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56 results on '"Ontario Research Fund"'

1. PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood (PEGASUS-2)

Author: Genome Quebec, Genome British Columbia, Genome Alberta, Ontario Research Fund, Laval University, St. Justine's Hospital, Ottawa Hospital Research Institute, McGill University, University of British Columbia, University of Alberta, Genome Canada, Canadian Institutes of Health Research (CIHR), and François Rousseau, Professor-doctor
Published: 2024

2. Cellular Immuno-Therapy for COVID-19 Acute Respiratory Distress Syndrome (CIRCA-19)

Author: Stem Cell Network and Ontario Research Fund
Published: 2021

3. Anterior and Posterior Segment Vascular Changes Following Laser and Anti-Vascular Endothelial Growth Factor (VEGF) Treatment of Diabetic Retinopathy (VEGF)

Author: Ontario Research Fund and Chris Hudson, Professor
Published: 2013

4. Retinal Oxygen Saturation, Blood Flow, Vascular Function and High Resolution Morphometric Imaging in the Living Human Eye

Author: Ontario Research Fund and Chris Hudson, Professor
Published: 2013

5. Prospective Study Phase: Retinal Oxygen Saturation, Blood Flow, Vascular Function and High Resolution Morphometric Imaging in the Living Human Eye

Author: Ontario Research Fund and Chris Hudson, Professor
Published: 2013

6. Soil fauna alter the responses of greenhouse gas emissions to changes in water and nitrogen availability

Author: National Science Foundation (US), National Key Research and Development Program (China), Ministerio de Ciencia e Innovación (España), European Commission, Junta de Andalucía, Natural Sciences and Engineering Research Council of Canada, Agencia Estatal de Investigación (España), Canada Foundation for Innovation, Ontario Research Fund, Chen, H.Y.H. [0000-0001-9477-5541], Zou, Xiaoming [0000-0001-9023-3067], Delgado-Baquerizo, Manuel [0000-0002-6499-576X], Ruan, Honghua [0000-0002-6075-474X], Li, Yuanyuan, Liao, Jiahui, Chen, H.Y.H., Zou, Xiaoming, Delgado-Baquerizo, Manuel, Ni, Juanping, Ren, Tingting, Xu, Hanmei, Ruan, Honghua, National Science Foundation (US), National Key Research and Development Program (China), Ministerio de Ciencia e Innovación (España), European Commission, Junta de Andalucía, Natural Sciences and Engineering Research Council of Canada, Agencia Estatal de Investigación (España), Canada Foundation for Innovation, Ontario Research Fund, Chen, H.Y.H. [0000-0001-9477-5541], Zou, Xiaoming [0000-0001-9023-3067], Delgado-Baquerizo, Manuel [0000-0002-6499-576X], Ruan, Honghua [0000-0002-6075-474X], Li, Yuanyuan, Liao, Jiahui, Chen, H.Y.H., Zou, Xiaoming, Delgado-Baquerizo, Manuel, Ni, Juanping, Ren, Tingting, Xu, Hanmei, and Ruan, Honghua
Abstract: Fertilization and drought are two of the most important global change drivers that impacting greenhouse gas (GHG) emissions. Soil organisms are among the fundamental biotic drivers of biogeochemical cycles and can play critical roles in mitigating global change. However, the contributions of soil macrofauna in explaining the responses of GHG emissions to fertilization and drought remain poorly understood. Here, we designed a three-factor microcosm experiment to examine how soil macrofauna (no fauna, earthworms, and millipedes) alter the responses of CO2, N2O, and CH4 emissions, as well as the C and N contents in response to contrasting levels of N (N0: without N addition, N+: N addition) and available soil water (40% and 60% of soil water holding capacity). We show that soil fauna were significant regulators of CO2 and N2O emissions in response to changes in water and N availability, as supported by multiple identified statistical interactions. Millipedes were observed to reduce the positive influence of soil water availability on soil CO2 emissions in response to the addition of N. Similarly, earthworms weakened the effects of elevated N and water availability on soil N2O emissions. Moreover, CH4 emissions occurred only when millipedes were present. The structural equation models revealed that earthworms and millipedes modified soil CO2 and N2O emissions through their influences on soil total dissolved nitrogen and microbial biomass carbon. Overall, this study demonstrated that soil macrofauna can notably mediate the responses of GHG emissions and soil biogeochemical cycles to global environmental changes.
Published: 2023

7. A multi-specific, multi-affinity antibody platform neutralizes sarbecoviruses and confers protection against SARS-CoV-2 in vivo

Author: Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Ministry of Colleges and Universities (Ontario), Bill & Melinda Gates Foundation, Hospital for Sick Children (Canada), Ontario Graduate Scholarship, Canada Research Chairs, Canada Foundation for Innovation, Ontario Research Fund, National Cancer Institute (US), National Institute of General Medical Sciences (US), Department of Energy (US), Burn Aschner, Clare, Muthuraman, Krithika, Kucharska, Iga, Cui, Hong, Prieto, Katherine, Nair, Manoj S., Wang, Maple, Huang, Yaoxing, Christie-Holmes, Natasha, Poon, Betty, Lam, Jessica, Sultana, Azmiri, Kozak, Robert, Mubareka, Samira, Rubinstein, John L., Rujas, Edurne, Treanor, Bebhinn, Ho, David D., Jetha, Arif, Julien, Jean-Philippe, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Ministry of Colleges and Universities (Ontario), Bill & Melinda Gates Foundation, Hospital for Sick Children (Canada), Ontario Graduate Scholarship, Canada Research Chairs, Canada Foundation for Innovation, Ontario Research Fund, National Cancer Institute (US), National Institute of General Medical Sciences (US), Department of Energy (US), Burn Aschner, Clare, Muthuraman, Krithika, Kucharska, Iga, Cui, Hong, Prieto, Katherine, Nair, Manoj S., Wang, Maple, Huang, Yaoxing, Christie-Holmes, Natasha, Poon, Betty, Lam, Jessica, Sultana, Azmiri, Kozak, Robert, Mubareka, Samira, Rubinstein, John L., Rujas, Edurne, Treanor, Bebhinn, Ho, David D., Jetha, Arif, and Julien, Jean-Philippe
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been responsible for a global pandemic. Monoclonal antibodies (mAbs) have been used as antiviral therapeutics; however, these therapeutics have been limited in efficacy by viral sequence variability in emerging variants of concern (VOCs) and in deployment by the need for high doses. In this study, we leveraged the multi-specific, multi-affinity antibody (Multabody, MB) platform, derived from the human apoferritin protomer, to enable the multimerization of antibody fragments. MBs were shown to be highly potent, neutralizing SARS-CoV-2 at lower concentrations than their corresponding mAb counterparts. In mice infected with SARS-CoV-2, a tri-specific MB targeting three regions within the SARS-CoV-2 receptor binding domain was protective at a 30-fold lower dose than a cocktail of the corresponding mAbs. Furthermore, we showed in vitro that mono-specific MBs potently neutralize SARS-CoV-2 VOCs by leveraging augmented avidity, even when corresponding mAbs lose their ability to neutralize potently, and that tri-specific MBs expanded the neutralization breadth beyond SARS-CoV-2 to other sarbecoviruses. Our work demonstrates how avidity and multi-specificity combined can be leveraged to confer protection and resilience against viral diversity that exceeds that of traditional monoclonal antibody therapies.
Published: 2023

8. Host adaptation and specialization in Tetranychidae mites

Author: Government of Canada, Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada, Bruinsma, Kristie [0000-0001-7913-7920], Rioja, Cristina [0000-0001-9713-1944], Zhurov, Vladimir [0000-0002-7120-4655], Santamaria, M. Estrella [0000-0003-4999-6227], Arbona, Vicent [0000-0003-2232-106X], Navarro, Marie [0009-0003-8441-3653], Cazaux, Marc [0009-0008-2329-0852], Auger, P. [0000-0002-2671-9561], Migeon, Alain [0000-0003-4041-5158], Wybouw, Nicky [0000-0001-7874-9765], Van Leeuwen, Thomas [0000-0003-4651-830X], Díaz, Isabel [0000-0001-9865-902X], Gómez-Cadenas, Aurelio [0000-0002-4598-2664], Sáenz-Navajas, María-Pilar [0000-0002-0702-4238], Bruinsma, Kristie, Rioja, Cristina, Zhurov, Vladimir, Santamaria, M. Estrella, Arbona, Vicent, Navarro, Marie, Cazaux, Marc, Auger, P., Migeon, Alain, Wybouw, Nicky, Van Leeuwen, Thomas, Díaz, Isabel, Gómez-Cadenas, Aurelio, Grbic, Miodrag, Sáenz-Navajas, María-Pilar, Grbić, Vojislava, Government of Canada, Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada, Bruinsma, Kristie [0000-0001-7913-7920], Rioja, Cristina [0000-0001-9713-1944], Zhurov, Vladimir [0000-0002-7120-4655], Santamaria, M. Estrella [0000-0003-4999-6227], Arbona, Vicent [0000-0003-2232-106X], Navarro, Marie [0009-0003-8441-3653], Cazaux, Marc [0009-0008-2329-0852], Auger, P. [0000-0002-2671-9561], Migeon, Alain [0000-0003-4041-5158], Wybouw, Nicky [0000-0001-7874-9765], Van Leeuwen, Thomas [0000-0003-4651-830X], Díaz, Isabel [0000-0001-9865-902X], Gómez-Cadenas, Aurelio [0000-0002-4598-2664], Sáenz-Navajas, María-Pilar [0000-0002-0702-4238], Bruinsma, Kristie, Rioja, Cristina, Zhurov, Vladimir, Santamaria, M. Estrella, Arbona, Vicent, Navarro, Marie, Cazaux, Marc, Auger, P., Migeon, Alain, Wybouw, Nicky, Van Leeuwen, Thomas, Díaz, Isabel, Gómez-Cadenas, Aurelio, Grbic, Miodrag, Sáenz-Navajas, María-Pilar, and Grbić, Vojislava
Abstract: Composite generalist herbivores are comprised of host-adapted populations that retain the ability to shift hosts. The degree and overlap of mechanisms used by host-adapted generalist and specialist herbivores to overcome the same host plant defenses are largely unknown. Tetranychidae mites are exceptionally suited to address the relationship between host adaptation and specialization in herbivores as this group harbors closely related species with remarkably different host ranges-an extreme generalist the two-spotted spider mite (Tetranychus urticae Koch [Tu]) and the Solanaceous specialist Tetranychus evansi (Te). Here, we used tomato-adapted two-spotted spider mite (Tu-A) and Te populations to compare mechanisms underlying their host adaptation and specialization. We show that both mites attenuate induced tomato defenses, including protease inhibitors (PIs) that target mite cathepsin L digestive proteases. While Te solely relies on transcriptional attenuation of PI induction, Tu and Tu-A have elevated constitutive activity of cathepsin L proteases, making them less susceptible to plant anti-digestive proteins. Tu-A and Te also rely on detoxification of tomato constitutive defenses. Te uses esterase and P450 activities, while Tu-A depends on the activity of all major detoxification enzymatic classes to disarm tomato defensive compounds to a lesser extent. Thus, even though both Tu-A and Te use similar mechanisms to counteract tomato defenses, Te can better cope with them. This finding is congruent with the ecological and evolutionary times required to establish mite adaptation and specialization states, respectively.
Published: 2023

9. The Arabidopsis thioredoxin TRXh5regulates the S-nitrosylation pattern of the TIRK receptor being both proteins essential in the modulation of defences to Tetranychus urticae

Author: European Commission, Ministerio de Ciencia e Innovación (España), Government of Canada, Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada, Arnaiz, A., Romero-Puertas, María C., Santamaria, M. Estrella, Rosa-Diaz, Irene, Arbona, Vicent, Muñoz, Alfonso, Grbic, V., González-Melendi, Pablo, Mar Castellano, M., Sandalio, Luisa M., Martinez, M., Diaz, I., European Commission, Ministerio de Ciencia e Innovación (España), Government of Canada, Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada, Arnaiz, A., Romero-Puertas, María C., Santamaria, M. Estrella, Rosa-Diaz, Irene, Arbona, Vicent, Muñoz, Alfonso, Grbic, V., González-Melendi, Pablo, Mar Castellano, M., Sandalio, Luisa M., Martinez, M., and Diaz, I.
Abstract: The interaction between plants and phytophagous arthropods encompasses a complex network of molecules, signals, and pathways to overcome defences generated by each interacting organism. Although most of the elements and modulators involved in this interplay are still unidentified, plant redox homeostasis and signalling are essential for the establishment of defence responses. Here, focusing on the response of Arabidopsis thaliana to the spider mite Tetranychus urticae, we demonstrate the involvement in plant defence of the thioredoxin TRXh5, a small redox protein whose expression is induced by mite infestation. TRXh5 is localized in the cell membrane system and cytoplasm and is associated with alterations in the content of reactive oxygen and nitrogen species. Protein S-nitrosylation signal in TRXh5 over-expression lines is decreased and alteration in TRXh5 level produces changes in the JA/SA hormonal crosstalk of infested plants. Moreover, TRXh5 interacts and likely regulates the redox state of an uncharacterized receptor-like kinase, named THIOREDOXIN INTERACTING RECEPTOR KINASE (TIRK), also induced by mite herbivory. Feeding bioassays performed withTRXh5 over-expression plants result in lower leaf damage and reduced egg accumulation after T. urticae infestation than in wild-type (WT) plants. In contrast, mites cause a more severe injury in trxh5 mutant lines where a greater number of eggs accumulates. Likewise, analysis of TIRK-gain and -loss-of-function lines demonstrate the defence role of this receptor in Arabidopsis against T. urticae. Altogether, our findings demonstrate the interaction between TRXh5 and TIRK and highlight the importance of TRXh5 and TIRK in the establishment of effective Arabidopsis defences against spider mite herbivory.
Published: 2023

10. Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells

Author: George Mason University, Thistledown Foundation, European Commission, Canadian Institute for Advanced Research, Canada Research Chairs, Ontario Research Fund, Canada Foundation for Innovation, Icho, Simoun, Rujas, Edurne, Muthuraman, Krithika, Tam, John, Liang, Huazhu, Harms, Shelby, Liao, Mingmin, Falzarano, Darryl, Julien, Jean-Philippe, Melnyk, Roman A., George Mason University, Thistledown Foundation, European Commission, Canadian Institute for Advanced Research, Canada Research Chairs, Ontario Research Fund, Canada Foundation for Innovation, Icho, Simoun, Rujas, Edurne, Muthuraman, Krithika, Tam, John, Liang, Huazhu, Harms, Shelby, Liao, Mingmin, Falzarano, Darryl, Julien, Jean-Philippe, and Melnyk, Roman A.
Abstract: An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the cell-surface route or the endosomal route, respectively. In cells expressing TMPRSS2, inhibiting endosomal proteases using nonspecific cathepsin inhibitors such as E64d or lysosomotropic compounds such as hydroxychloroquine fails to prevent viral entry, suggesting that the endosomal route of entry is unimportant; however, mechanism-based toxicities and poor efficacy of these compounds confound our understanding of the importance of the endosomal route of entry. Here, to identify better pharmacological agents to elucidate the role of the endosomal route of entry, we profiled a panel of molecules identified through a high-throughput screen that inhibit endosomal pH and/or maturation through different mechanisms. Among the three distinct classes of inhibitors, we found that inhibiting vacuolar-ATPase using the macrolide bafilomycin A1 was the only agent able to potently block viral entry without associated cellular toxicity. Using both pseudotyped and authentic virus, we showed that bafilomycin A1 inhibits SARS-CoV-2 infection both in the absence and presence of TMPRSS2. Moreover, synergy was observed upon combining bafilomycin A1 with Camostat, a TMPRSS2 inhibitor, in neutralizing SARS-CoV-2 entry into TMPRSS2-expressing cells. Overall, this study highlights the importance of the endosomal route of entry for SARS-CoV-2 and provides a rationale for the generation of successful intervention strategies against this virus that combine inhibitors of both entry pathways.
Published: 2022

11. Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile

Author: European Commission, National Institutes of Health (US), James B. Pendleton Charitable Trust, Japan Society for the Promotion of Science, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Eusko Jaurlaritza, Medical Research Council (UK), Wolfson Foundation, German Research Foundation, Leibniz Association, Wellcome Trust, John Fell Fund, Japan Agency for Medical Research and Development, Universidad del País Vasco, Azrieli Foundation, Canada Research Chairs, Ontario Research Fund, Carravilla, Pablo [0000-0001-6592-7630], Iloro, Ibon [0000-0002-9537-1714], Elortza, Félix [0000-0001-8839-5438], Julien, Jean-Philippe [0000-0001-7602-3995], Caaveiro, José M. M. [0000-0001-5568-2369], Rujas, Edurne, Leaman, Daniel P., Insausti, Sara, Carravilla, Pablo, García-Porras, Miguel, Largo, Eneko, Morillo, Izaskun, Sánchez-Eugenia, Rubén, Zhang, Lei, Cui, Hong, Iloro, Ibon, Elortza, Félix, Julien, Jean-Philippe, Eggeling, Christian, Zwick, Michael B., Caaveiro, José M. M., Nieva, José Luis, European Commission, National Institutes of Health (US), James B. Pendleton Charitable Trust, Japan Society for the Promotion of Science, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Eusko Jaurlaritza, Medical Research Council (UK), Wolfson Foundation, German Research Foundation, Leibniz Association, Wellcome Trust, John Fell Fund, Japan Agency for Medical Research and Development, Universidad del País Vasco, Azrieli Foundation, Canada Research Chairs, Ontario Research Fund, Carravilla, Pablo [0000-0001-6592-7630], Iloro, Ibon [0000-0002-9537-1714], Elortza, Félix [0000-0001-8839-5438], Julien, Jean-Philippe [0000-0001-7602-3995], Caaveiro, José M. M. [0000-0001-5568-2369], Rujas, Edurne, Leaman, Daniel P., Insausti, Sara, Carravilla, Pablo, García-Porras, Miguel, Largo, Eneko, Morillo, Izaskun, Sánchez-Eugenia, Rubén, Zhang, Lei, Cui, Hong, Iloro, Ibon, Elortza, Félix, Julien, Jean-Philippe, Eggeling, Christian, Zwick, Michael B., Caaveiro, José M. M., and Nieva, José Luis
Abstract: Broadly neutralizing antibodies (bnAbs) against HIV-1 are frequently associated with the presence of autoreactivity/polyreactivity, a property that can limit their use as therapeutic agents. The bnAb 4E10, targeting the conserved Membrane proximal external region (MPER) of HIV-1, displays almost pan-neutralizing activity across globally circulating HIV-1 strains but exhibits nonspecific off-target interactions with lipid membranes. The hydrophobic apex of the third complementarity-determining region of the heavy chain (CDRH3) loop, which is essential for viral neutralization, critically contributes to this detrimental effect. Here, we have replaced the aromatic/hydrophobic residues from the apex of the CDRH3 of 4E10 with a single aromatic molecule through chemical modification to generate a variant that preserves the neutralization potency and breadth of 4E10 but with reduced autoreactivity. Collectively, our study suggests that the localized accumulation of aromaticity by chemical modification provides a pathway to ameliorate the adverse effects triggered by the CDRH3 of anti-HIV-1 MPER bnAbs.
Published: 2021

12. Identification and characterization of the proteolytic flagellin from the common freshwater bacterium Hylemonella gracilis

Author: Peter and Traudl Engelhorn Foundation, Austrian Science Fund, Ontario Research Fund, Generalitat de Catalunya, European Commission, Japan Society for the Promotion of Science, Federal Ministry of Science, Research and Economy (Austria), Eckhard, Ulrich, Blöchl, Constantin, Jenkins, Benjamin G. L., Mansfield, Michael J., Huber, Christian G., Doxey, Andrew C., Brandstetter, Hans, Peter and Traudl Engelhorn Foundation, Austrian Science Fund, Ontario Research Fund, Generalitat de Catalunya, European Commission, Japan Society for the Promotion of Science, Federal Ministry of Science, Research and Economy (Austria), Eckhard, Ulrich, Blöchl, Constantin, Jenkins, Benjamin G. L., Mansfield, Michael J., Huber, Christian G., Doxey, Andrew C., and Brandstetter, Hans
Abstract: Flagellins are the protein components of bacterial flagella and assemble in up to 20,000 copies to form extracellular flagellar filaments. An unusual family of flagellins was recently discovered that contains a unique metalloprotease domain within its surface-exposed hypervariable region. To date, these proteolytic flagellins (also termed flagellinolysins) have only been characterized in the Gram-positive organism Clostridium haemolyticum, where flagellinolysin was shown to be proteolytically active and capable of cleaving extracellular protein substrates. The biological function of flagellinolysin and its activity in other organisms, however, remain unclear. Here, using molecular biochemistry and proteomics, we have performed an initial characterization of a novel flagellinolysin identified from Hylemonella gracilis, a Gram-negative organism originally isolated from pond water. We demonstrate that H. gracilis flagellinolysin (HgrFlaMP) is an active calcium-dependent zinc metallopeptidase and characterize its cleavage specificity profile using both trypsin and GluC-derived peptide libraries and protein substrates. Based on high-throughput degradomic assays, HgrFlaMP cleaved 784 unique peptides and displayed a cleavage site specificity similar to flagellinolysin from C. haemolyticum. Additionally, by using a set of six protein substrates, we identified 206 protein-embedded cleavage sites, further refining the substrate preference of HgrFlaMP, which is dominated by large hydrophobic amino acids in P1′, and small hydrophobic or medium-sized polar residues on the amino-terminal side of the scissile bond. Intriguingly, recombinant HgrFlaMP was also capable of cleaving full-length flagellins from another species, suggesting its potential involvement in interbacterial interactions. Our study reports the first experimentally characterized proteolytic flagellin in a Gram-negative organism, and provides new insights into flagellum-mediated enzymatic activity.
Published: 2020

13. Nanostructured Back Reflectors for Efficient Colloidal Quantum-Dot Infrared Optoelectronics

Author: Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada, National Research Foundation of Korea, Ministerio de Economía y Competitividad (España), European Research Council, Baek, Se-Woong, Molet, Pau, Choi, Min-Jae, Biondi, Margherita, Ouellette, Olivier, Fan, James, Hoogland, Sjoerd, García de Arquer, F. Pelayo, Mihi, Agustín, Sargent, Edward H., Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada, National Research Foundation of Korea, Ministerio de Economía y Competitividad (España), European Research Council, Baek, Se-Woong, Molet, Pau, Choi, Min-Jae, Biondi, Margherita, Ouellette, Olivier, Fan, James, Hoogland, Sjoerd, García de Arquer, F. Pelayo, Mihi, Agustín, and Sargent, Edward H.
Abstract: Colloidal quantum dots (CQDs) can be used to extend the response of solar cells, enabling the utilization of solar power that lies to the red of the bandgap of c‐Si and perovskites. To achieve largely complete absorption of infrared (IR) photons in CQD solids requires thicknesses on the micrometer range; however, this exceeds the typical diffusion lengths (≈300 nm) of photoexcited charges in these materials. Nanostructured metal back electrodes that grant the cell efficient IR light trapping in thin active layers with no deterioration of the electrical properties are demonstrated. Specifically, a new hole‐transport layer (HTL) is developed and directly nanostructured. Firstly, a material set to replace conventional rigid HTLs in CQD devices is developed with a moldable HTL that combines the mechanical and chemical requisites for nanoimprint lithography with the optoelectronic properties necessary to retain efficient charge extraction through an optically thick layer. The new HTL is nanostructured in a 2D lattice and conformally coated with MoO3/Ag. The photonic structure in the back electrode provides a record photoelectric conversion efficiency of 86%, beyond the Si bandgap, and a 22% higher IR power conversion efficiency compared to the best previous reports.
Published: 2019

14. Encompassing new use cases - level 3.0 of the HUPO-PSI format for molecular interactions

Author: Biotechnology and Biological Sciences Research Council (UK), European Commission, Ontario Research Fund, Canada Research Chairs, Fondation pour la Recherche Médicale, British Heart Foundation, European Research Council, Wellcome Trust, National Institutes of Health (US), Sivade (Dumousseau), M., Alonso-López, D., Ammari, M., Bradley, G., Campbell, N. H, Ceol, A., Cesareni, G., Combe, C. W., De Las Rivas, Javier, Toro, N. del, Heimbach, J., Hermjakob, H., Jurisica, I., Koch, M., Licata, L., Lovering, R. C., Lynn, D. J., Meldal, B. H. M., Micklem, G., Panni, S., Porras, P., Ricard-Blum, S., Roechert, B., Salwinski, L., Shrivastava, A., Sullivan, J., Thierry-Mieg, N., Yehudi, Y., Van Roey, K., Orchard, S., Biotechnology and Biological Sciences Research Council (UK), European Commission, Ontario Research Fund, Canada Research Chairs, Fondation pour la Recherche Médicale, British Heart Foundation, European Research Council, Wellcome Trust, National Institutes of Health (US), Sivade (Dumousseau), M., Alonso-López, D., Ammari, M., Bradley, G., Campbell, N. H, Ceol, A., Cesareni, G., Combe, C. W., De Las Rivas, Javier, Toro, N. del, Heimbach, J., Hermjakob, H., Jurisica, I., Koch, M., Licata, L., Lovering, R. C., Lynn, D. J., Meldal, B. H. M., Micklem, G., Panni, S., Porras, P., Ricard-Blum, S., Roechert, B., Salwinski, L., Shrivastava, A., Sullivan, J., Thierry-Mieg, N., Yehudi, Y., Van Roey, K., and Orchard, S.
Abstract: [Background]: Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes. [Results]: The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal. [Conclusions]: PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and dow
Published: 2018

15. Reactome pathway analysis: A high-performance in-memory approach

Author: National Institutes of Health (US), Ontario Research Fund, European Commission, Fabregat, Antonio, Sidiropoulos, Konstantinos, Viteri, Guilherme, Forner, Oscar, Marin-Garcia, Pablo, Arnau, Vicente, D’Eustachio, Peter, Stein, Lincoln, Hermjakob, Henning, National Institutes of Health (US), Ontario Research Fund, European Commission, Fabregat, Antonio, Sidiropoulos, Konstantinos, Viteri, Guilherme, Forner, Oscar, Marin-Garcia, Pablo, Arnau, Vicente, D’Eustachio, Peter, Stein, Lincoln, and Hermjakob, Henning
Abstract: [Background] Reactome aims to provide bioinformatics tools for visualisation, interpretation and analysis of pathway knowledge to support basic research, genome analysis, modelling, systems biology and education. Pathway analysis methods have a broad range of applications in physiological and biomedical research; one of the main problems, from the analysis methods performance point of view, is the constantly increasing size of the data samples., [Results] Here, we present a new high-performance in-memory implementation of the well-established over-representation analysis method. To achieve the target, the over-representation analysis method is divided in four different steps and, for each of them, specific data structures are used to improve performance and minimise the memory footprint. The first step, finding out whether an identifier in the user's sample corresponds to an entity in Reactome, is addressed using a radix tree as a lookup table. The second step, modelling the proteins, chemicals, their orthologous in other species and their composition in complexes and sets, is addressed with a graph. The third and fourth steps, that aggregate the results and calculate the statistics, are solved with a double-linked tree., [Conclusion] Through the use of highly optimised, in-memory data structures and algorithms, Reactome has achieved a stable, high performance pathway analysis service, enabling the analysis of genome-wide datasets within seconds, allowing interactive exploration and analysis of high throughput data. The proposed pathway analysis approach is available in the Reactome production web site either via the AnalysisService for programmatic access or the user submission interface integrated into the PathwayBrowser. Reactome is an open data and open source project and all of its source code, including the one described here, is available in the AnalysisTools repository in the Reactome GitHub ( https://github.com/reactome/ ).
Published: 2017

16. Tetranychus urticae mites do not mount an induced immune response against bacteria

Author: European Commission, Research Foundation - Flanders, Fundação Calouste Gulbenkian, Fundação para a Ciência e a Tecnologia (Portugal), Government of Canada, Genome Canada, Ontario Genomics Institute, Ontario Research Fund, Martins, Nelson E. [0000-0002-3923-2998], Zelé, Flore [0000-0003-2954-5488], Vontas, John [0000-0002-8704-2574], Sucena, Élio [0000-0001-8810-870X], Santos-Matos, G., Wybouw, Nicky, Martins, Nelson E., Zelé, Flore, Riga, Maria, Leitão, A.B., Vontas, John, Grbić, Miodrag, Van Leeuwen, Thomas, Magalhães, Sara, Sucena, Élio, European Commission, Research Foundation - Flanders, Fundação Calouste Gulbenkian, Fundação para a Ciência e a Tecnologia (Portugal), Government of Canada, Genome Canada, Ontario Genomics Institute, Ontario Research Fund, Martins, Nelson E. [0000-0002-3923-2998], Zelé, Flore [0000-0003-2954-5488], Vontas, John [0000-0002-8704-2574], Sucena, Élio [0000-0001-8810-870X], Santos-Matos, G., Wybouw, Nicky, Martins, Nelson E., Zelé, Flore, Riga, Maria, Leitão, A.B., Vontas, John, Grbić, Miodrag, Van Leeuwen, Thomas, Magalhães, Sara, and Sucena, Élio
Abstract: The genome of the spider mite Tetranychus urticae, a herbivore, is missing important elements of the canonical Drosophila immune pathways necessary to fight bacterial infections. However, it is not known whether spider mites can mount an immune response and survive bacterial infection. In other chelicerates, bacterial infection elicits a response mediated by immune effectors leading to the survival of infected organisms. In T. urticae, infection by either Escherichia coli or Bacillus megaterium did not elicit a response as assessed through genome-wide transcriptomic analysis. In line with this, spider mites died within days even upon injection with low doses of bacteria that are non-pathogenic to Drosophila. Moreover, bacterial populations grew exponentially inside the infected spider mites. By contrast, Sancassania berlesei, a litter-dwelling mite, controlled bacterial proliferation and resisted infections with both Gram-negative and Gram-positive bacteria lethal to T. urticae. This differential mortality between mite species was absent when mites were infected with heat-killed bacteria. Also, we found that spider mites harbour in their gut 1000-fold less bacteria than S. berlesei. We show that T. urticae has lost the capacity to mount an induced immune response against bacteria, in contrast to other mites and chelicerates but similarly to the phloem feeding aphid Acyrthosiphon pisum. Hence, our results reinforce the putative evolutionary link between ecological conditions regarding exposure to bacteria and the architecture of the immune response.
Published: 2017

