood that there is not much transparency at Spanish universities:

    “…..The deliberations of the Ethics commitee are confidential.

    Anyway, we suggest you to review the Material and Methods sections of the journals your examined, because they explain in detail the procedures used in the experiments and it will clarify most of your concerns. I remind you that this material is also subjected to revision of the journals editors and referees.

    Best regards,
    Ethics Committee.”

    Since the University of Oviedo is a public university I would assume that transparency in this kind of cases is an obligation. I do not know the law here, but at the home page of the university I found some information regarding transparency:

    “In accordance with the provisions of Law 19/2013, of December 9, transparency, access to public information and good governance, the Transparency Portal of the University of Oviedo makes available to the university community and the whole of the citizenship, relevant information and general interest about its organization and functioning as a public service of higher education and scientific and technical research, guaranteeing compliance with the obligations of active advertising provided by law.”

    Original text:

    “De conformidad con lo establecido en la Ley 19/2013, de 9 de diciembre, de transparencia, acceso a la información pública y buen gobierno, el Portal de Transparencia de la Universidad de Oviedo pone a disposición de la comunidad universitaria y del conjunto de la ciudadanía, información relevante y de interés general sobre su organización y funcionamiento como servicio público de educación superior e investigación científica y técnica, garantizando el cumplimiento de las obligaciones de publicidad activa previstas legalmente.”

    I will be grateful if someone can provide us with more information regarding transparency laws in Spain.

    Like

  2. If uniovi does not take the ppt report, why do not you upload that on youtube? It had worked well in the case of Shigeaki Kato. See the example.

    . After this, Kato left science.

    Like

  3. Nothern Blots are not only trick for Lopez-Otin. In previous thread, readers pointed out more doubts on WB, immunostaining, and colony countings. https://forbetterscience.com/2017/12/19/nature-rewards-data-manipulation-with-a-mentoring-award/
    Each technique reserves independent thread.

    Like

    • Ana Pedro

      But what type of reviewers/ journal editors let this type of things pass? For sure Lopez-Otin wouldn’t publish this alone

      Like

  4. MG Haan

    They have learned Northern Blot was such an out-dated technique. They jumped to WB, then immunostaining, and subjective colony countings.
    Their 2015 paper in NCB put those techniques together. Also, their tricks were put together.
    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 14 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    Like

  5. Pingback: Boletim de Notícias: Comissão da Câmara vota pacote de facilidades para agrotóxicos | Direto da Ciência

  6. Oarteze

    Looking forward to seeing how or whether uniovi reacts to the pile of new evidence, 23 papers! and for sure more papers to come. They cannot pretend the ignorance.

    Like

  7. Doubts on subjective colony countings on their 2015 paper in NCB paper continues.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 15 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    Like

  8. Their 2015 NCB paper is still accumulating lots of comments.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 17 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    None of their submitted original films of WB were labeled. Only retrospectively annotated for figure preparation, that allows possibility of calling any sample as they wanted. Even though they annotated molecular weight (KDa), I do not see molecular weight markers run on the whole membrane.

    Like

  9. More comments on 2015 NCB paper.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 21 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#20

    “I am following the former comments on the paper, considering arguments around NF-kB that affecting the main message of this study. NF-kB blots (EMSA) in this paper were too much intensely developed and lost its resolution as you can see in raw data. Nevertheless, their main figures showed relatively cleaner blots that can not found in raw image.
    Because of NF-kB being main points of this study, I would say that the author should go back to check the original blots.
    However, even if it were done, the problem still remains that none of the blots were formally labeled, so they could claim any lane as their ‘actual sample’…”

    Like

  10. More comments on 2015 NCB paper.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 23 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#23

    “The blots of p16 were flipped. The blots of lamin B1 seem to come from different membrane of unrelated samples. It is hard to presume which blots correspond to which sample, because 1) The order of sample differ between each blots even in the same set of experiment; 2) The orginal mambranes were not labeled. I would share the view of Purpuradusta Barbieri that “allows possibility of calling any sample as they wanted”.”

    Like

  11. 2015 NCB paper (Soria-Valles et al.) still gains more comments on Pubpeer.
    Suspicious flipping and jumping bands from different films, and inconsistent colony countings generate more attention.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 30 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#30

    “Lack of clear and solid standard of colony countings yields inconsistent results and representation.”

    “Weird… It is hard to see how they conducted experiments. Did they run all the samples same day to make corresponding raw data to fulfill demand of NCB?”

    “It is very concerning that each band were flipped, intensity of signal was artistically modulated, and came from random film. Rubrimonas Cliftonensis pointed the cherry-picking of bands from irrelevant films.”

    “Ok, extensive posts on this paper might be reconciled into two major issues.
    a. The blots are flipping and jumping aroud different films. And contrasts of bands are too much modified. This issue accounts for most half of the paper (figure 2a, 3c, 4g, 4i, 5f, 6b, 7a, 8b, s1e, s2b, s4c, s6a, s6c, s6e, s8a-e).
    b. The criteria of colony counting is unclear and subjective. This issue accounts for another half of the paper (figure 1b, 1d-g, 3c, 3e-g, 5a-b, 5d-f, 6a, 6c-d, 7b-c, s1g, s4a-b, s5b-c, s5e-f, s6b, and s6d).”

    Like

  12. New doubts on 2015 NCB paper (Soria-Valles et al.). Where are their beta-actin control bands coming from…?

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 32 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#32

    “The raw data of control beta actin bands are missing.
    P-p53, p53 and p16 bands were flipped.
    P21 bands seem to come from irrelevant membrane. Their layout and lanes never match with other samples.
    There is some weird baked membrane (or black box) on p16 membrane.”

    Like

  13. Cartuli

    You guys are starting a witch hunt against one of the most honest scientists in Spain (something I would not say of some of the other names you mention in your article, by the way).

