Breaking the silence: protein stabilization uncovers silenced biosynthetic gene clusters in the fungus Aspergillus nidulans
Authors: Ivo Feussner
Jennifer Gerke
Manuel Landesfeind
Gerhard H Braus
Kirstin Feussner
Ozgür Bayram
Ekaterina Shelest
Journal: Applied and Environmental Microbiology (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Filamentous fungi; gene clusters; secondary metabolites; protein degradation; Aspergillus nidulans
Affiliations: Abteilung für Molekulare Mikrobiologie & Genetik, Institut für Mikrobiologie & Genetik, Georg August Universität, Göttingen, Germany.

Abstract:  The genomes of filamentous fungi comprise numerous putative gene clusters coding for the biosynthesis of chemically and structurally diverse secondary metabolites (SMs), which are rarely expressed under laboratory conditions. Previous approaches to activate these genes were based primarily on artificially targeting the cellular protein synthesis apparatus. Here, we applied an alternative approach of genetically impairing the protein degradation apparatus of the model fungus Aspergillus nidulans by deleting the conserved eukaryotic csnE/CSN5 deneddylase subunit of the COP9 signalosome. This defect in protein degradation results in the activation of a previously silenced gene cluster comprising a polyketide synthase gene producing the antibiotic 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde (DHMBA). The csnE/CSN5 gene is highly conserved in fungi, and therefore, the deletion is a feasible approach for the identification of new SMs. 