17. MATI, a novel protein involved in the regulation of herbivore-associated signaling pathways

Author: Ministerio de Economía y Competitividad (España), Government of Canada, Genome Canada, Ontario Genomics Institute, Ontario Research Fund, European Commission, Santamaría, María Estrella, Martínez, Manuel, Arnáiz, Ana, Ortego, Félix, Grbić, Vojislava, Díaz, Isabel, Ministerio de Economía y Competitividad (España), Government of Canada, Genome Canada, Ontario Genomics Institute, Ontario Research Fund, European Commission, Santamaría, María Estrella, Martínez, Manuel, Arnáiz, Ana, Ortego, Félix, Grbić, Vojislava, and Díaz, Isabel
Abstract: The defense response of the plants against herbivores relies on a complex network of interconnected signaling pathways. In this work, we characterized a new key player in the response of Arabidopsis against the two-spotted spider mite Tetranychus urticae, the MATI (Mite Attack Triggered Immunity) gene. This gene was differentially induced in resistant Bla-2 strain relative to susceptible Kon Arabidopsis accessions after mite attack, suggesting a potential role in the control of spider mites. To study the MATI gene function, it has been performed a deep molecular characterization of the gene combined with feeding bioassays using modified Arabidopsis lines and phytophagous arthropods. The MATI gene belongs to a new gene family that had not been previously characterized. Biotic assays showed that it confers a high tolerance not only to T. urticae, but also to the chewing lepidopteran Spodoptera exigua. Biochemical analyses suggest that MATI encodes a protein involved in the accumulation of reducing agents upon herbivore attack to control plant redox homeostasis avoiding oxidative damage and cell death. Besides, molecular analyses demonstrated that MATI is involved in the modulation of different hormonal signaling pathways, affecting the expression of genes involved in biosynthesis and signaling of the jasmonic acid and salicylic acid hormones. The fact that MATI is also involved in defense through the modulation of the levels of photosynthetic pigments highlights the potential of MATI proteins to be exploited as biotechnological tools for pest control.
Published: 2017

18. Comparative genome-wide transcriptome analysis of vitis vinifera responses to adapted and non-adapted strains of two-spotted spider mite, tetranyhus urticae

Author: Ministerio de Economía y Competitividad (España), Research Foundation - Flanders, Government of Canada, Ontario Genomics Institute, Genome Canada, Ontario Research Fund, Díaz-Riquelme, José, Rioja, Cristina, Torres-Pérez, Rafael, Grimplet, Jérôme, Carbonell-Bejerano, Pablo, Martínez-Zapater, José M., Grbić, Miodrag, Grbić, Vojislava, Ministerio de Economía y Competitividad (España), Research Foundation - Flanders, Government of Canada, Ontario Genomics Institute, Genome Canada, Ontario Research Fund, Díaz-Riquelme, José, Rioja, Cristina, Torres-Pérez, Rafael, Grimplet, Jérôme, Carbonell-Bejerano, Pablo, Martínez-Zapater, José M., Grbić, Miodrag, and Grbić, Vojislava
Abstract: [Background] The two-spotted spider mite, Tetranychus urticae, is an extreme generalist plant pest. Even though mites can feed on many plant species, local mite populations form host races that do not perform equally well on all potential hosts. An acquisition of the ability to evade plant defenses is fundamental for mite's ability to use a particular plant as a host. Thus, understanding the interactions between the plant and mites with different host adaptation status allows the identification of functional plant defenses and ways mites can evolve to avoid them., [Results] The grapevine genome-wide transcriptional responses to spider mite strains that are non-adapted and adapted to grapevine as a host were examined. Comparative transcriptome analysis of grapevine responses to these mite strains identified the existence of weak responses induced by the feeding of the non-adapted strain. In contrast, strong but ineffective induced defenses were triggered upon feeding of the adapted strain. A comparative meta-analysis of Arabidopsis, tomato and grapevine responses to mite feeding identified a core of 36 highly conserved genes involved in the perception, regulation and metabolism that were commonly induced in all three species by mite herbivory., [Conclusions] This study describes the genome-wide grapevine transcriptional responses to herbivory of mite strains that differ in their ability to use grapevine as a host. It raises hypotheses whose testing will lead to our understanding of grapevine defenses and mite adaptations to them.
Published: 2016

19. Digestive proteases in bodies and faeces of the two-spotted spider mite, Tetranychus urticae

Author: Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), Genome Canada, Ontario Genomics Institute, Ontario Research Fund, Santamaría, María Estrella, González-Cabrera, Joel, Martínez, Manuel, Grbić, Vojislava, Castañera, Pedro, Díaz, Isabel, Ortego, Félix, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), Genome Canada, Ontario Genomics Institute, Ontario Research Fund, Santamaría, María Estrella, González-Cabrera, Joel, Martínez, Manuel, Grbić, Vojislava, Castañera, Pedro, Díaz, Isabel, and Ortego, Félix
Abstract: Digestive proteases of the phytophagous mite Tetranychus urticae have been characterised by comparing their activity in body and faecal extracts. Aspartyl, cathepsin B- and L-like and legumain activities were detected in both mite bodies and faeces, with a specific activity of aspartyl and cathepsin L-like proteases about 5- and 2-fold higher, respectively, in mite faeces than in bodies. In general, all these activities were maintained independently of the host plant where the mites were reared (bean, tomato or maize). Remarkably, this is the first report in a phytophagous mite of legumain-like activity, which was characterised for its ability to hydrolyse the specific substrate Z-VAN-AMC, its activation by DTT and inhibition by IAA but not by E-64. Gel free nanoLC–nanoESI-QTOF MS/MS proteomic analysis of mite faeces resulted in the identification of four cathepsins L and one aspartyl protease (from a total of the 29 cathepsins L, 27 cathepsins B, 19 legumains and two aspartyl protease genes identified the genome of this species). Gene expression analysis reveals that four cathepsins L and the aspartyl protease identified in the mite faeces, but also two cathepsins B and two legumains that were not detected in the faeces, were expressed at high levels in the spider mite feeding stages (larvae, nymphs and adults) relative to embryos. Taken together, these results indicate a digestive role for cysteine and aspartyl proteases in T. urticae. The expression of the cathepsins B and L, legumains and aspartyl protease genes analysed in our study increased in female adults after feeding on Arabidopsis plants over-expressing the HvCPI-6 cystatin, that specifically targets cathepsins B and L, or the CMe trypsin inhibitor that targets serine proteases. This unspecific response suggests that in addition to compensation for inhibitor-targeted enzymes, the increase in the expression of digestive proteases in T. urticae may act as a first barrier against ingested plant defensive pr
Published: 2015

20. A proteome-scale map of the human interactome network

Author: Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Ontario Research Fund, Avon Foundation for Women, Government of Canada, Krembil Foundation, European Commission, Research Foundation - Flanders, European Research Council, Ghent University, EMBO, Dana Foundation, Fonds de la Recherche Scientifique (Fédération Wallonie-Bruxelles), Celgene, National Cancer Institute (US), National Institutes of Health (US), National Science Foundation (US), National Human Genome Research Institute (US), Rolland, Thomas, Fontanillo, Celia, De Las Rivas, Javier, Vidal, Marc, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Ontario Research Fund, Avon Foundation for Women, Government of Canada, Krembil Foundation, European Commission, Research Foundation - Flanders, European Research Council, Ghent University, EMBO, Dana Foundation, Fonds de la Recherche Scientifique (Fédération Wallonie-Bruxelles), Celgene, National Cancer Institute (US), National Institutes of Health (US), National Science Foundation (US), National Human Genome Research Institute (US), Rolland, Thomas, Fontanillo, Celia, De Las Rivas, Javier, and Vidal, Marc
Abstract: Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ∼14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ∼30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a >broader> human interactome network than currently appreciated. The map also uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help >connect the dots> of the genomic revolution.
Published: 2014

21. The influence of landscape on gene flow in the eastern massasauga rattlesnake (Sistrurus c. catenatus): insight from computer simulations

Author: Natural Sciences and Engineering Research Council of Canada, University of Guelph, U.S. Fisheries and Wildlife Service, Ontario Ministry of Natural Resources and Forestry, World Wildlife Fund, National Geographic Society, Ontario Research Fund, Dileo, Michelle F., Rouse, Jeremy D., Dávila, José A., Lougheed, Stephen C., Natural Sciences and Engineering Research Council of Canada, University of Guelph, U.S. Fisheries and Wildlife Service, Ontario Ministry of Natural Resources and Forestry, World Wildlife Fund, National Geographic Society, Ontario Research Fund, Dileo, Michelle F., Rouse, Jeremy D., Dávila, José A., and Lougheed, Stephen C.
Abstract: Understanding how gene flow shapes contemporary population structure requires the explicit consideration of landscape composition and configuration. New landscape genetic approaches allow us to link such heterogeneity to gene flow within and among populations. However, the attribution of cause is difficult when landscape features are spatially correlated, or when genetic patterns reflect past events. We use spatial Bayesian clustering and landscape resistance analysis to identify the landscape features that influence gene flow across two regional populations of the eastern massasauga rattlesnake, Sistrurus c. catenatus. Based on spatially explicit simulations, we inferred how habitat distribution modulates gene flow and attempted to disentangle the effects of spatially confounded landscape features. We found genetic clustering across one regional landscape but not the other, and also local differences in the effect of landscape on gene flow. Beyond the effects of isolation-by-distance, water bodies appear to underlie genetic differentiation among individuals in one regional population. Significant effects of roads were additionally detected locally, but these effects are possibly confounded with the signal of water bodies. In contrast, we found no signal of isolation-by-distance or landscape effects on genetic structure in the other regional population. Our simulations imply that these local differences have arisen as a result of differences in population density or tendencies for juvenile rather than adult dispersal. Importantly, our simulations also demonstrate that the ability to detect the consequences of contemporary anthropogenic landscape features (e.g. roads) on gene flow may be compromised when long-standing natural features (e.g. water bodies) co-exist on the landscape.
Published: 2013