    There might be some sloppiness (specially in the changing the names from different wells across different articles) but, if you knew López-otin, you would never question his integrity.

    As far as I know, that blot was a commercial blot and not a cheap one, so they didn’t blot it over and over against actin to extend the lifespan of the blot itself, and be able to reuse it for longer period of times.
    Also, it actually means it was not totally needed to re-blot against the actin probe, since it was the same blot (same thing as in a WB, where you wouldn’t blot against actin every time you do the stripping if you are analyzing several proteins on the same gel), not different blots loaded by “a trained gene-modified laboratory monkey”, but maybe you didn’t care enough to read the methods sections where it states that the blot was purchased from Clontech?

    I’m all up for detecting fraud and making science better, but you should be more careful with your claims and your judgements before starting an unfair crusade.

    Also, you should keep to yourself your very-much-not-hidden disdain against the Iberian peninsula as a whole. There are definitely rotten apples, as in every other country, but there are no systematic “untouchables” nor anything close to your statement that “we all know what these award-winners did to create those big papers and we don’t mind at all”.

    Like

    • Smut Clyde

      Am I to understand that a single blot was acquired with proteins already gelled and transferred, then repeatedly stained (and stripped) for 23 different proteins?

      Like

      • RNA actually, not proteins. Which is much more unstable than protein (western blot) or DNA (southern blot) or bullshit (eastern blot). I wonder if anyone ever stripped an RNA blot more than once or twice, because you lose lots of bound material with each stripping. After 20 such washes over the years, I woudl expect the blot membrane to disintegrate, not just lose all traces of RNA it ever used to contain. But as we learned, that is a “special”, custom-made magical super-blot.

        Like

      • Carolyn

        They use a commercial Northern blot membrane, and if you see the commercial instructions from Clontech you can see that it can be reuse multiple times. However, it is very easy to talk about fraud and image duplication without having an idea of ​​what is a Northern-blot and without having ever perform one.

        Like

    • Zebedee

      “There might be some sloppiness (specially in the changing the names from different wells across different articles)”.

      That’s O.K. then. What a relief!

      Like

      • Cartuli

        No, sloppiness should be corrected in any paper where data is not correctly presented, of course.
        All i’m saying is that those are probably honest mistakes, mistakes that can happen to all of us (it did happen to me as well after publication, that we realized a couple of mistakes in one of our figures). Specially when you’re talking about someone with over 400 publications.

        As for Leonid’s comment, cause it doesn’t let me reply to you directly, i do have run quite some Northern Blots myself (have you?) and, precisely because stripping is not a good thing for northerns, what you typically do is let the radioactive signal decay by itself, before you probe it against whatever other gene of interest.
        I can assure you that, if you do it that way and you keep the blots correctly stored (not totally dried, and in a sealed bag at -20C), the blots can last for a LOONG TIME and can be reused many times.
        That’s the exact explanation as to why they wouldn’t strip and reblot against actin, to preserve the lifespan of the blot.
        Again, i would be surprised if you yourself had done many (or any) of these northern blots, but still you seem to indicate that you have the higher truth about it…

        Like

      • Thank you for your insights. Now we know how Lopez-Otin lab produced so many papers. Others have to do really boring, pedestrian things, like experiments. But the Lopez-Otin lab had one blot, and used it to make many papers, over many years. The loading control remains same old picture from years ago. And at some point, that blot grew new tissues on it!
        Ah well. You are right: I never did Northern Blots, so maybe the practice of data re-use is different in that particular community of Northern blot researchers.
        Also I never transplanted a trachea, so maybe I should also shut up there.
        I did quite a lot of Western Blots though, but then again never for Nature Cell Biology level, so I better shut up also there.
        Thanks again, anonymous expert!

        Liked by 1 person

      • Smut Clyde

        Carolyn is right to point out that radioactive decay is an alternative to stripping.
        If this theory is correct, and the same gel was preserved and used repeatedly, what level of agreement should we expect between the shapes and widths of the lanes and blots for the different RNAs it was probed for?

        Like

    • Charles

      With all due respect, arguments cannot work one way and the oposite, particularly among scientists. The decisions that Lopez-Otin deserved many prizes, many grants and many interviews in mass media were precisely based in the fact that his productivity had been much greater than that of his peers. Many scientists that competed for the same prize, grant or visibility had to accept that it was just fair that everything went to Lopez-Otin. After all, his group had published more than 400 papers! Now you cannot argue that because he has published 400 papers you cannot expect the same standards of quality that one would ask to someone with lower productivity (and more methodical rigour).

      Now we know that at least one aspect of that productivity was artificial, because many of us have done many, many, Northern blots, we can testify that publishing 23 times the same loading control is wrong, dead wrong. He could just had referred to the first control in the rest of the papers that followed the first one, clean an easy! What was wrong with admitting that he had not reprobed the original Northern blot for actin? Nothing, but his group would had lost 23 panels and would have received the expected 23 criticisms from the reviewers: you are relying in a membrane that you had stripped 23 times and stored over more than one decade? Give me a break! alent.

      The last point is that we only can identify the obvious flaws (panel repetitions or fabrications). How can we know if those are the exceptions or the tip of the iceberg?

      Like

  14. And EMBO gave the first author (Soria-Valles) of 2015 NCB paper long-term fellowship… “C.S.V. is an EMBO (ALTF 1240-2015) fellow”.

    She is from EMBO member Lopez-Otin lab. Traverse lineage of perennial bands.

    @schneiderleonid
    “@NatureCellBio asks authors to deposit full uncropped western blots. But @ERC_Research awardee & @EMBO member Carlos Lopez-Otin made a travesty of it. Nothing matches. Does the journal mind? @Magda_Skipper”

    Like

  15. Leonid, may worth covering Lopez-Otin’s more updated “sloppiness” in a new post. Pubpeer discussing lots of their new skills; flipping&jumping bands, subjective colony count techniques, and de novo synthesis of actin bands (NEW!). https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    Like

  16. Salute to Carlos Lopez-Otin’s ground-breaking new technology of de novo synthesis of proteins independent from “perennial” template RNAs – Soria-Valles et al., 2015 Nature Cell Biology.

