In order to contribute to the scientific development to the field and contribute to reproducibility, our lab developed an internal policy of total transparency.
All full scans of all publications are now freely available here in the website. In addition, we are in the process of providing all original raw data for each paper from our lab that was created in 2008 at the University of Chile. In the last years, all has been stored on a server organized by figure panel and is fully available for researchers upon request.
Here we have generated a data repository for full scans of Western blots and agarose gels. We are also currently including for recent papers statistical analysis of independent experiments. This will help our colleagues troubleshooting antibodies and also accessing raw data of cropped gels. In addition, since 2017 as part of this policy all lab books are revised once a moth and all image splicing and statistical analysis and number of replicates are indicated in figure legends.
Importantly, we are aware of the posts of PubPeer pointing out to possible errors in some of our publications. We have considered these comments seriously, and we have uploaded here responses to all queries to the papers of our lab as Principal investigator, an effort lead by each first author of the studies. In addition, we posted many of our responses to PubPeer for transparency. Editorial offices have been informed when errors were confirmed by our group to define further actions. All communication with editorial offices is included in the single files provided here.
University investigation and final outcome.
During March 2021, due to public questioning of our scientific integrity, the University of Chile stablished an advisory Committee to technically assess all queries presented in Pubpeer. This committee operated on an independent manner and was formed by researchers without any conflict of interest, generating a full report assessed by the Ethic department. The conclusions of this investigation are summarized here:
1. The Ethics Commission concludes that the evaluation process carried out did not detect any constitutive evidence of scientific fraud, understood as “a deliberate act of creating false data to support or demonstrate a certain scientific tesis. Importantly, the errors identified did not alter in any manner the conclusions of the study.
2. “As there are nuances in all human behavior, the Committee ends the task that was entrusted to it by recognizing that Dr. Hetz has carried out various proactive actions to solve the problems detected in the preparation and presentation of the figures of his experimental results in various publications of his authorship, the corrections that he proposed to the journals were accepted ”.
3. “The Committee reiterates its opinion in the sense that, although Dr. Hetz must fully assume his main responsibility for the errors or sloppiness reported in publications where he participated as the corresponding author, this responsibility is also shared with the co-authors.“
4. “Regarding the work carried out by PubPeer, the Committee regrets the anonymous nature of the comments and complaints published there, which favors the occurrence of persecutory actions and the publication of unfounded complaints, some of which were detected during the process of work of this Committee”.
5. “Finally, the Committee appreciates the measures that Dr. Hetz has resolved to adopt in his laboratory to prevent the situations that motivated the Committee’s work”.
Lab Strategy and improvements
This process led us to stablish a strategy as a laboratory to improve the quality control, supervision and ensure research integrity:
- Review by a team of researchers internally (not just the first author). A team of 5 people, including myself, will review in a one-day session where we will dedicate ourselves exclusively to curating the data.
- We have established new quality control points where an independent researcher to the laboratory will review our articles in preparation before they are sent to publication.
- As a teacher in charge, mentor students one-on-one on data integrity topics.
- Reduce the number of laboratory researchers by 30% to be able to monitor the detailed results of the results in greater depth (less than 20 people).
- Improve original data backup systems by using an external professional service. We will use triple backup.
- Review of laboratory notebooks monthly.
- Obligation to provide all the original data support and quantifications before sending an article to be published.
- We generate a freely available space on our website to deposit original images and Excel files with raw data and statistical analyzes.
- Digital images will be analyzed with software to detect undeclared processing or possible duplications.
Presentation to the community about the process, conclusion and also future improvements.
ANSWERS TO PUBPEER QUERIES
SUPORTING DATA OF PUBLICATIONS
Medinas D. et al. (2022). Mutant PDIA3 causes neurodevelopmental impairment by disturbing endoplasmic reticulum proteostasis. EMBO J. 41(2): e105531.
Pihan P. et al. (2021). Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1. Science Advances. 7(46): eabe5469.
Pérez-Arancibia R. et al. (2021). A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington’s disease. PLoS One. 16(7):e0254834.
Vidal RL. et al.(2021). Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration. Mol Ther. S1525-0016(21)00067-8.#*
Rozas P. et al. (2021). Protein disulfide isomerase ERp57 protects early muscle denervation in experimental ALS. Acta Neuropathol Commun. 9(1):21.#*
Dufey E., et al. (2020). Genotoxic stress triggers the activation of IRE1a-dependent RNA decay to modulate the DNA damage response. Nature Communications. 11(1):2401.#*
Garcia-Huerta P., et al. (2020). Insulin-like growth factor 2 (IGF2) protects against Huntington’s disease through the extracellular disposal of protein aggregates. Acta Neuropathol. 10.1007/s00401-020-02183-1.
