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1. Teaching Bioprocess Engineering to Undergraduates: Multidisciplinary Hands-On Training in a One-Week Practical Course

Author: Henkel, Marius, Zwick, Michaela, and Beuker, Janina
Abstract: Bioprocess engineering is a highly interdisciplinary field of study which is strongly benefited by practical courses where students can actively experience the interconnection between biology, engineering, and physical sciences. This work describes a lab course developed for 2nd year undergraduate students of bioprocess engineering and related disciplines, where students are challenged with a real-life bioprocess-engineering application, the production of recombinant protein in a fed-batch process. The lab course was designed to introduce students to the subject of operating and supervising an experiment in a bioreactor, along with the analysis of collected data and a final critical evaluation of the experiment. To provide visual feedback of the experimental outcome, the organism used during class was "Escherichia coli" which carried a plasmid to recombinantly produce enhanced green fluorescent protein (eGFP) upon induction. This can easily be visualized in both the bioreactor and samples by using ultraviolet light. The lab course is performed with bioreactors of the simplest design, and is therefore highly flexible, robust and easy to reproduce. As part of this work the implementation and framework, the results, the evaluation and assessment of student learning combined with opinion surveys are presented, which provides a basis for instructors intending to implement a similar lab course at their respective institution.
Published: 2015
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2. Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology

Author: Lars Björndahl, Christopher L R Barratt, David Mortimer, Ashok Agarwal, Robert J Aitken, Juan G Alvarez, Natalie Aneck-Hahn, Stefan Arver, Elisabetta Baldi, Lluís Bassas, Florence Boitrelle, Riana Bornman, Douglas T Carrell, José A Castilla, Gerardo Cerezo Parra, Jerome H Check, Patricia S Cuasnicu, Sally Perreault Darney, Christiaan de Jager, Christopher J De Jonge, Joël R Drevet, Erma Z Drobnis, Stefan S Du Plessis, Michael L Eisenberg, Sandro C Esteves, Evangelini A Evgeni, Alberto Ferlin, Nicolas Garrido, Aleksander Giwercman, Ilse G F Goovaerts, Trine B Haugen, Ralf Henkel, Lars Henningsohn, Marie-Claude Hofmann, James M Hotaling, Piotr Jedrzejczak, Pierre Jouannet, Niels Jørgensen, Jackson C Kirkman Brown, Csilla Krausz, Maciej Kurpisz, Ulrik Kvist, Dolores J Lamb, Hagai Levine, Kate L Loveland, Robert I McLachlan, Ali Mahran, Liana Maree, Sarah Martins da Silva, Michael T Mbizvo, Andreas Meinhardt, Roelof Menkveld, Sharon T Mortimer, Sergey Moskovtsev, Charles H Muller, Maria José Munuce, Monica Muratori, Craig Niederberger, Cristian O’Flaherty, Rafael Oliva, Willem Ombelet, Allan A Pacey, Michael A Palladino, Ranjith Ramasamy, Liliana Ramos, Nathalie Rives, Eduardo Rs Roldan, Susan Rothmann, Denny Sakkas, Andrea Salonia, Maria Cristina Sánchez-Pozo, Rosanna Sapiro, Stefan Schlatt, Peter N Schlegel, Hans-Christian Schuppe, Rupin Shah, Niels E Skakkebæk, Katja Teerds, Igor Toskin, Herman Tournaye, Paul J Turek, Gerhard van der Horst, Monica Vazquez-Levin, Christina Wang, Alex Wetzels, Theodosia Zeginiadou, Armand Zini, Faculty of Medicine and Pharmacy, Clinical sciences, Biology of the Testis, Centre for Reproductive Medicine - Gynaecology, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Neuroendocrine, Endocrine and Germinal Differentiation Communication (NorDic), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Björndahl, L, Barratt, Clr, Mortimer, D, Agarwal, A, Aitken, Rj, Alvarez, Jg, Aneck-Hahn, N, Arver, S, Baldi, E, Bassas, L, Boitrelle, F, Bornman, R, Carrell, Dt, Castilla, Ja, Cerezo Parra, G, Check, Jh, Cuasnicu, P, Darney, Sp, de Jager, C, De Jonge, Cj, Drevet, Jr, Drobnis, Ez, Du Plessis, S, Eisenberg, Ml, Esteves, Sc, Evgeni, Ea, Ferlin, A, Garrido, N, Giwercman, A, Goovaerts, Igf, Haugen, Tb, Henkel, R, Henningsohn, L, Hofmann, Mc, Hotaling, Jm, Jedrzejczak, P, Jouannet, P, Jørgensen, N, Kirkman Brown, Jc, Krausz, C, Kurpisz, M, Kvist, U, Lamb, Dj, Levine, H, Loveland, Kl, Mclachlan, Ri, Mahran, A, Maree, L, Martins da Silva, S, Mbizvo, Mt, Meinhardt, A, Menkveld, R, Mortimer, St, Moskovtsev, S, Muller, Ch, Munuce, Mj, Muratori, M, Niederberger, C, O'Flaherty, C, Oliva, R, Ombelet, W, Pacey, Aa, Palladino, Ma, Ramasamy, R, Ramos, L, Rives, N, Roldan, Er, Rothmann, S, Sakkas, D, Salonia, A, Sánchez-Pozo, Mc, Sapiro, R, Schlatt, S, Schlegel, Pn, Schuppe, Hc, Shah, R, Skakkebæk, Ne, Teerds, K, Toskin, I, Tournaye, H, Turek, Pj, van der Horst, G, Vazquez-Levin, M, Wang, C, Wetzels, A, Zeginiadou, T, Zini, A., Pacey, Allan/0000-0002-4387-8871, Arver, Stefan/0000-0002-2925-355X, Mortimer, David/0000-0002-0638-2893, Barratt, christopher/0000-0003-0062-9979, Kirkman-Brown, Jackson, C/0000-0003-2833-8970, Bjorndahl, Lars/0000-0002-4709-5807, Baldi, Elisabetta/0000-0003-1808-3097, Aitken, Robert John/0000-0002-9152-156X, Bjorndahl, Lars, Barratt, Christopher L. R., Mortimer, David, Agarwal, Ashok, Aitken, Robert J., Alvarez, Juan G., Aneck-Hahn, Natalie, Arver, Stefan, Baldi, Elisabetta, Bassas, Lluis, Boitrelle, Florence, Bornman, Riana, Carrell, Douglas T., Castilla, Jose A., Cerezo Parra, Gerardo, Check, Jerome H., Cuasnicu, Patricia S., Darney, Sally Perreault, de Jager, Christiaan, De Jonge, Christopher J., Drevet, Joel R., Drobnis, Erma Z., Du Plessis, Stefan S., Eisenberg, Michael L., Esteves, Sandro C., Evgeni, Evangelini A., Ferlin, Alberto, Garrido, Nicolas, Giwercman, Aleksander, Goovaerts, Ilse G. F., Haugen, Trine B., Henkel, Ralf, Henningsohn, Lars, Hofmann, Marie-Claude, Hotaling, James M., Jedrzejczak, Piotr, Jouannet, Pierre, Jorgensen, Niels, Brown, Jackson C. Kirkman, Krausz, Csilla, Kurpisz, Maciej, Kvist, Ulrik, Lamb, Dolores J., Levine, Hagai, Loveland, Kate L., McLachlan, Robert, I, Mahran, Ali, Maree, Liana, da Silva, Sarah Martins, Mbizvo, Michael T., Meinhardt, Andreas, Menkveld, Roelof, Mortimer, Sharon T., Moskovtsev, Sergey, Muller, Charles H., Jose Munuce, Maria, Muratori, Monica, Niederberger, Craig, O'Flaherty, Cristian, Oliva, Rafael, OMBELET, Willem, Pacey, Allan A., Palladino, Michael A., Ramasamy, Ranjith, Ramos, Liliana, Rives, Nathalie, Roldan, Eduardo Rs, Rothmann, Susan, Sakkas, Denny, Salonia, Andrea, Cristina Sanchez-Pozo, Maria, Sapiro, Rosanna, Schlatt, Stefan, Schlegel, Peter N., Schuppe, Hans-Christian, Shah, Rupin, Skakkebaek, Niels E., Teerds, Katja, Toskin, Igor, Tournaye, Herman, Turek, Paul J., van der Horst, Gerhard, Vazquez-Levin, Monica, Wang, Christina, Wetzels, Alex, Zeginiadou, Theodosia, and Zini, Armand
Subjects: Reproducitibility, [SDV]Life Sciences [q-bio], andrology, basic semen examination, journal requirements, laboratory training, patient security, quality control, reproducibility, reproductive medicine, science development, standardized laboratory procedures, Humans, Reproducibility of Results, Publishing, Semen, Semen Analysis, Andrology, Obstetrics & Reproductive Medicine, Biology, 11 Medical and Health Sciences, Reproductive Biology, Science & Technology, Rehabilitation, Obstetrics & Gynecology, Obstetrics and Gynecology, Reproductive Medicine, 16 Studies in Human Society, Human and Animal Physiology, Fysiologie van Mens en Dier, Human medicine, Life Sciences & Biomedicine
Abstract: Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.
Published: 2022

3. The Global Soil Mycobiome consortium dataset for boosting fungal diversity research

Author: Eske De Crop, Annemieke Verbeken, Cathy Sharp, Jaan Pärn, Vladimir S. Mikryukov, Karin Pritsch, R. Henrik Nilsson, Jose G. Maciá-Vicente, Vladimir G. Onipchenko, César Marín, Kassim I. Tchan, Sten Anslan, Kadri Runnel, D. Q. Dai, Isabel C. Barrio, Miklós Bálint, Joosep Sarapuu, Jacob Heilmann-Clausen, Marcela Eugenia da Silva Cáceres, Juha M. Alatalo, S. V. Dudov, Vladimir E. Fedosov, John Y. Kupagme, Irma Zettur, Andrea Rinaldi, Alessandro Saitta, Jelena Ankuda, Urmas Kõljalg, Franz Buegger, Nourou S. Yorou, Alexandre Antonelli, Brendan R. Furneaux, Daniyal Gohar, Elisabeth M. Biersma, Francis Q. Brearley, Kevin K. Newsham, Dipon Sharmah, Louis J. Lamit, Camila Duarte Ritter, Sergei Põlme, Evgeny A. Davydov, Rebeca Casique-Valdés, Geoffrey Zahn, Leho Tedersoo, W. A. Erandi Yasanthika, Inga Hiiesalu, Young Woon Lim, Adriana Corrales, Casper Nyamukondiwa, Kristel Panksep, Genevieve Gates, Darta Klavina, Boris Tamgnoue, Roberto Godoy, Talaat Ahmed, Kessy Abarenkov, Abdul Nasir Khalid, Erin K. Cameron, Meike Piepenbring, Saleh A. Al-Farraj, Rein Drenkhan, Aída-M. Vasco-Palacios, Roberto Garibay-Orijel, Joseph Djeugap Fovo, Gregory Bonito, Peter Meidl, Kalev Adamson, Kęstutis Armolaitis, Kari A. Bråthen, Ahto Agan, Malka Saba, Peter E. Mortimer, Lateef A. Adebola, Felipe E. Albornoz, Jutamart Monkai, Niloufar Hagh-Doust, Indrek Hiiesalu, Mohammad Bahram, Tarquin Netherway, Bobby P. Sulistyo, Saleh Rahimlou, Sunil Mundra, Kevin D. Hyde, Kadri Põldmaa, Terry W. Henkel, Olavi Kurina, Tomas Roslin, Nalin N. Wijayawardene, Marieka Gryzenhout, Julieta Alvarez-Manjarrez, Rasmus Puusepp, József Geml, Eveli Otsing, Marijn Bauters, Maria Tuomi, Tedersoo L., Mikryukov V., Anslan S., Bahram M., Khalid A.N., Corrales A., Agan A., Vasco-Palacios A.-M., Saitta A., Antonelli A., Rinaldi A.C., Verbeken A., Sulistyo B.P., Tamgnoue B., Furneaux B., Ritter C.D., Nyamukondiwa C., Sharp C., Marin C., Dai D.Q., Gohar D., Sharmah D., Biersma E.M., Cameron E.K., De Crop E., Otsing E., Davydov E.A., Albornoz F.E., Brearley F.Q., Buegger F., Gates G., Zahn G., Bonito G., Hiiesalu I., Zettur I., Barrio I.C., Parn J., Heilmann-Clausen J., Ankuda J., Kupagme J.Y., Sarapuu J., Macia-Vicente J.G., Fovo J.D., Geml J., Alatalo J.M., Alvarez-Manjarrez J., Monkai J., Poldmaa K., Runnel K., Adamson K., Brathen K.A., Pritsch K., Tchan K.I., Armolaitis K., Hyde K.D., Newsham K.K., Panksep K., Adebola L.A., Lamit L.J., Saba M., da Silva Caceres M.E., Tuomi M., Gryzenhout M., Bauters M., Balint M., Wijayawardene N., Hagh-Doust N., Yorou N.S., Kurina O., Mortimer P.E., Meidl P., Nilsson R.H., Puusepp R., Casique-Valdes R., Drenkhan R., Garibay-Orijel R., Godoy R., Alfarraj S., Rahimlou S., Polme S., Dudov S.V., Mundra S., Ahmed T., Netherway T., Henkel T.W., Roslin T., Fedosov V.E., Onipchenko V.G., Yasanthika W.A.E., Lim Y.W., Piepenbring M., Klavina D., Koljalg U., and Abarenkov K.
Subjects: PacBio sequencing, Fungal richness, Biotic component, Ecology, Biogeography, Biodiversity, Global dataset, Plant Ecology and Nature Conservation, Edaphic, Soil fungi, Biology, Fungal richne, Phylogenetic diversity, Microbial ecology, Mycology, Settore BIO/03 - Botanica Ambientale E Applicata, Plantenecologie en Natuurbeheer, Biologie, Ecology, Evolution, Behavior and Systematics, Macroecology
Abstract: This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at https://doi.org/10.1007/s13225-021-00493-7. Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
Published: 2021

4. Ectomycorrhizal fungal community assembly on seedlings of a Neotropical monodominant tree

Author: Rachel A. Koch, Carolyn A. Delevich, M. Catherine Aime, and Terry W. Henkel
Subjects: Thelephoraceae, biology, Seedling, Clavulina, Botany, Dicymbe, Colonization, Fabaceae, Russulaceae, biology.organism_classification, Ecology, Evolution, Behavior and Systematics, Clavulinaceae
Abstract: Ectomycorrhizal tree species may benefit from positive plant–soil feedbacks, where soil environments near adult trees enhance conspecific seedling growth and survival. In tropical monodominant forests, seedling survival is particularly important, as seedling banks help maintain stand-level dominance over generations. Positive plant–soil feedbacks may be mediated by diverse ectomycorrhizal fungal communities, which improve nutrient acquisition of heavily shaded seedlings. Despite the potential importance of these fungi, little is known about ectomycorrhizal fungal community development on seedlings of tropical monodominant trees. In Guyana, we sequentially monitored percent colonization and species composition of ectomycorrhizal fungi on an even-age cohort of seedlings of the tropical monodominant tree Dicymbe corymbosa (Fabaceae subfamily Detarioideae). Ectomycorrhizal fungi found on D. corymbosa seedlings over a 12-month period of early development were compared to those of conspecific adults and four other ectomycorrhizal tree species in the region. Species turnover was high (80%) between 6- and 12-month-old seedlings, though the /russula-lactarius, /clavulina, and /tomentella-thelephora lineages were species-rich on seedlings at all ages. The number of ectomycorrhizal morphotypes per seedling increased with age, but extent of fungal colonization did not. Seedling ectomycorrhizal fungi were shared with sympatric conspecific adults (55%) and, to a lesser extent, regional heterospecific adults (27%), but numerous species were previously unrecorded for Guyana. Over their development D. corymbosa seedlings did not rely strictly on adult trees for their mycobionts but appeared to foster unique assemblages of ectomycorrhizal fungi.
Published: 2021

5. Long-term consequences of sexually transmitted infections on men’s sexual function: A systematic review

Author: Ralf Henkel
Subjects: Infertility, Sexually transmitted diseases, medicine.medical_specialty, Trichomoniasis, biology, business.industry, genital tract infection, Urology, Prostatitis, Review Article, medicine.disease_cause, biology.organism_classification, medicine.disease, obstruction, male infertility, Internal medicine, medicine, Neisseria gonorrhoeae, Urethritis, Sexual function, Chlamydia trachomatis, Mycoplasma genitalium, business, long-term effects
Abstract: Objective: To systematically review the available literature on the long-term effects of sexually transmitted diseases (STIs) on male reproductive functions. Methods: A PubMed search was conducted on 3 January 2021, and as a result, 952 articles were retrieved. Exclusion of irrelevant articles resulted in 36 articles, dating from 1998 to 2020, which were analysed. Results: Only 52.8% of these articles described original research, while the rest were reviews. The majority (26) of the articles dealt with bacterial infections, of which 20 described Chlamydia trachomatis. There were 11 articles that described research on viruses, with five on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The analysis of the articles showed further that not much new knowledge on the long-term effects on male reproductive functions has been added. The existing knowledge that ascending infections can cause epididymo-orchitis, prostatitis or urethritis was confirmed. Due to epithelial inflammatory responses these infections can result in scarring with resulting infertility due to obstruction. These effects were described for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium or Treponema pallidum, as well as for the Zika and SARS-CoV-2 viruses. Even trichomoniasis can lead to long-term compromised male fertility if not treated. Conclusion: In conclusion, problem awareness needs to be raised and more research on this important topic needs to be conducted.
Published: 2021

6. Reply to Pallotti et al. Comment on 'Boitrelle et al. The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis. Life 2021, 11, 1368'

Author: Florence Boitrelle, Rupin Shah, Ramadan Saleh, Ralf Henkel, Hussein Kandil, Eric Chung, Paraskevi Vogiatzi, Armand Zini, Mohamed Arafa, and Ashok Agarwal
Subjects: Life Sciences & Biomedicine - Other Topics, Science & Technology, Space and Planetary Science, Paleontology, Life Sciences & Biomedicine, Biology, Microbiology, General Biochemistry, Genetics and Molecular Biology, Ecology, Evolution, Behavior and Systematics
Abstract: We would like to thank F. Pallotti and his colleagues for their positive comments [...]
Published: 2022

7. Introgression of ASIP and TYRP1 Alleles Explains Coat Color Variation in Valais Goats

Author: Ursula Herren, Alexandra Dubacher, Jan Henkel, Erika Bangerter, Tosso Leeb, P. Ammann, Cord Drögemüller, and Christine Flury
Subjects: 0301 basic medicine, Coat, DNA Copy Number Variations, Genotype, 0206 medical engineering, Zoology, Introgression, 02 engineering and technology, Gene flow, 03 medical and health sciences, Genetics, Capra hircus, Animals, Allele, Molecular Biology, Alleles, Genetics (clinical), biology, Goats, biology.organism_classification, Breed, White (mutation), Phenotype, 030104 developmental biology, Capra, 020602 bioinformatics, Biotechnology
Abstract: The Valais Blackneck goat is a Swiss goat breed with a characteristic coat color phenotype. Before the revision of the breed standard in 1938, 4 different color varieties of Valais goats were known. Besides Blackneck animals resembling the modern breed standard, the brown and white Copperneck goat, the white Capra Sempione, and the greyish Grüenochte comprised the historic Valais goats. The brown pigmentation of Copperneck goats had previously been traced back to an introgression of a mutant TYRP1 allele from Toggenburg goats. In the present study, we identified additional introgression events of distinct ASIP alleles causing the remaining 2 rare coat color patterns within the Valais Blackneck goat breed. We identified the introgression of the AWt allele from Appenzell or Saanen goats in white Capra Sempione goats. Similarly, introgression of the Apc allele from Peacock goats resulted in the greyish Grüenochte phenotype. These results demonstrate past hybridization events between breeds that are separated today. A perfect genotype-phenotype association in 393 Valais goats supported the causality of the genotyped variants for the different coat color phenotypes. Our study gives insights into the introgression of functionally relevant copy number variant (CNV) alleles controlling pigmentation between goat breeds with strikingly different coat color patterns.
Published: 2021