    Like

  17. kpasanen

    Uniovi has indeed failed in some transparency index on Spanis universities. Its also typical on spain universities institucional endogamy, wit a lot of dark tins involvin teachers assignations

    Like

  18. Readers found that 2015 NCB paper (Soria-Valles et al.) violates data deposition policy of the journal.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 35 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#35

    “The raw blots were too much modulated to correlate with images in figures. Raw films were so black, and figures were too white! The submitted raw blots (supplementary figure 9) lacks molecular size markers in every single film, and constrast was adjusted too high.
    NCB has policy below to raw blots. “Positive and negative controls, as well as molecular size markers, should be included on each gel and blot” “High-contrast gels and blots are discouraged, as overexposure may mask additional bands. ”
    And the criteria of the authors do not meet with the policy…

    Like

  19. More violation to NCB policy by Soria-Valles et al., 2015 from Lopez-Otin lab.
    Not only WB, but also microscopic image processing.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 37 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#37

    “Another NCB policy regarding quantification of microscopic images was not followed in this paper. It has been unclear and unnamed how the authors processed software of image quantification that occupied half of their data (figure 1b, 1d-g, 3c, 3e-g, 5a-b, 5d-f, 6a, 6c-d, 7b-c, s1g, s4a-b, s5b-c, s5e-f, s6b, and s6d). Tetramerium Zeta pointed that intuitive counting skill ended up similar percentage in two different experiments, but obvioulsy looking very different…
    NCB policy; “Processing software should be named and manipulations indicated (such as type of deconvolution, three-dimensional reconstructions, surface and volume rendering, “gamma changes,” filtering, thresholding and projection).”

    Like

  20. It is clear now that Lopez-Otin’s magical Northern blotting skill was descended to new generation in a form of elusive bands and phantasmagoric images as we are appreciating in Soria-Valles, 2015 Nature Cell Biology.
    Their wonder wand casts a spell of evasion to journal policy.
    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#37

    Like

  21. Zebedee

    Reply to Cartuli June 8, 2018 at 12:58

    “Specially when you’re talking about someone with over 400 publications.”
    That is the problem. Over 400 publications, but not over 400 separate pieces of scientific work.
    He has more publications than his data can support.
    The rule that you should only publish your data once is so that people can scrutinize the scientific record for data appearing more than once. It is not a pernickety rule, but the rule which allows scientific scrutiny of what is readily observable. Without scrutiny it is all worthless.

    Like

  22. More and more violation to NCB policy by Soria-Valles et al., 2015 from Lopez-Otin lab…

    Control bands of WB and EMSA assays are missing from author’s submitted raw blots.
    6 serial posts on Pubpeer pointed out each case of missing bands.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 43 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#43

    “I need multiple posts to address elusive bands appearing from nowhere. In addition to missing b-actin bands in supplementary figure 6a, there are multiple cases where b-actin or Oct1 (control of EMSA assay) are missing.
    First, Figure 4i. H3K79Me2 bands are flipped. B-actin bands are missing from submitted raw blots from authors.”

    “Figure 5f. ATM bands are distorted. b-actin bands are missing from raw blots submitted by authors.”

    “Figure 7a.
    Never specified which Oct1 bands are used. 4 out of 15 lanes. P-ATM bands are flipped. B-actin bands are missing from raw blots submitted by authors.”

    “Supplementary figure 6e.
    NF-kB bands do not match. Oct1 (control) bands are missing from raw blots submitted by authors.”

    “Supplementary figure 8. Part 1 of 2.
    Oct1 (control) bands are missing from raw blots submitted by authors. 9 lanes shown in the panel, but only 4 can be found.”

    “Supplementary figure 8. Part 2 of 2.
    B-actin bands are missing from raw blots submitted by authors.”

    Like

  23. I did respect high standard of Nature Cell Biology journal. But now Soria-Valles (2015) paper from Lopez-Otin convinced me double standard of this journal. Really disappointing that control bands appeared from nowhere.

    Like

  24. Isn’t is weird that their perinnial blots are gone now, and even cannot show control bands in more recent paper…? Go to extremes… Finally their Clontech bots got expired after two decades. Or they got worried to show off their favorite “master-stock” of control bands on Nature Cell Biology?

    Like

    • Smut Clyde

      No, I have no problem with López-Otín and his colleagues shifting their focus to another research area. You go where the funding is, and if they received a grant to study a particular topic, earlier projects will not receive so much attention.

      Like

  25. Like the idea of lab stock of control bands that you can copy and paste on any paper. That’s a key to 400 publications…

    Like

  26. Lopez-Otin’s 2015 NCB paper (Soria-Valles et al.) lacks both cotrols and molecular size markers on blotts. Violation to NCB policy.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 48 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#44

    “Policy of Nature Cell Biology on gel data deposition – “Positive and negative controls, as well as molecular size markers, should be included on each gel and blot”. The paper lacks both controls and molecular size markers. I wonder if the editor of Nature Cell Biology, Alexia-Ileana Zaromytidou, is aware of it?”

    Like

  27. More than band issue in Lopez-Otin 2015 NCB paper (Soria-Valles et al.). Problems in microscopic image processing.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 48 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#48

    “My point is that the authors cannot depend on subjective colony counting. Unless conveyed machine and software-based counting, how could you be confident of the results…? I carefully looked for methods section in this paper, but never found any specific description regarding how the authors did counting. Indeed, counting from independent experiments did not correlate. Later posts argued that very different two samples ended up “same” number of colonies, supplementary figure 5 b and e (if machine-based count was done, it would never occurred).
    I also tried to do counting on their representative image on figure 5, and I have no idea how the authors could come to the exact number claimed in the bar graph (I saw apparently way more colonies in the image).
    Paraplanocera Oligoglena”

    Like

  28. Carlos should appreciate film deposit policy of Nature Cell Biology that revealed his lab master stock of control bands did not expire over 2 decades!