Carreras-Sureda A., et al. (2019). Non-canonical role of IRE1 as a functional determinant of mitochondria-associated endoplasmatic reticulum composition to control calcium transfer and bioenergetics. Nature Cell Biology. 21(6):755-767.#*
Urra H., et al. (2018). IRE1 governs cytoskeleton remodeling and cell migration through a direct interaction with Filamin A. Nature Cell Biology. 20:942-953.#*
Medinas D., et al. (2018). Endoplasmatic reticulum stress leads to accumulation of wild-type SOD1 aggreegates associated with sporadic amyotrophic lateral sclerosis. Proc. Natl. Acad. Asci USA. pii: 201801109.#*
Sepulveda D., et al. (2018). Interactome screening identifies a novel function of the collagen chaperon Hsp47 as an adjustor of the unfolded protein response (UPR) transducer IRE1. Mol Cell. 69:238-252. #*
Mercado G., et al. (2018). Targeting PERK signaling with the small molecule GSK2606414 prevents neurodegeneration in a model of Parkinson’s disease. Neurobiol. Dis. 112:136-148.#*
Duran-Aniotz C., et al. 2017 . IRE1 signaling exacerbates Alzheimer’s disease pathogenesis. Acta Neuropathol. 134:489-506.*#
Bargsted L., et al 2017. Disulfide cross-linked multimers of TDP-43 and spinal motor neuron loss in a TDP-43A315T ALS/FTD mouse model. Scientific Reports. 7:14266*#
Martínez G., et al. (2016). Regulation of memory formation by the transcription factor XBP1. Cell Rep. 14:1382-1394. *#
Woehlbier U., et al. (2016). ALS-linked Protein Disulfide Isomerase Variants cause motor dysfunction. EMBO J. 35:845-65. *#
Torres M., et al. (2015). The Protein Disulfide Isomerase ERp57 Regulates the Steady-State Levels of the Prion Protein. J Biol Chem. 290:23631-45*#
Castillo V., et al. (2015). Functional Role of the Disulfide Isomerase ERp57 in Axonal Regenerartion. PLoS One. 10:eo136620.*
Nassif M., et al. (2014). Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis. Autophagy. 10: 1256-1271#*.
Matus L., et al. (2013). Functional role of the transcription factor ATF4 in the pathogenesis of amyotrophic lateral sclerosis. PloS One. 8:e66672.
Rodriguez D., et al. (2012). BH3-only proteins are part of a regulatory network that control the sustained signaling of the Unfolded Protein Response sensor IRE1. EMBO J. 31(10):2322-35. #*
Vidal R., et al. (2012). Targeting the UPR transcription factor XBP1 protects against Huntington’s disease through the regulation of FoxO1 and autophagy. Hum. Mol. Gen. 21(10):2245-62. #*
Rojas-Rivera D., et al. (2012). TMBIM3/GRINA is a novel Unfolded Protein Response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis. Cell Death Diff. 9:1013-26. *#
Zamorano S., et al. (2012). A BAX/BAK and Cyclophilin D-independent Intrinsic Apoptosis Pathway. PLoS One :e37782. *#
Valenzuela V, et al. (2012). Activation of the Unfolded Protein Response enhances motor recovery after spinal cord injury. Cell Death Dis. 3, e272 *#
Torres M., et al. (2012). Altered Prion protein expression pattern in CSF as a biomarker for Creutzfeldt-Jakob Disease. PLoS One .7:e36159. *#
Castillo K, et al. (2011). BAX inhibitor-1 regulates autophagy by controlling the IRE1?/JNK branch of the unfolded protein response. EMBO J. 4465-78 *#
Torres M., et al. (2010). Prion Protein Misfolding Affects Calcium Homeostasis and Sensitizes Cells to Endoplasmic Reticulum Stress. PlosOne. 5: e15658- e15658.*#
Hetz C., et al. (2009). XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes & Dev. 23:2294–2306 *#
Lisbona F., et al. (2009). BAX Inhibitor-1 is a negative regulator of the ER stress sensor IRE1. Mol. Cell. 33:679-691.*#