8. Bacillus subtilis High Cell Density Fermentation Using a Sporulation-Deficient Strain for the Production of Surfactin

Author: Mareen Hoffmann, Moritz Aschern, Katja Hennemann, Rudolf Hausmann, Marius Henkel, Peter Klausmann, Kambiz Morabbi Heravi, Chantal Treinen, and Lars Lilge
Subjects: Cell Count, Bacillus subtilis, Applied Microbiology and Biotechnology, Peptides, Cyclic, chemistry.chemical_compound, Ammonia, Lipopeptides, Food science, Strain (chemistry), biology, Chemistry, Biosurfactant, General Medicine, biology.organism_classification, Biotechnological Products and Process Engineering, Spore, Culture Media, Titer, Cyclic lipopeptide, Sporulation, Fermentation, Elongation, Surfactin, Biotechnology
Abstract: Abstract Bacillus subtilis 3NA is a strain capable of reaching high cell densities. A surfactin producing sfp+ variant of this strain, named JABs32, was utilized in fed-batch cultivation processes. Both a glucose and an ammonia solution were fed to set a steady growth rate μ of 0.1 h-1. In this process, a cell dry weight of up to 88 g L-1 was reached after 38 h of cultivation, and surfactin titers of up to 26.5 g L-1 were detected in this high cell density fermentation process, achieving a YP/X value of 0.23 g g-1 as well as a qP/X of 0.007 g g-1 h-1. In sum, a 21-fold increase in surfactin titer was obtained compared with cultivations in shake flasks. In contrast to fed-batch operations using Bacillus subtilis JABs24, an sfp+ variant derived from B. subtilis 168, JABs32, reached an up to fourfold increase in surfactin titers using the same fed-batch protocol. Additionally, a two-stage feed process was established utilizing strain JABs32. Using an optimized mineral salt medium in this high cell density fermentation approach, after 31 h of cultivation, surfactin titers of 23.7 g L-1 were reached with a biomass concentration of 41.3 g L-1, thus achieving an enhanced YP/X value of 0.57 g g-1 as well as a qP/X of 0.018 g g-1 h-1. The mutation of spo0A locus and an elongation of AbrB in the strain utilized in combination with a high cell density fed-batch process represents a promising new route for future enhancements on surfactin production. Key points • Utilization of a sporulation deficient strain for fed-batch operations • High cell density process with Bacillus subtilis for lipopeptide production was established • High titer surfactin production capabilities confirm highly promising future platform strain
Published: 2021

9. Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab

Author: Emily Henkel, Ruy Carrasco, Megan A Trainor, and Lucia Z. Diaz
Subjects: 0301 basic medicine, Antifungal Agents, medicine.medical_treatment, Arthritis, Case Report, Disseminated coccidioidomycosis, Diseases of the musculoskeletal system, Pediatrics, 0302 clinical medicine, Immunology and Allergy, Fluconazole, Coccidioidomycosis, biology, Immunosuppression, Treatment Outcome, Pneumonia, Necrotizing, Antirheumatic Agents, Disease Progression, Female, medicine.drug, medicine.medical_specialty, Adolescent, Coccidioides immitis, 030106 microbiology, RJ1-570, 03 medical and health sciences, Rheumatology, Monitoring, Immunologic, Amphotericin B, 030225 pediatrics, Immune Tolerance, medicine, Humans, Corticosteroids, Coccidioides, business.industry, Choroid Diseases, Juvenile idiopathic arthritis, biology.organism_classification, medicine.disease, Dermatology, Arthritis, Juvenile, Infliximab, Meningitis, Fungal, Pneumonia, Methotrexate, RC925-935, Pediatrics, Perinatology and Child Health, Tumor necrosis factor alpha (TNF-α) inhibitors, business
Abstract: Background Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy. Case presentation We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody. Conclusions Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.
Published: 2021

10. Evaluation of an oxygen‐dependent self‐inducible surfactin synthesis in B. subtilis by substitution of native promoter P srfA by anaerobically active P narG and P nasD

Author: Mareen Hoffmann, Diana Stephanie Fernandez Cano Luna, Katharina Rief, Alina Braig, Rudolf Hausmann, Philipp Becker, Chantal Treinen, Marius Henkel, Peter Klausmann, Kambiz Morabbi Heravi, and Lars Lilge
Subjects: Lipopeptide biosurfactants, Microaerobic, biology, Strain (chemistry), Operon, Biophysics, Bacillus subtilis, Reductase, biology.organism_classification, Nitrite reductase, Applied Microbiology and Biotechnology, Microbiology, QR1-502, Oxygen, chemistry.chemical_compound, Biochemistry, chemistry, Bioreactor, Promoter exchange, Nitrite, Surfactin, TP248.13-248.65, Biotechnology
Abstract: A novel approach targeting self-inducible surfactin synthesis under oxygen-limited conditions is presented. Because both the nitrate (NarGHI) and nitrite (NasDE) reductase are highly expressed during anaerobic growth ofB. subtilis, the native promoter PsrfAof the surfactin operon in strainB. subtilisJABs24 was replaced by promoters PnarGand PnasDto induce surfactin synthesis anaerobically. Shake flask cultivations with varying oxygen availabilities indicated no significant differences in native PsrfAexpression. As hypothesized, activity of PnarGand PnasDincreased with lower oxygen levels and surfactin was not produced by PsrfA::PnarGas well as PsrfA::PnasDmutant strains under conditions with highest oxygen availability. PnarGshowed expressions similar to PsrfAat lowest oxygen availability, while maximum value of PnasDwas more than 5.5-fold higher. Although the promoter exchange PsrfA::PnarGresulted in a decreased surfactin titer at lowest oxygen availability, the strain carrying PsrfA::PnasDreached a 1.4-fold increased surfactin concentration with 696 mg/L and revealed an exceptional high overallYP/Xof 1.007 g/g. This value also surpassed theYP/Xof the reference strain JABs24 at highest and moderate oxygen availability. Bioreactor cultivations illustrated that significant cell lysis occurred when the process of “anaerobization” was performed too fast. However, processes with a constantly low agitation and aeration rate showed promising potential for process improvement, especially by employing the strain carrying PsrfA::PnasDpromoter exchange. Additionally, replacement of other native promoters by nitrite reductase promoter PnasDrepresents a promising tool for anaerobic-inducible bioprocesses inBacillus.
Published: 2021

11. A SYNOPSIS OF THE WOOD-DECAY GENUS LAXITEXTUM (HERICIACEAE, RUSSULALES, BASIDIOMYCOTA) AND A NEW SPECIES FROM CAMEROON

Author: Leif Ryvarden and Terry W. Henkel
Subjects: Hericiaceae, biology, Genus, Botany, Basidiomycota, Plant Science, Laxitextum, biology.organism_classification, Ecology, Evolution, Behavior and Systematics, Russulales
Abstract: Descriptions of and a key to the globally known species of the genus Laxitextum are provided. A new species from Cameroon, Laxitextum globisporum, is described.
Published: 2021

12. A Thioether-Ligated Cupric Superoxide Model with Hydrogen Atom Abstraction Reactivity

Author: Keith O. Hodgson, Maxime A. Siegler, Markus Lerch, Kenneth D. Karlin, Wesley J. Transue, Jung Yoon C. Lee, Britt Hedman, Siegfried Schindler, Adam Neuba, Patrick Josephs, Ryan E. Cowley, Mayukh Bhadra, Hyeongtaek Lim, Gerald Henkel, and Edward I. Solomon
Subjects: Molecular Conformation, Sulfides, 010402 general chemistry, Hydrogen atom abstraction, 01 natural sciences, Biochemistry, Medicinal chemistry, Article, Catalysis, chemistry.chemical_compound, Colloid and Surface Chemistry, Thioether, Superoxides, Kinetic isotope effect, Reactivity (chemistry), Density Functional Theory, biology, Extended X-ray absorption fine structure, Superoxide, Active site, General Chemistry, Resonance (chemistry), 0104 chemical sciences, Kinetics, chemistry, biology.protein, Spectrophotometry, Ultraviolet, Oxidation-Reduction, Copper, Hydrogen
Abstract: The central role of cupric superoxide intermediates proposed in hormone and neurotransmitter biosynthesis by noncoupled binuclear copper monooxygenases like dopamine-β-monooxygenase has drawn significant attention to the unusual methionine ligation of the Cu(M) (“Cu(B)”) active site characteristic of this class of enzymes. The copper–sulfur interaction has proven critical for turnover, raising still-unresolved questions concerning Nature’s selection of an oxidizable Met residue to facilitate C–H oxygenation. We describe herein a model for Cu(M), [((TMG)N(3)S)Cu(I)](+) ([1](+)), and its O(2)-bound analog [((TMG)N(3)S)Cu(II)(O(2)(•−))](+) ([1·O(2)](+)). The latter is the first reported cupric superoxide with an experimentally proven Cu–S bond which also possesses demonstrated hydrogen atom abstraction (HAA) reactivity. Introduction of O(2) to a precooled solution of the cuprous precursor [1]B(C(6)F(5))(4) (−135 °C, 2-methyltetrahydrofuran (2-MeTHF)) reversibly forms [1·O(2)]B(C(6)F(5))(4) (UV/vis spectroscopy: λ(max) 442, 642, 742 nm). Resonance Raman studies (413 nm) using (16)O(2) [(18)O(2)] corroborated the identity of [1·O(2)](+) by revealing Cu–O (446 [425] cm(−1)) and O–O (1105 [1042] cm(−1)) stretches, and extended X-ray absorption fine structure (EXAFS) spectroscopy showed a Cu–S interatomic distance of 2.55 Å. HAA reactivity between [1·O(2)](+) and TEMPO–H proceeds rapidly (1.28 × 10(−1) M(−1) s(−1), −135 °C, 2-MeTHF) with a primary kinetic isotope effect of k(H)/k(D) = 5.4. Comparisons of the O(2)-binding behavior and redox activity of [1](+) vs [2](+), the latter a close analog of [1](+) but with all N atom ligation (i.e., N(3)S vs N(4)), are presented.
Published: 2021

13. Inflammatory macrophage memory in nonsteroidal anti-inflammatory drug–exacerbated respiratory disease

Author: Adam Chaker, Ulrike Bernhardt, Carsten B. Schmidt-Weber, Alexander Cecil, Yan Ge, Matthias Heinig, Dominique Thomas, Ulrich M. Zissler, Mark Haid, Cornelia Prehn, Janina Tokarz, Sonja Schindela, Xavier Pastor, Pascal Haimerl, Julia Esser-von Bieren, Fiona Henkel, Jerzy Adamski, and Antonie Lechner
Subjects: 0301 basic medicine, Chemokine, Immunology, Proinflammatory cytokine, 03 medical and health sciences, chemistry.chemical_compound, Nasal Polyps, 0302 clinical medicine, Acylcarnitines, Chemokines, Eicosanoids, Lipid Mediator, Macrophages, Metabolomics, Nsaid-exacerbated Respiratory Disease, Trained Immunity, Type 2 Inflammation, Humans, Immunology and Allergy, Medicine, Macrophage, Epigenetics, Leukotriene, biology, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Lipid signaling, Macrophage Activation, Asthma, 030104 developmental biology, 030228 respiratory system, chemistry, biology.protein, Arachidonic acid, business, Immunologic Memory, Reprogramming
Abstract: Background Nonsteroidal anti-inflammatory drug–exacerbated respiratory disease (N-ERD) is a chronic inflammatory condition, which is driven by an aberrant arachidonic acid metabolism. Macrophages are major producers of arachidonic acid metabolites and subject to metabolic reprogramming, but they have been neglected in N-ERD. Objective This study sought to elucidate a potential metabolic and epigenetic macrophage reprogramming in N-ERD. Methods Transcriptional, metabolic, and lipid mediator profiles in macrophages from patients with N-ERD and healthy controls were assessed by RNA sequencing, Seahorse assays, and LC-MS/MS. Metabolites in nasal lining fluid, sputum, and plasma from patients with N-ERD (n = 15) and healthy individuals (n = 10) were quantified by targeted metabolomics analyses. Genome-wide methylomics were deployed to define epigenetic mechanisms of macrophage reprogramming in N-ERD. Results This study shows that N-ERD monocytes/macrophages exhibit an overall reduction in DNA methylation, aberrant metabolic profiles, and an increased expression of chemokines, indicative of a persistent proinflammatory activation. Differentially methylated regions in N-ERD macrophages included genes involved in chemokine signaling and acylcarnitine metabolism. Acylcarnitines were increased in macrophages, sputum, nasal lining fluid, and plasma of patients with N-ERD. On inflammatory challenge, N-ERD macrophages produced increased levels of acylcarnitines, proinflammatory arachidonic acid metabolites, cytokines, and chemokines as compared to healthy macrophages. Conclusions Together, these findings decipher a proinflammatory metabolic and epigenetic reprogramming of macrophages in N-ERD.
Published: 2021

14. Oxidative Stress and Toxicity in Reproductive Biology and Medicine: Historical Perspectives and Future Horizons in Male Fertility

Author: Ralf, Henkel
Subjects: Male, Oxidative Stress, Fertility, Humans, Reactive Oxygen Species, Biology, Antioxidants
Abstract: Since the discovery by John MacLeod in 1943 that spermatozoa produce small amounts of hydrogen peroxide, a member of the so-called reactive oxygen species (ROS), the importance and functions of these highly reactive oxygen derivatives in physiology and pathology are a subject of numerous studies. It has been shown that they play essential roles, not only in causing oxidative stress if their concentration is excessively high, but also in triggering crucial cellular functions if their concentration is low. On the other hand, antioxidants counterbalance the action of ROS to maintain a fine balance between oxidation and reduction as an excessive amount of antioxidants leads to a condition called reductive stress and is as harmful as oxidative stress. This book "Oxidative Stress and Toxicity in Reproductive Biology and Medicine - A Comprehensive Update on Male Infertility" authoritatively summarizes the current knowledge of various causes of oxidative stress including various andrological conditions and environmental pollution as well as the physiological effects of ROS. Moreover, this book expands into the treatment of oxidative stress with antioxidants and phytomedicine, a rapidly developing area. As a first of its kind, this book also sheds light on the effects of the redox potential during the fertilization process and thus highlights the importance of the correct balance of oxidants and antioxidants, even in the culture medium in assisted reproduction. The editors have brought together an impressive group of renowned experts to share their knowledge on the topic of oxidative stress and its clinical management in andrology and assisted reproduction.
Published: 2022

15. Amanita in the Guineo-Congolian rainforest: Epitypes and new species from the Dja Biosphere Reserve, Cameroon

Author: Kennan S Mighell, Mei Lin Chin, Rachel A. Koch, Terry W. Henkel, M. Catherine Aime, and Mia A Brann
Subjects: Amanita, biology, Physiology, Zoology, Cell Biology, General Medicine, Rainforest, biology.organism_classification, Agaricomycetes, Taxon, Genus, Genetics, Agaricales, Amanitaceae, Internal transcribed spacer, Molecular Biology, Ecology, Evolution, Behavior and Systematics
Abstract: Four epitypes and three new species of Amanita (Amanitaceae, Agaricales, Agaricomycetes, Basidiomycota) are described from Guineo-Congolian rainforests of Cameroon. Amanita echinulata, A. fulvopulverulenta, A. robusta, and A. bingensis are epitypified based on collections that are the first since the species were described nearly a century ago. Morphological features of the epitypes are described and enumerated. Amanita minima, Amanita luteolamellata, and A. goossensfontanae are described as new and added to the known macromycota of tropical Africa. Habit, habitat, and known distribution are provided for each species. Sequence data for the internal transcribed spacer (ITS) locus are provided for types and other collections of all taxa, and a molecular phylogenetic analysis across the genus Amanita corroborates morphology-based infrageneric placement for each.
Published: 2020

16. Crystalline iron oxides stimulate methanogenic benzoate degradation in marine sediment-derived enrichment cultures

Author: Oluwatobi Emmanuel Oni, Susann Henkel, Rolf Nimzyk, Tilmann Harder, Michael W. Friedrich, Marcus Elvert, Daniela Tienken, Sabine Kasten, Sten Littmann, Ajinkya Kulkarni, Jan Tebben, David A. Aromokeye, Kai-Uwe Hinrichs, Xiuran Yin, Tim Richter-Heitmann, and Jenny Wendt
Subjects: chemistry.chemical_classification, 0303 health sciences, biology, 030306 microbiology, Methanogenesis, Iron oxide, engineering.material, Hematite, Deltaproteobacteria, biology.organism_classification, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Environmental chemistry, visual_art, engineering, visual_art.visual_art_medium, Organic matter, Lepidocrocite, Microbial biodegradation, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Magnetite
Abstract: Elevated dissolved iron concentrations in the methanic zone are typical geochemical signatures of rapidly accumulating marine sediments. These sediments are often characterized by co-burial of iron oxides with recalcitrant aromatic organic matter of terrigenous origin. Thus far, iron oxides are predicted to either impede organic matter degradation, aiding its preservation, or identified to enhance organic carbon oxidation via direct electron transfer. Here, we investigated the effect of various iron oxide phases with differing crystallinity (magnetite, hematite, and lepidocrocite) during microbial degradation of the aromatic model compound benzoate in methanic sediments. In slurry incubations with magnetite or hematite, concurrent iron reduction, and methanogenesis were stimulated during accelerated benzoate degradation with methanogenesis as the dominant electron sink. In contrast, with lepidocrocite, benzoate degradation, and methanogenesis were inhibited. These observations were reproducible in sediment-free enrichments, even after five successive transfers. Genes involved in the complete degradation of benzoate were identified in multiple metagenome assembled genomes. Four previously unknown benzoate degraders of the genera Thermincola (Peptococcaceae, Firmicutes), Dethiobacter (Syntrophomonadaceae, Firmicutes), Deltaproteobacteria bacteria SG8_13 (Desulfosarcinaceae, Deltaproteobacteria), and Melioribacter (Melioribacteraceae, Chlorobi) were identified from the marine sediment-derived enrichments. Scanning electron microscopy (SEM) and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) images showed the ability of microorganisms to colonize and concurrently reduce magnetite likely stimulated by the observed methanogenic benzoate degradation. These findings explain the possible contribution of organoclastic reduction of iron oxides to the elevated dissolved Fe2+ pool typically observed in methanic zones of rapidly accumulating coastal and continental margin sediments.
Published: 2020

17. Chip‐based duplex real‐time PCR for water quality monitoring concerning Legionella pneumophila and Legionella spp

Author: Oliver Aehlig, Antje Breitenstein, Stefanie Hentschel, Wolfgang Fritzsche, Eileen Heinrich, Cornelia Reuter, Andrea Csáki, and Thomas Henkel
Subjects: Environmental Engineering, Real-time polymerase chain reaction, biology, Legionella, Duplex (telecommunications), Water quality, Management, Monitoring, Policy and Law, biology.organism_classification, Pollution, Legionella pneumophila, Water Science and Technology, Microbiology
Published: 2020