    Like

  29. NF-kB blot is missing. Raw data submitted by Soria-Valles were irrelevant to presented figures. 2015 NCB paper from Lopez-Otin group.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 50 Comments
    doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679 pubmed: 26214134

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#49

    “The earlier posts argued that NF-kB blotts did not match with deposited raw data from Soria-Valles et al. Adding to this discussion, I point out that number of blotts were different between figures and deposited raw data. In Supplementary figure 6 and 8, one lane is missing from their raw data. Moreover, shape of bands and order of lanes indicated in deposited films did not correlate with figures. They seems to randomly cropped unrelated films.”

    Like

  30. Caroline

    I hope Nature Cell Biology editor Alexia-Ileana Zaromytidou has recogized and will react to this series of violation against its policy regarding raw data deposition, image manipulation and image quantification in the paper from Soria-Valles et al. This paper is getting 50 comments on pubpeer. https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#50

    Like

  31. 2015 NCB paper from Soria-Valles’s master stock of control bands had been slipped into the supplement.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 53 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#52

    “Control Oct-1 bands came from scratch. Figure 7 shows 4 lanes of NF-kB and corresponding Oct-1 bands. However, Oct-1 bands were selected from irrelevant film with multiple lanes. Unspecified which lanes were chosen. Moreover, this Oct-1 film was serving as a stock of control bands in several different figures around the paper.”

    https://imgur.com/a/B94jiKR

    Like

    • Lopez-Otin’s practice in control bands continuing over 2 decades. Copied and pasted in many J. Biol. Chem. papers 90s to 00s. They have learned to have master stock of bands that usually hidden. Fortunately (unfortunate to him), Nature Cell Biology’s policy revelated their hidden master stock.

      Like

  32. New Pubpeer comments on 2015 NCB paper from Soria-Valles et al. regarding master stock of control bands.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 55 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1476-4679 issn: 1465-7392

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#54

    “I cannot spot NF-kB and Oct-1 lanes in figure 7a to the original films as slipped into the supplement. Indeed, there is a significant discrepancy both in bands width and shape.”

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#55

    “The policy of Nature Cell Biology regarding immunoblot. “Loading controls (e.g. GAPDH, actin) must be run on the same blot.” As pointed out by Volvatella Angeliniana, loading control (Oct-1) and sample (NF-kB) are not on the same blot (figure 7a).”

    Like

  33. Spaniard

    It is just crazy how Lopez-Otin can just get out of this issue unharmed.

    Like

  34. The authors of a 1999 J Biol Chem paper retracted it in 2016 after image duplication was pointed out.
    So it can happen.

    https://retractionwatch.com/2016/09/23/author-asks-to-retract-nearly-20-year-old-paper-over-figure-questions-lack-of-data/

    2016 retraction notice.
    http://www.jbc.org/content/291/44/23364.long
    “This article has been withdrawn by the authors. Several features in Fig. 6, B and C, were duplicated.”

    Quite a few of the flagged Lopez-Otin papers are in J Biol Chem.

    Like

  35. Will see if J Biol Chem data integrity manager Carol Sakabe and Nature Cell Biol editor Alexia-Ileana Zaromytidou would take any action or comments. Most of comments on Lopez-Otin’s work are flagged on thse 2 journals.

    Like

  36. With 2015 NCB paper, Lopez-Otin’s tried to sucessfully switch the field from degradome to stem cell biology. And indeed high impact study on stem cell reprogramming. Salute his new life in more carnivorous field!

    Like

    • Teodoro

      So probably Lopez-Otin wanted to switch to field where more research funding is, but he forgot to renew his old stock of bands…

      Like

  37. Apparently they have unexpectedly shown off their stock film of control bands in 2015 Nature Cell Biology paper, Soria-Valles et al. I see they have made patchwork of bands.
    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#56

    Like

  38. Patchwork of bands were revealed in 2015 NCB paper from Soria-Valles et al.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 60 Comments

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#60

    “Oct-1 bands were randomely chosen from one film, and slipped into 3 independent experiments (figures 3c, 6b, 7a). A stock of control bands on donor film were repeatedly used in irrelevant samples and experiments throughout entire paper.”

    “NF-kB bands came from scratch. Number of lanes and shapes of bands do not match with deposited raw blots. As noted before, corresponding control bands were chosen from irrelevant pile of Oct-1 bands.”

    “In supplementary figure 8 c and d, Oct-1 bands were chosend from one film, and slipped into 2 irrelevant experiments. It is against the policy of Nature Cell Biology “Loading controls (e.g. GAPDH, actin) must be run on the same blot.” Moereover, This Oct-1 film as well ther other one were used as a stock of bands slipped into irrelevant experiments through out paper.”

    “In addition to Oct-1, NF-kB bands and lanes do not match with original blots. 2 lanes were randomely chosen from film and slipped into independent experiments respectively.”

    Like

  39. Caroline

    I believe Nature Cell Biology editor Alexia-Ileana Zaromytidou has been aware of this series of violation against its policy regarding raw data in the paper from Soria-Valles et al. Their “misrepresentation” of blots is not acceptable. This paper is getting 60 comments on pubpeer now… https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#60

    Like

  40. Perennial Northern blots captured on Soria-Valles et al., 2015 NCB?

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 71 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#65

    “Figure 3c. There are some smears on the WB film of P-IKK2. They seems to be certain blots such as Nothern blot of unrelated samples. It is difficult to understand how WB and Nothern blots can be on the same film.
    And there is no molecular size marker. How the authors tell the size of bands?”