22. Reduced El Niño variability in the mid-Pliocene according to the PlioMIP2 ensemble

Author: Sathyanadh, Anusha, Monteil, Guillaume, Scholze, Marko, Klosterhalfen, Anne, Laudon, Hjalmar, Wu, Zhendong, Gerbig, Christoph, Peters, Wouter, Bastrikov, Vladislav, Nilsson, Mats, Peichl, Matthias, Oldeman, Arthur, Baatsen, Michiel, von Der Heydt, Anna, Dijkstra, Henk, Tindall, Julia, Abe-Ouchi, Ayako, Booth, Alice, Brady, Esther, Chan, Wing-Le, Chandan, Deepak, Chandler, Mark, Contoux, Camille, Feng, Ran, Guo, Chuncheng, Haywood, Alan, Hunter, Stephen, Kamae, Youichi, Li, Qiang, Li, Xiangyu, Lohmann, Gerrit, Lunt, Daniel, Nisancioglu, Kerim, Otto-Bliesner, Bette, Peltier, W, Pontes, Gabriel, Ramstein, Gilles, Sohl, Linda, Stepanek, Christian, Tan, Ning, Zhang, Qiong, Zhang, Zhongshi, Wainer, Ilana, Williams, Charles, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), 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), Modélisation du climat (CLIM), 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), This research has been supported by the Netherlands Earth System Science Centre (OCW (grant no. 024.002.001)), The work by Arthur M. Oldeman, Anna S. von der Heydt, Michiel L. J. Baatsen and Henk A. Dijkstra was carried out under the program of the Netherlands Earth System Science Centre (NESSC), financially supported by the Ministry of Education, Culture and Science (OCW grant no. 024.002.001). Simulations with CCSM4-Utr were performed at the SURFsara Dutch national computing facilities and were sponsored by NWO-EW (Netherlands Organisation for Scientific Research, Exact Sciences) (project no. 17189).Alan M. Haywood, Julia C. Tindall and Stephen J. Hunter acknowledge the FP7 Ideas programme from the European Research Council (grant no. PLIO-ESS, 278636), the Past Earth Network (EPSRC grant no. EP/M008.363/1) and the University of Leeds Advanced Research Computing service. Julia C. Tindall was also supported through the Centre for Environmental Modelling and Computation (CEMAC), University of Leeds.Bette L. Otto-Bliesner, Esther C. Brady and Ran Feng acknowledge that material for their participation is based upon work supported by the National Center for Atmospheric Research, which is a major facility sponsored by the National Science Foundation (NSF) (cooperative agreement no. 1852977 and NSF OPP grant no. 1418411). Ran Feng is also supported by NSF grant no. 1903650. The CESM project is supported primarily by the National Science Foundation. Computing and data storage resources, including the Cheyenne supercomputer (https://doi.org/10.5065/D6RX99HX), were provided by the Computational and Information Systems Laboratory (CISL) at NCAR. NCAR is sponsored by the National Science Foundation.Ning Tan, Camille Contoux and Gilles Ramstein were granted access to the HPC resources of TGCC under the allocations 2016-A0030107732, 2017-R0040110492 and 2018-R0040110492 (gencmip6) and 2019-A0050102212 (gen2212) provided by GENCI. The IPSL-CM6 team of the IPSL Climate Modelling Centre (https://cmc.ipsl.fr/, last access: 28 April 2021) is acknowledged for having developed, tested, evaluated and tuned the IPSL climate model, as well as having performed and published the CMIP6 experiments.Christian Stepanek acknowledges funding from the Helmholtz Climate Initiative REKLIM. Christian Stepanek and Gerrit Lohmann acknowledge funding via the Alfred Wegener Institute’s research programme Marine, Coastal and Polar Systems.Qiong Zhang acknowledges support from the Swedish Research Council (2013-06476 and 2017-04232). Simulations with EC-Earth were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Centre (NSC).Wing-Le Chan and Ayako Abe-Ouchi acknowledge funding from JSPS (KAKENHI grant no. 17H06104 and MEXT KAKENHI grant no. 17H06323). Their simulations with MIROC4m were performed on the Earth Simulator at JAMSTEC, Yokohama, Japan.W. Richard Peltier and Deepak Chandan wish to acknowledge that data they have contributed from the CCSM4-UoT model was produced with the support of Canadian NSERC Discovery Grant A9627 t WRP, and they wish to acknowledge the support of the SciNet HPC Consortium for providing computing facilities. SciNet is funded by the Canada Foundation for Innovation under the auspices of Compute Canada, the Government of Ontario, the Ontario Research Fund – Research Excellence and the University of Toronto.Zhongshi Zhang and Xiangyu Li acknowledge financial support from the National Natural Science Foundation of China (grant no. 42005042), the China Scholarship Council (201804910023) and the China Postdoctoral Science Foundation (project no. 2015M581154). The NorESM simulations benefitted from resources provided by UNINETT Sigma2 – the National Infrastructure for High Performance Computing and Data Storage in Norway.Charles J. R. Williams and Dan Lunt are thankful for NERC grant NE/P01903X/1 and the NEXCS High Performance Computing facility funded by the Natural Environment Research Council and delivered by the Met Office.Gabriel M. Pontes and Ilana Wainer acknowledge the São Paulo Research Foundation (FAPESP 2016/23670-0)., 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)-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), Swedish University of Agricultural Sciences (SLU), Department of Physical Geography and Ecosystem Science [Lund], Lund University [Lund], Max Planck Institute for Biogeochemistry (MPI-BGC), Max-Planck-Gesellschaft, Meteorology and Air Quality Department [Wageningen] (MAQ), Wageningen University and Research [Wageningen] (WUR), and The work by Arthur M. Oldeman, Anna S. von der Heydt, Michiel L. J. Baatsen and Henk A. Dijkstra was carried out under the program of the Netherlands Earth System Science Centre (NESSC), financially supported by the Ministry of Education, Culture and Science (OCW grant no. 024.002.001). Simulations with CCSM4-Utr were performed at the SURFsara Dutch national computing facilities and were sponsored by NWO-EW (Netherlands Organisation for Scientific Research, Exact Sciences) (project no. 17189).Alan M. Haywood, Julia C. Tindall and Stephen J. Hunter acknowledge the FP7 Ideas programme from the European Research Council (grant no. PLIO-ESS, 278636), the Past Earth Network (EPSRC grant no. EP/M008.363/1) and the University of Leeds Advanced Research Computing service. Julia C. Tindall was also supported through the Centre for Environmental Modelling and Computation (CEMAC), University of Leeds.Bette L. Otto-Bliesner, Esther C. Brady and Ran Feng acknowledge that material for their participation is based upon work supported by the National Center for Atmospheric Research, which is a major facility sponsored by the National Science Foundation (NSF) (cooperative agreement no. 1852977 and NSF OPP grant no. 1418411). Ran Feng is also supported by NSF grant no. 1903650. The CESM project is supported primarily by the National Science Foundation. Computing and data storage resources, including the Cheyenne supercomputer (https://doi.org/10.5065/D6RX99HX), were provided by the Computational and Information Systems Laboratory (CISL) NCAR . NCAR is sponsored by the National Science Foundation.Ning Tan, Camille Contoux and Gilles Ramstein were granted access to the HPC resources of TGCC under the allocations 2016-A0030107732, 2017-R0040110492 and 2018-R0040110492 (gencmip6) and 2019-A0050102212 (gen2212) provided by GENCI. The IPSL-CM6 team of the IPSL Climate Modelling Centre (https://cmc.ipsl.fr/, last access: 28 April 2021) is acknowledged for having developed, tested, evaluated and tuned the IPSL climate model, as well as having performed and published the CMIP6 experiments.Christian Stepanek acknowledges funding from the Helmholtz Climate Initiative REKLIM. Christian Stepanek and Gerrit Lohmann acknowledge funding via the Alfred Wegener Institute’s research programme Marine, Coastal and Polar Systems.Qiong Zhang acknowledges support from the Swedish Research Council (2013-06476 and 2017-04232). Simulations with EC-Earth were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Centre (NSC).Wing-Le Chan and Ayako Abe-Ouchi acknowledge funding from JSPS (KAKENHI grant no. 17H06104 and MEXT KAKENHI grant no. 17H06323). Their simulations with MIROC4m were performed on the Earth Simulator at JAMSTEC, Yokohama, Japan.W. Richard Peltier and Deepak Chandan wish to acknowledge that data they have contributed from the CCSM4-UoT model was produced with the support of Canadian NSERC Discovery Grant A9627 t WRP, and they wish to acknowledge the support of the SciNet HPC Consortium for providing computing facilities. SciNet is funded by the Canada Foundation for Innovation under the auspices of Compute Canada, the Government of Ontario, the Ontario Research Fund – Research Excellence and the University of Toronto.Zhongshi Zhang and Xiangyu Li acknowledge financial support from the National Natural Science Foundation of China (grant no. 42005042), the China Scholarship Council (201804910023) and the China Postdoctoral Science Foundation (project no. 2015M581154). The NorESM simulations benefitted from resources provided by UNINETT Sigma2 – the National Infrastructure for High Performance Computing and Data Storage in Norway.Charles J. R. Williams and Dan Lunt are thankful for NERC grant NE/P01903X/1 and the NEXCS High Performance Computing facility funded by the Natural Environment Research Council and delivered by the Met Office.Gabriel M. Pontes and Ilana Wainer acknowledge the São Paulo Research Foundation (FAPESP 2016/23670-0).
Subjects: 010504 meteorology & atmospheric sciences, Stratigraphy, 0207 environmental engineering, Empirical orthogonal functions, 02 engineering and technology, 01 natural sciences, Environmental protection, Environmental pollution, TD169-171.8, GE1-350, 14. Life underwater, 020701 environmental engineering, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, 0105 earth and related environmental sciences, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Global and Planetary Change, Spatial structure, Palaeontology, Ensemble average, Paleontology, Environmental sciences, Sea surface temperature, Amplitude, El Niño Southern Oscillation, El Niño, TD172-193.5, 13. Climate action, Climatology, Environmental science, Climate model, OCEANOGRAFIA
Abstract: The mid-Pliocene warm period (3.264–3.025 Ma) is the most recent geological period during which atmospheric CO2 levels were similar to recent historical values (∼400 ppm). Several proxy reconstructions for the mid-Pliocene show highly reduced zonal sea surface temperature (SST) gradients in the tropical Pacific Ocean, indicating an El Niño-like mean state. However, past modelling studies do not show these highly reduced gradients. Efforts to understand mid-Pliocene climate dynamics have led to the Pliocene Model Intercomparison Project (PlioMIP). Results from the first phase (PlioMIP1) showed clear El Niño variability (albeit significantly reduced) and did not show the greatly reduced time-mean zonal SST gradient suggested by some of the proxies. In this work, we study El Niño–Southern Oscillation (ENSO) variability in the PlioMIP2 ensemble, which consists of additional global coupled climate models and updated boundary conditions compared to PlioMIP1. We quantify ENSO amplitude, period, spatial structure and “flavour”, as well as the tropical Pacific annual mean state in mid-Pliocene and pre-industrial simulations. Results show a reduced ENSO amplitude in the model-ensemble mean (−24 %) with respect to the pre-industrial, with 15 out of 17 individual models showing such a reduction. Furthermore, the spectral power of this variability considerably decreases in the 3–4-year band. The spatial structure of the dominant empirical orthogonal function shows no particular change in the patterns of tropical Pacific variability in the model-ensemble mean, compared to the pre-industrial. Although the time-mean zonal SST gradient in the equatorial Pacific decreases for 14 out of 17 models (0.2 ∘C reduction in the ensemble mean), there does not seem to be a correlation with the decrease in ENSO amplitude. The models showing the most “El Niño-like” mean state changes show a similar ENSO amplitude to that in the pre-industrial reference, while models showing more “La Niña-like” mean state changes generally show a large reduction in ENSO variability. The PlioMIP2 results show a reasonable agreement with both time-mean proxies indicating a reduced zonal SST gradient and reconstructions indicating a reduced, or similar, ENSO variability.
Published: 2021

23. Stalled developmental programs at the root of pediatric brain tumors

Author: Nicolas De Jay, Gustavo Turecki, Florence M.G. Cavalli, Yixing Hu, Alexis Blanchet-Cohen, Corina Nagy, W. Todd Farmer, Andréa Allaire, Hervé Sartelet, Louis Crevier, Roy W. R. Dudley, Jiannis Ragoussis, Marie Coutelier, Maxime Richer, Maria C. Vladoiu, Livia Garzia, Michael D. Taylor, Claudia L. Kleinman, Valerie Larouche, Jean Monlong, Jeffrey Atkinson, Nada Jabado, Guillaume Bourque, Laura K. Donovan, Keith K. Murai, Benjamin Ellezam, Pierre-Eric Lutz, Jean-Pierre Farmer, Brice Poreau, Leonie G. Mikael, Alexander G. Weil, Mariella G. Filbin, Steven Hébert, Selin Jessa, Santiago Costantino, Steffen Albrecht, Damien Faury, Peter B. Dirks, Brian Krug, Melissa K. McConechy, McGill University = Université McGill [Montréal, Canada], Lady Davis Institute for Medical Research [Montréal], McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, The Hospital for sick children [Toronto] (SickKids), McGill University Health Center [Montreal] (MUHC), Centre Hospitalier Universitaire [Grenoble] (CHU), Santa Cruz Genomics Institute, University of California [Santa Cruz] (UCSC), University of California-University of California, Zebralog GmbH & Co. KG, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry [Montréal], Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montreal General Hospital, McGill University and Genome Quebec Innovation Centre, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], This work was supported by funding from: a Large-Scale Applied Research Project grant from Genome Quebec, Genome Canada, the Government of Canada and the Ministère de l'Économie, de la Science et de l’Innovation du Québec, with the support of the Ontario Research Fund through funding provided by the Government of Ontario to N.J., M.D.T., C.L.K., P.B.D., G.B., J.R. and L.G., the Canadian Institutes for Health Research (CIHR grant nos. PJT-156086, to C.L.K., and MOP-286756 and FDN-154307, to N.J.), the US National Institutes of Health (NIH grant nos. P01-CA196539, to N.J., R01CA148699 and R01CA159859, to M.D.T.), the Canadian Cancer Society (CCSRI grant no. 705182), NSERC (grant no. RGPIN-2016-04911) and the Fonds de Recherche du Québec en Santé (FRQS) salary award to C.L.K., National Sciences and Engineering Research Council (grant no. NSERC-448167-2013) and FRQS (grant no. 25348) to G.B., CFI Leaders Opportunity Fund (grant nos. 32557, to J.R., and 33902, to C.L.K.), Genome Canada Science Technology Innovation Centre, Compute Canada Resource Allocation Project (grant no. WST-164-AB) and Genome Canada Genome Innovation Node (grant no. 244819) to J.R., and and the Fondation Charles-Bruneau. Data analyses were enabled by computer and storage resources provided by Compute Canada and Calcul Québec. N.J. is a member of the Penny Cole Laboratory and the recipient of a Chercheur Boursier, Chaire de Recherche Award from the FRQS. This work was performed within the context of the International Childhood Astrocytoma Integrated Genomic and Epigenomic (ICHANGE) consortium, and the Stand Up to Cancer (SU2C) Canada Cancer Stem Cell Dream Team Research Funding (grant no. SU2C-AACR-DT-19-15, to M.D.T. and N.J.) and SU2C St. Baldrick’s Pediatric Dream Team Translational Research Grant (no. SU2C-AACR-DT1113, to M.D.T.), with funding from Genome Canada and Genome Quebec. Stand Up to Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. M.D.T. is supported by The Pediatric Brain Tumour Foundation, The Canadian Institutes of Health Research, The Cure Search Foundation, b.r.a.i.n.child, Meagan’s Walk, SWIFTY Foundation, Genome Canada, Genome BC, Genome Quebec, the Ontario Research Fund, Worldwide Cancer Research, V-Foundation for Cancer Research, Cancer Research UK Brain Tumour Award, Canadian Cancer Society Research Institute Impact grant and the Garron Family Chair in Childhood Cancer Research at the Hospital for Sick Children and the University of Toronto. S.J. is supported by a fellowship from CIHR. A.B.-C. is supported by a fellowship from FRQS and TD/LDI. N.D.J. is a recipient of a fellowship from FRQS and RMGA. M.K.M. is funded by a CIHR Banting postdoctoral fellowship. We thank K. Mann, S. Spira and J. Di Noia for critical reading of the manuscript, and S. Krumholtz for graphical editing of figures. We are especially grateful for the generous philanthropic donations of the Fondation Charles-Bruneau, and the Kat D-DIPG, Poppies for Irina and We Love You Connie Foundations.
Subjects: [SDV]Life Sciences [q-bio], Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, Transcriptome, Mice, 03 medical and health sciences, Nerve Fibers, Prosencephalon, 0302 clinical medicine, Single-cell analysis, Cell Line, Tumor, Genetics, medicine, Animals, Humans, Progenitor cell, Rhabdoid Tumor, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Neuroectoderm, Brain Neoplasms, Wnt signaling pathway, Brain, Gene Expression Regulation, Developmental, Infant, Neoplasms, Germ Cell and Embryonal, 3. Good health, medicine.anatomical_structure, Forebrain, Single-Cell Analysis, Neuroscience, 030217 neurology & neurosurgery, Medulloblastoma
Abstract: International audience; Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics. Projection of bulk tumor transcriptomes onto this dataset shows that WNT medulloblastomas match the rhombic lip-derived mossy fiber neuronal lineage and embryonal tumors with multilayered rosettes fully recapitulate a neuronal lineage, while group 2a/b atypical teratoid/rhabdoid tumors may originate outside the neuroectoderm. Importantly, single-cell tumor profiles reveal highly defined cell hierarchies that mirror transcriptional programs of the corresponding normal lineages. Our findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.
Published: 2019