18. Two distinct immunopathological profiles in autopsy lungs of COVID-19

Author: Tobias Junt, Gieri Cathomas, Kirsten D. Mertz, Viktor H. Koelzer, Holger Moch, Francesca Demichelis, Thomas Hoyler, Alexandar Tzankov, Nathalie Schwab, Niels Willi, Maurice Henkel, Werner Kempf, Angela Frank, Ronny Nienhold, Thomas Menter, Markus Tolnay, Veronika Zsikla, Mattia Barbareschi, Jasmin D. Haslbauer, Yari Ciani, University of Zurich, and Mertz, Kirsten D
Subjects: Male, 0301 basic medicine, Pathology, General Physics and Astronomy, Autopsy, CD8-Positive T-Lymphocytes, medicine.disease_cause, Transcriptome, 0302 clinical medicine, Interferon, Sequencing, lcsh:Science, Lung, Coronavirus, Aged, 80 and over, Multidisciplinary, Respiratory disease, virus diseases, Middle Aged, Viral Load, respiratory system, 3100 General Physics and Astronomy, Vaccination, 030220 oncology & carcinogenesis, Cytokines, Female, Infection, Coronavirus Infections, Viral load, medicine.drug, medicine.medical_specialty, Immunopathogenesis, Coronavirus disease 2019 (COVID-19), Science, Pneumonia, Viral, 610 Medicine & health, 1600 General Chemistry, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Betacoronavirus, 03 medical and health sciences, Immune system, 1300 General Biochemistry, Genetics and Molecular Biology, 10049 Institute of Pathology and Molecular Pathology, medicine, Humans, Pandemics, Gene, Aged, SARS-CoV-2, business.industry, Gene Expression Profiling, Macrophages, COVID-19, General Chemistry, medicine.disease, respiratory tract diseases, Pneumonia, 030104 developmental biology, Viral infection, Normal lung, Immunology, lcsh:Q, Interferons, business, CD8
Abstract: Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment., The immunopathological features of SARS-CoV-2 infection in the lungs remain unclear. Here, the authors provide a comprehensive characterization of post mortem lung tissues of COVID-19 patients and find two distinct patterns characterized by differential expression of interferon stimulated genes (ISGs), which correlate to viral loads, cytokines, lung damage and time of hospitalization, suggesting ISG profiles to mark disease progression
Published: 2020

19. Scientific landscape of oxidative stress in male reproductive research: A scientometric study

Author: Ashok Agarwal, Ralf Henkel, Kathy Amy Robert, Concetta Iovine, Saradha Baskaran, Manesh Kumar Panner Selvam, Renata Finelli, Catalina Barbarosie, and Kruyanshi Master
Subjects: Male, 0301 basic medicine, Reproduction, media_common.quotation_subject, Scopus, Biology, medicine.disease, Biochemistry, Antioxidants, Male infertility, Oxidative Stress, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Physiology (medical), medicine, Humans, Reactive Oxygen Species, Infertility, Male, 030217 neurology & neurosurgery, Demography, media_common
Abstract: Unraveling the role of reactive oxygen species and associated oxidative stress (OS) in male reproduction is one of the key areas of male reproductive research. This article illustrates the scientific landscape of OS in male reproductive research over the past several decades (1941–2018) using a scientometric approach. Scientometric data (articles per year, authors, affiliations, journals, and countries) on OS related to male reproduction were retrieved from the Scopus database and analyzed for each decade. Our analysis revealed an increasing trend in OS-based male reproductive research from 1941 to 2018 with a steep raise in publications and research collaborations starting from the period 1991–2000 (R2 = 0.81). Semen abnormalities and varicocele were the major areas investigated in relation to OS with the highest positive trend in publications from the time interval 1981–1990 to 2011–2018. Analysis of publications based on OS assessment techniques revealed chemiluminescence (n = 180) and evaluation of antioxidants (n = 300) as the most widely used direct and indirect tests, respectively. Furthermore, prognostic/diagnostic studies on OS evaluation increased significantly over the time. Our analysis highlights the evolution of OS in male reproductive research and its emergence as an important prognostic and diagnostic tool in the evaluation of male infertility.
Published: 2020

20. New species of Entolomataceae from Cameroon

Author: Noah Siegel, K M Hageman, Olivier Séné, M.C. Aime, David L. Largent, Terry W. Henkel, and Rachel A. Koch
Subjects: entolomatoid fungi, Agaricomycetes, Central Africa, biology, Entoloma, Rainforest, biology.organism_classification, Agricultural and Biological Sciences (miscellaneous), Biochemistry, Genetics and Molecular Biology (miscellaneous), Microbiology, Article, new taxa, Taxon, Entolomataceae, monodominant forests, Botany, Agaricales, Gilbertiodendron, Uapaca, Ecology, Evolution, Behavior and Systematics
Abstract: Six species of Entoloma (Entolomataceae, Agaricales, Basidiomycota) are described from recent Cameroonian collections: E. bisterigmatum, E. brunneoloaurantiacum, E. djaense, E. intricatum, E. versiforme, and E. parvistellatum. These species occur in tropical rainforests dominated by ectomycorrhizal trees in the genera Gilbertiodendron and Uapaca. Data on macromorphology, micromorphology, DNA sequences, habitat and comparisons with similar taxa are provided for each. This is the first contemporary taxonomic work on the Entolomataceae from Cameroon.
Published: 2020

21. Anatomical and biochemical evidence for Treponema pallidum in a 19th to early twentieth century skeletal cadaver

Author: Ned Farley, Joel G. Davis, and James S. Henkel
Subjects: Male, Pediatrics, medicine.medical_specialty, Disease, 01 natural sciences, Bone and Bones, Facial Bones, Mass Spectrometry, Rapid plasma reagin, Pathology and Forensic Medicine, Indirect evidence, Craniosynostoses, 03 medical and health sciences, 0302 clinical medicine, Cadaver, medicine, Edema, Humans, Treponema pallidum, 030216 legal & forensic medicine, Bone Resorption, Aged, Anodontia, Treponema, biology, medicine.diagnostic_test, business.industry, Syphilis, Congenital, Malnutrition, 010401 analytical chemistry, Osteophyte, Mercury, General Medicine, History, 20th Century, Middle Aged, biology.organism_classification, medicine.disease, Antibodies, Bacterial, 0104 chemical sciences, Congenital syphilis, Joints, Syphilis, business, Antibody detection
Abstract: This report summarizes findings relating to the biochemical and skeletal evidence for Treponema pallidum in an unusually old case of congenital syphilis. In 1951, the Milwaukee Public Museum acquired skeletal remains from the Surgical School of Marquette University. The male was identified as a 60-65-year-old, that was suffering from congenital syphilis. His remains are now part of the anthropological collections of Wisconsin Lutheran College (Milwaukee, Wisconsin). Venereal Disease Research Laboratory (VDRL) and Rapid Plasma Reagin (RPR) tests were used to verify the presence of the bacteria-generated antibodies, while mass spectrometry testing provided indirect evidence for the historical treatment of the disease. Notably, antibody detection in human remains of this age is rare. These initial results support what is known of syphilis and its treatment prior to the wide scale, clinical use of penicillin therapy, and describe evidence for long-term skeletal symptoms of congenital syphilis in century-old human remains.
Published: 2020

22. Assessing Accuracy of Sampling Schemes to Estimate Western Snowy Plover Reproductive Success

Author: Lynne E. Stenzel, Laird A. Henkel, R. William Stein, and Kriss Neuman
Subjects: 0106 biological sciences, education.field_of_study, Ecology, biology, Reproductive success, Plover, Population, Wildlife, Sampling (statistics), biology.organism_classification, 01 natural sciences, 010605 ornithology, 010601 ecology, Fishery, Geography, Animal Science and Zoology, Charadrius nivosus, education, Ecology, Evolution, Behavior and Systematics, Nature and Landscape Conservation
Abstract: Like many wildlife species of management concern, the western snowy plover Charadrius nivosus nivosus is the subject of intensive population monitoring. However, intensive monitoring of reproductive success for this shorebird is time-consuming, financially costly, and potentially disruptive to the birds of interest. These constraints mean that intensive monitoring is not feasible throughout the range of the federally threatened Pacific Coast population. In this study, we used data collected from one intensively monitored subpopulation to assess how reductions in monitoring effort (number of chicks individually marked) would affect the accuracy of estimates of fledging success for western snowy plover chicks. We used monitoring data collected on chicks hatching at 1,845 nests from 2003 to 2012 as a theoretical subpopulation from which to draw random samples for this assessment. As expected, we found that accuracy (as measured by the inverse of percentage difference between sampled and actual fledge rates) increased with increasing percentage of the subpopulation monitored each year. We also found that the day of the week that chicks hatched and were banded had no effect on fledging success. Thus, reducing monitoring effort by banding chicks on specific days of the week is one suitable method for subpopulation sampling that has no embedded biases in the subsequent estimate of fledging success. The results of our analyses provide estimates of the accuracy of different sampling schemes, which should help managers of this threatened shorebird assess appropriate monitoring methods. We recommend use of our methods for others interested in assessing accuracy of sampling schemes for reproductive success of western snowy plover or other birds with similar life-history traits.
Published: 2020

23. Runs of homozygosity in Swiss goats reveal genetic changes associated with domestication and modern selection

Author: Heidi Signer-Hasler, Jan Henkel, Erika Bangerter, Zafer Bulut, The VarGoats Consortium, Cord Drögemüller, Tosso Leeb, and Christine Flury
Subjects: Genome, 630 Agriculture, Goats, Homozygote, 610 Medicine & health, General Medicine, QH426-470, Polymorphism, Single Nucleotide, SF1-1100, Animal culture, Domestication, Genetics, Animals, 590 Animals (Zoology), 570 Life sciences, biology, Animal Science and Zoology, Selection, Genetic, Switzerland, Ecology, Evolution, Behavior and Systematics, Research Article
Abstract: Background The domestication of goat (Capra hircus) started 11,000 years ago in the fertile crescent. Breed formation in the nineteenth century, establishment of herd books, and selection for specific traits resulted in 10 modern goat breeds in Switzerland. We analyzed whole-genome sequencing (WGS) data from 217 modern goats and nine wild Bezoar goats (Capra aegagrus). After quality control, 27,728,288 biallelic single nucleotide variants (SNVs) were used for the identification of runs of homozygosity (ROH) and the detection of ROH islands. Results Across the 226 caprine genomes from 11 populations, we detected 344 ROH islands that harbor 1220 annotated genes. We compared the ROH islands between the modern breeds and the Bezoar goats. As a proof of principle, we confirmed a signature of selection, which contains the ASIP gene that controls several breed-specific coat color patterns. In two other ROH islands, we identified two missense variants, STC1:p.Lys139Arg and TSHR:p.Ala239Thr, which might represent causative functional variants for domestication signatures. Conclusions We have shown that the information from ROH islands using WGS data is suitable for the analysis of signatures of selection and allowed the detection of protein coding variants that may have conferred beneficial phenotypes during goat domestication. We hypothesize that the TSHR:p.Ala239Thr variant may have played a role in changing the seasonality of reproduction in modern domesticated goats. The exact functional significance of the STC1:p.Lys139Arg variant remains unclear and requires further investigation. Nonetheless, STC1 might represent a new domestication gene affecting relevant traits such as body size and/or milk yield in goats.
Published: 2022

24. Network Effects in Biology R&D

Author: Henkel, Joachim and Maurer, Stephen M.
Published: 2010

25. Eye-transcriptome and genome-wide sequencing for Scolecophidia: implications for inferring the visual system fo the ancestral snake

Author: Nicholas R. Casewell, Christiaan V. Henkel, Freek J. Vonk, Sonja Meimann, Kate L. Sanders, David J. Gower, James F. Fleming, Leo Peichl, Bruno F. Simões, Davide Pisani, Harald M. I. Kerkkamp, and Michael K. Richardson
Subjects: Paraphyly, AcademicSubjects/SCI01140, Candidate gene, vision, Squamata, genetic structures, Context (language use), Biology, phylogeny, Genome, Evolution, Molecular, Phylogenetics, Genetics, Animals, Ecology, Evolution, Behavior and Systematics, Mammals, Scolecophidia, regressive evolution, Opsins, opsins, Fossorial, AcademicSubjects/SCI01130, Lizards, Snakes, gene loss, biology.organism_classification, eye diseases, Evolutionary biology, Transcriptome, Research Article
Abstract: Molecular genetic data have recently been incorporated in attempts to reconstruct the ecology of the ancestral snake, though this has been limited by a paucity of data for one of the two main extant snake taxa, the highly fossorial Scolecophidia. Here we present and analyze vision genes from the first eye-transcriptomic and genome-wide data for Scolecophidia, for Anilios bicolor, and A. bituberculatus, respectively. We also present immunohistochemistry data for retinal anatomy and visual opsin-gene expression in Anilios. Analyzed in the context of 19 lepidosaurian genomes and 12 eye transcriptomes, the new genome-wide and transcriptomic data provide evidence for a much more reduced visual system in Anilios than in non-scolecophidian (=alethinophidian) snakes and in lizards. In Anilios, there is no evidence of the presence of 7 of the 12 genes associated with alethinophidian photopic (cone) phototransduction. This indicates extensive gene loss and many of these candidate gene losses occur also in highly fossorial mammals with reduced vision. Although recent phylogenetic studies have found evidence for scolecophidian paraphyly, the loss in Anilios of visual genes that are present in alethinophidians implies that the ancestral snake had a better-developed visual system than is known for any extant scolecophidian.
Published: 2021

26. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1

Author: Klionsky, Daniel, Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie, Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis, Adeli, Khosrow, Adolph, Timon, Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat, Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed, Agrotis, Alexander, Aguilar, Patricia, Ahmad, S Tariq, Ahmed, Zubair, Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed, Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay, Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo, Altan-Bonnet, Nihal, Altieri, Dario, Álvarez, Élida, Alves, Sara, Alves Da Costa, Cristine, Alzaharna, Mazen, Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal, Ammanathan, Veena, An, Zhenyi, Andersen, Stig, Andrabi, Shaida, Andrade-Silva, Magaiver, Andres, Allen, Angelini, Sabrina, Ann, David, Anozie, Uche, Ansari, Mohammad, Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner, Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen, Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela, Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas, Au, Alicia, Auberger, Patrick, Auner, Holger, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan, Backues, Steven, Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric, Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima, Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio, Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter, Barmada, Sami, Barreiro, Esther, Barreto, George, Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav, Basagoudanavar, Suresh, Bassham, Diane, Bast, Robert, Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne, Baumgarner, Bradley, Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz, Beck, George, Beers, Michael, 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Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier, Hesselson, Daniel, Hetz, Claudio, Heussler, Volker, Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph, Hlavacek, William, Ho, Emmanuel, Ho, Idy, Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G Aaron, Hochstrasser, Mark, Hoet, Peter, Hofius, Daniel, Hofman, Paul, Höhn, Annika, Holmberg, Carina, Hombrebueno, Jose, Yi-Ren Hong, Chang-Won Hong, Hooper, Lora, Hoppe, Thorsten, Horos, Rastislav, Hoshida, Yujin, Hsin, I-Lun, Hsu, Hsin-Yun, Hu, Bing, Hu, Dong, Hu, Li-Fang, Hu, Ming Chang, Hu, Ronggui, Hu, Wei, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Jinlian, Hua, Yingqi, Huan, Chongmin, Huang, Canhua, Huang, Chuanshu, Huang, Chuanxin, Huang, Chunling, Huang, Haishan, Huang, Kun, Huang, Michael, Huang, Rui, Huang, Shan, Huang, Tianzhi, Huang, Xing, Huang, Yuxiang Jack, Huber, Tobias, Hubert, Virginie, Hubner, Christian, Hughes, Stephanie, 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Da-Hye, Lee, Edward, Lee, Erinna, Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason, Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella, Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu, Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia, Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy, Levine, Beth, Lewis, Patrick, Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl, Lilly, Mary, Lim, Hyunjung, Lima, Thania, Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie, Lin, Kurt, Lin, Kwang-Huei, Lin, Liang-Tzung, LIN, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia, Liou, Yih-Cherng, Lipinski, Marta, Lipovšek, Saška, Lira, Vitor, Lisiak, Natalia, Liton, Paloma, Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, 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Mengxiao, Ma, Ning-Fang, Ma, Quan-Hong, Ma, Xinliang, Ma, Yueyun, Ma, Zhenyi, MacDougald, Ormond, Macian, Fernando, MacIntosh, Gustavo, MacKeigan, Jeffrey, Macleod, Kay, Maday, Sandra, Madeo, Frank, Madesh, Muniswamy, Madl, Tobias, Madrigal-Matute, Julio, Maeda, Akiko, Maejima, Yasuhiro, Magarinos, Marta, Mahavadi, Poornima, Maiani, Emiliano, Maiese, Kenneth, Maiti, Panchanan, Maiuri, Maria Chiara, Majello, Barbara, Major, Michael, Makareeva, Elena, Malik, Fayaz, Mallilankaraman, Karthik, Malorni, Walter, Maloyan, Alina, Mammadova, Najiba, Man, Gene Chi Wai, Manai, Federico, Mancias, Joseph, Mandelkow, Eva-Maria, Mandell, Michael, Manfredi, Angelo, Manjili, Masoud, Manjithaya, Ravi, Manque, Patricio, Manshian, Bella, Manzano, Raquel, Manzoni, Claudia, Mao, Kai, Marchese, Cinzia, Marchetti, Sandrine, Marconi, Anna Maria, Marcucci, Fabrizio, Mardente, Stefania, Mareninova, Olga, Margeta, Marta, Mari, Muriel, Marinelli, Sara, Marinelli, Oliviero, Mariño, Guillermo, Mariotto, Sofia, Marshall, Richard, Marten, Mark, Martens, Sascha, Martin, Alexandre, Martin, Katie, Martin, Sara, Martin, Shaun, Martín-Segura, Adrián, Martín-Acebes, Miguel, Martin-Burriel, Inmaculada, Martin-Rincon, Marcos, Martin-Sanz, Paloma, Martina, José, Martinet, Wim, Martinez, Aitor, Martinez, Ana, Martinez, Jennifer, Martinez Velazquez, Moises, Martinez-Lopez, Nuria, Martinez-Vicente, Marta, Martins, Daniel, Martins, Joilson, Martins, Waleska, Martins-Marques, Tania, Marzetti, Emanuele, Masaldan, Shashank, Masclaux-Daubresse, Celine, Mashek, Douglas, Massa, Valentina, Massieu, Lourdes, Masson, Glenn, Masuelli, Laura, Masyuk, Anatoliy, Masyuk, Tetyana, Matarrese, Paola, Matheu, Ander, Matoba, Satoaki, Matsuzaki, Sachiko, Mattar, Pamela, Matte, Alessandro, Mattoscio, Domenico, Mauriz, José, Mauthe, Mario, Mauvezin, Caroline, Maverakis, Emanual, Maycotte, Paola, Mayer, Johanna, Mazzoccoli, Gianluigi, Mazzoni, Cristina, Mazzulli, Joseph, McCarty, Nami, Mcdonald, Christine, McGill, Mitchell, 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Sahni, Sumit, Saito, Nayuta, Saito, Shigeru, Saito, Tsunenori, Sakai, Ryohei, Sakai, Yasuyoshi, Sakamaki, Jun-Ichi, Saksela, Kalle, Salazar, Gloria, Salazar-Degracia, Anna, Salekdeh, Ghasem, Saluja, Ashok, Sampaio-Marques, Belém, Sanchez, Maria Cecilia, Sanchez-Alcazar, Jose, Sanchez-Vera, Victoria, Sancho-Shimizu, Vanessa, Sanderson, J Thomas, Sandri, Marco, Santaguida, Stefano, Santambrogio, Laura, Santana, Magda, Santoni, Giorgio, Sanz, Alberto, Sanz, Pascual, Saran, Shweta, Sardiello, Marco, Sargeant, Timothy, Sarin, Apurva, Sarkar, Chinmoy, Sarkar, Sovan, Sarrias, Maria-Rosa, Sarkar, Surajit, Sarmah, Dipanka Tanu, Sarparanta, Jaakko, Sathyanarayan, Aishwarya, Sathyanarayanan, Ranganayaki, Scaglione, K Matthew, Scatozza, Francesca, Schaefer, Liliana, Schafer, Zachary, Schaible, Ulrich, Schapira, Anthony, Scharl, Michael, Schatzl, Hermann, Schein, Catherine, Scheper, Wiep, Scheuring, David, Schiaffino, Maria Vittoria, Schiappacassi, Monica, Schindl, Rainer, Schlattner, Uwe, Schmidt, Oliver, Schmitt, Roland, Schmidt, Stephen, Schmitz, Ingo, Schmukler, Eran, Schneider, Anja, Schneider, Bianca, Schober, Romana, Schoijet, Alejandra, Schott, Micah, Schramm, Michael, Schröder, Bernd, Schuh, Kai, Schüller, Christoph, Schulze, Ryan, Schürmanns, Lea, Schwamborn, Jens, Schwarten, Melanie, Scialo, Filippo, Sciarretta, Sebastiano, Scott, Melanie, Scotto, Kathleen, Scovassi, A Ivana, Scrima, Andrea, Scrivo, Aurora, Sebastian, David, Sebti, Salwa, Sedej, Simon, Segatori, Laura, Segev, Nava, Seglen, Per, Seiliez, Iban, Seki, Ekihiro, Selleck, Scott, Sellke, Frank, Selsby, Joshua, Sendtner, Michael, Senturk, Serif, Seranova, Elena, Sergi, Consolato, Serra-Moreno, Ruth, Sesaki, Hiromi, Settembre, Carmine, Setty, Subba Rao Gangi, Sgarbi, Gianluca, Sha, Ou, Shacka, John, Shah, Javeed, Shang, Dantong, Shao, Changshun, Shao, Feng, Sharbati, Soroush, Sharkey, Lisa, Sharma, Dipali, Sharma, Gaurav, Sharma, Kulbhushan, Sharma, Pawan, Sharma, Surendra, Shen, Han-Ming, Shen, Hongtao, Shen, Jiangang, Shen, Ming, Shen, Weili, Shen, Zheni, Sheng, Rui, Sheng, Zhi, Sheng, Zu-Hang, Shi, Jianjian, Shi, Xiaobing, Shi, Ying-Hong, Shiba-Fukushima, Kahori, Shieh, Jeng-Jer, Shimada, Yohta, Shimizu, Shigeomi, Shimozawa, Makoto, Shintani, Takahiro, Shoemaker, Christopher, Shojaei, Shahla, Shoji, Ikuo, Shravage, Bhupendra, Shridhar, Viji, Shu, Chih-Wen, Shu, Hong-Bing, Shui, Ke, Shukla, Arvind, Shutt, Timothy, Sica, Valentina, Siddiqui, Aleem, Sierra, Amanda, Sierra-Torre, Virginia, Signorelli, Santiago, Sil, Payel, Silva, Bruno, Silva, Johnatas, Silva-Pavez, Eduardo, Silvente-Poirot, Sandrine, Simmonds, Rachel, Simon, Anna Katharina, Simon, Hans-Uwe, Simons, Matias, Singh, Anurag, Singh, Lalit, Singh, Rajat, Singh, Shivendra, Singh, Shrawan, Singh, Sudha, Singh, Sunaina, Singh, Surinder Pal, Sinha, Debasish, Sinha, Rohit Anthony, Sinha, Sangita, Sirko, Agnieszka, Sirohi, Kapil, Sivridis, Efthimios, Skendros, Panagiotis, Skirycz, Aleksandra, Slaninová, Iva, Smaili, Soraya, Smertenko, Andrei, Smith, Matthew, Soenen, Stefaan, Sohn, Eun Jung, Sok, Sophia, Solaini, Giancarlo, Soldati, Thierry, Soleimanpour, Scott, Soler, Rosa, Solovchenko, Alexei, Somarelli, Jason, Sonawane, Avinash, Song, Fuyong, Song, Hyun Kyu, Song, Ju-Xian, Song, Kunhua, Song, Zhiyin, Soria, Leandro, Sorice, Maurizio, Soukas, Alexander, Soukup, Sandra-Fausia, Sousa, Diana, Sousa, Nadia, Spagnuolo, Paul, Spector, Stephen, Srinivas Bharath, M., St Clair, Daret, Stagni, Venturina, Staiano, Leopoldo, Stalnecker, Clint, Stankov, Metodi, Stathopulos, Peter, Stefan, Katja, Stefan, Sven Marcel, Stefanis, Leonidas, Steffan, Joan, Steinkasserer, Alexander, Stenmark, Harald, Sterneckert, Jared, Stevens, Craig, Stoka, Veronika, Storch, Stephan, Stork, Björn, Strappazzon, Flavie, Strohecker, Anne Marie, Stupack, Dwayne, Su, Huanxing, Su, Ling-Yan, Su, Longxiang, Suarez-Fontes, Ana, Subauste, Carlos, Subbian, Selvakumar, Subirada, Paula, Sudhandiran, Ganapasam, Sue, Carolyn, Sui, Xinbing, Summers, Corey, Sun, Guangchao, Sun, Jun, SUN, Kang, Sun, Meng-xiang, Sun, Qiming, Sun, Yi, Sun, Zhongjie, Sunahara, Karen, Sundberg, Eva, Susztak, Katalin, Sutovsky, Peter, Suzuki, Hidekazu, Sweeney, Gary, Symons, J David, Sze, Stephen Cho Wing, Szewczyk, Nathaniel, Tabęcka-Łonczynska, Anna, Tabolacci, Claudio, Tacke, Frank, Taegtmeyer, Heinrich, Tafani, Marco, Tagaya, Mitsuo, Tai, Haoran, Tait, Stephen, Takahashi, Yoshinori, Takats, Szabolcs, Talwar, Priti, Tam, Chit, Tam, Shing Yau, Tampellini, Davide, Tamura, Atsushi, Tan, Chong Teik, Tan, Eng-King, Tan, Ya-Qin, Tanaka, Masaki, Tanaka, Motomasa, Tang, Daolin, Tang, Jingfeng, Tang, Tie-Shan, Tanida, Isei, Tao, Zhipeng, Taouis, Mohammed, Tatenhorst, Lars, Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory, Taylor, Joan, Tchetina, Elena, Tee, Andrew, Tegeder, Irmgard, Teis, David, Teixeira, Natercia, Teixeira-Clerc, Fatima, Tekirdag, Kumsal, Tencomnao, Tewin, Tenreiro, Sandra, Tepikin, Alexei, Testillano, Pilar, Tettamanti, Gianluca, Tharaux, Pierre-Louis, Thedieck, Kathrin, Thekkinghat, Arvind, Thellung, Stefano, Thinwa, Josephine, Thirumalaikumar, V.P., Thomas, Sufi Mary, Thomes, Paul, Thorburn, Andrew, Thukral, Lipi, Thum, Thomas, Thumm, Michael, Tian, Ling, Tichy, Ales, Till, Andreas, Timmerman, Vincent, Titorenko, Vladimir, Todi, Sokol, Todorova, Krassimira, Toivonen, Janne, Tomaipitinca, Luana, Tomar, Dhanendra, Tomas-Zapico, Cristina, Tomić, Sergej, Tong, Benjamin Chun-Kit, Tong, Chao, Tong, Xin, Tooze, Sharon, Torgersen, Maria, Torii, Satoru, Torres-López, Liliana, Torriglia, Alicia, Towers, Christina, Towns, Roberto, Toyokuni, Shinya, Trajkovic, Vladimir, Tramontano, Donatella, Tran, Quynh-Giao, Travassos, Leonardo, Trelford, Charles, Tremel, Shirley, Trougakos, Ioannis, Tsao, Betty, Tschan, Mario, Tse, Hung-Fat, Tse, Tak Fu, Tsugawa, Hitoshi, Tsvetkov, Andrey, Tumbarello, David, Tumtas, Yasin, Tuñón, María, Turcotte, Sandra, Turk, Boris, Turk, Vito, Turner, Bradley, Tuxworth, Richard, Tyler, Jessica, Tyutereva, Elena, Uchiyama, Yasuo, Ugun-Klusek, Aslihan, Uhlig, Holm, Ułamek-Kozioł, Marzena, Ulasov, Ilya, Umekawa, Midori, Ungermann, Christian, Unno, Rei, Urbe, Sylvie, Uribe-Carretero, Elisabet, Üstün, Suayib, Uversky, Vladimir, Vaccari, Thomas, Vaccaro, Maria, Vahsen, Björn, Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Maria, Valko, Ayelén, Vallee, Richard, Valverde, Angela, Van Den Berghe, Greet, van der Veen, Stijn, Van Kaer, Luc, van Loosdregt, Jorg, van Wijk, Sjoerd, Vandenberghe, Wim, Vanhorebeek, Ilse, Vannier-Santos, Marcos, Vannini, Nicola, Vanrell, M Cristina, Vantaggiato, Chiara, Varano, Gabriele, Varela-Nieto, Isabel, Varga, Máté, Vasconcelos, M Helena, Vats, Somya, Vavvas, Demetrios, Vega-Naredo, Ignacio, Vega-Rubin-de-Celis, Silvia, Velasco, Guillermo, Velázquez, Ariadna, Vellai, Tibor, Vellenga, Edo, Velotti, Francesca, Verdier, Mireille, Verginis, Panayotis, Vergne, Isabelle, Verkade, Paul, Verma, Manish, Verstreken, Patrik, Vervliet, Tim, Vervoorts, Jörg, Vessoni, Alexandre, Victor, Victor, Vidal, Michel, Vidoni, Chiara, Vieira, Otilia, Vierstra, Richard, Viganó, Sonia, Vihinen, Helena, Vijayan, Vinoy, Vila, Miquel, Vilar, Marçal, Villalba, José, Villalobo, Antonio, Villarejo-Zori, Beatriz, Villarroya, Francesc, Villarroya, Joan, Vincent, Olivier, Vindis, Cecile, Viret, Christophe, Viscomi, Maria Teresa, Visnjic, Dora, Vitale, Ilio, Vocadlo, David, Voitsekhovskaja, Olga, Volonté, Cinzia, Volta, Mattia, Vomero, Marta, Von Haefen, Clarissa, Vooijs, Marc, Voos, Wolfgang, Vucicevic, Ljubica, Wade-Martins, Richard, Waguri, Satoshi, Waite, Kenrick, Wakatsuki, Shuji, Walker, David, Walker, Mark, Walker, Simon, Walter, Jochen, Wandosell, Francisco, Wang, Bo, Wang, Chao-Yung, Wang, Chen, Wang, Chenran, Wang, Chenwei, Wang, Cun-Yu, Wang, Dong, Wang, Fangyang, Wang, Feng, Wang, Fengming, Wang, Guansong, Wang, Han, Wang, Hao, Wang, Hexiang, Wang, Hong-Gang, Wang, Jianrong, Wang, Jigang, Wang, Jiou, Wang, Jundong, Wang, Kui, Wang, Lianrong, Wang, Liming, Wang, Maggie Haitian, Wang, Meiqing, Wang, Nanbu, Wang, PengWei, Wang, PeiPei, Wang, Ping, Wang, Qing Jun, Wang, Qing, Wang, Qing Kenneth, Wang, Qiong, Wang, Wen-Tao, Wang, Wuyang, Wang, Xinnan, Wang, Xuejun, Wang, Yan, Wang, Yanchang, Wang, Yanzhuang, Wang, Yen-Yun, Wang, Yihua, Wang, Yipeng, Wang, Yu, wang, yuqi, Wang, Zhe, Wang, Zhenyu, Wang, Zhouguang, Warnes, Gary, Warnsmann, Verena, Watada, Hirotaka, Watanabe, Eizo, Watchon, Maxinne, Wawrzyńska, Anna, Weaver, Timothy, Wegrzyn, Grzegorz, Wehman, Ann, Wei, Huafeng, Wei, Lei, Wei, Taotao, Wei, Yongjie, Weiergräber, Oliver, Weihl, Conrad, Weindl, Günther, Weiskirchen, Ralf, Wells, Alan, Wen, Runxia, Wen, Xin, Werner, Antonia, Weykopf, Beatrice, Wheatley, Sally, Whitton, J Lindsay, Whitworth, Alexander, Wiktorska, Katarzyna, Wildenberg, Manon, Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin, Williams, Roger, Williamson, Peter, Wilson, Richard, Winner, Beate, Winsor, Nathaniel, Witkin, Steven, Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard, Wong, Vincent Kam Wai, Wong, W Wei-Lynn, Wu, An-Guo, Wu, Chengbiao, Wu, Jian, Wu, Junfang, Wu, Kenneth, Wu, Min, Wu, Shan-Ying, Wu, Shengzhou, Wu, Shu-Yan, Wu, Shufang, Wu, William, Wu, Xiaohong, Wu, Xiaoqing, Wu, Yao-Wen, Wu, Yihua, Xavier, Ramnik, Xia, Hongguang, Xia, Lixin, Xia, Zhengyuan, Xiang, Ge, Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xiao, Guozhi, Xiao, Hengyi, Xiao, Hong-tao, Xiao, Jian, Xiao, Lan, Xiao, Shi, Xiao, Yin, Xie, Baoming, Xie, Chuan-Ming, Xie, Min, Xie, Yuxiang, Xie, Zhiping, Xie, Zhonglin, Xilouri, Maria, Xu, Congfeng, Xu, En, Xu, Haoxing, Xu, Jing, Xu, Jinrong, Xu, Liang, Xu, Wen Wen, Xu, Xiulong, Xue, Yu, Yakhine-Diop, Sokhna, Yamaguchi, Masamitsu, Yamaguchi, Osamu, Yamamoto, Ai, Yamashina, Shunhei, Yan, Shengmin, Yan, Shian-Jang, Yan, Zhen, Yanagi, Yasuo, Yang, Chuanbin, Yang, Dun-Sheng, Yang, Huan, Yang, Huang-Tian, Yang, Hui, Yang, Jin-Ming, Yang, Jing, Yang, Jingyu, Yang, Ling, Yang, Liu, Yang, Ming, Yang, Pei-Ming, Yang, Qian, Yang, Seungwon, Yang, Shu, Yang, Shun-Fa, Yang, Wannian, Yang, Wei Yuan, Yang, Xiaoyong, Yang, Xuesong, Yang, Yi, Yang, Ying, Yao, Honghong, Yao, Shenggen, Yao, Xiaoqiang, Yao, Yong-Gang, Yao, Yong-Ming, Yasui, Takahiro, Yazdankhah, Meysam, Yen, Paul, Yi, Cong, Yin, Xiao-Ming, Yin, Yanhai, Yin, Zhangyuan, Yin, Ziyi, Ying, Meidan, Ying, Zheng, Yip, Calvin, Yiu, Stephanie Pei Tung, Yoo, Young, Yoshida, Kiyotsugu, Yoshii, Saori, Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan, Yu, Haiyang, Yu, Jun, Yu, Li, Yu, Ming-Lung, Yu, Seong-Woon, Yu, Victor, Yu, W Haung, Yu, Zhengping, Yu, Zhou, Yuan, Junying, Yuan, Ling-Qing, Yuan, Shilin, Yuan, Shyng-Shiou, Yuan, Yanggang, Yuan, Zengqiang, Yue, Jianbo, Yue, Zhenyu, Yun, Jeanho, Yung, Raymond, Zacks, David, Zaffagnini, Gabriele, Zambelli, Vanessa, Zanella, Isabella, Zang, Qun, Zanivan, Sara, Zappavigna, Silvia, Zaragoza, Pilar, Zarbalis, Konstantinos, Zarebkohan, Amir, Zarrouk, Amira, Zeitlin, Scott, Zeng, Jialiu, Zeng, Ju-deng, Žerovnik, Eva, Zhan, Lixuan, Zhang, Bin, Zhang, Donna, Zhang, Hanlin, Zhang, Hong, Zhang, Honghe, Zhang, Huafeng, Zhang, Huaye, Zhang, Hui, Zhang, Hui-Ling, Zhang, Jianbin, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Kalin, Zhang, Leshuai, Zhang, Lin, Zhang, Lisheng, Zhang, Lu, Zhang, Luoying, Zhang, Menghuan, Zhang, Peng, Zhang, Sheng, Zhang, Wei, Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei, Zhang, Xiaoyan, Zhang, Xin, Zhang, Xinxin, Zhang, Xu Dong, Zhang, Yang, Zhang, Yanjin, Zhang, Yi, Zhang, Ying-Dong, Zhang, Yingmei, Zhang, Yuan-Yuan, Zhang, Yuchen, Zhang, Zhe, Zhang, Zhengguang, Zhang, Zhibing, Zhang, Zhihai, Zhang, Zhiyong, Zhang, Zili, Zhao, Haobin, Zhao, Lei, Zhao, Shuang, Zhao, Tongbiao, Zhao, Xiao-Fan, Zhao, Ying, Zhao, Yongchao, Zhao, Yongliang, Zhao, Yuting, Zheng, Guoping, Zheng, Kai, Zheng, Ling, Zheng, Shizhong, Zheng, Xi-Long, Zheng, Yi, Zheng, Zu-Guo, Zhivotovsky, Boris, Zhong, Qing, Zhou, Ao, Zhou, Ben, Zhou, Cefan, ZHOU, Gang, Zhou, Hao, Zhou, Hong, Zhou, Hongbo, Zhou, Jie, Zhou, Jing, Zhou, Jiyong, Zhou, Kailiang, Zhou, Rongjia, Zhou, Xu-jie, Zhou, Yanshuang, Zhou, Yinghong, Zhou, Yubin, Zhou, Zheng-Yu, Zhou, Zhou, Zhu, Binglin, Zhu, Changlian, Zhu, Guo-Qing, Zhu, Haining, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Yanping, Zhu, Yushan, Zhuang, Haixia, Zhuang, Xiaohong, Zientara-Rytter, Katarzyna, Zimmermann, Christine, Ziviani, Elena, Zoladek, Teresa, Zong, Wei-Xing, Zorov, Dmitry, Zorzano, Antonio, Zou, Weiping, Zou, Zhen, Zou, Zhengzhi, Zuryn, Steven, Zwerschke, Werner, Brand-Saberi, Beate, Dong, X Charlie, Kenchappa, Chandra Shekar, Li, Zuguo, Lin, Yong, Oshima, Shigeru, Rong, Yueguang, Sluimer, Judith, Stallings, Christina, Tong, Chun-Kit, Ahmad, S. Tariq, Alim Al-Bari, M. Abdul, Bechara, Luiz R.G., Behrens, Georg M.N., Bhuiyan, Md. Shenuarin, Broaddus, V. Courtney, Buchan, J. Ross, Burón, M. Isabel, Carter, A. Brent, Chan, Matthew T.V., Choi, Augustine M.K., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew, D’Orazi, Gabriella, De Meyer, Guido R.Y., Delpino, M. Victoria, Distler, Jörg H.W., Dixon, Ian M.C., Dobson, Renwick C.J., 2nd Dorn, Gerald, Eissa, N. Tony, Engelsen, Agnete S.T., Fairlie, W. Douglas, Ferreira, Julio C.B., H.B., Ranjitha, Hanson, Phyllis I., Hejtmancik, J. Fielding, Ho, Idy H.T., Hobbs, G. Aaron, Hoet, Peter H.M., Huang, Michael L.H., Iyer, Anand Krishnan V., Johnson, Gail V.W., Joosten, Leo A.B., Karim, Md. Razaul, Kaufmann, Stefan H.E., Ko, Ben C.B., Leck, Lionel Y.W., Lima, Thania R.R., Livingston, J. Andrew, Martin, Alexandre P.J., Montes, L. Ruth, Murphy, J. Patrick, Ng, Charlene C.W., Nicolao, M. Celeste, O’Donovan, Tracey, O’Leary, Seónadh, O’Rourke, Eyleen, O’Sullivan, Mary, O’Sullivan, Timothy, Omary, M. Bishr, Pereira, Gustavo J.S., Ratnayaka, J. Arjuna, Riazuddin, S. Amer, Rouschop, Kasper M.A., Sanderson, J. Thomas, Scaglione, K. Matthew, Schapira, Anthony H.V., Scovassi, A. Ivana, St. Clair, Daret, Sunahara, Karen K.S., Symons, J. David, Triola, Gemma, van Wijk, Sjoerd J.L., Vanrell, M. Cristina, Vasconcelos, M. Helena, Whitton, J. Lindsay, Williams, Robin S.B., Wong, W. Wei-Lynn, Wu, William K.K., Yakhine-Diop, Sokhna M.S., Yu, W. Haung, Zhang, Kalin Y.B., Dong, X. Charlie, Ain Shams University [ASU], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Medical University Graz, Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Institut Pasteur d'Iran, Leibniz Institute of Plant Biochemistry [IPB], The University of Texas M.D. Anderson Cancer Center [Houston], Institut de pharmacologie moléculaire et cellulaire [IPMC], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre méditerranéen de médecine moléculaire [C3M], Institut de Biologie Valrose [IBV], Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Institut Cochin [IC UM3 (UMR 8104 / U1016)], Institut NeuroMyoGène [INMG], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Marqueurs cardiovasculaires en situation de stress [MASCOT (UMR_S_942 / U942)], Institut de Recherche sur le Cancer et le Vieillissement [IRCAN], Centre de Recherche en Cancérologie de Marseille [CRCM], Centre for Integrative Biology - CBI [Inserm U964 - CNRS UMR7104 - IGBMC], Oncogenesis, Stress, Signaling [OSS], Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)], Institut de Biologie Intégrative de la Cellule [I2BC], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH], Centre de Recherches en Cancérologie de Toulouse [CRCT], Physiopathologie et traitement des maladies du foie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC], Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] [BIO-PEROXIL], Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], Unité de génétique et biologie des cancers [U830], Laboratoire d'Optique et Biosciences [LOB], Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC], Différenciation et communication neuronale et neuroendocrine [DC2N], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], Centre d'Immunologie de Marseille - Luminy [CIML], Physiopathologie et imagerie des troubles neurologiques [PhIND], Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [LBFA], Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163], Institut Mondor de Recherche Biomédicale [IMRB], Franco-czech Laboratory for clinical research on obesity, University of Michigan [Ann Arbor], University of Michigan System, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Nutrition, Métabolisme, Aquaculture (NuMéA), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institute of genetics and molecular and cellular biology-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epithelial biology and disease - Liliane Bettencourt Chair of Developmental Biology (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the National Institute of General Medical Sciences [GM131919]., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Department of Women's and Children's Health [Stockholm, Sweden], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École polytechnique (X), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Life Sciences Institute [Ann Arbor, MI, USA], University of Michigan System-University of Michigan System, European Institute of Oncology IRCCS [Milan, Italy] (EIO), Ain Shams University (ASU), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Réseau International des Instituts Pasteur (RIIP), Leibniz Institute of Plant Biochemistry (IPB), Hebrew University of Jerusalem, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncogenesis, Stress, Signaling (OSS), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., Agrewala, J. N., Agrotis, A., Aguilar, P. V., Ahmad, S. T., Ahmed, Z. M., Ahumada-Castro, U., Aits, S., Aizawa, S., Akkoc, Y., Akoumianaki, T., Akpinar, H. A., Al-Abd, A. M., Al-Akra, L., Al-Gharaibeh, A., Alaoui-Jamali, M. A., Alberti, S., Alcocer-Gomez, E., Alessandri, C., Ali, M., Alim Al-Bari, M. A., Aliwaini, S., Alizadeh, J., Almacellas, E., Almasan, A., Alonso, A., Alonso, G. D., Altan-Bonnet, N., Altieri, D. C., Alvarez, E. M. C., Alves, S., Alves da Costa, C., Alzaharna, M. M., Amadio, M., Amantini, C., Amaral, C., Ambrosio, S., Amer, A. O., Ammanathan, V., An, Z., Andersen, S. U., Andrabi, S. A., Andrade-Silva, M., Andres, A. M., Angelini, S., Ann, D., Anozie, U. C., Ansari, M. Y., Antas, P., Antebi, A., Anton, Z., Anwar, T., Apetoh, L., Apostolova, N., Araki, T., Araki, Y., Arasaki, K., Araujo, W. L., Araya, J., Arden, C., Arevalo, M. -A., Arguelles, S., Arias, E., Arikkath, J., Arimoto, H., Ariosa, A. R., Armstrong-James, D., Arnaune-Pelloquin, L., Aroca, A., Arroyo, D. S., Arsov, I., Artero, R., Asaro, D. M. L., Aschner, M., Ashrafizadeh, M., Ashur-Fabian, O., Atanasov, A. G., Au, A. K., Auberger, P., Auner, H. W., Aurelian, L., Autelli, R., Avagliano, L., Avalos, Y., Aveic, S., Aveleira, C. A., Avin-Wittenberg, T., Aydin, Y., Ayton, S., Ayyadevara, S., Azzopardi, M., Baba, M., Backer, J. M., Backues, S. K., Bae, D. -H., Bae, O. -N., Bae, S. H., Baehrecke, E. H., Baek, A., Baek, S. -H., Baek, S. H., Bagetta, G., Bagniewska-Zadworna, A., Bai, H., Bai, J., Bai, X., Bai, Y., Bairagi, N., Baksi, S., Balbi, T., Baldari, C. T., Balduini, W., Ballabio, A., Ballester, M., Balazadeh, S., Balzan, R., Bandopadhyay, R., Banerjee, S., Banreti, A., Bao, Y., Baptista, M. S., Baracca, A., Barbati, C., Bargiela, A., Barila, D., Barlow, P. G., Barmada, S. J., Barreiro, E., Barreto, G. E., Bartek, J., Bartel, B., Bartolome, A., Barve, G. R., Basagoudanavar, S. H., Bassham, D. C., Bast, R. C., Basu, A., Batoko, H., Batten, I., Baulieu, E. E., Baumgarner, B. L., Bayry, J., Beale, R., Beau, I., Beaumatin, F., Bechara, L. R. G., Beck, G. R., Beers, M. F., Begun, J., Behrends, C., Behrens, G. M. N., Bei, R., Bejarano, E., Bel, S., Behl, C., Belaid, A., Belgareh-Touze, N., Bellarosa, C., Belleudi, F., Bello Perez, M., Bello-Morales, R., Beltran, J. S. D. O., Beltran, S., Benbrook, D. M., Bendorius, M., Benitez, B. A., Benito-Cuesta, I., Bensalem, J., Berchtold, M. W., Berezowska, S., Bergamaschi, D., Bergami, M., Bergmann, A., Berliocchi, L., Berlioz-Torrent, C., Bernard, A., Berthoux, L., Besirli, C. G., Besteiro, S., Betin, V. M., Beyaert, R., Bezbradica, J. S., Bhaskar, K., Bhatia-Kissova, I., Bhattacharya, R., Bhattacharya, S., Bhattacharyya, S., Bhuiyan, M. S., Bhutia, S. K., Bi, L., Bi, X., Biden, T. J., Bijian, K., Billes, V. A., Binart, N., Bincoletto, C., Birgisdottir, A. B., Bjorkoy, G., Blanco, G., Blas-Garcia, A., Blasiak, J., Blomgran, R., Blomgren, K., Blum, J. S., Boada-Romero, E., Boban, M., Boesze-Battaglia, K., Boeuf, P., Boland, B., Bomont, P., Bonaldo, P., Bonam, S. R., Bonfili, L., Bonifacino, J. S., Boone, B. A., Bootman, M. D., Bordi, M., Borner, C., Bornhauser, B. C., Borthakur, G., Bosch, J., Bose, S., Botana, L. M., Botas, J., Boulanger, C. M., Boulton, M. E., Bourdenx, M., Bourgeois, B., Bourke, N. M., Bousquet, G., Boya, P., Bozhkov, P. V., Bozi, L. H. M., Bozkurt, T. O., Brackney, D. E., Brandts, C. H., Braun, R. J., Braus, G. H., Bravo-Sagua, R., Bravo-San Pedro, J. M., Brest, P., Bringer, M. -A., Briones-Herrera, A., Broaddus, V. C., Brodersen, P., Brodsky, J. L., Brody, S. L., Bronson, P. G., Bronstein, J. M., Brown, C. N., Brown, R. E., Brum, P. C., Brumell, J. H., Brunetti-Pierri, N., Bruno, D., Bryson-Richardson, R. J., Bucci, C., Buchrieser, C., Bueno, M., Buitrago-Molina, L. E., Buraschi, S., Buch, S., Buchan, J. R., Buckingham, E. M., Budak, H., Budini, M., Bultynck, G., Burada, F., Burgoyne, J. R., Buron, M. I., Bustos, V., Buttner, S., Butturini, E., Byrd, A., Cabas, I., Cabrera-Benitez, S., Cadwell, K., Cai, J., Cai, L., Cai, Q., Cairo, M., Calbet, J. A., Caldwell, G. A., Caldwell, K. A., Call, J. A., Calvani, R., Calvo, A. C., Calvo-Rubio Barrera, M., Camara, N. O. S., Camonis, J. H., Camougrand, N., Campanella, M., Campbell, E. M., Campbell-Valois, F. -X., Campello, S., Campesi, I., Campos, J. C., Camuzard, O., Cancino, J., Candido de Almeida, D., Canesi, L., Caniggia, I., Canonico, B., Canti, C., Cao, B., Caraglia, M., Carames, B., Carchman, E. 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K., Chang, C. -P., Chang, C., Chang, H. -C., Chang, K., Chao, J., Chapman, T., Charlet-Berguerand, N., Chatterjee, S., Chaube, S. K., Chaudhary, A., Chauhan, S., Chaum, E., Checler, F., Cheetham, M. E., Chen, C. -S., Chen, G. -C., Chen, J. -F., Chen, L. L., Chen, L., Chen, M., Chen, M. -K., Chen, N., Chen, Q., Chen, R. -H., Chen, S., Chen, W., Chen, X. -M., Chen, X. -W., Chen, X., Chen, Y., Chen, Y. -G., Chen, Y. -J., Chen, Y. -Q., Chen, Z. S., Chen, Z., Chen, Z. -H., Chen, Z. J., Cheng, H., Cheng, J., Cheng, S. -Y., Cheng, W., Cheng, X., Cheng, X. -T., Cheng, Y., Cheng, Z., Cheong, H., Cheong, J. K., Chernyak, B. V., Cherry, S., Cheung, C. F. R., Cheung, C. H. A., Cheung, K. -H., Chevet, E., Chi, R. J., Chiang, A. K. S., Chiaradonna, F., Chiarelli, R., Chiariello, M., Chica, N., Chiocca, S., Chiong, M., Chiou, S. -H., Chiramel, A. I., Chiurchiu, V., Cho, D. -H., Choe, S. -K., Choi, A. M. K., Choi, M. E., Choudhury, K. R., Chow, N. S., Chu, C. T., Chua, J. P., Chua, J. J. 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M., Villalobo, A., Villarejo-Zori, B., Villarroya, F., Villarroya, J., Vincent, O., Vindis, C., Viret, C., Viscomi, M. T., Visnjic, D., Vitale, I., Vocadlo, D. J., Voitsekhovskaja, O. V., Volonte, C., Volta, M., Vomero, M., Von Haefen, C., Vooijs, M. A., Voos, W., Vucicevic, L., Wade-Martins, R., Waguri, S., Waite, K. A., Wakatsuki, S., Walker, D. W., Walker, M. J., Walker, S. A., Walter, J., Wandosell, F. G., Wang, B., Wang, C. -Y., Wang, C., Wang, D., Wang, F., Wang, G., Wang, H., Wang, H. -G., Wang, J., Wang, K., Wang, L., Wang, M. H., Wang, M., Wang, N., Wang, P., Wang, Q. J., Wang, Q., Wang, Q. K., Wang, Q. A., Wang, W. -T., Wang, W., Wang, X., Wang, Y., Wang, Y. -Y., Wang, Z., Warnes, G., Warnsmann, V., Watada, H., Watanabe, E., Watchon, M., Wawrzynska, A., Weaver, T. E., Wegrzyn, G., Wehman, A. M., Wei, H., Wei, L., Wei, T., Wei, Y., Weiergraber, O. H., Weihl, C. C., Weindl, G., Weiskirchen, R., Wells, A., Wen, R. H., Wen, X., Werner, A., Weykopf, B., Wheatley, S. P., Whitton, J. L., Whitworth, A. J., Wiktorska, K., Wildenberg, M. E., Wileman, T., Wilkinson, S., Willbold, D., Williams, B., Williams, R. S. B., Williams, R. L., Williamson, P. R., Wilson, R. A., Winner, B., Winsor, N. J., Witkin, S. S., Wodrich, H., Woehlbier, U., Wollert, T., Wong, E., Wong, J. H., Wong, R. W., Wong, V. K. W., Wong, W. W. -L., Wu, A. -G., Wu, C., Wu, J., Wu, K. K., Wu, M., Wu, S. -Y., Wu, S., Wu, W. K. K., Wu, X., Wu, Y. -W., Wu, Y., Xavier, R. J., Xia, H., Xia, L., Xia, Z., Xiang, G., Xiang, J., Xiang, M., Xiang, W., Xiao, B., Xiao, G., Xiao, H., Xiao, H. -T., Xiao, J., Xiao, L., Xiao, S., Xiao, Y., Xie, B., Xie, C. -M., Xie, M., Xie, Y., Xie, Z., Xilouri, M., Xu, C., Xu, E., Xu, H., Xu, J., Xu, L., Xu, W. W., Xu, X., Xue, Y., Yakhine-Diop, S. M. S., Yamaguchi, M., Yamaguchi, O., Yamamoto, A., Yamashina, S., Yan, S., Yan, S. -J., Yan, Z., Yanagi, Y., Yang, C., Yang, D. -S., Yang, H., Yang, H. -T., Yang, J. -M., Yang, J., Yang, L., Yang, M., Yang, P. -M., Yang, Q., Yang, S., Yang, S. -F., Yang, W., Yang, W. Y., Yang, X., Yang, Y., Yao, H., Yao, S., Yao, X., Yao, Y. -G., Yao, Y. -M., Yasui, T., Yazdankhah, M., Yen, P. M., Yi, C., Yin, X. -M., Yin, Y., Yin, Z., Ying, M., Ying, Z., Yip, C. K., Yiu, S. P. T., Yoo, Y. H., Yoshida, K., Yoshii, S. R., Yoshimori, T., Yousefi, B., Yu, B., Yu, H., Yu, J., Yu, L., Yu, M. -L., Yu, S. -W., Yu, V. C., Yu, W. H., Yu, Z., Yuan, J., Yuan, L. -Q., Yuan, S., Yuan, S. -S. F., Yuan, Y., Yuan, Z., Yue, J., Yue, Z., Yun, J., Yung, R. L., Zacks, D. N., Zaffagnini, G., Zambelli, V. O., Zanella, I., Zang, Q. S., Zanivan, S., Zappavigna, S., Zaragoza, P., Zarbalis, K. S., Zarebkohan, A., Zarrouk, A., Zeitlin, S. O., Zeng, J., Zeng, J. -D., Zerovnik, E., Zhan, L., Zhang, B., Zhang, D. D., Zhang, H., Zhang, H. -L., Zhang, J., Zhang, J. -P., Zhang, K. Y. B., Zhang, L. W., Zhang, L., Zhang, M., Zhang, P., Zhang, S., Zhang, W., Zhang, X., Zhang, X. -W., Zhang, X. D., Zhang, Y., Zhang, Y. -D., Zhang, Y. -Y., Zhang, Z., Zhao, H., Zhao, L., Zhao, S., Zhao, T., Zhao, X. -F., Zhao, Y., Zheng, G., Zheng, K., Zheng, L., Zheng, S., Zheng, X. -L., Zheng, Y., Zheng, Z. -G., Zhivotovsky, B., Zhong, Q., Zhou, A., Zhou, B., Zhou, C., Zhou, G., Zhou, H., Zhou, J., Zhou, K., Zhou, R., Zhou, X. -J., Zhou, Y., Zhou, Z. -Y., Zhou, Z., Zhu, B., Zhu, C., Zhu, G. -Q., Zhu, H., Zhu, W. -G., Zhu, Y., Zhuang, H., Zhuang, X., Zientara-Rytter, K., Zimmermann, C. M., Ziviani, E., Zoladek, T., Zong, W. -X., Zorov, D. B., Zorzano, A., Zou, W., Zou, Z., Zuryn, S., Zwerschke, W., Brand-Saberi, B., Dong, X. C., Kenchappa, C. S., Lin, Y., Oshima, S., Rong, Y., Sluimer, J. C., Stallings, C. L., Tong, C. -K., and Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Programmed cell death, Settore BIO/06, Autophagosome, Autolysosome, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Autophagy-Related Proteins, Review, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Settore MED/04, 03 medical and health sciences, stress, Chaperone-mediated autophagy, ddc:570, Autophagy, LC3, Animals, Humans, cancer, Settore BIO/10, flux, lysosome, macroautophagy, neurodegeneration, phagophore, vacuole, Set (psychology), Molecular Biology, 030102 biochemistry & molecular biology, business.industry, Interpretation (philosophy), Autophagosomes, Cell Biology, Multicellular organism, 030104 developmental biology, Knowledge base, Biological Assay, Lysosomes, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 232759.pdf (Publisher’s version ) (Closed access) In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Published: 2021