    Like

  41. In addition to patchwork of bands, their tradition of perennial blots appear again in Soria-Valles’s Nature Cell Biology paper.
    All the tricks of Lopez-Otin group, both traditional ones and brush-up ones gathered in this paper.
    May see more examples coming…

    Like

  42. The 2015 Nature Cell Biology paper from Soria-Valles is receiving almost 80 commments.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 78 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#79

    “Figure 3c and 6b. The complete lack of molecular size marker makes it difficult to tell if the entire film was submitted for deposition. The size of P-IKK2 and IKBA implies that they were from independent film. Just bands were pasted to represent entire film.”

    “Cell senescence assay in supplementary figure 5. Both samples A and B have very similar number of senescent cells under microscopic images. But the cell count says one is 5% (A) and the other is 60% (B). How did the authors count the cells?
    I could not find the quantification method in the paper. “Cell senescence was assessed by detecting the senescence associated β-galactosidase activity at pH6.0 (SA-β-Gal) using a commercial kit (Cell Signaling).”

    “Figure 6d. Colony number between IKKi and IKK2-KI has no difference according to bar graph. Though I found that actual image of colonies very differ.IKK2-KI has apparently >2-fold more colonies. Despite, error bars are really tiny.”

    Like

  43. Pubpeer comment on Soria-Valles et al. 2015 NCB paper.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 82 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#77

    “Here is the image of figure 6b. NF-kB bands were contrasted a lot. Oct-1 bands were distorted. They came from different membranes, and received very different contrast respectively.”

    https://imgur.com/a/LsicJBw

    Like

  44. Image duplication was found in Soria-Valles et al., 2015 NCB paper.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 82 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#78

    “Duplicated images in figure 3 and figure 4. Beta-actin bands were copied and pasted.”

    https://imgur.com/a/TdoK4Pm

    Like

  45. Carlos Lopez-Otin at uniovi and George Daley, Dean of Harvard Medical School, produced a very fruitful paper. Pubpeer >80 comments and image duplication (actually triplication!). @uniovi_info @harvardmed @G_Q_Daley @NatureCellBio @alexia_zz

    Like

  46. Triplicated images in Soria-Valles Nature Cell Biology 2015.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 83 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#83

    “The beta-actin bands were triplicated in 3 figures. Figs. 3, 4 and supplimentary 6.”

    Like

  47. Fernando

    Image duplication, suspicious bar graphs, missing raw data. Say Bingo! to the editor of Nature Cell Bio.

    Like

  48. Need a version 2.0 thread for this topic. The list of comments keeps growing… Now you guys got a new target in addition to NCB.

    Like

  49. Another paper authored by Lopez-Otin is gaining attentions on pubpeer. Similar claim to Soria-Valles NCB, duplication of WB controls.
    I see common co-authors between these papers including Soria-Valles.

    Nuclear lamina defects cause ATM-dependent NF- B activation and link accelerated aging to a systemic inflammatory response
    Genes & Development (2012) – 4 Comments
    pubmed: 23019125 doi: 10.1101/gad.197954.112 issn: 1549-5477 issn: 0890-9369

    Fernando G Osorio , Clea Bárcena , Clara Soria-Valles , Andrew J Ramsay , Félix De Carlos , Juan Cobo , Antonio Fueyo , José M P Freije , Carlos López-Otín

    https://pubpeer.com/publications/4E89FBEE8E6605B592593CF801E7BD#5

    “Duplicated images. Figures 2 and 5.”

    Like

    • Smut Clyde

      Some of the responses in that PubPeer thread are arguing that the two Figures are probably reporting results from the same experiment (at least the details are the same in both cases), so the repeat of the beta-actin band is legitimate and appropriate.

      Like

  50. The first author of Nature Cell Biology (2015), Soria-Valles, is currently a postdoc of George Daley’s group, a dean of Harvard Medical School and her senior co-author of the paper.
    Daley lab website
    https://daley.med.harvard.edu/people

    PCTC website
    https://translationalcells.org/content/clara-soria-valles

    Like

  51. Interesting to see the association of the first author of NCB paper with senior author George Daley, dean of Harvard Medical School. At Daley lab Soria-Valles got trained for the NCB paper and stays there to continue postdoc traning.

    Like

  52. Pubpeer comment described how the raw data were made by Soria-Valles et al., 2015 Nature Cell Biology.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 86 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#87

    “Comprehensive view of 3 figures with raw films.
    How come one single control serves over 7 blots.
    Some of the samples were apparently coming from different gels.
    Identical bands were detected on different blots. Pasted…?
    Trace of cropping bands were detected.”

    NF-κB activation impairs somatic cell reprogramming in ageingClaraSoria-Valles1,8,FernandoG.Osorio1,8,AnaGutiérrez-Fernández1,AlejandroDeLosAngeles2,ClaraBueno3, PabloMenéndez3,4,JoséI.Martín-Subero5,GeorgeQ.Daley2,6,7,JoséM.P.Freije1,9 andCarlosLópez-Ot

    //s.imgur.com/min/embed.js

    Like

  53. Veo cierto ensañamiento con una persona brillante y honesta.
    Cabe preguntarse:
    -¿Parte todo esto de las personas de la Universidad de Oviedo que no sacaron la plaza de profesores por su curriculum mediocre? Quizás ahí están los vestigios de la España con pasado fascista que dice el autor de este blog, que da la sensación que se está convirtiendo en la correa de transmisión de envidias de gente de baja ralea.
    -¿Son reproducibles los resultados fundamentales de los trabajos que se citan?
    – ¿Se está poniendo en duda la credibilidad de unas revistas científicas de alto prestigio? No creo que estas revistas arriesguen su prestigio para salvar a una persona.

    Escribo en castellano porque creo que es la lengua materna de los que comentan esta entrada del blog.