24. Active and adaptive Legionella CRISPR‐Cas reveals a recurrent challenge to the pathogen

Author: Ken Dewar, Jessica Wasserscheid, Carmen Pelaz, Alexander W. Ensminger, Joseph Bondy-Denomy, Chitong Rao, Cyril Guyard, University of Toronto, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, Ontario Research Fund, University of Toronto (Cánada), Natural Sciences and Engineering Research Council (Canada), and Ontario Research Fund - Research Excellence (ORF-RE)
Subjects: 0301 basic medicine, 030106 microbiology, Immunology, Genomics, Microbiology, Legionella pneumophila, Genome, Conserved sequence, Evolution, Molecular, Bacteriophage, 03 medical and health sciences, Plasmid, Virology, CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats, Gene, Conserved Sequence, Genetics, Acanthamoeba castellanii, Microbial Viability, Base Sequence, biology, Sequence Analysis, DNA, biology.organism_classification, Editor's Choice, Genes, Bacterial, Host-Pathogen Interactions
Abstract: Clustered regularly interspaced short palindromic repeats with CRISPR-associated gene (CRISPR-Cas) systems are widely recognized as critical genome defense systems that protect microbes from external threats such as bacteriophage infection. Several isolates of the intracellular pathogen Legionella pneumophila possess multiple CRISPR-Cas systems (type I-C, type I-F and type II-B), yet the targets of these systems remain unknown. With the recent observation that at least one of these systems (II-B) plays a non-canonical role in supporting intracellular replication, the possibility remained that these systems are vestigial genome defense systems co-opted for other purposes. Our data indicate that this is not the case. Using an established plasmid transformation assay, we demonstrate that type I-C, I-F and II-B CRISPR-Cas provide protection against spacer targets. We observe efficient laboratory acquisition of new spacers under 'priming' conditions, in which initially incomplete target elimination leads to the generation of new spacers and ultimate loss of the invasive DNA. Critically, we identify the first known target of L. pneumophila CRISPR-Cas: a 30 kb episome of unknown function whose interbacterial transfer is guarded against by CRISPR-Cas. We provide evidence that the element can subvert CRISPR-Cas by mutating its targeted sequences - but that primed spacer acquisition may limit this mechanism of escape. Rather than generally impinging on bacterial fitness, this element drives a host specialization event - with improved fitness in Acanthamoeba but a reduced ability to replicate in other hosts and conditions. These observations add to a growing body of evidence that host range restriction can serve as an existential threat to L. pneumophila in the wild. This work was supported by the University of Toronto and operating grants awarded to AWE by the Canadian Institutes of Health Research (MOP‐133406) and the Natural Sciences and Engineering Research Council of Canada (RGPIN‐2014‐03641), along with an infrastructure grant awarded to AWE from the Canada Foundation for Innovation and the Ontario Research Fund (30364). The authors have no conflict of interest to declare. Sí
Published: 2016

25. Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells

Author: Simoun Icho, Edurne Rujas, Krithika Muthuraman, John Tam, Huazhu Liang, Shelby Landreth, Mingmin Liao, Darryl Falzarano, Jean-Philippe Julien, Roman A. Melnyk, George Mason University, Thistledown Foundation, European Commission, Canadian Institute for Advanced Research, Canada Research Chairs, Ontario Research Fund, and Canada Foundation for Innovation
Subjects: SARS, Pharmacology, Vacuolar Proton-Translocating ATPases, SARS-CoV-2, Serine Endopeptidases, V-ATPase, virus, Endosomes, Virus Internalization, COVID-19 Drug Treatment, Virus, Infectious Diseases, Spike Glycoprotein, Coronavirus, Endosome, Humans, Pharmacology (medical), endosome, TMPRSS2
Abstract: An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the cell-surface route or the endosomal route, respectively. In cells expressing TMPRSS2, inhibiting endosomal proteases using nonspecific cathepsin inhibitors such as E64d or lysosomotropic compounds such as hydroxychloroquine fails to prevent viral entry, suggesting that the endosomal route of entry is unimportant; however, mechanism-based toxicities and poor efficacy of these compounds confound our understanding of the importance of the endosomal route of entry. Here, to identify better pharmacological agents to elucidate the role of the endosomal route of entry, we profiled a panel of molecules identified through a high-throughput screen that inhibit endosomal pH and/or maturation through different mechanisms. Among the three distinct classes of inhibitors, we found that inhibiting vacuolar-ATPase using the macrolide bafilomycin A1 was the only agent able to potently block viral entry without associated cellular toxicity. Using both pseudotyped and authentic virus, we showed that bafilomycin A1 inhibits SARS-CoV-2 infection both in the absence and presence of TMPRSS2. Moreover, synergy was observed upon combining bafilomycin A1 with Camostat, a TMPRSS2 inhibitor, in neutralizing SARS-CoV-2 entry into TMPRSS2-expressing cells. Overall, this study highlights the importance of the endosomal route of entry for SARS-CoV-2 and provides a rationale for the generation of successful intervention strategies against this virus that combine inhibitors of both entry pathways., This research was funded (S.I. and R.A.M.) from Fast Grants, part of the Emergent Ventures Program at the Mercatus Centre at George Mason University, with support from Thistledown Foundation. This research was supported by the European Union’s Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant 790012 (E.R.). This work was further supported by the CIFAR Azrieli Global Scholar program (J.-P.J.), the Ontario Early Researcher Award program (J.-P.J.) and the Canada Research Chair program (J.-P.J.). The Synergy Neo2 Multi-Mode Assay Microplate Reader instrument was accessed at the Structural and Biophysical Core Facility, The Hospital for Sick Children, supported by the Canada Foundation for Innovation and Ontario Research Fund.
Published: 2022

26. National-scale changes in crop diversity through the Anthropocene

Author: Marney E. Isaac, Denis Vile, Marc W. Cadotte, Rachel O. Mariani, Adam R. Martin, Cyrille Violle, University of Toronto [Scarborough, Canada], Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Canada Foundation for Innovation, and the Ontario Research Fund., European Union and the Region Languedoc-Roussillon 'Chercheur d’Avenir' (FEDER FSE IEJ 2014–2020, Grant Project 'APSEVIR')., University of Toronto Scarborough’s (UTSC) Vice Principal Research Office in support of UTSC’s Centre for Agroecosystems Research, European Project: 639706,H2020,ERC-2014-STG,CONSTRAINTS(2015), University of Toronto at Scarborough, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, 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), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Environmental change, 010504 meteorology & atmospheric sciences, Science, 0211 other engineering and technologies, 02 engineering and technology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, 01 natural sciences, Article, Crop, 03 medical and health sciences, Anthropocene, 030304 developmental biology, 0105 earth and related environmental sciences, 2. Zero hunger, 0303 health sciences, Multidisciplinary, Resistance (ecology), business.industry, Agroforestry, 021107 urban & regional planning, Biodiversity, Geography, Sustainability, Crop diversity, Agriculture, Medicine, Species evenness, Species richness, business, Agroecology
Abstract: Expansion of crops beyond their centres of domestication is a defining feature of the Anthropocene Epoch. This process has fundamentally altered the diversity of croplands, with likely consequences for the ecological functioning and socio-economic stability of agriculture under environmental change. While changes in crop diversity through the Anthropocene have been quantified at large spatial scales, the patterns, drivers, and consequences of change in crop diversity and biogeography at national-scales remains less explored. We use production data on 339 crops, grown in over 150 countries from 1961 to 2017, to quantify changes in country-level crop richness and evenness. Virtually all countries globally have experienced significant increases in crop richness since 1961, with the early 1980s marking a clear onset of a ~ 9-year period of increase in crop richness in countries worldwide. While these changes have increased the similarity of diversity of croplands among countries, only half of countries experienced increases in crop evenness through time. Ubiquitous increases in crop richness within nearly all countries between 1980 and 2000 are a unique biogeographical feature of the Anthropocene. At the same time, we detected opposing changes in crop evenness, and only modest signatures of increased homogenization of croplands among countries. Therefore context-dependent and, at least, national-scale assessments are needed to understand and predict how changes in crop diversity influence agricultural resistance and resilience to environmental change.
Published: 2021

27. Identification and characterization of the proteolytic flagellin from the common freshwater bacterium Hylemonella gracilis

Author: Ulrich Eckhard, Constantin Blöchl, Benjamin G. L. Jenkins, Michael J. Mansfield, Christian G. Huber, Andrew C. Doxey, Hans Brandstetter, Peter and Traudl Engelhorn Foundation, Austrian Science Fund, Ontario Research Fund, Generalitat de Catalunya, European Commission, Japan Society for the Promotion of Science, and Federal Ministry of Science, Research and Economy (Austria)
Subjects: Proteomics, Proteome, lcsh:R, lcsh:Medicine, Fresh Water, Proteases, Microbiology, Article, Substrate Specificity, Comamonadaceae, Open Reading Frames, Proteolysis, lcsh:Q, Amino Acids, lcsh:Science, Water Microbiology, Genome, Bacterial, Phylogeny, Flagellin
Abstract: © The Author(s) 2020., Flagellins are the protein components of bacterial flagella and assemble in up to 20,000 copies to form extracellular flagellar filaments. An unusual family of flagellins was recently discovered that contains a unique metalloprotease domain within its surface-exposed hypervariable region. To date, these proteolytic flagellins (also termed flagellinolysins) have only been characterized in the Gram-positive organism Clostridium haemolyticum, where flagellinolysin was shown to be proteolytically active and capable of cleaving extracellular protein substrates. The biological function of flagellinolysin and its activity in other organisms, however, remain unclear. Here, using molecular biochemistry and proteomics, we have performed an initial characterization of a novel flagellinolysin identified from Hylemonella gracilis, a Gram-negative organism originally isolated from pond water. We demonstrate that H. gracilis flagellinolysin (HgrFlaMP) is an active calcium-dependent zinc metallopeptidase and characterize its cleavage specificity profile using both trypsin and GluC-derived peptide libraries and protein substrates. Based on high-throughput degradomic assays, HgrFlaMP cleaved 784 unique peptides and displayed a cleavage site specificity similar to flagellinolysin from C. haemolyticum. Additionally, by using a set of six protein substrates, we identified 206 protein-embedded cleavage sites, further refining the substrate preference of HgrFlaMP, which is dominated by large hydrophobic amino acids in P1′, and small hydrophobic or medium-sized polar residues on the amino-terminal side of the scissile bond. Intriguingly, recombinant HgrFlaMP was also capable of cleaving full-length flagellins from another species, suggesting its potential involvement in interbacterial interactions. Our study reports the first experimentally characterized proteolytic flagellin in a Gram-negative organism, and provides new insights into flagellum-mediated enzymatic activity., This study was supported by a post-doctoral fellowship from the Peter and Traudl Engelhorn Foundation (U.E.) and the Austrian Science Fund (FWF, project number: W1213; H.B., C.B. and C.G.H.). A.C.D. is supported by an Ontario Early Research Award and by the Natural Sciences and Engineering Research Council of Canada (NSERC) through a Discovery Grant. U.E. is currently supported by the Beatriu de Pinós Program (2020-2023), funded by the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 program of research and innovation of the European Union under the Marie Sklodowska-Curie COFUND actions. Michael Mansfeld gratefully acknowledges funding from the Japan Society for the Promotion of Science as a JSPS International Research Fellow (Luscombe Unit, Okinawa Institute of Science and Technology Graduate University), and Michael Kohlberger is acknowledged for technical assistance during PICS library preparations. Financial support for the Christian Doppler Laboratory for Biosimilar Characterization by the Austrian Federal Ministry of Science, Research, and Economy and by a Start-up Grant of the State of Salzburg is gratefully acknowledged.
Published: 2020

28. Comparing the Effects of Docosahexaenoic and Eicosapentaenoic Acids on Inflammation Markers Using Pairwise and Network Meta-Analyses of Randomized Controlled Trials

Author: Cécile Vors, Benoît Lamarche, Tauseef Khan, Sonia Blanco Mejia, Janie Allaire, John L. Sievenpiper, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), STELA Dairy Research Center [Institute of Nutrition anf Functional Foods - University of Laval], Université Laval [Québec] (ULaval), University of Toronto, St. Michael's Hospital, European Marie Sklodowska-Curie ActionsCanadian Institutes of Health Research (CIHR)Fonds de recherche du Quebec-Sante (FRQ-S)Canadian Institutes of Health Research (CIHR)129920Appeared in source as:Canadian Institutes of Health Research through the Canada-wide Human Nutrition Trialists'Network (NTN)Canada Foundation for InnovationMinistry of Research and Innovation's Ontario Research Fund (ORF)PSI Graham Farquharson Knowledge Translation FellowshipDiabetes Canada Clinician Scientist AwardCanadian Institutes of Health Research (CIHR)Appeared in source as:CIHR INMD/CNS New Investigator Partnership PrizeBanting and Best Diabetes Centre Sun Life Financial New Investigator Award, CarMeN, laboratoire, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Inflammation, Review, Cochrane Library, Systemic inflammation, Gastroenterology, law.invention, C-reactive protein, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, systematic review, law, cardiovascular disease, Internal medicine, medicine, 030212 general & internal medicine, 030109 nutrition & dietetics, Nutrition and Dietetics, Adiponectin, biology, business.industry, interleukin, Epa, 3. Good health, meta-analysis, Dha, [SDV] Life Sciences [q-bio], inflammation, Meta-analysis, biology.protein, Pairwise comparison, lipids (amino acids, peptides, and proteins), medicine.symptom, omega-3, business, Food Science
Abstract: International audience; Recent data from randomized clinical trials (RCTs) suggest that DHA may have stronger anti-inflammatory effects than EPA. This body of evidence has not yet been quantitatively reviewed. The aim of this study was to compare the effect of DHA and EPA on several markers of systemic inflammation by pairwise and network meta-analyses of RCTs. MEDLINE, EMBASE, and The Cochrane Library were searched through to September 2019. We included RCTs of ≥7 d on adults regardless of health status that directly compared the effects of DHA with EPA and RCTs of indirect comparisons, in which the effects of DHA or EPA were compared individually to a control fatty acid. Differences in circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and adiponectin were the primary outcome measures. Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic) in the pairwise meta-analysis. Inconsistency and transitivity were evaluated in the network meta-analysis. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Eligibility criteria were met by 5 RCTs (N = 411) for the pairwise meta-analysis and 20 RCTs (N = 1231) for the network meta-analysis. In the pairwise meta-analysis, DHA and EPA had similar effects on plasma CRP [MDDHA versus EPA = 0.14 mg/L (95% CI: -0.57, 0.85); I2 = 61%], IL-6 [MDDHA versus EPA = 0.10 pg/mL (-0.15, 0.34); I2 = 40%], and TNF-α [MDDHA versus EPA = -0.10 pg/mL (-0.37, 0.18); I2 = 40%]. In the network meta-analysis, the effects of DHA and EPA on plasma CRP [MDDHA versus EPA = -0.33 mg/L (-0.75, 0.10)], IL-6 [MDDHA versus EPA = 0.09 pg/mL (-0.12, 0.30)], and TNF-α [MDDHA versus EPA = -0.02 pg/mL (-0.25, 0.20)] were also similar. DHA and EPA had similar effects on plasma adiponectin in the network meta-analysis. Results from pairwise and network meta-analyses suggest that supplementation with either DHA or EPA does not differentially modify systemic markers of subclinical inflammation.
Published: 2020