Retracted: No

PubPeer comments:
 More than half of the 2008 Cambridge University Press paper:  **Extending Depth of Field in LC-SEM Scenes by Partitioning Sharpness Transforms. Microscopy Today**  Harishwaran Hariharan, Andreas Koschan, Besma Abidi, David Page, Mongi Abidi, J. Frafjord , S. Dekanich [University of Tennessee; Y12 National Security Complex] was copied from the 2007 IEEE copyrighted papers:  **Multifocus Image Fusion by Establishing Focal Connectivity**  Harishwaran Hariharan, Andreas Koschan, and Mongi Abidi  DOI: 10.1109 icip.2007.4379311 and:  **An Adaptive Focal Connectivity Algorithm for Multifocus Fusion**  DOI: 10.1109 CVPR.2007.383434 The 2008 Cambridge paper did not enclose copied passages in quotation marks, did not cite the sources, and did not indicate permission from the copyright holder. The 2008 Cambridge paper added authors Besma Abidi, David Page, J. Frafjord , S. Dekanich who were absent from the original IEEE versions of the work. The work was funded by the US Department of Energy DOE URPR under grant DOE-DE-FG02-86NE37968 and BWXT-Y12 #4300056316. The journal Microscopy Today claims to follow Cambridge University Press s [ethical guidelines](http: web.archive.org web 20210506214354 https: www.cambridge.org core services aop-file-manager file 5b44807ace5b3fca0954531e CUP-Research-Publishing-Ethics-Guidelines-2019.pdf) which state that: We do not tolerate plagiarism in any of our publications ... Submissions containing suspected plagiarism, in whole or part, will be rejected. If plagiarism is discovered postpublication, we will follow our guidance outlined in the Retractions, Corrections and Expressions of Concern section of these guidelines.  ... self-plagiarismu2019, occurs when a work, or substantial parts of a work, is published more than once by the author(s) of the work without appropriate cross-referencing or justification for the overlap. ... We do not support substantial overlap between publications, unless:  u2022 it is felt that editorially this will strengthen the academic discourse; and  u2022 we have clear approval from the original publication; and  u2022 we include citation of the original source.  We expect our readers, reviewers and editors to raise any suspicions of duplicate or redundant publication, either by contacting the relevant editor or by emailing publishingethics@cambridge.org Examples are shown below, with the later 2008 Cambridge version on the right. The excerpts on left in purple come from section **3.1. Synthesis of the fused image **in the 2007 IEEE paper An Adaptive Focal Connectivity Algorithm for Multifocus Fusion. Other passages are found in the 2007 IEEE paper **Multifocus Image Fusion by Establishing Focal Connectivity** or in both IEEE papers. ![file] ![file] ![file] ![file] ![file] ![file] ![file] , 
 Regarding the two IEEE papers from which the Cambridge paper was copied, approximately half of the September 2007 IEEE paper:  [**Multifocus Image Fusion by Establishing Focal Connectivity**]  doi: 10.1109 icip.2007.4379311 was copied paraphrased from the June 22, 2007 paper:  [**An Adaptive Focal Connectivity Algorithm for Multifocus Fusion**](http: web.archive.org web 20210722194809 http: citeseerx.ist.psu.edu viewdoc download?doi=10.1.1.75.572 rep=rep1 type=pdf)  DOI: 10.1109 CVPR.2007.383434 The copied passages were not enclosed in quotation marks and did not cite the source. The papers were under concurrent review (see chronology below). The [publisher claims to require](http: web.archive.org web 20210303074503 https: magazines.ieeeauthorcenter.ieee.org get-started-with-ieee-magazines publishing-ethics guidelines-policies submission-and-peer-review-policies ) that: authors should only submit original work that has neither appeared elsewhere for publication, nor is under review for another refereed publication. The 2007 IEEE papers were under simultaneous review. Although the June 2007 paper was published first, its [submission deadline](http: web.archive.org web 20210722195527 http: vcipl-okstate.org pbvs 07 CFPOTCBVS07.pdf) came second, in March 2007, with acceptance notice on April 17, 2007. The [deadline](http: web.archive.org web 20210722195827 http: www.icip2007org.creditcrunch.org CallForPapers.html) for the  later September 2007 IEEE paper occurred first, in January 2007, with acceptance notice on April 27, 2007. The  earlier June IEEE paper was therefore submitted, reviewed, and accepted during the interval that the  later September IEEE paper was under review. Co-author Andreas Koschan served as a [reviewer] for the September 2007 IEEE conference. [Besma Abidi](http: web.archive.org web 20210722202626 https: www.imaging.utk.edu publications public Abidi201801.pdf), co-author of the 2008 Cambridge version, served on the [Program Committee](http: web.archive.org web 20210722195527 http: vcipl-okstate.org pbvs 07 CFPOTCBVS07.pdf) for the June 2007 IEEE conference. The chronology of the interwoven 2007 IEEE publications is summarized below. Jan 19: Submission deadline for September conference (Andreas Koschan, reviewer)  Mar 20: Submission deadline for June conference (Besma Abidi, program committee)  Note: the June conference  [**solicits original contributions**](http: web.archive.org web 20210722195527 http: vcipl-okstate.org pbvs 07 CFPOTCBVS07.pdf)  Apr 17: Acceptance notice for June conference  Apr 25: Final version submitted for June conference  Apr 27: Acceptance notice for September conference  Jun 08: Final version submitted for September conference  Jun 22: OTCBVS conference held in Minneapolis, MN  Sep 16: ICIP conference held in San Antonio, TX Examples of unacknowledged copying paraphrasing between the two IEEE papers are shown below. | June 2007 IEEE paper | September 2007 IEEE paper | | --- | --- | | `Typically, lenses experience` the problem of limited depth of field (DOF) and this `makes the acquisition of` such an all-in-focus image difficult. | `Cameras suffer from` the problem of limited depth of field (DOF) and this `disallows a typical imaging system to obtain` such an all-in-focus image.| |This is a `major` problem in `many imaging applications, e.g.` inspection of microscopic scenes| This is a `prominent` problem in inspection of microscopic scenes.| |In multifocus fusion, `the central idea is` to acquire `focal` information from different focal planes `in the scene` and fuse them into one image where all `the focal planes` appear to be in focus| In multifocus fusion, `one aims` to acquire information from different focal planes and fuse them into one image where all `objects in the scene` appear to be in focus | | Commonly, two input images are `used for` fusion | Commonly, two input images are fused| | In certain applications, such as microscopic `scene inspection`, the `extremely` narrow DOF requires `numerous image acquisitions` to gather all the information contained in the scene. | In certain applications, such as microscopy, the narrow DOF requires `multiple shots of the 3D scene` to gather all the information contained in the scene.| | The main contribution in this paper is that we segment regions from the `set of` input images `by establishing` focal connectivity, and not `by physical` connectivity. | The main contribution in this paper is that we segment regions from the input images `based on` focal connectivity, and not `on object` connectivity.| | In region based methods, regions are `classically` selected in the image based on edge `geometries. ` | In region based methods, regions are `typically` selected in the image based on edges.| | These effects are not very `visible` when using simple datasets but `become a serious` issue in `precise` scene inspection. | These effects are not very `prominent to the end user` when using simple datasets but `stands out as an` issue in `accurate` scene inspection.| | Learning based methods use training `machines` which learn to `segregate` between sharp and blurred regions.| Learning based methods use training `engines` which learn to `classify` between sharp and blurred regions| | Training is `performed on` prescribed focused and unfocussed training data sets.| Training is `normally done with` prescribed focused and unfocussed training data sets.| |This increases the accuracy of the decisions `by making certain` that areas with better focus influence the `choice` of its neighbors.| This increases the accuracy of the decisions `to follow by ensuring` that areas with better focus influence the `decision` of its neighbors.| | These sharpness maps are `scrutinized` for regions of higher `sharpness` with their respective counterparts.| These sharpness maps are `examined` for regions of higher `focus` with their respective counterparts.| | While `acquiring` images `of` a 3D scene, the `dimensions` of the objects and their relative positions in the scene `characterize` the complexity of `the` multifocus fusion `algorithm needed`.| While imaging a 3D scene, the `size` of the objects and their relative positions in the scene `defines` the complexity of multifocus fusion.| | If the objects are placed well apart `without` focal overlaps, the problem of multifocus fusion becomes `simpler.`| If the objects are placed well apart `such that there are no` focal overlaps, the problem of multifocus fusion becomes `relatively easier.`| | If the DOF is `extremely` narrow and `information from` the scene is imaged with many individual frames, the fusion algorithm requires more intelligent `operations to perform fusion.`| If the DOF is `very` narrow and the scene is imaged with many individual frames, `with focal overlap` the fusion algorithm requires more intelligence `and finesse.`| | `In practice,` it is possible to image an object at adjacent planes that have `overlapping` regions in focus.| It is possible to image an object at adjacent planes that `appears to` have `common` regions in focus.| Attendees of the September 2007 IEEE conference -- where copied material was presented and published -- were  [invited to a fun-filled opening reception at Alamo Plaza](http: web.archive.org web 20210722214725 http: www.icip2007org.creditcrunch.org SocialActivities.html). In addition, the September conference included:  The Conference Banquet ... held atop the 750-foot-tall Tower of the Americas ... you will enjoy a reception including drinks and appetizers. ... A seated dinner, accompanied by live music, will be served in the revolving restaurant at the top of the Tower.  Lodging was provided by the [Hyatt Regency San Antonio](http: web.archive.org web 20210722214903 http: www.icip2007org.creditcrunch.org Housing.html), which offers [massage therapy](http: web.archive.org web 20210722181647 https: www.dasaspa.com massagetherapy) at its Spa. ,