    Like

  54. Comments on G&D paper continue.

    Nuclear lamina defects cause ATM-dependent NF- B activation and link accelerated aging to a systemic inflammatory response
    Genes & Development (2012) – 5 Comments
    pubmed: 23019125 doi: 10.1101/gad.197954.112 issn: 1549-5477 issn: 0890-9369

    Fernando G Osorio , Clea Bárcena , Clara Soria-Valles , Andrew J Ramsay , Félix De Carlos , Juan Cobo , Antonio Fueyo , José M P Freije , Carlos López-Otín

    https://pubpeer.com/publications/4E89FBEE8E6605B592593CF801E7BD#6

    “They are identical. However, the samples in figure 2 and 5 seems to be the same, and therefore not so critical, although I am always sceptical when I see too many blots with one single loading control, like in this example.”

    “How likely 9 strips come the same blot? If they are done together they should stacked above each other in the same figure.
    Also, in figure 2 the nNEMO and tNEMO panels do not look like they come from the same blot.”

    “Indeed the shapes of nNEMO and tNEMO bands so differ in figure 2. More logical explanation is that they came from independent blots that one missing loading control.”

    Like

  55. Leonid, need a new post on Iberian mess on science. So much things are going on. Carlos Lopez-Otin, Jose Rojas and dead scientists. We now are seeing new generation of Lopez-Otin’s lab churning out papers done with similar tricks as decades ago..

    Like

  56. New issue on 2012 G&D paper.
    Horizontal flip of bands to make up different samples.

    Nuclear lamina defects cause ATM-dependent NF- B activation and link accelerated aging to a systemic inflammatory response
    Genes & Development (2012) – 8 Comments
    pubmed: 23019125 doi: 10.1101/gad.197954.112 issn: 1549-5477 issn: 0890-9369

    Fernando G Osorio , Clea Bárcena , Clara Soria-Valles , Andrew J Ramsay , Félix De Carlos , Juan Cobo , Antonio Fueyo , José M P Freije , Carlos López-Otín

    https://pubpeer.com/publications/4E89FBEE8E6605B592593CF801E7BD#9

    “Figures 2 and 6”

    Like

  57. PubPeer pointed out 2015 NCB paper from Soria-Valles et al. having more issues on loading controls.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 90 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#

    “This paper does not comply with NCB guideline that “Loading controls (e.g. GAPDH, actin) must be run on the same blot. ” All the loading control were run on different blots as revealed in supplimentary figure 9, deposit of all the blots used in the paper.”

    https://imgur.com/a/0A7IHDM

    Like

  58. New PubPeer comments on Soria-Valles 2015 NCB paper.
    Readers pointing out the authors non-compliance to NCB policy on raw data.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 90 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    “They need to comply with the policy of NCB journal to explain how they had counted cells. “Authors should list all image acquisition tools and image processing software packages used. Authors should document key image-gathering settings and processing manipulations in the Methods.” The current method section has no description on this regard.”

    “This mismatch of bands with original blots is an allegation against NCB polycy; The bands were too much overexposed and contrasted to be in shape, if the bands in original blots actually correpsond to the ones in figures. “High-contrast gels and blots are discouraged, as overexposure may mask additional bands. Authors should strive for exposures with gray backgrounds. ”

    “The quantification in figure 4i depends on irrelevant loading controls from unrelated samples.
    Even if the actin bands were to come from corresponding samples (unlikely though), the guideline of Nature Celll Biology says “Loading controls (e.g. GAPDH, actin) must be run on the same blot.”

    Like

  59. J Biol Chem. 2005 Jan 21;280(3):1953-61. Epub 2004 Nov 9.
    Human polyserase-2, a novel enzyme with three tandem serine protease domains in a single polypeptide chain.
    Cal S1, Quesada V, Llamazares M, Díaz-Perales A, Garabaya C, López-Otín C.
    Author information
    1
    Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.

    2018 correction.
    http://www.jbc.org/content/293/30/11784.short

    There was an error in Fig. 3. The actin panel for the Northern blot containing spleen, thymus, prostate, testis, ovary, intestine, colon, and leukocyte samples was inadvertently rotated 180 degrees. Since the amount of RNA in each lane was equivalent, this error does not alter the interpretation of the results shown in the figure. Additionally, the actin panels shown in this figure were reused from previous publications describing the hybridization of other human genes to a different set of the same commercial filters used in this article (Multiple Tissue poly(A) Northern blots, Clontech). This commercial product was guaranteed by the manufacturer to have equal loading (approximately 2 μg of polyadenylated RNA per lane). Therefore, the corrected version of Fig. 3 is provided in which these panels are omitted. The authors apologize for these errors. This correction does not affect the results or conclusions of this work.

    Like

  60. J Biol Chem. 2003 Apr 11;278(15):13382-9. Epub 2003 Jan 31.
    Identification and characterization of ADAMTS-20 defines a novel subfamily of metalloproteinases-disintegrins with multiple thrombospondin-1 repeats and a unique GON domain.
    Llamazares M1, Cal S, Quesada V, López-Otín C.
    Author information
    1
    Departamento de Bioquíimica y Biologíia Molecular, Facultad de Medicina, Instituto Universitario de Oncologíia, Universidad de Oviedo, 33006-Oviedo, Spain.

    2018 correction.
    http://www.jbc.org/content/293/30/11785.short

    In Fig. 4A, the actin panel for the Northern blot containing spleen, thymus, prostate, testis, ovary, intestine, colon, and leukocyte samples was inadvertently rotated 180°. Since the amount of RNA in each lane was equivalent, this change does not affect the results for the Northern blot detecting ADAMTS-20. Additionally, the actin panels shown in this figure were reused from previous publications describing the hybridization of other human genes to a different set of the same commercial filters used in this article (Multiple Tissue polyA Northern blots, Clontech). This commercial product was guaranteed by the manufacturer to have equal loading (approximately 2 μg of polyadenylated RNA per lane). Therefore, the corrected version of Fig. 4A is provided in which these panels are omitted. The authors apologize for any inconvenience these errors may have caused. This correction does not affect the results or conclusions of this work.