29. The Pliocene Model Intercomparison Project Phase 2: Large-scale climate features and climate sensitivity

Author: A. M. Haywood, J. C. Tindall, H. J. Dowsett, A. M. Dolan, K. M. Foley, S. J. Hunter, D. J. Hill, W.-L. Chan, A. Abe-Ouchi, C. Stepanek, G. Lohmann, D. Chandan, W. R. Peltier, N. Tan, C. Contoux, G. Ramstein, X. Li, Z. Zhang, C. Guo, K. H. Nisancioglu, Q. Zhang, Q. Li, Y. Kamae, M. A. Chandler, L. E. Sohl, B. L. Otto-Bliesner, R. Feng, E. C. Brady, A. S. von der Heydt, M. L. J. Baatsen, D. J. Lunt, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), 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), Modélisation du climat (CLIM), 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), 17189 University of Toronto, U of T Vetenskapsrådet, VR: 2013-06476, 2017-04232 Engineering and Physical Sciences Research Council, EPSRC: EP/M008.363/1 University of Leeds Natural Sciences and Engineering Research Council of Canada, NSERC: A9627 Government of Ontario Ministerio de Educación, Cultura y Deporte, MECD: 024.002.001 National Science Foundation, NSF: 1418411, 1852977 National Center for Atmospheric Research, NCAR Seventh Framework Programme, FP7 China Scholarship Council, CSC: 201804910023 China Postdoctoral Science Foundation: 2015M581154 Netherlands Earth System Science Centre, NESSC European Research Council, ERC: 278636 Japan Society for the Promotion of Science, KAKEN: 17H06104 Ministry of Education, Culture, Sports, Science and Technology, Monbusho: 17H06323 Canada Foundation for Innovation U.S. Geological Survey, USGS Engineering and Physical Sciences Research Council, EPSRC: EP/M008.363/1, Acknowledgements. We acknowledge the use of NOAA_ERSST_V5 data provided by the NOAA/OAR/ESRL PSD, Boulder, Colorado, USA, from their website at https://www.esrl.noaa.gov/psd/ (last access: 12 September 2019). Alan M. Haywood, Julia C. Tindall, Aisling M. Dolan, Stephen J. Hunter and Daniel J. Hill acknowledge the FP7 Ideas programme: European Research Council (grant no. PLIO-ESS, 278636), the Past Earth Network (EPSRC grant no. EP/M008.363/1) and the University of Leeds Advanced Research Computing service. Julia C. Tindall was also supported through the Centre for Environmental Modelling and Computation (CEMAC), University of Leeds. Harry J. Dowsett and Kevin M. Foley acknowledge support from the USGS Climate Research and Development Program. This research used samples and/or data provided by the Ocean Drilling Program (ODP) and International Ocean Discovery Program (IODP). Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government. Bette L. Otto-Bliesner, Esther C. Brady and Ran Feng acknowledge that material for their participation is based upon work supported by the National Center for Atmospheric Research, which is a major facility sponsored by the National Science Foundation (NSF) (cooperative agreement no. 1852977 and NSF OPP grant no. 1418411). The CESM project is supported primarily by the National Science Foundation. Computing and data storage resources, including the Cheyenne supercomputer (https://doi.org/10.5065/D6RX99HX), were provided by the Computational and Information Systems Laboratory (CISL) at NCAR. NCAR is sponsored by the National Science Foundation. Ning Tan, Camille Contoux and Gilles Ramstein were granted access to the HPC resources of TGCC under the allocations 2016-A0030107732, 2017-R0040110492 and 2018-R0040110492 (gencmip6) and 2019-A0050102212 (gen2212) provided by GENCI. The IPSL-CM6 team of the IPSL Climate Modelling Centre (https://cmc.ipsl.fr, last access: 16 September 2020) is acknowledged for having developed, tested, evaluated and tuned the IPSL climate model, as well as per- formed and published the CMIP6 experiments. Christian Stepanek acknowledges funding from the Helmholtz Climate Initiative REKLIM. Christian Stepanek and Gerrit Lohmann acknowledge funding via the Alfred Wegener Institute’s research programme Marine, Coastal and Polar Systems. Qiong Zhang acknowledge support from the Swedish Research Council (2013-06476 and 2017-04232). Simulations with EC-Earth were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at the National Supercomputer Centre (NSC). Wing-Le Chan and Ayako Abe-Ouchi acknowledge funding from JSPS (KAKENHI grant no. 17H06104 and MEXT KAKENHI grant no. 17H06323). Their simulations with MIROC4m were performed on the Earth Simulator at JAMSTEC, Yokohama, Japan. The work by Anna S. von der Heydt and Michiel L. J. Baatsen was carried out under the program of the Netherlands Earth System Science Centre (NESSC), financially supported by the Ministry of Education, Culture and Science (OCW grant no. 024.002.001). Simulations with CCSM4-Utr were performed at the SURFsara Dutch national computing facilities and were sponsored by NWO-EW (Netherlands Organisation for Scientific Research, Exact Sciences) (project no. 17189). W. Richard Peltier and Deepak Chandan were supported by Canadian NSERC Discovery Grant A9627, and they wish to acknowledge the support of SciNet HPC Consortium for providing computing facilities. SciNet is funded by the Canada Foundation for Innovation under the auspices of Compute Canada, the Government of Ontario, the Ontario Research Fund – Research Excellence, and the University of Toronto. Xiangyu Li acknowledges financial support from the China Scholarship Council (201804910023) and the China Postdoctoral Science Foundation (project no. 2015M581154). The NorESM simulations benefitted from resources provided by UNINETT Sigma2 – the National Infrastructure for High Performance Computing and Data Storage in Norway. The authors would also like to thank Tim Herbert and an anonymous reviewer for helpful comments on an earlier version of this paper., Financial support. This research has been supported by the Past Earth Network (EPSRC grant no. EP/M008.363/1)., 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), and 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)
Subjects: 010504 meteorology & atmospheric sciences, lcsh:Environmental protection, Stratigraphy, Climate change, Zonal and meridional, 010502 geochemistry & geophysics, Atmospheric sciences, 01 natural sciences, lcsh:Environmental pollution, Pliocene climate, lcsh:TD169-171.8, Precipitation, lcsh:Environmental sciences, 0105 earth and related environmental sciences, lcsh:GE1-350, Global and Planetary Change, geography, geography.geographical_feature_category, Paleontology, 13. Climate action, [SDU.STU.CL]Sciences of the Universe [physics]/Earth Sciences/Climatology, lcsh:TD172-193.5, Polar amplification, Environmental science, Climate sensitivity, Climate model, Ice sheet
Abstract: The Pliocene epoch has great potential to improve our understanding of the long-term climatic and environmental consequences of an atmospheric CO2 concentration near ∼400 parts per million by volume. Here we present the large-scale features of Pliocene climate as simulated by a new ensemble of climate models of varying complexity and spatial resolution based on new reconstructions of boundary conditions (the Pliocene Model Intercomparison Project Phase 2; PlioMIP2). As a global annual average, modelled surface air temperatures increase by between 1.7 and 5.2 ∘C relative to the pre-industrial era with a multi-model mean value of 3.2 ∘C. Annual mean total precipitation rates increase by 7 % (range: 2 %–13 %). On average, surface air temperature (SAT) increases by 4.3 ∘C over land and 2.8 ∘C over the oceans. There is a clear pattern of polar amplification with warming polewards of 60∘ N and 60∘ S exceeding the global mean warming by a factor of 2.3. In the Atlantic and Pacific oceans, meridional temperature gradients are reduced, while tropical zonal gradients remain largely unchanged. There is a statistically significant relationship between a model's climate response associated with a doubling in CO2 (equilibrium climate sensitivity; ECS) and its simulated Pliocene surface temperature response. The mean ensemble Earth system response to a doubling of CO2 (including ice sheet feedbacks) is 67 % greater than ECS; this is larger than the increase of 47 % obtained from the PlioMIP1 ensemble. Proxy-derived estimates of Pliocene sea surface temperatures are used to assess model estimates of ECS and give an ECS range of 2.6–4.8 ∘C. This result is in general accord with the ECS range presented by previous Intergovernmental Panel on Climate Change (IPCC) Assessment Reports.
Published: 2020

30. Focal accumulation of aromaticity at the CDRH3 loop mitigates 4E10 polyreactivity without altering its HIV neutralization profile

Author: José L. Nieva, Eneko Largo, Daniel P. Leaman, Michael B. Zwick, Jean-Philippe Julien, Felix Elortza, Miguel García-Porras, Edurne Rujas, Sara Insausti, Pablo Carravilla, Lei Zhang, Christian Eggeling, Hong Cui, Jose M. M. Caaveiro, Izaskun Morillo, Rubén Sánchez-Eugenia, Ibon Iloro, European Commission, National Institutes of Health (US), James B. Pendleton Foundation, Japan Society for the Promotion of Science, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Eusko Jaurlaritza, Medical Research Council (UK), Wolfson Foundation, Deutsche Forschungsgemeinschaft, Leibniz Association, Wellcome Trust, John Fell Fund, Japan Agency for Medical Research and Development, Universidad del País Vasco, Azrieli Foundation, Canada Research Chairs, Ontario Research Fund, Carravilla, Pablo, Iloro, Ibon, Elortza, Félix, Julien, Jean-Philippe, and Caaveiro, José M. M.
Subjects: Science, Immunology, Human immunodeficiency virus (HIV), medicine.disease_cause, Article, Neutralization, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, health care economics and organizations, 030304 developmental biology, 0303 health sciences, Heavy chain, Multidisciplinary, biology, Chemistry, Chemical modification, Aromaticity, 3. Good health, Membrane, Biophysics, biology.protein, Antibody, 030217 neurology & neurosurgery
Abstract: Summary Broadly neutralizing antibodies (bnAbs) against HIV-1 are frequently associated with the presence of autoreactivity/polyreactivity, a property that can limit their use as therapeutic agents. The bnAb 4E10, targeting the conserved Membrane proximal external region (MPER) of HIV-1, displays almost pan-neutralizing activity across globally circulating HIV-1 strains but exhibits nonspecific off-target interactions with lipid membranes. The hydrophobic apex of the third complementarity-determining region of the heavy chain (CDRH3) loop, which is essential for viral neutralization, critically contributes to this detrimental effect. Here, we have replaced the aromatic/hydrophobic residues from the apex of the CDRH3 of 4E10 with a single aromatic molecule through chemical modification to generate a variant that preserves the neutralization potency and breadth of 4E10 but with reduced autoreactivity. Collectively, our study suggests that the localized accumulation of aromaticity by chemical modification provides a pathway to ameliorate the adverse effects triggered by the CDRH3 of anti-HIV-1 MPER bnAbs., Graphical abstract, Highlights • Aromatic grafting is employed to improve functionality of the HIV antibody 4E10 • Engineering the CDRH3 loop slashes its polyreactivity profile but also its potency • Site-specific chemical modification rescues the activity of the engineered antibody • Collectively, this procedure mitigates the polyreactivity of an MPER antibody, Immunology; Virology
Published: 2021

31. Nanostructured Back Reflectors for Efficient Colloidal Quantum‐Dot Infrared Optoelectronics

Author: Min-Jae Choi, Agustín Mihi, James Z. Fan, Edward H. Sargent, Olivier Ouellette, Margherita Biondi, Se-Woong Baek, Pau Molet, F. Pelayo García de Arquer, Sjoerd Hoogland, Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada, National Research Foundation of Korea, Ministerio de Economía y Competitividad (España), and European Research Council
Subjects: Materials science, media_common.quotation_subject, Library science, 02 engineering and technology, Conjugated polymers, 010402 general chemistry, 01 natural sciences, 7. Clean energy, Nanoimprinting, Excellence, media_common.cataloged_instance, General Materials Science, European union, media_common, Hole transporting layers, Colloidal quantum dots, Mechanical Engineering, European research, 021001 nanoscience & nanotechnology, Infrared optoelectronics, 0104 chemical sciences, Mechanics of Materials, Christian ministry, 0210 nano-technology, Engineering research
Abstract: Colloidal quantum dots (CQDs) can be used to extend the response of solar cells, enabling the utilization of solar power that lies to the red of the bandgap of c‐Si and perovskites. To achieve largely complete absorption of infrared (IR) photons in CQD solids requires thicknesses on the micrometer range; however, this exceeds the typical diffusion lengths (≈300 nm) of photoexcited charges in these materials. Nanostructured metal back electrodes that grant the cell efficient IR light trapping in thin active layers with no deterioration of the electrical properties are demonstrated. Specifically, a new hole‐transport layer (HTL) is developed and directly nanostructured. Firstly, a material set to replace conventional rigid HTLs in CQD devices is developed with a moldable HTL that combines the mechanical and chemical requisites for nanoimprint lithography with the optoelectronic properties necessary to retain efficient charge extraction through an optically thick layer. The new HTL is nanostructured in a 2D lattice and conformally coated with MoO3/Ag. The photonic structure in the back electrode provides a record photoelectric conversion efficiency of 86%, beyond the Si bandgap, and a 22% higher IR power conversion efficiency compared to the best previous reports., S.-W.B., P.M., and M.-J.C. contributed equally to this work. This work was supported by Ontario Research Fund-Research Excellence program (ORF7-Ministry of Research and Innovation, Ontario Research FundResearch Excellence Round 7), and by the Natural Sciences and Engineering Research Council (NSERC) of Canada. This work was also supported by the National Research Foundation of Korea (NRF) funded by NRF-2018R1A6A3A03012630. The authors thank the Spanish Ministry of Economy and Competitiveness (MINECO) for its support through grant nos. MAT2016-79053-P and SEV-2015-0496. This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant no. 637116). The authors thank L. Levina, R. Wolowiec, D. Kopilovic, E. Palmiano, and J. L. Garcia-Pomar for their help over the course of this research.
Published: 2019
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32. Biallelic Mutations in LRRC56, Encoding a Protein Associated with Intraflagellar Transport, Cause Mucociliary Clearance and Laterality Defects