27. Relevance of leukocytospermia and semen culture and its true place in diagnosing and treating male infertility

Author: Sajal Gupta, Damayanthi Durairajanayagam, Florence Boitrelle, Ralf Henkel, Rupin Shah, Pallav Sengupta, Kelton Tremellen, Marco G. Alves, Marlon Martinez, Mesut Altan, Renata Finelli, Lucia Rocco, Marjan Sabbaghian, Parviz Kavoussi, Juan G. Alvarez, Rakesh Sharma, Christina Anagnostopoulou, Sava Micic, Haitham Elbardisi, Marcelo Rodríguez Peña, Osvaldo Rajmil, Hyun Jun Park, Ashok Agarwal, Taymour Mostafa, Sunil Jindal, Rafael F. Ambar, Gian Maria Busetto, Giovanni M. Colpi, Mohamed Arafa, Nicholas N. Tadros, Kareim Khalafalla, Edmund Y. Ko, Jonathan Ramsay, Hassan N. Sallam, Armand Zini, Sheena E.M. Lewis, Paraskevi Vogiatzi, Neel Parekh, Jaime Gosálvez, Israel Maldonado Rosas, Sijo Parekattil, Mara Simopoulou, Ayad Palani, Ramadan A Saleh, Hussein Kandil, Sami Alsaid, Sharma, R., Gupta, S., Agarwal, A., Henkel, R., Finelli, R., Parekh, N., Saleh, R., Arafa, M., Ko, E., Zini, A., Tadros, N., Shah, R., Ambar, R. F., Elbardisi, H., Sengupta, P., Martinez, M., Boitrelle, F., Simopoulou, M., Vogiatzi, P., Gosalvez, J., Kavoussi, P., Kandil, H., Palani, A., Pena, M. R., Rajmil, O., Busetto, G. M., Anagnostopoulou, C., Micic, S., Alves, M. G., Rocco, L., Mostafa, T., Alvarez, J. G., Jindal, S., Sallam, H. N., Rosas, I. M., Lewis, S. E. M., Alsaid, S., Altan, M., Park, H. J., Ramsay, J., Parekattil, S., Sabbaghian, M., Tremellen, K., Khalafalla, K., Durairajanayagam, D., Colpi, G. M., Cleveland Clinic, Imperial College London, University of the Western Cape, Sohag University, Weill Cornell Medicine [Qatar], Loma Linda University, McGill University = Université McGill [Montréal, Canada], Southern Illinois University School of Medicine, Lilavati Hospital and Research Centre, UNIVERSITY OF SANTO TOMAS MANILA PHL, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHI Poissy-Saint-Germain, National and Kapodistrian University of Athens (NKUA), Universidad Autonoma de Madrid (UAM), Hospital de la Santa Creu i Sant Pau, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Università degli studi della Campania 'Luigi Vanvitelli', Cairo University - Faculty of Medicine, Harvard Medical School [Boston] (HMS), Alexandria University [Alexandrie], Ankara University School of Medicine [Turkey], Pusan National University, Hammersmith Hospital NHS Imperial College Healthcare, University of Central Florida [Orlando] (UCF), Academic Center for Education, Culture and Research (ACECR), Flinders University [Adelaide, Australia], Hamad Medical Corporation [Doha, Qatar], Universiti Teknologi MARA [Shah Alam] (UiTM ), and Procrea Institute
Subjects: Aging, Culture, 030232 urology & nephrology, medicine.disease_cause, urologic and male genital diseases, Male infertility, 0302 clinical medicine, Leukocytes, Pharmacology (medical), Andrology, OXIDATIVE STRESS, 030219 obstetrics & reproductive medicine, biology, medicine.diagnostic_test, Health Policy, UREAPLASMA-UREALYTICUM, Urology & Nephrology, Spermatozoa, 3. Good health, Psychiatry and Mental health, Epididymitis, GRANULOCYTE ELASTASE, Infection, Life Sciences & Biomedicine, Urology, Semen, Mycoplasma hominis, Semen analysis, Infections, WHITE BLOOD-CELLS, 03 medical and health sciences, Endocrinology & Metabolism, medicine, Inflammation, Science & Technology, business.industry, Public Health, Environmental and Occupational Health, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, CHLAMYDIA-TRACHOMATIS INFECTION, Leukocyte, biology.organism_classification, medicine.disease, SPERM DNA FRAGMENTATION, Health Care Sciences & Services, ACCESSORY-GLAND INFECTION, GENITAL-TRACT INFECTION, Reproductive Medicine, Immunology, Endtz, Neisseria gonorrhoeae, MONOCLONAL-ANTIBODIES, Chlamydia trachomatis, business, IN-VITRO FERTILIZATION, Ureaplasma urealyticum
Abstract: International audience; The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.
Published: 2021