    Like

  61. J Biol Chem. 2013 May 17;288(20):14647-56. doi: 10.1074/jbc.M112.439893. Epub 2013 Apr 2.
    Matrix metalloproteinase Mmp-1a is dispensable for normal growth and fertility in mice and promotes lung cancer progression by modulating inflammatory responses.
    Fanjul-Fernández M1, Folgueras AR, Fueyo A, Balbín M, Suárez MF, Fernández-García MS, Shapiro SD, Freije JM, López-Otín C.
    Author information
    1
    Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.

    2018 correction.
    http://www.jbc.org/content/293/30/11970.short

    Fig. 2A did not indicate the borders between different sections of the same gel. Additionally, an unused lane was mistakenly included in the original assembly of the actin panel causing a shift in lanes 12–14. Fig. 4B did not indicate the borders between different sections of the same immunoblot. Also, the incorrect β-actin immunoblots were used for the left CHI3L3 panel and the RAGE panel. The RAGE immunoblot was performed with the same samples run in parallel for the detection of CHI3L3 and β-actin shown in the left-most panel. These errors have now been corrected and do not affect the results or conclusions of this work.

    Like

  62. Fernando

    Big shame on JBC and spanish science. JBC admits that you can add and remove any fraudulent data later on. Prestigious of Nature award recipients! @uniovi_info @nature @jbiolchem @alison_c_abbott @ASBMB

    “the corrected version of Fig. 4A is provided in which these panels are omitted.”
    http://www.jbc.org/content/293/30/11785.short

    Like

  63. More comment on G&D paper 2012.

    Nuclear lamina defects cause ATM-dependent NF- B activation and link accelerated aging to a systemic inflammatory response
    Genes & Development (2012) – 15 Comments
    pubmed: 23019125 doi: 10.1101/gad.197954.112 issn: 1549-5477 issn: 0890-9369

    Fernando G Osorio , Clea Bárcena , Clara Soria-Valles , Andrew J Ramsay , Félix De Carlos , Juan Cobo , Antonio Fueyo , José M P Freije , Carlos López-Otín

    https://pubpeer.com/publications/4E89FBEE8E6605B592593CF801E7BD#16

    “I compiled issues in figures 2, 5 and 6. beta-actin bands were duplicated between figures 2 and 5 (both were Zmpste24 samples). Lamin A/C bands were horizontally flipped between figures 2 and 6 (Zmpste24 and Lmna samples).”

    Like

  64. Soria-Valles 2015 Nature Cell Biology paper is increasing its comments on Pubpeer…

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 94 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#95

    “Figure 8b, H3K79me2 and b-actin bands came from different samples. The bands were cropped from different blots of apparently irrelevant lanes.”

    NF-κB activation impairs somatic cell reprogramming in ageingClaraSoria-Valles1,8,FernandoG.Osorio1,8,AnaGutiérrez-Fernández1,AlejandroDeLosAngeles2,ClaraBueno3, PabloMenéndez3,4,JoséI.Martín-Subero5,GeorgeQ.Daley2,6,7,JoséM.P.Freije1,9 andCarlosLópez-Ot

    //s.imgur.com/min/embed.js

    Like

  65. Weirdness in ‘original blots’ from Soria-Valles et al., 2015 Nature Cell Biolohy paper, commented on Pubpeer.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 96 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#97

    “Both rabbit (Lmnb1) and mouse (p21) primary abs were exposed on the same blot used in figure 2a and supplementary figure 6a. The whole blots submitted by authors seem to be actually patchwork of bands.”

    Like

  66. Almost breaking-record number of PubPeer comments, the collaborative paper on @NatureCellBio from Carlos Lopez-Otin @uniovi_info and George Daley @G_Q_Daley dean of Harvard medical school @harvardmed is receiving.
    https://daley.med.harvard.edu/publications

    Like

  67. Additional comment on Pubpeer regarding Soria-Valles et al., 2015 NCB.
    More evidence of WB from irrelevant samples, involving band fipping.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 98 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    “Also, in figure 2a, p16 and Lmnb1 came from different samples. The bands were cropped from different blots of apparently irrelevant lanes. What’s more, p16 bands were flipped during cropping.”

    Like

  68. More PubPeer comments on Soria-Valles et al., 2015 NCB.
    High-contrast image reveals that NF-kB bands seems to be artificial.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 100 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#101

    “High-contrast image revealed that NF-kB bands used in figure 7a are actually smear and artificial (indicated in blue rectangle). Real bands appear on above area (red rectangle). Refer blot B, below one, for actual size of NF-kB (red rectangle).”

    Like

  69. Tradition of band splicing. Both labs of Carlos Lopez-Otin and George Daley were made to match.

    Like

  70. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome
    Science (1990) – 7 Comments
    pubmed: 2406902 issn: 0036-8075

    G Q Daley , R A Van Etten , D Baltimore

    https://pubpeer.com/publications/32494494DF1BA35389D4DD4215FDB6

    Inappropriate splicing on George Daley’s most important gel at David Baltimore lab.
    Interestingly, 5 out of 7 comments were moderated (deleted) on pubpeer. Do pubpeer fellas surrender to the power of Harvard Medical School Dean?

    Like

  71. Pubpeer censored for upper class PIs.
    Such a frequent record of “moderation” on posts related with Harvard Medical School Dean, George Q. Daley.
    Pubpeer is biased, unfortunately.

    5 out of 7 comments deleted.
    https://pubpeer.com/publications/32494494DF1BA35389D4DD4215FDB6

    2 out 2 comments deleted.
    https://pubpeer.com/publications/9FFA7E2C80B6F11BDF006C3E6A1C1D

    1 out of 5 comments deleted.
    https://pubpeer.com/publications/CC2645E6699CB04102B6632962552C

    Several comments had been deleted without traces being left, peers claiming those were totally gone and unseen.
    https://pubpeer.com/publications/03698513C41957E1BFDE9396741C97

    Like

  72. //s.imgur.com/min/embed.js

    Like

  73. Funny to see the Pubpeer moderation (censor) is so frequent to George Daley, Dean of Harvard Medical School. Pubpeer is favor of big power PIs.
    That’s why Leonid should keep working.