Author: Bonnefoy, Serge, M.Watson, Christopher, Kernohan, Kristin, Lemos, Moara, Hutchinson, Sebastian, A. Poulter, James, Crinnion, Laura, Berry, Ian, Simmonds, Jennifer, Vasudevan, Pradeep, O'Callaghan, Chris, Hirst, Robert, Rutman, Andrew, Huang, Lijia, Hartley, Taila, Grynspan, David, Moya, Eduardo, Li, Chunmei, Carr, Ian, Bonthron, David, Leroux, Michel, Canada Consortium, Care4Rare, Boycott, Kym, Bastin, Philippe, Sheridan, Eamonn, Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, University of Ottawa [Ottawa], University of Leicester, University College of London [London] (UCL), Children's Hospital of Eastern Ontario, Bradford Royal Infirmary, Simon Fraser University (SFU.ca), Research at the Institut Pasteur is funded by an ANR grant (ANR-14-CE35-0009-01), by a French Government Investissement d’Avenir programme, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID), and by La Fondation pour la Recherche Médicale (Equipe FRM DEQ20150734356). This work was supported, in part, by the Care4Rare Canada Consortium funded by Genome Canada, the Canadian Institutes of Health Research (CIHR), the Ontario Genomics Institute, Ontario Research Fund, Genome Quebec, and Children’s Hospital of Eastern Ontario Foundation and the Canadian Rare Diseases: Models and Mechanisms Network funded by CIHR and Genome Canada. The authors wish to acknowledge the contribution of the high-throughput sequencing platform of the McGill University and Génome Québec Innovation Centre, Montréal, Canada. Research at the University of Leeds was supported by grants MR/M009084/1 and MR/L01629X/1 awarded by the UK Medical Research Council., We wish to thank the families reported here for their willingness to participate in these research efforts. We thank the Ultrastructural BioImaging Plateforme for providing access to the TEM equipment. We thank Bruno Louis and Jean-François Papon, Institut National de la Santé et de la Recherche Médicale, U955, Créteil, France, for help in video-microscopy., ANR-14-CE35-0009,DECODIFT,Molecular bases for the role of IFT172 in ciliogenesis and in ciliopathy(2014), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bastin, Philippe, Appel à projets générique - Molecular bases for the role of IFT172 in ciliogenesis and in ciliopathy - - DECODIFT2014 - ANR-14-CE35-0009 - Appel à projets générique - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Biologie cellulaire des Trypanosomes
Subjects: Male, 0301 basic medicine, Axoneme, [SDV]Life Sciences [q-bio], Video microscopy, [SDV.GEN] Life Sciences [q-bio]/Genetics, left-right asymmetry, 0302 clinical medicine, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Cilium, dynein arms, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Phenotype, Mucociliary Clearance, Motile cilium, Female, flagella, Adult, Mucociliary clearance, Trypanosoma brucei brucei, Dynein, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Flagellum, Biology, Article, Cell Line, 03 medical and health sciences, trypanosome, Intraflagellar transport, Genetics, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Alleles, [SDV.GEN]Life Sciences [q-bio]/Genetics, intraflagellar transport, leucine-rich repeat protein, Chlamydomonas, cilia, Dyneins, Infant, Proteins, Biological Transport, Epithelial Cells, HEK293 Cells, 030104 developmental biology, Mutation, ciliopathies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Primary defects in motile cilia result in dysfunction of the apparatus responsible for generating fluid flows. Defects in these mechanisms underlie disorders characterized by poor mucus clearance, resulting in susceptibility to chronic recurrent respiratory infections, often associated with infertility; laterality defects occur in about 50% of such individuals. Here we report biallelic variants in LRRC56 (known as oda8 in Chlamydomonas) identified in three unrelated families. The phenotype comprises laterality defects and chronic pulmonary infections. High-speed video microscopy of cultured epithelial cells from an affected individual showed severely dyskinetic cilia but no obvious ultra-structural abnormalities on routine transmission electron microscopy (TEM). Further investigation revealed that LRRC56 interacts with the intraflagellar transport (IFT) protein IFT88. The link with IFT was interrogated in Trypanosoma brucei. In this protist, LRRC56 is recruited to the cilium during axoneme construction, where it co-localizes with IFT trains and is required for the addition of dynein arms to the distal end of the flagellum. In T. brucei carrying LRRC56-null mutations, or a variant resulting in the p.Leu259Pro substitution corresponding to the p.Leu140Pro variant seen in one of the affected families, we observed abnormal ciliary beat patterns and an absence of outer dynein arms restricted to the distal portion of the axoneme. Together, our findings confirm that deleterious variants in LRRC56 result in a human disease and suggest that this protein has a likely role in dynein transport during cilia assembly that is evolutionarily important for cilia motility.
Published: 2018

33. Encompassing new use cases - level 3.0 of the HUPO-PSI format for molecular interactions

Author: Anjali Shrivastava, Luana Licata, M. Sivade, Colin W. Combe, Grace Bradley, K. Van Roey, Mais G. Ammari, Birgit H M Meldal, David J. Lynn, Pablo Porras, Nancy H. Campbell, Julie Sullivan, Sylvie Ricard-Blum, Noemi del-Toro, Diego Alonso-López, Nicolas Thierry-Mieg, Yo Yehudi, Arnaud Ceol, Henning Hermjakob, J. Heimbach, Lukasz Salwinski, J. De Las Rivas, Giovanni Cesareni, Maximilian Koch, Gos Micklem, Bernd Roechert, Igor Jurisica, Simona Panni, Sandra Orchard, Ruth C. Lovering, Apollo - University of Cambridge Repository, Biotechnology and Biological Sciences Research Council (UK), European Commission, Ontario Research Fund, Canada Research Chairs, Fondation pour la Recherche Médicale, British Heart Foundation, European Research Council, Wellcome Trust, National Institutes of Health (US), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Cancer Research Center (IBMCC-CIC, CSIC-USAL), University of Arizona, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), University College of London [London] (UCL), Fondazione Istituto Italiano di Tecnologia, Genova, University of Rome TorVergata, University of Edinburgh, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Orchard, S [0000-0002-8878-3972]
Subjects: 0301 basic medicine, Proteomics, Proteome, Computer science, computer.internet_protocol, HUPO-PSI, Protein complexes, lcsh:Computer applications to medicine. Medical informatics, Biochemistry, Data type, 03 medical and health sciences, Databases, 0302 clinical medicine, Protein-protein interaction, Structural Biology, Data standards, Molecular interactions, PSI-MI, XML, Databases, Protein, Humans, Mutation, Systems Biology, Protein Interaction Maps, Use case, lcsh:QH301-705.5, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Information retrieval, Settore BIO/18, Applied Mathematics, Protein, Experimental data, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Computer Science Applications, 030104 developmental biology, lcsh:Biology (General), Structural biology, lcsh:R858-859.7, computer, Software, 030217 neurology & neurosurgery, Molecular exchange
Abstract: [Background]: Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes. [Results]: The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal. [Conclusions]: PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and download., MD, MK, AS, JS, JH and YY were funded by BBSRC MIDAS grant (BB/L024179/1), this grant provided the funds for the design of PSI-MI XML3.0 and its implementation by the IntAct database. KVR was funded by European Commission (FP7-HEALTH-2009-242129 SyBoSS), LL by ELIXIR-IIB, the Italian Node of the European ELIXIR infrastructure, IJ was funded by Ontario Research Fund (GL2–01-030, #34876) and Canada Research Chair Program (#225404), DJL by EMBL Australia and FP7-HEALTH2011-278568, SRB and NTM by Fondation pour la Recherche Médicale (grant n° DBI20141231336) and by the French Institute of Bioinformatics (2015 call), NHC and RCL by British Heart Foundation (RG/13/5/30112), GC by the European Research Council (Grant Agreement 32274), CC was funded by the Wellcome Trust (grant numbers 103139, 063412, 203149) and LS by National Institutes of Health.
Published: 2018

34. Genetic traits leading to invasion: plasticity in cold hardiness explains current distribution of an invasive agricultural pest, Tetranychus evansi (Acari: Tetranychidae)

Author: Maria Navajas, Philippe Auger, Ruth A. Hufbauer, Alain Migeon, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), Colorado State University [Fort Collins] (CSU), ANR 2010 BLAN 1715 02, GI-046 grant from Genome Canada and the Ontario Genomics Institute and the GL2-01-035 grant from the Ontario Research Fund–Global Leadership in Genomics and Life Sciences, United States Department of Agriculture through the Colorado Experiment Station, Fulbright-France, and NSF RCN 0541673
Subjects: Ecology, biology, Invaded area, [SDV]Life Sciences [q-bio], Lineage (evolution), Species distribution, 15. Life on land, Cold tolerance, biology.organism_classification, Overwintering, Invasive species, Fluctuating thermal regime, 13. Climate action, Spider mite, Mite, Acari, Adaptation, Hardiness (plants), Ecology, Evolution, Behavior and Systematics
Abstract: International audience; Among the factors limiting species distribution,low temperatures play a key role for tropical invasive species in temperate areas. Susceptibility to cold winter conditions has been recognized as the limiting factor in Europe for Tetranychus evansi, an invasive spider mite feeding on Solanaceous plants originated from tropical South America and now present on every continent except Australia. Two genetically distinct lineages of this species were introduced to Europe; one (lineage 1) is widely distributed, while the other (lineage 2) has a limited distribution. Whether this difference corresponds to differences in cold hardiness is evaluated here by assessing phenotypic response of T. evansi to the winter conditions that the mite encounters in the coldest parts of the current invaded area. We designed the thermal regimes to mimic winter conditions, including temperature fluctuations between day and night (L:D 8:16, 12:4 C) and exposed mites to this regime for 5, 10 or 15 weeks. We tested T. evansi from three locations, one from the tropical native area (Piracicaba, Brazil) and two, corresponding to the two introduced lineages, from the temperate invaded area (lineage 1 from Nice and lineage 2 from Perpignan, France). After 5 weeks of treatment, mites from all the locations showed high survival rates but the two introduced populations grew, producing more than one offspring per female. After 10 weeks, survival rates declined for mites from Brazil and Perpignan, but not Nice. After 15 weeks, only the mites from Nice survived and produced offspring. Thus, mites belonging to the widespread lineage 1 exhibit increased cold tolerance suggesting broader adaptability, helping to explain its current geographical distribution.
Published: 2015

35. Disruption of a horizontally transferred phytoene desaturase abolishes carotenoid accumulation and diapause in Tetranychus urticae

Author: Luc Tirry, John Vontas, Astrid Bryon, Robert Greenhalgh, Masahiro Osakabe, Richard M. Clark, Maria Riga, Wannes Dermauw, Miodrag Grbic, Thomas Van Leeuwen, Andre H. Kurlovs, Research Foundation - Flanders, University of Utah, National Science Foundation (US), Ontario Research Fund, Government of Canada, Genome Canada, Ontario Genomics Institute, Foundation for the National Institutes of Health, Japan Society for the Promotion of Science, Vontas, John, and Vontas, John [0000-0002-8704-2574]
Subjects: Male, 0106 biological sciences, 0301 basic medicine, Spider mites, Xanthophylls, 01 natural sciences, polycyclic compounds, Gall, Tetranychus urticae, ACARI-TETRANYCHIDAE, Carotenoid, chemistry.chemical_classification, Multidisciplinary, biology, Pigmentation, KOCH, food and beverages, Horizontal gene transfer, PHOTOPERIODIC INDUCTION, PNAS Plus, Female, Oxidoreductases, Tetranychidae, Phytoene desaturase, Gene Transfer, Horizontal, Bulked segregant analysis, METABOLISM, Diapause, GENE-TRANSFER, Arthropod Proteins, 03 medical and health sciences, Spider mite, β-carotene, Botany, Mite, Animals, BIOSYNTHESIS, FUSARIUM-FUJIKUROI, organic chemicals, 2-SPOTTED SPIDER-MITE, BETA-CAROTENE, fungi, Genetic Complementation Test, Biology and Life Sciences, biology.organism_classification, Carotenoids, EVOLUTION, biological factors, 010602 entomology, 030104 developmental biology, chemistry, Xanthophyll, Mutation
Abstract: Carotenoids underlie many of the vibrant yellow, orange, and red colors in animals, and are involved in processes ranging from vision to protection from stresses. Most animals acquire carotenoids from their diets because de novo synthesis of carotenoids is primarily limited to plants and some bacteria and fungi. Recently, sequencing projects in aphids and adelgids, spider mites, and gall midges identified genes with homology to fungal sequences encoding de novo carotenoid biosynthetic proteins like phytoene desaturase. The finding of horizontal gene transfers of carotenoid biosynthetic genes to three arthropod lineages was unprecedented; however, the relevance of the transfers for the arthropods that acquired them has remained largely speculative, which is especially true for spider mites that feed on plant cell contents, a known source of carotenoids. Pigmentation in spider mites results solely from carotenoids. Using a combination of genetic approaches, we show that mutations in a single horizontally transferred phytoene desaturase result in complete albinism in the twospotted spider mite, Tetranychus urticae, as well as in the citrus red mite, Panonychus citri. Further, we show that phytoene desaturase activity is essential for photoperiodic induction of diapause in an overwintering strain of T. urticae, consistent with a role for this enzyme in provisioning provitamin A carotenoids required for light perception. Carotenoid biosynthetic genes of fungal origin have therefore enabled some mites to forgo dietary carotenoids, with endogenous synthesis underlying their intense pigmentation and ability to enter diapause, a key to the global distribution of major spider mite pests of agriculture., This work was supported by Research Foundation Flanders (FWO) Grant G009312N (to L.T. and T.V.L.) and Grant G053815N (to L.T., T.V.L., and W.D.); incentive funds from the University of Utah (to R.M.C.); National Science Foundation Grant DEB1457346 (to R.M.C.); Ontario Research Fund–Research 753 Excellence Round 8 Grant RE08-067 (to M.G.); and the Government of Canada through Genome Canada and the Ontario Genomics Institute (Grant OGI-046) (to M.G.). R.G. was funded by National Institutes of Health Genetics Training Grant T32GM007464, and W.D. is a postdoctoral fellow of the Research Foundation Flanders (FWO). M.O. was supported by Japan Society for the Promotion of Science Kakenhi Grant 26292029.
Published: 2017

36. MATI, a novel protein involved in the regulation of herbivore-associated signaling pathways

Author: M. Estrella Santamaria, Félix Ortego, Isabel Diaz, Manuel Martinez, Vojislava Grbic, Ana Arnaiz, Ministerio de Economía y Competitividad (España), Government of Canada, Genome Canada, Ontario Genomics Institute, Ontario Research Fund, and European Commission
Subjects: 0106 biological sciences, 0301 basic medicine, Arabidopsis thaliana, Plant–herbivore interaction, Plant Science, lcsh:Plant culture, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Arabidopsis, Spodoptera exigua, Hormonal signaling pathways, Botany, Gene family, lcsh:SB1-1110, Tetranychus urticae, Gene, Original Research, biology, Jasmonic acid, Plant redox status, biology.organism_classification, 3. Good health, Cell biology, 030104 developmental biology, chemistry, Signal transduction, Function (biology), 010606 plant biology & botany
Abstract: 18 p.-8 fig., The defense response of the plants against herbivores relies on a complex network of interconnected signaling pathways. In this work, we characterized a new key player in the response of Arabidopsis against the two-spotted spider mite Tetranychus urticae, the MATI (Mite Attack Triggered Immunity) gene. This gene was differentially induced in resistant Bla-2 strain relative to susceptible Kon Arabidopsis accessions after mite attack, suggesting a potential role in the control of spider mites. To study the MATI gene function, it has been performed a deep molecular characterization of the gene combined with feeding bioassays using modified Arabidopsis lines and phytophagous arthropods. The MATI gene belongs to a new gene family that had not been previously characterized. Biotic assays showed that it confers a high tolerance not only to T. urticae, but also to the chewing lepidopteran Spodoptera exigua. Biochemical analyses suggest that MATI encodes a protein involved in the accumulation of reducing agents upon herbivore attack to control plant redox homeostasis avoiding oxidative damage and cell death. Besides, molecular analyses demonstrated that MATI is involved in the modulation of different hormonal signaling pathways, affecting the expression of genes involved in biosynthesis and signaling of the jasmonic acid and salicylic acid hormones. The fact that MATI is also involved in defense through the modulation of the levels of photosynthetic pigments highlights the potential of MATI proteins to be exploited as biotechnological tools for pest control., This work was supported by projects from Ministerio de Economía y Competitividad of Spain (projects BIO2014-53508- R and 618105-FACCE-Era Net Plus) and the Government of Canada through Genome Canada and the Ontario Genomics Institute (OGI–046), the Ontario Research Fund (RE08-067) and the Natural Sciences and Engineering Research Council of Canada.
Published: 2017