28. The architecture of Recent brachiopod shells: diversity of biocrystal and biopolymer assemblages in rhynchonellide, terebratulide, thecideide and craniide shells

Author: Roda, Maria Simonet, Griesshaber, Erika, Angiolini, Lucia, Rollion-Bard, Claire, Harper, Elizabeth, Bitner, Maria Aleksandra, Milner Garcia, Sara, Ye, Facheng, Henkel, Daniela, Häussermann, Vreni, Eisenhauer, Anton, Gnägi, Helmut, Brand, Uwe, Logan, Alan, Schmahl, Wolfgang, Roda, Maria, Bitner, Maria, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Paléocéanographie (PALEOCEAN), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Griesshaber, Erika [0000-0002-5433-9929], Apollo - University of Cambridge Repository, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Häussermann, Vreni [0000-0001-9630-7477]
Subjects: 010506 paleontology, EBSD, Brachiopod microstructure and environment, Aquatic Science, 010502 geochemistry & geophysics, Geologic record, 01 natural sciences, Mineralization (biology), Texture (geology), chemistry.chemical_compound, Paleontology, Diversity of brachiopod crystal and biopolymer assembly, 14. Life underwater, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, Ecology, Evolution, Behavior and Systematics, 0105 earth and related environmental sciences, Calcite, Brachiopod microstructure and lifestyle, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Review, Concept, and Synthesis, Ecology, biology, Chemistry, biology.organism_classification, Determinants of microstructure and texture, [SDU]Sciences of the Universe [physics], Carbonate, AFM, Terebratulida, Rhynchonellida, Electron backscatter diffraction
Abstract: International audience; Biological hard tissues are a rich source of design concepts for the generation of advanced materials. They represent the most important library of information on the evolution of life and its environmental conditions. Organisms produce soft and hard tissues in a bottom-up process, a construction principle that is intrinsic to biologically secreted materials. This process emerged early on in the geological record, with the onset of biological mineralization. The phylum Brachiopoda is a marine animal group that has an excellent and continuous fossil record from the early Cambrian to the Recent. Throughout this time interval, the Brachiopoda secreted phosphate and carbonate shells and populated many and highly diverse marine habitats. This required great flexibility in the adaptation of soft and hard tissues to the different marine environments and living conditions. This review presents, juxtaposes and discusses the main modes of mineral and biopolymer organization in Recent, carbonate shell-producing, brachiopods. We describe shell tissue characteristics for taxa of the orders Rhynchonellida, Terebratulida, Thecideida and Craniida. We highlight modes of calcite and organic matrix assembly at the macro-, micro-, and nano-scales based on results obtained by Electron Backscatter Diffraction, Atomic Force Microscopy, Field Emission Scanning Electron Microscopy and Scanning Transmission Electron Microscopy. We show variation in composite hard tissue organization for taxa with different lifestyles, visualize nanometer-scale calcite assemblies for rhynchonellide and terebratulide fibers, highlight thecideide shell microstructure, texture and chemistry characteristics, and discuss the feasibility to use thecideide shells as archives of proxies for paleoenvironment and paleoclimate reconstructions. Keywords Diversity of brachiopod crystal and biopolymer assembly • Determinants of microstructure and texture • Brachiopod microstructure and lifestyle • Brachiopod microstructure and environment • EBSD • AFM Responsible Editor: A.G. Checa.
Published: 2021

29. Lithium elemental and isotope systematics of modern and cultured brachiopods : implications for seawater evolution

Author: Hana Jurikova, Natalie Gaspers, Anton Eisenhauer, Tomáš Magna, Karem Azmy, Daniela Henkel, Adam Tomašových, and University of St Andrews. School of Earth & Environmental Sciences
Subjects: 010504 meteorology & atmospheric sciences, Range (biology), T-NDAS, Weathering, 010502 geochemistry & geophysics, 01 natural sciences, Foraminifera, chemistry.chemical_compound, Geochemistry and Petrology, Phanerozoic, QE, 14. Life underwater, SDG 14 - Life Below Water, Controlled culturing experiements, 0105 earth and related environmental sciences, Calcite, biology, Isotope, Brachiopod calcite, Paleo-proxy, Geology, Seawater history, Plankton, biology.organism_classification, Lithium isotopes, QE Geology, chemistry, 13. Climate action, Environmental chemistry, Seawater
Abstract: This study was funded by the European Union's Horizon 2020 research and innovation programme under the grant agreement No. 643084 - Marie Sklodowska-Curie Innovative Training Network (ITN) ‘BASE-LiNE Earth’. Lithium has proven a powerful tracer of weathering processes and chemical seawater evolution. Skeletal components of marine calcifying organisms, and in particular brachiopods, present promising archives of Li signatures. However, Li incorporation mechanisms and potential influence from biological processes or environmental conditions require a careful assessment. In order to constrain Li systematics in brachiopod shells, we present Li concentrations and isotope compositions for 11 calcitic brachiopod species collected from six different geographic regions, paralleled with data from culturing experiments where brachiopods were grown under varying environmental conditions and seawater chemistry (pH–pCO2, temperature, Mg/Ca ratio). The recent brachiopod specimens collected across different temperate and polar environments showed broadly consistent δ7Li values ranging from 25.2 to 28.1‰ (with mean δ7Li of 26.9 ± 1.5‰), irrespective of taxonomic rank, indicating that incorporation of Li isotopes into brachiopod shells is not strongly affected by vital effects related to differences among species. This results in Δ7Licalcite–seawater values (per mil difference in 7Li/6Li between brachiopod calcite shell and seawater) from −2.9‰ to −5.8‰ (with mean Δ7Licalcite–seawater value of −3.6‰), which is larger than the Δ7Licalcite–seawater values calculated based on data from planktonic foraminifera (~0‰ to ~−4‰). This range of values is further supported by results from brachiopods cultured experimentally. Under controlled culturing conditions simulating the natural marine environment, the Δ7Licalcite–seawater for Magellania venosa was −2.5‰ and not affected by an increase in temperature from 10 to 16 °C. In contrast, a decrease in Mg/Ca (or Li/Ca) ratio of seawater by addition of CaCl2 as well as elevated pCO2, and hence low-pH conditions, resulted in an increased Δ7Licalcite-seawater up to −4.6‰. Collectively, our results indicate that brachiopods represent valuable archives and provide an envelope for robust Li-based reconstruction of seawater evolution over the Phanerozoic. Publisher PDF
Published: 2021

30. Expression of degQ gene and its effect on lipopeptide production as well as formation of secretory proteases in Bacillus subtilis strains

Author: Isabel Adiek, Mareen Hoffmann, Philipp Becker, Rudolf Hausmann, Chanthiya Kuppusamy Nesamani, Maliheh Vahidinasab, Chantal Treinen, Marius Henkel, Kambiz Morabbi Heravi, and Lars Lilge
Subjects: Proteases, medicine.medical_treatment, Bacillus subtilis, Microbiology, surfactin, Peptides, Cyclic, chemistry.chemical_compound, Lipopeptides, Bacterial Proteins, degQ, Gene expression, medicine, Promoter Regions, Genetic, Protease, secretory proteases, Strain (chemistry), biology, Chemistry, Fatty Acids, Lipopeptide, Original Articles, Gene Expression Regulation, Bacterial, biology.organism_classification, Molecular biology, QR1-502, Response regulator, plipastatin, lipopeptide, Mutation, Trans-Activators, Original Article, Surfactin, Oligopeptides, Peptide Hydrolases
Abstract: Bacillus subtilis is described as a promising production strain for lipopeptides. In the case of B. subtilis strains JABs24 and DSM10T, surfactin and plipastatin are produced. Lipopeptide formation is controlled, among others, by the DegU response regulator. The activating phospho‐transfer by the DegS sensor kinase is stimulated by the pleiotropic regulator DegQ, resulting in enhanced DegU activation. In B. subtilis 168, a point mutation in the degQ promoter region leads to a reduction in gene expression. Corresponding reporter strains showed a 14‐fold reduced expression. This effect on degQ expression and the associated impact on lipopeptide formation was examined for B. subtilis JABs24, a lipopeptide‐producing derivative of strain 168, and B. subtilis wild‐type strain DSM10T, which has a native degQ expression. Based on the stimulatory effects of the DegU regulator on secretory protease formation, the impact of degQ expression on extracellular protease activity was additionally investigated. To follow the impact of degQ, a deletion mutant was constructed for DSM10T, while a natively expressed degQ version was integrated into strain JABs24. This allowed strain‐specific quantification of the stimulatory effect of degQ expression on plipastatin and the negative effect on surfactin production in strains JABs24 and DSM10T. While an unaffected degQ expression reduced surfactin production in JABs24 by about 25%, a sixfold increase in plipastatin was observed. In contrast, degQ deletion in DSM10T increased surfactin titer by threefold but decreased plipastatin production by fivefold. In addition, although significant differences in extracellular protease activity were detected, no decrease in plipastatin and surfactin produced during cultivation was observed., The lipopeptide‐producing Bacillus subtilis strains JABs24 and DSM10T differ by one single base substitution in the degQ promoter region, resulting in drastically reduced degQ expression in JABs24. Subsequent deletion of the degQ gene in DSM10T or integration of a natively expressed degQ version in JABs24 revealed, among others, the differential effects of DegQ on the formation of the lipopeptides surfactin and plipastatin. Additional effects on the formation of secretory proteases do not seem to have any influence on lipopeptide stability.
Published: 2021

31. Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors

Author: E. Klinker, Yair Reisner, Florian Oyen, Ana Marcu, Camelia-Maria Monoranu, Matthias Wölfl, Johanna Lager, Nico Trautwein, Lisa M. Henkel, J. Krauss, Anne Keupp, Pascal Johann, Andreas Schlosser, Martin Ebinger, Martin U. Schuhmann, Thorsten Pietsch, Juliane S. Walz, Paul-Gerhardt Schlegel, Hans-Georg Rammensee, Ulrich-W. Thomale, and Matthias Eyrich
Subjects: Male, Cancer Research, medicine.medical_treatment, Peptide, Genome, Mass Spectrometry, Epitope, Central Nervous System Neoplasms, antigens, HLA Antigens, Human proteome project, Immunology and Allergy, Child, RC254-282, chemistry.chemical_classification, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Oncology, Child, Preschool, Molecular Medicine, Female, Immunotherapy, pediatrics, Adolescent, Immunology, Human leukocyte antigen, Biology, Peptides, Cyclic, Immune system, Antigen, medicine, Humans, ddc:610, Rhabdoid Tumor, Pharmacology, Rhabdoid tumors, Basic Tumor Immunology, Oncogenes, medicine.disease, vaccination, epitope mapping, Epitope mapping, chemistry, Cancer research, Peptides, neoplasm, CD8, Glioblastoma
Abstract: BackgroundAtypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS tumors of infancy and early childhood. Hallmark is the surprisingly simple genome with inactivating mutations or deletions in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T cells. However, it is unclear which epitopes T cells might recognize on AT/RT cells.MethodsHere, we report a comprehensive mass spectrometry (MS)-based analysis of naturally presented human leukocyte antigen (HLA) class I and class II ligands on 23 AT/RTs. MS data were validated by matching with a human proteome dataset and exclusion of peptides that are part of the human benignome. Cryptic peptide ligands were identified using Peptide-PRISM.ResultsComparative HLA ligandome analysis of the HLA ligandome revealed 55 class I and 139 class II tumor-exclusive peptides. No peptide originated from the SMARCB1 region. In addition, 61 HLA class I tumor-exclusive peptide sequences derived from non-canonically translated proteins. Combination of peptides from natural and cryptic class I and class II origin gave optimal representation of tumor cell compartments. Substantial overlap existed with the cryptic immunopeptidome of glioblastomas, but no concordance was found with extracranial tumors. More than 80% of AT/RT exclusive peptides were able to successfully prime CD8+T cells, whereas naturally occurring memory responses in AT/RT patients could only be detected for class II epitopes. Interestingly, >50% of AT/RT exclusive class II ligands were also recognized by T cells from glioblastoma patients but not from healthy donors.ConclusionsThese findings highlight that AT/RTs, potentially paradigmatic for other pediatric tumors with a low mutational load, present a variety of highly immunogenic HLA class I and class II peptides from canonical as well as non-canonical protein sources. Inclusion of such cryptic peptides into therapeutic vaccines would enable an optimized mapping of the tumor cell surface, thereby reducing the likelihood of immune evasion.
Published: 2021

32. Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy

Author: Robert E. McCullumsmith, Nicholas D. Henkel, Rammohan Shukla, Nicholas O. Fischer, Xiaojun Wu, Hunter M. Eby, Marissa A. Smail, and Heather A. Enright
Subjects: Male, Cell type, Science, Vasoactive intestinal peptide, Datasets as Topic, Biology, Genome informatics, Hippocampus, Article, Temporal lobe, Transcriptome, Mice, Epilepsy, Downregulation and upregulation, Interneurons, Target identification, Drug Discovery, medicine, Animals, Humans, RNA-Seq, Multidisciplinary, Pyramidal Cells, Pilocarpine, medicine.disease, Temporal Lobe, Disease Models, Animal, Epilepsy, Temporal Lobe, Gene Expression Regulation, Medicine, Anticonvulsants, Data integration, Gene ontology, Single-Cell Analysis, Systems biology, Neuroscience, Biomarkers, Homeostasis, medicine.drug
Abstract: Animal models have expanded our understanding of temporal lobe epilepsy (TLE). However, translating these to cell-specific druggable hypotheses is not explored. Herein, we conducted an integrative insilico-analysis of an available transcriptomics dataset obtained from animals with pilocarpine-induced-TLE. A set of 119 genes with subtle-to-moderate impact predicted most forms of epilepsy with ~ 97% accuracy and characteristically mapped to upregulated homeostatic and downregulated synaptic pathways. The deconvolution of cellular proportions revealed opposing changes in diverse cell types. The proportion of nonneuronal cells increased whereas that of interneurons, except for those expressing vasoactive intestinal peptide (Vip), decreased, and pyramidal neurons of the cornu-ammonis (CA) subfields showed the highest variation in proportion. A probabilistic Bayesian-network demonstrated an aberrant and oscillating physiological interaction between nonneuronal cells involved in the blood–brain-barrier and Vip interneurons in driving seizures, and their role was evaluated insilico using transcriptomic changes induced by valproic-acid, which showed opposing effects in the two cell-types. Additionally, we revealed novel epileptic and antiepileptic mechanisms and predicted drugs using causal inference, outperforming the present drug repurposing approaches. These well-powered findings not only expand the understanding of TLE and seizure oscillation, but also provide predictive biomarkers of epilepsy, cellular and causal micro-circuitry changes associated with it, and a drug-discovery method focusing on these events.
Published: 2021

33. Modeling the time course of ComX: towards molecular process control for Bacillus wild-type cultivations

Author: Marius Henkel, Kambiz Morabbi Heravi, Olivia Magosch, Lars Lilge, Rudolf Hausmann, Chantal Treinen, Peter Klausmann, Berit Würtz, Jens Pfannstiel, and Mareen Hoffmann
Subjects: Computer science, Biophysics, Biomass, Bacillus, Bacillus subtilis, Surfactin lipopeptide, Microbiology, Applied Microbiology and Biotechnology, chemistry.chemical_compound, ComX, Bioreactor, Molecular process control, Process control, Wild-type cultivation, biology, Wild type, Quorum Sensing, biology.organism_classification, QR1-502, Quorum sensing, chemistry, Original Article, Biochemical engineering, Surfactin, TP248.13-248.65, Biotechnology
Abstract: Wild-type cultivations are of invaluable relevance for industrial biotechnology when it comes to the agricultural or food sector. Here, genetic engineering is hardly applicable due to legal barriers and consumer’s demand for GMO-free products. An important pillar for wild-type cultivations displays the genus Bacillus. One of the challenges for Bacillus cultivations is the global ComX-dependent quorum sensing system. Here, molecular process control can serve as a tool to optimize the production process without genetic engineering. To realize this approach, quantitative knowledge of the mechanism is essential, which, however, is often available only to a limited extent. The presented work provides a case study based on the production of cyclic lipopeptide surfactin, whose expression is in dependence of ComX, using natural producer B. subtilis DSM 10 T. First, a surfactin reference process with 40 g/L of glucose was performed as batch fermentation in a pilot scale bioreactor system to gain novel insights into kinetic behavior of ComX in relation to surfactin production. Interestingly, the specific surfactin productivity did not increase linearly with ComX activity. The data were then used to derive a mathematic model for the time course of ComX in dependence of existing biomass, biomass growth as well as a putative ComX-specific protease. The newly adapted model was validated and transferred to other batch fermentations, employing 20 and 60 g/L glucose. The applied approach can serve as a model system for molecular process control strategies, which can thus be extended to other quorum sensing dependent wild-type cultivations.
Published: 2021