    Like

  74. Nature Cell Biology paper from Soria-Valles et al. has received over 100 comments on pubpeer.
    Readers are pointing out how the raw data were made.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 109 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    “Single blot in supplementary figure 1e had three lines of bands (top one is beta-actin, middle and bottom ones are unknown), but they do not match with lanes each other. Each line of bands came from irrelevant lanes.”

    “Both rabbit (IKBA) and mouse (p16) primary abs were exposed on the same blot used in figure 7a and supplementary figure 6a. The whole blots submitted by authors seem to be actually patchwork of bands. Indeed, there was a trace of band cropping around p16 bands.”

    “beta-actin bands for figure 3c actually came from irrelevant lanes. beta-actin bands do not match with sample lanes on the raw blot, apparently pasted from somewhere.”

    Like

  75. Pubpeer readers found out more evidence of sample flipping practices in Soria-Valles et al., 2015 Nature Cell Biology paper.

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 112 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18#113

    “figures 3c, 4i and supp. 6a. -uncertain bands and objects on blots -trace of crop in p16 lane -bands were collected from random blots for p-p53, p53, p21 and p16 -image duplications”

    https://imgur.com/a/6rS8F8e

    “In figure 2a, p16 flipped the order of samples CTR and NGPS.”

    https://imgur.com/a/mRHhj0f

    “Band flipping coincides with ageing… P-IKK2 and P-ATM blots were developed from the same gel, as can seen in the shape and spot at right upper corner of gel (white arrow). P-ATM was developed, and striped. Then, P-IKK2 was developed. Bands of P-ATM were flipped when panel figure 7a was prepared.”

    https://imgur.com/a/70Q0n25

    Like

  76. Correction induced another question on Fanjul-Fernandez et al. 2013 JBC paper.

    Matrix metalloproteinase Mmp-1a is dispensable for normal growth and fertility in mice and promotes lung cancer progression by modulating inflammatory responses
    Journal of Biological Chemistry (2013) – 3 Comments
    pubmed: 23548910 doi: 10.1074/jbc.m112.439893 issn: 0021-9258 issn: 1083-351X

    Miriam Fanjul-Fernández , Alicia R. Folgueras , Antonio Fueyo , Milagros Balbín , María F. Suárez , M. Soledad Fernández-García , Steven D. Shapiro , José M. P. Freije , Carlos López-Otín

    “Compareing with corrected figure 2A with original one, I cannot understand how bands of lane 13-14 can be totally different from original figure if they are still subsequent samples from lane 12, that corrected figure tries to assure lane 12-14 are subsequent.”

    Like

  77. More cases of sample flipping in Soria-Valles et al., Nature Cell Biology (2015).

    NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 114 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    “Another sample flip occured on the other half of the same gel (figure 6b). In addition, samples were shifted. P-IKK2 and P-ATM blots were developed from the same gel, as can seen in the shape of right upper corner of above gel. P-ATM was developed, and striped. Then, P-IKK2 was developed. Bands of P-ATM were shifted and flipped when panel figure 6b was prepared.”

    Like

  78. Progeria Researcher

    Hello Leonid,
    I have been following PubPeer comments on Carlos Lopez-Otin’s Nature Cell Biology paper (Soria-Valles et al). “this paper is dedicated to the memory of Néstor M.O.” a donor of Néstor-Guillermo progeria syndrome (NGPS) used in figure 2a that was distrustfully flipped to make up over-expression of p16 in Néstor’s cells. And sadly more sample switches of HGPS (another type of progeria) at figure 6b and of >87 yrs aged-donor cells at figure 7a to make up activation of NF-kB pathway.
    As a researcher involved in ageing study, I cannot believe their working ethics for samples provided by progeria patients and aged donors (>87 yrs). The patients (and their families) had donated their own cells and tissues hoping to advance science, but Lopez-Otin and colleagues, including Pabro Menéndes (Jossep Carreras Imstitute) and George Q. Daley (Dean of Harvard Medical School) who provided crucial materials, bit the hand that feeds. Lopez-Otin and colleagues should be rewarded on their disrespectful manner on science and their patients.
    I have posted on PubPeer. In case they do not accept, I would like to post the capture here.

    Like

  79. Seems that pubpeer did not put a post by above Progeria Researcher.
    Leonid, can you cover recent issues on Lopez-Otin and colleagues? Situation has evolved since your last article with Smut Clyde.
    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    Like

  80. NF-κB activation impairs somatic cell reprogramming in ageing
    Nature Cell Biology (2015) – 125 Comments
    pubmed: 26214134 doi: 10.1038/ncb3207 issn: 1465-7392 issn: 1476-4679

    Clara Soria-Valles , Fernando G. Osorio , Ana Gutiérrez-Fernández , Alejandro De Los Angeles , Clara Bueno , Pablo Menéndez , José I. Martín-Subero , George Q. Daley , José M. P. Freije , Carlos López-Otín

    More examples of sample flipping and lack of controls in Soria-Valles et al., 2015 Nature Cell Biology.

    https://pubpeer.com/publications/836AB3A8AB4FD562A2D4CBFBF8ED18

    Samples were flipped in figure 8b. Results of WB quantification became completely opposite.

    “b-actin loading control for panel figure 5f was totally missing from raw data shown in supplementary figure 9. As mentioned in earlier posts, there was no label, exposure time and markers on blots, so how the authors could orientate lanes?”

    Like

  81. Pingback: How Lopez-Otin et al mocked data policy at Nature Cell Biology – For Better Science

  82. Pingback: Lopez-Otin and Kroemer: birds of a feather flock together – For Better Science

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