Retraction: M. Grondin, F. Hamel, D. A. Averill-Bates, and F. Sarhan, "Wheat Proteins Improve Cryopreservation of Rat Hepatocytes," Biotechnology and Bioengineering 103, no. 3 (2009): 582-591, https://doi.org/10.1002/bit.22270. The above article, published online on 20 January 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Douglas S. Clark; and Wiley Periodicals, LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, several micrographs presented in Figure 4 were found to contain numerous repetitive elements (i.e., cells) suggesting inappropriate image processing. Furthermore, data presented in Figure 4 and part of the data presented in Figure 1 were found to have been previously published by the same author group [Grondin et al, (2009); https://doi.org/10.3727/096368909788237104]. Investigation by the publisher has confirmed the validity of the concerns. The authors were unable to retrieve the raw data underlying Figure 4 due to the time elapsed since original publication. They also stated that the images presented in Figure 4 were acquired as original images and have not been altered in any form. They conducted an independent analysis of the magnified published images, highlighting that the cells identified as duplicated exhibit differences. According to the authors, the observed similarities are characteristic of cells within a homogeneous population (i.e., hepatocytes) and are therefore to be expected, thereby refuting allegations of inappropriate image editing. With respect to the duplication of previously published data in Figure 1 and Figure 4, the authors stated that this was due to an honest oversight because of the concurrent publication of the two studies. The authors stated that the issues identified do not affect the conclusions of the article. However, the editors have deemed the clarification from the authors as insufficient to resolve their concerns. The similarities detected in Figure 4 were found to outweigh the differences highlighted by the authors and were considered unlikely to result solely from morphological resemblance within a homogeneous population of primary isolated hepatocytes. The editors have determined that the new experimental data generated by the authors to replace the images in Figure 4 were unsuitable for direct comparison with the originally published data, due to the substantial time gap between the two experimental sets. Therefore, the concerns of the editors were not addressed acceptably and accordingly, the article must be retracted. The authors disagree with the retraction decision.
Retraction: F. Hamel, M. Grondin, F. Denizeau, D. A. Averill-Bates, and F. Sarhan, "Wheat Extracts as an Efficient Cryoprotective Agent for Primary Cultures of Rat Hepatocytes," Biotechnology and Bioengineering 95, no. 4 (2006): 661-670, https://doi.org/10.1002/bit.20953. The above article, published online on 21 August 2006 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Douglas S. Clark; and Wiley Periodicals, LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, the micrographs presented in Figure 3B, C and D were found to contain numerous repetitive elements (i.e., cells) suggesting inappropriate image processing. Investigation by the publisher has confirmed the validity of the concerns. The authors were unable to retrieve the raw data underlying Figure 3 due to the time elapsed since original publication. They also stated that the images presented in Figure 3 were acquired as original images and have not been altered in any form. They conducted an independent analysis of the magnified published images, highlighting that the cells identified as duplicated exhibit differences. According to the authors, the observed similarities are characteristic of cells within a homogeneous population (i.e., hepatocytes) and are therefore to be expected, thereby refuting allegations of inappropriate image editing. The authors stated that the issues identified do not affect the conclusions of the article. However, the editors have deemed the clarification from the authors as insufficient to resolve their concerns. The similarities detected in Figure 3 were found to outweigh the differences highlighted by the authors and were considered unlikely to result solely from morphological resemblance within a homogeneous population of primary isolated hepatocytes. The editors have determined that the new experimental data generated by the authors to replace the images in Figure 3 were unsuitable for direct comparison with the originally published data, due to the substantial time gap between the two experimental sets. Therefore, the concerns of the editors were not addressed acceptably and accordingly, the article must be retracted. The authors disagree with the retraction decision.
Toluene o-xylene monooxygenase (ToMO) of Pseudomonas sp. OX1 was investigated as a drug-metabolizing enzyme for the first time and was found to metabolize chlorzoxazone and resveratrol to form human metabolites 6-chlorzoxazone (0.045 ± 0.016 nmol/hr/mg protein) and piceatannol (0.014 ± 0.009 nmol/hr/mg protein), respectively, though at low rates. ToMO also forms 2-acetamidophenol (2-AAP, 27%), 3-AAP (42%), and 4-AAP (31%) from acetanilide at 3.6 ± 0.3 nmol/hr/mg protein. Multiple-site saturation mutagenesis at positions I100/E103/A107 of the alpha-subunit along with site-directed mutagenesis approaches were used to isolate thirty-seven different ToMO variants with enhanced activities and/or fine-tuned specificities. Specifically, variant I100V/E103T was identified with 2.1- and 49-fold higher activities towards acetanilide and chlorzoxazone, respectively, compared to native ToMO. Variant I100V/E103T also had the regiospecificity of acetanilide change from 31% to 100% 4-AAP, mimicking human liver enzyme behavior. In addition, several variants showed up to 3.7-, 1.6-, and 3.2-fold improved selectivity for 2-, 3-, and 4-AAP formation, respectively. For resveratrol, variant I100T/E103L was a better catalyst than native ToMO, exhibiting 34-fold higher activity. The results presented here demonstrate the potential of nonhuman ToMO variants in drug metabolism and contribute to the list of research on probing this promising enzyme.