34. SBML Level 3: an extensible format for the exchange and reuse of biological models

Author: Edda Klipp, Marco Antoniotti, Frank Bergmann, James C. Schaff, Peter D. Karp, Daniel Lucio, Kedar Nath Natarajan, Thomas M. Hamm, Leandro Watanabe, Henning Hermjakob, David Tolnay, John Wagner, Joerg Stelling, Alida Palmisano, Falk Schreiber, Yukiko Matsuoka, Harold F. Gómez, Huaiyu Mi, Carole J. Proctor, Ulrike Wittig, Neil Swainston, Jan Červený, Denis Thieffry, Piero Dalle Pezze, Julio Saez-Rodriguez, Maciej J. Swat, Bin Hu, Martina Kutmon, Thomas Pfau, Bas Teusink, Sarah M. Keating, Fedor A. Kolpakov, Andreas Dräger, Pedro Mendes, Martin Scharm, Emek Demir, Ioannis Xenarios, Christoph Flamm, Axel von Kamp, Darren J. Wilkinson, Nick Juty, Fengkai Zhang, Leonard A. Harris, Michael Schubert, Dagmar Waltemath, Lucian P. Smith, Steffen Klamt, Herbert M. Sauro, Ali Ebrahim, Wolfram Liebermeister, Christian Knüpfer, Nicolas Rodriguez, Tramy Nguyen, Naoki Tanimura, Christopher Cox, Stuart C. Sealfon, Nicholas Alexander Allen, Clemens Wrzodek, Bastian R. Angermann, Martin Meier-Schellersheim, Anna Zhukova, Jean-Baptiste Pettit, Hovakim Grabski, Devin P. Sullivan, Claudine Chaouiya, Michael L. Blinov, John Doyle, Ilya Kiselev, Roman Schulte, Alex Gutteridge, Mélanie Courtot, Eric Mjolsness, Finja Wrzodek, Rahuman S Malik-Sheriff, Ronan M. T. Fleming, Bruce E. Shapiro, Kimberly Begley, Leslie M. Loew, Colin S. Gillespie, Ibrahim Vazirabad, Michael Hucka, Akira Funahashi, Bernhard O. Palsson, Hamid Bolouri, Tomáš Helikar, Camille Laibe, William S. Denney, Chris T. Evelo, Florian Mittag, William S. Hlavacek, Ron Henkel, Harish Dharuri, Julien Dorier, Karthik Raman, Martina Fröhlich, Conor Lawless, Rainer Machné, Falko Krause, Damon Hachmeister, Matthias König, Clifford A. Shaffer, Benjamin D. Heavner, Douglas B. Kell, Jonathan R. Karr, Mihai Glont, Lukas Endler, Melanie I. Stefan, Robert Phair, Lu Li, Henning Schmidt, Dirk Drasdo, Johan Elf, Allyson L. Lister, Hiroaki Kitano, Richard R. Adams, Oliver A. Ruebenacker, Roland Keller, Sven Sahle, Ion I. Moraru, Gary D. Bader, Poul M. F. Nielsen, Johann M. Rohwer, Johannes Eichner, Daniel R. Hyduke, James R. Faeder, Stefan Hoops, Emanuel Gonçalves, Yuichiro Inagaki, Aurélien Naldi, Koichi Takahashi, Sylvain Soliman, Brett G. Olivier, Kieran Smallbone, Stuart L. Moodie, Pedro T. Monteiro, Chris J. Myers, Martin Golebiewski, Tomas Radivoyevitch, Jeremy Zucker, Hidde de Jong, Andrew Finney, Keating, S, Waltemath, D, König, M, Zhang, F, Dräger, A, Chaouiya, C, Bergmann, F, Finney, A, Gillespie, C, Helikar, T, Hoops, S, Malik-Sheriff, R, Moodie, S, Moraru, I, Myers, C, Naldi, A, Olivier, B, Sahle, S, Schaff, J, Smith, L, Swat, M, Thieffry, D, Watanabe, L, Wilkinson, D, Blinov, M, Begley, K, Faeder, J, Gómez, H, Hamm, T, Inagaki, Y, Liebermeister, W, Lister, A, Lucio, D, Mjolsness, E, Proctor, C, Raman, K, Rodriguez, N, Shaffer, C, Shapiro, B, Stelling, J, Swainston, N, Tanimura, N, Wagner, J, Meier-Schellersheim, M, Sauro, H, Palsson, B, Bolouri, H, Kitano, H, Funahashi, A, Hermjakob, H, Doyle, J, Hucka, M, Adams, R, Allen, N, Angermann, B, Antoniotti, M, Bader, G, Červený, J, Courtot, M, Cox, C, Dalle Pezze, P, Demir, E, Denney, W, Dharuri, H, Dorier, J, Drasdo, D, Ebrahim, A, Eichner, J, Elf, J, Endler, L, Evelo, C, Flamm, C, Fleming, R, Fröhlich, M, Glont, M, Gonçalves, E, Golebiewski, M, Grabski, H, Gutteridge, A, Hachmeister, D, Harris, L, Heavner, B, Henkel, R, Hlavacek, W, Hu, B, Hyduke, D, Jong, H, Juty, N, Karp, P, Karr, J, Kell, D, Keller, R, Kiselev, I, Klamt, S, Klipp, E, Knüpfer, C, Kolpakov, F, Krause, F, Kutmon, M, Laibe, C, Lawless, C, Li, L, Loew, L, Machne, R, Matsuoka, Y, Mendes, P, Mi, H, Mittag, F, Monteiro, P, Natarajan, K, Nielsen, P, Nguyen, T, Palmisano, A, Jean-Baptiste, P, Pfau, T, Phair, R, Radivoyevitch, T, Rohwer, J, Ruebenacker, O, Saez-Rodriguez, J, Scharm, M, Schmidt, H, Schreiber, F, Schubert, M, Schulte, R, Sealfon, S, Smallbone, K, Soliman, S, Stefan, M, Sullivan, D, Takahashi, K, Teusink, B, Tolnay, D, Vazirabad, I, Kamp, A, Wittig, U, Wrzodek, C, Wrzodek, F, Xenarios, I, Zhukova, A, Zucker, J, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Heidelberg University Hospital [Heidelberg], Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), European Molecular Biology Laboratory (EMBL), University of Connecticut (UCONN), National Institutes of Health [Bethesda] (NIH), Chercheur indépendant, Amazon Web Services [Seattle] (AWS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University of Toronto, Masaryk University [Brno] (MUNI), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, The University of Tennessee [Knoxville], The Babraham Institute [Cambridge, UK], Oregon Health and Science University [Portland] (OHSU), Human Predictions LLC, Illumina, Swiss-Prot Group, Swiss Institute of Bioinformatics [Genève] (SIB), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California [San Diego] (UC San Diego), University of California (UC), Center for Bioinformatics (ZBIT), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Uppsala University, Institut für Populationsgenetik [Vienna], Veterinärmedizinische Universität Wien, Maastricht University [Maastricht], Alpen-Adria-Universität Klagenfurt [Klagenfurt, Austria], Medizinische Universität Wien = Medical University of Vienna, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg Institute for Theoretical Studies (HITS ), Russian-Armenian University (RAU), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Microsoft Technology Licensing (MTL), Microsoft Corporation [Redmond, Wash.], Vanderbilt University School of Medicine [Nashville], University of Washington [Seattle], University of Rostock, Los Alamos National Laboratory (LANL), Lorentz Institute, Universiteit Leiden, Tegmine Therapeutics, Modeling, simulation, measurement, and control of bacterial regulatory networks (IBIS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Jean Roget, SRI International [Menlo Park] (SRI), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Liverpool, Universitätsklinikum Tübingen - University Hospital of Tübingen, Institute of Information and Computational Technologies (IICT), Max Planck Institute for Dynamics of Complex Technical Systems, Max-Planck-Gesellschaft, Max-Planck-Institut für Molekulare Genetik (MPIMG), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Humboldt University Of Berlin, Newcastle University [Newcastle], École polytechnique (X), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], The Systems Biology Institute [Tokyo] (SBI), Centro de Quimica Estrutural (CQE), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST), University of Southern California (USC), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, University of Southern Denmark (SDU), University of Auckland [Auckland], University of Utah, Virginia Tech [Blacksburg], University of Luxembourg [Luxembourg], Integrative Bioinformatics Inc [Mountain View], Cleveland Clinic, Stellenbosch University, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Universität Heidelberg [Heidelberg] = Heidelberg University, Leibniz Institute of Plant Genetics and Crop Plant Research [Gatersleben] (IPK-Gatersleben), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Manchester [Manchester], Computational systems biology and optimization (Lifeware), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), California Institute of Technology (CALTECH), Encodia Inc [San Diego], Shinshu University [Nagano], University of Amsterdam [Amsterdam] (UvA), Versiti Blood Center of Wisconsin, Greifswald University Hospital, Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Pacific Northwest National Laboratory (PNNL), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Department of Bioengineering, University of California (UC)-University of California (UC), ANSYS, Virginia Polytechnic Institute and State University [Blacksburg], Eight Pillars Ltd, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Universität Heidelberg, Bioquant, Applied Biomathematics [New York], SimCYP Ltd, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Utah School of Medicine [Salt Lake City], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Mizuho Information and Research Institute, Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Oxford, Computer Science (North Carolina State University), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of California [Irvine] (UC Irvine), Indian Institute of Technology Madras (IIT Madras), California State University [Northridge] (CSUN), Biotechnology and Biological Sciences Research Council (BBSRC), IBM Research [Melbourne], Benaroya Research Institute [Seattle] (BRI), Okinawa Institute of Science and Technology Graduate University, Keio University, Department of Computing and Mathematical sciences, members, SBML Level 3 Community, Université de Lausanne (UNIL), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of California, Universiteit Leiden [Leiden], Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Inria Grenoble - Rhône-Alpes, Humboldt University of Berlin, Universität Heidelberg [Heidelberg], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Humboldt-Universität zu Berlin, University of California-University of California, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], University of California [Irvine] (UCI), Biotechnology and Biological Sciences Research Council, Computer Science, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)
Subjects: computational modeling, Medicine (General), Markup language, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, INFORMATION, Interoperability, interoperability, Review, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], ANNOTATION, 0302 clinical medicine, Software, file forma, Models, Biology (General), 0303 health sciences, Computational model, Applied Mathematics, Systems Biology, systems biology, File format, 3. Good health, Networking and Information Technology R&D, Networking and Information Technology R&D (NITRD), Computational Theory and Mathematics, SIMULATION, General Agricultural and Biological Sciences, STANDARDS, REPOSITORY, Information Systems, QH301-705.5, Bioinformatics, Systems biology, Software ecosystem, Reviews, Bioengineering, Methods & Resources, Biology, MARKUP LANGUAGE, Models, Biological, SBML Level 3 Community members, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, R5-920, Animals, Humans, SBML, reproducibility, 030304 developmental biology, ENVIRONMENT, General Immunology and Microbiology, file format, business.industry, Computational Biology, Biological, ONTOLOGY, Metabolism, Logistic Models, Biochemistry and Cell Biology, Other Biological Sciences, Software engineering, business, 030217 neurology & neurosurgery
Abstract: Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., Over the past two decades, scientists from different fields have been developing SBML, a standard format for encoding computational models in biology and medicine. This article summarizes recent progress and gives perspectives on emerging challenges.
Published: 2020

35. Unravelling the changes during induced vitellogenesis in female European eel through RNA-Seq: What happens to the liver?

Author: Michelle Grace Pinto Jørgensen, Jonna Tomkiewicz, Christiaan V. Henkel, Sylvie Dufour, Francesca Bertolini, Bertolini, Francesca, Jørgensen, Michelle Grace Pinto, Henkel, Christiaan, Dufour, Sylvie, Tomkiewicz, Jonna, Technical University of Denmark [Lyngby] (DTU), Norwegian University of Life Sciences (NMBU), Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), and Danmarks Tekniske Universitet = Technical University of Denmark (DTU)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Gene Expression, Biochemistry, Transcriptome, 0302 clinical medicine, Animal Cells, Gene expression, Medicine and Health Sciences, Morphogenesis, RNA-Seq, media_common, Eels, Multidisciplinary, biology, Reproduction, Fatty Acids, Vitellogenesis, Eukaryota, Lipids, Cell biology, Liver, Osteichthyes, OVA, [SDE]Environmental Sciences, Vertebrates, Medicine, Female, Cellular Types, Anatomy, Vitellogenins, Research Article, media_common.quotation_subject, Science, Biosynthesis, 03 medical and health sciences, Vitellogenin, Genetics, Animals, 14. Life underwater, Gene, Animal, Organisms, Biology and Life Sciences, Estrogens, Cell Biology, Anguilla, Hormones, Fish, Germ Cells, 030104 developmental biology, Oocytes, biology.protein, Zoology, 030217 neurology & neurosurgery, Developmental Biology
Abstract: The life cycle of European eel (Anguilla anguilla), a catadromous species, is complex and enigmatic. In nature, during the silvering process prior to their long spawning migration, reproductive development is arrested, and they cease feeding. In studies of reproduction using hormonal induction, eels are equivalently not feed. Therefore, in female eels that undergo vitellogenesis, the liver plays different, essential roles being involved both in vitellogenins synthesis and in reallocating resources for the maintenance of vital functions, performing the transoceanic reproductive migration and completing reproductive development. The present work aimed at unravelling the major transcriptomic changes that occur in the liver during induced vitellogenesis in female eels. mRNA-Seq data from 16 animals (eight before induced vitellogenesis and eight after nine weeks of hormonal treatment) were generated and differential expression analysis was performed comparing the two groups. This analysis detected 1,328 upregulated and 1,490 downregulated transcripts. Overrepresentation analysis of the upregulated genes included biological processes related to biosynthesis, response to estrogens, mitochondrial activity and localization, while downregulated genes were enriched in processes related to morphogenesis and development of several organs and tissues, including liver and immune system. Among key genes, the upregulated ones included vitellogenin genes (VTG1 and VTG2) that are central in vitellogenesis, together with ESR1 and two novel genes not previously investigated in European eel (LMAN1 and NUPR1), which have been linked with reproduction in other species. Moreover, several upregulated genes, such as CYC1, ELOVL5, KARS and ACSS1, are involved in the management of the effect of fasting and NOTCH, VEGFA and NCOR are linked with development, autophagy and liver maintenance in other species. These results increase the understanding of the molecular changes that occur in the liver during vitellogenesis in this complex and distinctive fish species, bringing new insights on European eel reproduction and broodstock management.
Published: 2020

36. Association among sperm chromatin condensation, sperm DNA fragmentation and 8-OHdG in seminal plasma and semen parameters in infertile men with oligoasthenoteratozoospermia

Author: Dilara Hologlu, Ramazan Asci, Ralf Henkel, Sezgin Gunes, and Tolga Guvenc
Subjects: Male, endocrine system, Urology, Motility, Semen, DNA Fragmentation, Andrology, Endocrinology, Prophase, Humans, Infertility, Male, biology, urogenital system, Sperm chromatin condensation, General Medicine, Oligospermia, Sperm, Spermatozoa, Chromatin, Staining, Histone, Asthenozoospermia, biology.protein, Sperm Motility, DNA fragmentation
Abstract: The present study aimed to investigate the clinical role of standard sperm diagnosis parameters (sperm concentration, motility, morphology) as well as aniline blue staining of histones, 8-OHdG, TUNEL assay were performed on semen samples in infertile men with oligoasthenoteratozoospermia (OAT). Thirty-two infertile and ten proven fertile men were included in the study. Chromatin condensation sperm in infertile men was significantly lower compared to the fertile men (p < 0.0001). Age, sperm concentration, morphology and motility were significantly negatively correlated with chromatin condensation (p < 0.05). However, no significant correlations among the chromatin condensation, SDF and sperm DNA damage were detected in terms of 8-OHdG concentration.
Published: 2021

37. Dog colour patterns explained by modular promoters of ancient canid origin

Author: DoGA consortium, Bannasch, Danika L., Kaelin, Christopher B., Letko, Anna, Loechel, Robert, Hug, Petra, Jagannathan, Vidhya, Henkel, Jan, Roosje, Petra, Hytönen, Marjo K., Lohi, Hannes, Arumilli, Meharji, Minor, Katie M., Mickelson, James R., Drogemuller, Cord, Barsh, Gregory S., Leeb, Tosso, Iivanainen, Antti, Medicum, Haartman Institute (-2014), Biosciences, Veterinary Biosciences, Helsinki One Health (HOH), Hannes Tapani Lohi / Principal Investigator, Veterinary Genetics, Department of Medical and Clinical Genetics, Antti Iivanainen / Principal Investigator, Veterinary Anatomy and Developmental Biology, and Developmental interactions
Subjects: BLACK-AND-TAN, Evolutionary biology, 413 Veterinary science, Domestication, 0302 clinical medicine, Hair cycle, 2.2 Factors relating to the physical environment, Aetiology, 610 Medicine & health, SADDLE TAN, Phylogeny, DoGA consortium, 0303 health sciences, Natural selection, Ecology, Phylogenetic tree, 630 Agriculture, Inheritance (genetic algorithm), ASSOCIATION, ADMIXTURE, White (mutation), 590 Animals (Zoology), EXPRESSION, Coat, Genotype, Color, PHENOTYPES, Biology, INHERITANCE, Article, 03 medical and health sciences, Dogs, Genetic, Genetics, Animals, Selection, Genetic, Selection, Ecology, Evolution, Behavior and Systematics, Animal breeding, 030304 developmental biology, Wolves, IDENTIFICATION, MUTATIONS, Haplotype, PIGMENTATION, 570 Life sciences, biology, 030217 neurology & neurosurgery
Abstract: Distinctive colour patterns in dogs are an integral component of canine diversity. Colour pattern differences are thought to have arisen from mutation and artificial selection during and after domestication from wolves but important gaps remain in understanding how these patterns evolved and are genetically controlled. In other mammals, variation at the ASIP gene controls both the temporal and spatial distribution of yellow and black pigments. Here, we identify independent regulatory modules for ventral and hair cycle ASIP expression, and we characterize their action and evolutionary origin. Structural variants define multiple alleles for each regulatory module and are combined in different ways to explain five distinctive dog colour patterns. Phylogenetic analysis reveals that the haplotype combination for one of these patterns is shared with Arctic white wolves and that its hair cycle-specific module probably originated from an extinct canid that diverged from grey wolves more than 2 million years ago. Natural selection for a lighter coat during the Pleistocene provided the genetic framework for widespread colour variation in dogs and wolves., Dogs exhibit remarkable variation in colour patterns. Here, the authors identify structural variants of independent regulatory modules for ventral and hair cycle expression of the ASIP gene that explain five distinctive dog colour patterns and trace back the origin of one colour pattern to an extinct canid.
Published: 2021

38. 3D Atlas of the Pituitary Gland of the Model Fish Medaka (Oryzias latipes)

Author: Rasoul Nourizadeh-Lillabadi, Gergely Csucs, Maja Puchades, Finn-Arne Weltzien, Christiaan V. Henkel, Khadeeja Siddique, Romain Fontaine, Muhammad Rahmad Royan, and Jan G. Bjaalie
Subjects: Pituitary gland, education.field_of_study, endocrine system, medaka, teleost, Somatotropic cell, multihormonal cells, Endocrinology, Diabetes and Metabolism, Population, hormone, In situ hybridization, Biology, Gonadotropic cell, RC648-665, pituitary, Diseases of the endocrine glands. Clinical endocrinology, Cell biology, medicine.anatomical_structure, Anterior pituitary, Thyrotropic cell, medicine, atlas, Corticotropic cell, education
Abstract: In vertebrates, the anterior pituitary plays a crucial role in regulating several essential physiological processes via the secretion of at least seven peptide hormones by different endocrine cell types. Comparative and comprehensive knowledge of the spatial distribution of those endocrine cell types is required to better understand their physiological functions. Using medaka as a model and several combinations of multi-color fluorescence in situ hybridization, we present the first 3D atlas revealing the gland-wide distribution of seven endocrine cell populations: lactotropes, thyrotropes, Lh and Fsh gonadotropes, somatotropes, and pomca-expressing cells (corticotropes and melanotropes) in the anterior pituitary of a teleost fish. By combining in situ hybridization and immunofluorescence techniques, we deciphered the location of corticotropes and melanotropes within the pomca-expressing cell population. The 3D localization approach reveals sexual dimorphism of tshba-, pomca-, and lhb-expressing cells in the adult medaka pituitary. Finally, we show the existence of bi-hormonal cells co-expressing lhb-fshb, fshb-tshba and lhb-sl using single-cell transcriptomics analysis and in situ hybridization. This study offers a solid basis for future comparative studies of the teleost pituitary and its functional plasticity.
Published: 2021

39. A discussion to help establish release specifications for master cell banks of parental host cells

Author: George J Taylor, David Colton, Aaron Mack, Heather Lesnik, BioPhorum, Helen Hay, Carlos A. Benitez, Cornelia Henkel, Kim Nguyen, Greg Stromberg, and Misty Mashburn
Subjects: medicine.anatomical_structure, Cell, medicine, Biology, Host (network), Cell biology
Published: 2021

40. Potent inhibition of arenavirus infection by a novel fusion inhibitor

Author: Ashley Dagley, Shibani Naik, Eric Brown, Brian B. Gowen, Alexandra Fetsko, Jonna B. Westover, Greg Henkel, Nicole Anderson, Dallan J. Blotter, Ken McCormack, and Vidyasagar Reddy Gantla
Subjects: 0301 basic medicine, Male, New World Arenavirus, viruses, 030106 microbiology, Administration, Oral, Disease, Antiviral Agents, Membrane Fusion, Virus, Article, Small Molecule Libraries, 03 medical and health sciences, chemistry.chemical_compound, Mice, Viral Envelope Proteins, Glycoprotein complex, Virology, Chlorocebus aethiops, Ribavirin, Medicine, Animals, Arenaviridae Infections, Dosing, Vero Cells, Arenaviruses, New World, Pharmacology, Arenavirus, biology, business.industry, Virus Internalization, biology.organism_classification, Hemorrhagic Fevers, 030104 developmental biology, chemistry, business
Abstract: Several arenaviruses, including Lassa and Lujo viruses in Africa and five New World arenavirus (NWA) species in the Americas, cause life-threatening viral hemorrhagic fevers. In the absence of licensed antiviral therapies, these viruses pose a significant public health risk. The envelope glycoprotein complex (GPC) mediates arenavirus entry through a pH-dependent fusion of the viral and host endosomal membranes. It thus is recognized as a viable target for small-molecule fusion inhibitors. Here, we report on the antiviral activity and pre-clinical development of the novel broad-spectrum arenavirus fusion inhibitors, ARN-75039 and ARN-75041. In Tacaribe virus (TCRV) pseudotyped and native virus assays, the ARN compounds were active in the low to sub-nanomolar range with selectivity indices exceeding 1000. Pharmacokinetic analysis of the orally administered compounds revealed an extended half-life in mice supporting once-daily dosing, and the compounds were well tolerated at the highest tested dose of 100 mg/kg. In a proof-of-concept prophylactic efficacy study, doses of 10 and 35 mg/kg of either compound dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues. Additionally, in contrast to surviving mice that received ribavirin or placebo, animals treated with ARN-75039 or ARN-75041 were cured of TCRV infection. In a follow-up study with ARN-75039, impressive therapeutic efficacy was demonstrated under conditions where treatment was withheld until after the onset of disease. Taken together, the data strongly support the continued development of ARN-75039 as a candidate therapeutic for the treatment of severe arenaviral diseases.
Published: 2021

41. Integrative transcriptomics reveals ectopic lipid homeostasis mechanisms in non-endocrine cells of the teleost pituitary

Author: von Krogh K, Eirill Ager-Wick, Gersende Maugars, Khadeeja Siddique, Finn-Arne Weltzien, Rasoul Nourizadeh-Lillabadi, Christiaan V. Henkel, and Romain Fontaine
Subjects: Transcriptome, Pituitary gland, medicine.anatomical_structure, medicine, Endocrine system, Ectopic expression, Biology, Homeostasis, Lipid Transport, Endocrine gland, Hormone, Cell biology
Abstract: Directing both organismal homeostasis and physiological adaptation, the pituitary is a key endocrine gland in all vertebrates. It communicates the needs of the organism to different organs by secreting hormones into the bloodstream. Here, we have used the model fish medaka to investigate the developmental dynamics in the pituitary using a comprehensive RNA-seq time series. Using expression trend analyses we show that one of the most prominent changes during sexual maturation is the strong decrease of transcripts encoding secreted lipid transport proteins, which are typically only produced by the liver. By integrating developmental trends with single-cell transcriptomics, we demonstrate that rare, previously uncharacterized cells are responsible for this expression pattern. With levels as high as for established peptide hormone-encoding genes, this ectopic expression exposes a major new mechanism in the juvenile teleost pituitary. In addition, it implies the existence of unexpected connections between endocrine communication, sexual maturation, and lipid homeostasis.
Published: 2021

42. Male Infertility, Oxidative Stress and Antioxidants

Author: Ashok Agarwal, Renata Finelli, Ralf Henkel, Sava Micic, Sheqibe Beadini, Vegim Zhaku, and Nexhbedin Beadini
Subjects: 0301 basic medicine, chemistry.chemical_classification, medicine.medical_specialty, Reactive oxygen species, 030219 obstetrics & reproductive medicine, Biology, medicine.disease_cause, medicine.disease, Male infertility, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Endocrinology, chemistry, Internal medicine, medicine, Oxidative stress
Abstract: Within the male reproductive system, oxidative stress (OS) has been identified as prevailing etiology of male infertility. The effects of reactive oxygen species (ROS) on male fertility depend on the dimensions, “modus operandi” of the ROS and the oxido-reduction potential (ORP) of the male reproductive tract. Hereupon, for an adequate response to OS, the cells of our body are endowed with a well-sophisticated system of defense in order to be protected. Various antioxidant enzymes and small molecular free radical scavengers, maintain the delicate balance between oxidants and reductants (antioxidants), crucial to cellular function and fertility. Therapeutic use of antioxidants is an optimal and coherent option in terms of mitigating OS and improving semen parameters. Therefore, recognizing and managing OS through either decreasing ROS levels or by increasing antioxidant force, appear to be a requesting approach in the management of male infertility. However, a clear defined attitude of the experts about the clinical efficacy of antioxidant therapy is still deprived. Prominently, antioxidant such as coenzyme Q10, vitamin C and E, lycopene, carnitine, zinc and selenium have been found useful in controlling the balance between ROS production and scavenging activities. In spite of that, healthy lifestyle, without smoke and alcohol, everyday exercise, reduction of psychological stress and quality well-designed meals, are habits that can overturn male infertility.
Published: 2021

43. A deletion spanning the promoter and first exon of the hair cycle‐specific ASIP transcript isoform in black and tan rabbits

Author: Tosso Leeb, V. Jagannathan, Cord Drögemüller, Anna Letko, Fabienne Leuthard, Claude Schelling, B. Ammann, Jan Henkel, Miguel Carneiro, University of Zurich, and Leeb, Tosso
Subjects: 0301 basic medicine, Gene isoform, non, genome sequence, Mutant, 610 Medicine & health, Biology, Oryctolagus cuniculus, 03 medical and health sciences, Exon, structural variant, 1311 Genetics, Hair cycle, Genotype, Genetics, Animals, pigmentation, 11434 Center for Clinical Studies, Allele, Hair Color, Promoter Regions, Genetic, Gene, Alleles, Sequence Deletion, coding, promoter, whole, 630 Agriculture, integumentary system, 0402 animal and dairy science, Exons, 04 agricultural and veterinary sciences, General Medicine, 040201 dairy & animal science, Molecular biology, Phenotype, 10187 Department of Farm Animals, 030104 developmental biology, 590 Animals (Zoology), 570 Life sciences, biology, Agouti Signaling Protein, Animal Science and Zoology, Rabbits, 1103 Animal Science and Zoology, coat colour
Abstract: Black and tan animals have tan-coloured ventral body surfaces separated by sharp boundaries from black-coloured dorsal body surfaces. In the at mouse mutant, a retroviral 6 kb insertion located in the hair cycle-specific promoter of the murine Asip gene encoding agouti signalling protein causes the black and tan phenotype. In rabbits, three ASIP alleles are thought to exist, including an at allele causing a black and tan coat colour that closely resembles the mouse black and tan phenotype. The goal of our study was to identify the functional genetic variant causing the rabbit at allele. We performed a WGS-based comparative analysis of the ASIP gene in one black and tan and three wt agouti-coloured rabbits. The analysis identified 75 at -associated variants including an 11 kb deletion. The deletion is located in the region of the hair cycle-specific ASIP promoter and thus in a region homologous to the site of the retroviral insertion causing the at allele in mice. We observed perfect association of the genotypes at this deletion with the coat colour phenotype in 49 rabbits. The comparative analysis and the previous knowledge about the regulation of ASIP expression suggest that the 11 kb deletion is the most likely causative variant for the black and tan phenotype in rabbits.
Published: 2019

44. Evaluation of small organic acids present in fast pyrolysis bio‐oil from lignocellulose as feedstocks for bacterial bioconversion

Author: Manuel Kiefer, Stefanie Arnold, Tatjana Tews, Rudolf Hausmann, and Marius Henkel
Subjects: Bacillus (shape), biology, biomass, Renewable Energy, Sustainability and the Environment, Chemistry, Bioconversion, Pseudomonas, lcsh:TJ807-830, Corynebacterium, lcsh:Renewable energy sources, Biomass, Forestry, Bacillus, biology.organism_classification, lcsh:HD9502-9502.5, lcsh:Energy industries. Energy policy. Fuel trade, bio‐oil, Food science, bacteria, Waste Management and Disposal, Agronomy and Crop Science, Pyrolysis, Bacteria, bioeconomy
Abstract: Small organic acids derived from fast pyrolysis of lignocellulosic biomass represent a significant proportion of microbially accessible carbon in bio‐oil. However, using bio‐oil for microbial cultivation is a highly challenging task due to its strong adverse effects on microbial growth as well as its complex composition. In this study, the main small organic acids present in bio‐oil as acetate, formate and propionate were evaluated with respect to their suitability as feedstocks for bacterial growth. For this purpose, the growth behavior of four biotechnological production hosts—Escherichia coli, Pseudomonas putida, Bacillus subtilis, and Corynebacterium glutamicum—was quantified and compared. The bacteria were cultivated on single acids and mixtures of acids in different concentrations and evaluated using common biotechnological efficiency parameters. In addition, cultivation experiments on pretreated fast pyrolysis‐derived bio‐oil fractions were performed with respect to the suitability of the bacterial strains to tolerate inhibitory substances. Results suggest that both P. putida and C. glutamicum metabolize acetate—the major small organic acid generated during fast pyrolysis of lignocellulosic biomass—as sole carbon source over a wide concentration range, are able to grow on mixtures of small organic acids present in bio‐oil and can, to a limited extent, tolerate the highly toxic inhibitory substances within bio‐oil. This work provides an important step in search of suitable bacterial strains for bioconversion of lignocellulosic‐based feedstocks and thus contributes to establishing efficient bioprocesses within a future bioeconomy.
Published: 2019

45. A new and unusual species of Hericium (Basidiomycota: Russulales, Hericiaceae) from the Dja Biosphere Reserve, Cameroon

Author: Danny Haelewaters, Bryn T. M. Dentinger, M. Catherine Aime, Blaise Jumbam, Rachel A. Koch, and Terry W. Henkel
Subjects: Species complex, biology, Ecology, Biodiversity, Hericium, Rainforest, Species richness, biology.organism_classification, Agricultural and Biological Sciences (miscellaneous), Uapaca, Evergreen forest, Ecology, Evolution, Behavior and Systematics, Russulales
Abstract: Tropical rainforests form the most species-rich biome on the earth. The Dja Biosphere Reserve (DBR) in Cameroon is a biodiverse tropical forest characterized in part by upland monodominant stands of the ectomycorrhizal (ECM) Gilbertiodendron dewevrei and ECM Uapaca spp. scattered along river banks. This mostly primary Guineo-Congolian evergreen forest harbors natural populations of large megafauna and numerous plant and fungal species. Studies have indicated that some ECM fungal groups of the large order Russulales are abundant in certain localities in the tropics, including the DBR. However, currently, other predominantly wood-decaying families of Russulales are poorly represented in Africa. For example, only three records of the saprotrophic genus Hericium (Russulales, Hericiaceae) are known from the African continent. Here, we describe a new species of Hericium recently collected from the DBR. Morphological characteristics and molecular phylogenetic analyses support placement of the Cameroonian collection in Hericium and its recognition as a new species within a larger H. coralloides species complex. The new species, H. bembedjaense, differs from H. coralloides in its smaller basidiospores (2.6–3.0 × 1.7–2.2 μm compared to 3.5–5.0 × 2.8–4.2 μm) and longer basidia (up to 27.0 μm compared to 15.0 μm). It differs from all other described Hericium species in the production of pleurocystidia. This is the first species of Hericiaceae known from sub-Saharan lowland tropical evergreen forests. This study highlights the need to increase fungal sampling in species-rich tropical forests such as those of the Congo Basin.
Published: 2019

46. Implications of a long‐term mast seeding cycle for climatic entrainment, seedling establishment and persistent monodominance in a Neotropical, ectomycorrhizal canopy tree

Author: Jordan R. Mayor and Terry W. Henkel
Subjects: Tree canopy, Monodominance, biology, Ecology, Seedling, Seeding, Mast (botany), biology.organism_classification, Detarioideae, Ecology, Evolution, Behavior and Systematics
Published: 2019

47. UAV BASED MULTI SEASONAL DECIDUOUS TREE SPECIES ANALYSIS IN THE HAINICH NATIONAL PARK USING MULTI TEMPORAL AND POINT CLOUD CURVATURE FEATURES

Author: A. Henkel, S. Hese, and Christian Thiel
Subjects: lcsh:Applied optics. Photonics, Carpinus betulus, biology, lcsh:T, forestry, Point cloud, lcsh:TA1501-1820, biology.organism_classification, lcsh:Technology, Bürgerwissenschaften, Standard deviation, Tree (data structure), Deciduous, Hornbeam, Fagus sylvatica, lcsh:TA1-2040, point clouds, Environmental science, low cost UAV, lcsh:Engineering (General). Civil engineering (General), Beech, Remote sensing
Abstract: Low cost UAV systems are a flexible and mobile platform for very detailed spatial high-resolution point cloud and surface height mapping projects. This study investigates the potential of the DJI Phantom 4 Pro 3D point clouds and derived crown surface height information in combination with RGB spectral information for mapping of deciduous tree species in the Hainich national park area. RGB image data was captured in August, early October and November 2018 to create a multi seasonal spectral dataset for a 100 ha test area. The flight campaigns were controlled from the Hainich flux tower platform in 40 m height owned and operated by University of Göttingen in the central part of the park area. Absolut georeferencing accuracy of the datasets was improved using 7 DGPS measured control points within the stand structure on small forest clearings. Image files and ground control points were processed to a dense point cloud model with 2.6 billion points (approximately 200k points per tree crown object) using the Agisoft Metashape cluster processing environment. Additionally, a digital surface model and a true ortho image mosaic with 3 cm spatial resolution was generated. For the differentiation of deciduous tree species, a reference data set with coordinates for the tree species Fagus sylvatica (beech), Fraxinus excelsior (ash), Acer pseudoplatanus (sycamore maple), Carpinus betulus (hornbeam) and dead trees and early defoliated trees was defined. The study site is however dominated by Fagus sylvatica and Fraxinus excelsior. We studied two different groups of features: tree crown surface height variability parameters using point cloud densities, point cloud height variance, local standard deviation of gaussian curvature, standard deviation of local point cloud roughness and multi temporal normalised spectral features using multi seasonal uncalibrated UAV RGB data. Analysis of feature separability showed that very high-resolution point cloud surface curvature properties with small neighbourhood radii can differentiate some tree species types but we also found multitemporal spectral ratios based on RGB data to be very successful in differentiating the main tree species.Results of this work show that super fine very dense point cloud models and derived roughness measures of mixed forest stand surfaces hold valuable information for deciduous species discrimination and will likely also be very useful for morphological analysis of tree crown types.
Published: 2019

48. Novel metagenome-derived ornithine lipids identified by functional screening for biosurfactants

Author: Leonardo Joaquim van Zyl, Anita Burger, Iris Klaiber, Rudolf Hausmann, Lovemore Kunorozva, Marius Henkel, Marla Trindade, Wesley Williams, and Jens Pfannstiel
Subjects: Ornithine, Sequence analysis, Phenotypic screening, Genetic Vectors, medicine.disease_cause, Applied Microbiology and Biotechnology, Surface-Active Agents, 03 medical and health sciences, Shuttle vector, Acetyltransferases, Escherichia coli, medicine, Genetic Testing, Gene Library, 030304 developmental biology, 0303 health sciences, biology, Pseudomonas putida, 030306 microbiology, Chemistry, Sequence Analysis, DNA, General Medicine, biology.organism_classification, Lipids, Fosmid, Mutagenesis, Insertional, Biochemistry, Metagenomics, DNA Transposable Elements, lipids (amino acids, peptides, and proteins), Transposon mutagenesis, Biotechnology
Abstract: Biosurfactants are amphiphilic molecules that interact with the surfaces of liquids leading to many useful applications. Most biosurfactants have been identified from cultured microbial sources, leaving a largely untapped resource of uncultured bacteria with potentially novel biosurfactant structures. To access the uncultured bacteria, a metagenomic library was constructed in Escherichia coli from environmental DNA within an E. coli, Pseudomonas putida and Streptomyces lividans shuttle vector. Phenotypic screening of the library in E. coli and P. putida by the paraffin spray assay identified a P. putida clone with biosurfactant activity. Sequence analysis and transposon mutagenesis confirmed that an ornithine acyl-ACP N-acyltransferase was responsible for the activity. Although the fosmid was not active in E. coli, overexpression of the olsB gene could be achieved under the control of the inducible T7 promoter, resulting in lyso-ornithine lipid production and biosurfactant activity in the culture supernatants. Screening for activity in more than one host increases the range of sequences that can be identified through metagenomic, since olsB would not have been identified if only E. coli had been used as a host. The potential of lyso-ornithine lipids as a biosurfactant has not been fully explored. Here, we present several biosurfactant parameters of lyso-ornithine lipid to assess its suitability for industrial application.
Published: 2019

49. Animal-fungal interactions 3: first report of mycophagy by the African Brush-tailed Porcupine Atherurus africanus Gray, 1842 (Mammalia: Rodentia: Hystricidae)

Author: Todd F. Elliott, Olivier Séné, Camille Truong, and Terry W. Henkel
Subjects: Atherurus africanus, lcsh:QH1-199.5, biology, Zoology, African brush-tailed porcupine, elaphomyces, fungivory, truffles, ascomycota, hystricidae, lcsh:General. Including nature conservation, geographical distribution, Management, Monitoring, Policy and Law, biology.organism_classification, lcsh:QH540-549.5, parasitic diseases, Animal Science and Zoology, lcsh:Ecology, Ecology, Evolution, Behavior and Systematics, Nature and Landscape Conservation
Abstract: Fungi are an important food source for a diversity of animals throughout the world, but these associations have been poorly studied in Africa. In this short note based on an observation from the Congo Basin of Cameroon, we provide the first report of mycophagy by the African brush-tailed porcupine and the first account of the hypogeous fungal genus Elaphomyces being eaten by an animal in Africa.
Published: 2019

50. In memoriam: Martha Christensen, 1932−2017

Author: Michael F. Allen, Stephen E. Williams, Jack S. States, Dorothy E. Tuthill, and Terry W. Henkel
Subjects: Systematics, Physiology, Anthropology, Ecology (disciplines), Genetics, Cell Biology, General Medicine, Biology, Molecular Biology, Ecology, Evolution, Behavior and Systematics
Abstract: Professor Martha Christensen, an international leader in fungal systematics and ecology, died on 19 March 2017. Martha was a professor of mycology in the Department of Botany at the Univers...
Published: 2019

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