37. Human exposure to power frequency magnetic fields up to 7.6 mT: An integrated EEG/fMRI study

Author: Modolo, Julien, Thomas, Alex W., Legros, Alexandre, Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Lawson Health Research Institute, Hydro-Québec (Canada), EDF-RTE (France), CIHR (Canadian Institutes of Health Research). Grant Number: 187204, CFI/ORF (Canadian Fund for Innovation/Ontario Research Fund) Biomedical Multimodality Hybrid Imaging. Grant Number: 11358, University of Western Ontario (UWO), Lawson Health Research Institute [London (ON) Canada], Euromov (EuroMov), Université de Montpellier (UM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Adult, Male, Adolescent, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SCCO.NEUR]Cognitive science/Neuroscience, Threshold, fMRI, Brain, Electroencephalography, Environmental Exposure, Magnetic Resonance Imaging, extremely low frequency magnetic fields, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Young Adult, Magnetic Fields, Stress, Physiological, Surveys and Questionnaires, 50 and 60 Hz, Humans, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, EEG, human, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; We assessed the effects of power-line frequency (60 Hz in North America) magnetic fields (MF) in humans using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twenty-five participants were enrolled in a pseudo-double-blind experiment involving "real" or "sham" exposure to sinusoidal 60 Hz MF exposures delivered using the gradient coil of an MRI scanner following two conditions: (i) 10 s exposures at 3 mT (10 repetitions); (ii) 2 s exposures at 7.6 mT (100 repetitions). Occipital EEG spectral power was computed in the alpha range (8-12 Hz, reportedly the most sensitive to MF exposure in the literature) with/without exposure. Brain functional activation was studied using fMRI blood oxygen level-dependent (BOLD, inversely correlated with EEG alpha power) maps. No significant effects were detected on occipital EEG alpha power during or post-exposure for any exposure condition. Consistent with EEG results, no effects were observed on fMRI BOLD maps in any brain region. Our results suggest that acute exposure (2-10 s) to 60 Hz MF from 3 to 7.6 mT (30,000 to 76,000 times higher than average public exposure levels for 60 Hz MF) does not induce detectable changes in EEG or BOLD signals. Combined with previous findings in which effects were observed on the BOLD signal after 1 h exposure to 3 mT, 60 Hz MF, this suggests that MF exposure in the low mT range (
Published: 2017

38. Genotype-specific interactions between parasitic arthropods

Author: Marion Orsucci, Maria Navajas, S Fellous, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), e GI-046 grant from Genome Canada and the Ontario Genomics Institute and the GL2-01-035 grant from the Ontario Research Fund–Global Leadership in Genomics and Life Sciences. Funding was provided by the French Agence Nationale de la Recherche (ANR 2010 BLAN 1715 02)., and 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)
Subjects: 0106 biological sciences, 0301 basic medicine, interaction entre parasites, Genotype, [SDV]Life Sciences [q-bio], Population, Zoology, Biology, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, Solanum lycopersicum, Human population genetics, Genetics, medicine, Mite, Parasite hosting, Animals, Genetic variability, Tetranychus urticae, Herbivory, education, Genetics (clinical), tetranychus urticae, education.field_of_study, Models, Genetic, Ecology, Host (biology), Reproduction, Tetranychus evansi, medicine.disease, biology.organism_classification, coinfection, Plant Leaves, 030104 developmental biology, Genetics, Population, coévolution, Coinfection, Linear Models, Original Article, Tetranychidae, acarien
Abstract: Despite the ubiquity of coinfection, we know little of the effects of intra-specific genetic variability on coinfection by distinct parasite species. Here we test the hypothesis that parasite multiplication depends on the combination of parasite genotypes that coinfect the host (that is Genotype. parasite x Genotype. parasite interaction). To that aim, we infected tomato leaves with the ectoparasitic mites Tetranychus urticae and Tetranychus evansi. We tested all possible combinations between four T. urticae and two T. evansi populations sampled on different hosts or localities. There was no universal (that is genotype-independent) effect of coinfection on mite multiplication; in many cases the two species had no effect on each other. However, several combinations of T. evansi and T. urticae populations led to elevated T. evansi numbers. Similarly, T. urticae reproduction largely depended on the interaction between T. urticae and T. evansi populations. This evidence for genotype-by-genotype interaction between coinfecting parasites indicates that the effect of coinfection on parasite epidemiology and evolution may vary in space according to the genetic composition of local parasite populations; it further suggests the possibility of coevolution between parasites species that share the same hosts.
Published: 2017

39. RNAi-based reverse genetics in the chelicerate model Tetranychus urticae: A comparative analysis of five methods for gene silencing

Author: Rebecca De Clercq, Maria Andreia Nunes, Miodrag Grbic, Hooman Hosseinzadeh Namin, Vojislava Grbic, Pierre Hilson, Nicolas Bensoussan, Pengyu Jin, Takeshi Suzuki, María Urizarna España, Vladimir Zhurov, Tawhid Rahman, Graduate School of Bio-applications and Systems Engineering, Tokyo University of Agriculture and Technology (TUAT), Department of Biology, Northern Arizona University [Flagstaff], Centro de Citricultura Sylvio Moreira, Partenaires INRAE, Saskatoon Research Center, Flanders Institute for Biotechnology, Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Saclay (COmUE), Department of plant Biotechnology and Bioinformatics, University of Gent, Universidad de La Rioja (UR), Government of Canada through the Ontario Research Fund Research Excellence Round 8 [RE08-067], University of Western Ontario through the Western Strategic Support program, Postdoctoral Fellowship for Research Abroad, KAKENHI - Japan Society for the Promotion of Science (JSPS) [16K18661], National Counsel of Technological and Scientific Development (CNPq/Brazil), and Grbic, Vojislava
Subjects: 0106 biological sciences, 0301 basic medicine, Leaves, Life Cycles, [SDV]Life Sciences [q-bio], Inbred Strains, lcsh:Medicine, Genetically modified crops, Plant Science, 01 natural sciences, Biochemistry, Genetically Modified Plants, RNA interference, Larvae, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Tetranychus urticae, lcsh:Science, Acari, INTERFERENCE, Genetics, Mites, Multidisciplinary, biology, Plant Anatomy, Genetically Modified Organisms, food and beverages, Plants, ARABIDOPSIS, GENOME, Nucleic acids, RNA silencing, Genetic interference, Fecundity, Experimental Organism Systems, Gene Targeting, C-ELEGANS, Insect Proteins, Epigenetics, Genetic Engineering, Research Article, Biotechnology, Vacuolar Proton-Translocating ATPases, Arthropoda, Arabidopsis Thaliana, Brassica, EUKARYOTES, Research and Analysis Methods, SEQUENCE, 03 medical and health sciences, Model Organisms, Population Metrics, Spider mite, Plant and Algal Models, Mite, Gene silencing, Animals, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Gene Silencing, Population Biology, lcsh:R, fungi, Organisms, Biology and Life Sciences, INSECT, ACIDS, biology.organism_classification, Invertebrates, Reverse genetics, 030104 developmental biology, RNA, Plant Biotechnology, lcsh:Q, Gene expression, DSRNA, GENERATION, 010606 plant biology & botany, Developmental Biology
Abstract: RNA interference (RNAi) can be used for the protection against agricultural pests through the silencing of genes required for pest fitness. To assess the potential of RNAi approaches in the two-spotted spider mite, Tetranychus urticae, we compared 5 methods for the delivery of double-stranded RNA (dsRNA). These methods include mite feeding on either (i) leaves floating on a dsRNA solution, (ii) dsRNA-expressing plants, (iii) artificial diet supplemented with dsRNA, or (iv) dsRNA-coated leaves, and (v) mite soaking in a dsRNA solution. In all cases, the gene targeted for method validation was the Vacuolar-type H+-ATPase (TuVATPase), encoding a constitutively expressed ATP-driven proton pump located in the membrane. Down-regulation of TuVATPase increased mortality and/or reduced fecundity in all methods, but with variable efficiency. The most efficient methods for dsRNA delivery were direct soaking of mites in the dsRNA solution and mite feeding on dsRNA-coated leaves that mimics dsRNA application as a sprayable pesticide. Both resulted in a dark-body phenotype not observed in mites treated with a control dsRNA. Although with lower efficiency, dsRNA designed for TuVATPase silencing and expressed in transgenic Arabidopsis plants impacted the fitness of mites feeding on these plants. RNAi may thus be a valuable strategy to control spider mite populations, either as a sprayable pesticide or through transgenic crops. This comparative methodological study focusing on the induction of RNAi-based gene silencing in T. urticae paves the way for reverse genetics approaches in this model chelicerate system and prepares large-scale systematic RNAi screens as a first step towards the development of specific RNA-based pesticides. Such alternative molecules may help control spider mites that cause significant damages to crops and ornamental plant species, as well as other chelicerates detrimental to agriculture and health. © 2017 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published: 2017

40. Combining experimental evolution and field population assays to study the evolution of host range breadth

Author: Maria Navajas, Marion Orsucci, Isabelle Olivieri, Alain Migeon, S. Fellous, Philippe Auger, G. Angot, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Genome Canada [GI-046], Ontario Genomics Institute, Ontario Research Fund-Global Leadership in Genomics and Life Sciences [GL2-01-035], and French Agence Nationale de la Recherche [ANR 2010 BLAN 1715 02]
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, 0106 biological sciences, tetranychus-urticae acari, Range (biology), [SDE.MCG]Environmental Sciences/Global Changes, Niche, herbivore, host range, Zoology, plant, Generalist and specialist species, 010603 evolutionary biology, 01 natural sciences, Host Specificity, spider mite, resistance, specialization, 03 medical and health sciences, Spider mite, evolution, Animals, Tetranychus urticae, generalist, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Experimental evolution, phytophagous mite, biology, Ecology, Host (biology), genotype interactions, spider-mite, Plants, biology.organism_classification, Biological Evolution, rna virus, ecological specialization, parasite, Adaptation, Tetranychidae, local adaptation
Abstract: International audience; Adapting to specific hosts often involves trade-offs that limit performance on other hosts. These constraints may either lead to narrow host ranges (i.e. specialists, able to exploit only one host type) or wide host ranges often leading to lower performance on each host (i.e. generalists). Here, we combined laboratory experiments on field populations with experimental evolution to investigate the impact of adaptation to the host on host range evolution and associated performance over this range. We used the two-spotted spider mite, Tetranychus urticae, a model organism for studies on the evolution of specialization. Field mite populations were sampled on three host plant species: tomato, citrus tree and rosebay (Nerium oleander). Testing these populations in the laboratory revealed that tomato populations of mites could exploit tomato only, citrus populations could exploit citrus and tomato whereas Nerium populations could exploit all three hosts. Besides, the wider niche ranges of citrus and Nerium populations came at the cost of low performance on their non-native hosts. Experimental lines selected to live on the same three host species exhibited similar patterns of host range and relative performance. This result suggests that adaptation to a new host species may lead to wider host ranges but at the expense of decreased performance on other hosts. We conclude that experimental evolution may reliably inform on evolution in the field.
Published: 2014

41. Regional and global shifts in crop diversity through the Anthropocene

Author: Denis Vile, Rubén Milla, Marc W. Cadotte, Cyrille Violle, Marney E. Isaac, Adam R. Martin, University of Toronto at Scarborough, Universidad Rey Juan Carlos [Madrid] (URJC), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Natural Sciences and Engineering Research Council of Canada Discovery Grant, Canada Foundation for Innovation, Ontario Research Fund, Natural Sciences and Engineering Research Council of Canada (Grant number 386151), Région Languedoc-Roussillon, 'Chercheur d’Avenir' (FEDER FSE IEJ 2014–2020, Grant Project 'APSEVIR'), Ministerio de Economía y Competitividad of Spain (grants CGL2014-56567-R and PCIN-2014-053), European Union (Eco-serve project, BiodivERsA/001/2014, Horizon 2020), Marie Curie International Outgoing Fellowship (DiversiTraits project, no. 221060), uropean Research Council (ERC) Starting Grant Project StG-2014-639706-CONSTRAINTS., European Project: 221060,EC:FP7:PEOPLE,FP7-PEOPLE-2007-4-1-IOF,DIVERSITRAITS(2009), University of Toronto [Scarborough, Canada], Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and 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)-Institut de Recherche pour le Développement (IRD [France-Sud])
Subjects: Plant Phylogenetics, 0106 biological sciences, Conservation genetics, Plant Evolution, Conservation Biology, Biodiversité et Ecologie, Plant Science, 01 natural sciences, Data Management, Conservation Science, 2. Zero hunger, Plant evolution, 0303 health sciences, Multidisciplinary, Geography, Ecology, Agricultural diversification, food and beverages, Agriculture, Biodiversity, Crop Production, Phylogenetics, Phylogeography, Biogeography, Conservation Genetics, Medicine, Research Article, Crops, Agricultural, Computer and Information Sciences, Ecological Metrics, Science, Crops, Biodiversity and Ecology, 03 medical and health sciences, Anthropocene, Genetics, Humans, Evolutionary Systematics, Taxonomy, 030304 developmental biology, Evolutionary Biology, Population Biology, business.industry, Ecology and Environmental Sciences, fungi, Biology and Life Sciences, Species diversity, Species Diversity, 15. Life on land, [SDE.ES]Environmental Sciences/Environmental and Society, Organismal Evolution, Phylogenetic diversity, Crop diversity, 13. Climate action, Earth Sciences, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, human activities, Population Genetics, Crop Science, 010606 plant biology & botany
Abstract: International audience; The Anthropocene epoch is partly defined by anthropogenic spread of crops beyond their centres of origin. At global scales, evidence indicates that species-level taxonomic diversity of crops being cultivated on large-scale agricultural lands has increased linearly over the past 50 years. Yet environmental and socioeconomic differences support expectations that temporal changes in crop diversity vary across regions. Ecological theory also suggests that changes in crop taxonomic diversity may not necessarily reflect changes in the evolutionary diversity of crops. We used data from the Food and Agricultural Organization (FAO) of the United Nations to assess changes in crop taxonomic-and phylogenetic diversity across 22 subcontinental-scale regions from 1961-2014. We document certain broad consistencies across nearly all regions: i) little change in crop diversity from 1961 through to the late 1970s; followed by ii) a 10-year period of sharp diversification through the early 1980s; followed by iii) a "levelling-off" of crop diversification beginning in the early 1990s. However, the specific onset and duration of these distinct periods differs significantly across regions and are unrelated to agricultural expansion, indicating that unique policy or environmental conditions influence the crops being grown within a given region. Additionally, while the 1970s and 1980s are defined by region-scale increases in crop diversity this period marks the increasing dominance of a small number of crop species and lineages; a trend resulting in detectable increases in the similarity of crops being grown across regions. Broad similarities in the species-level taxonomic and phylogenetic diversity of crops being grown across regions, primarily at large industrial scales captured by FAO data, represent a unique feature of the Anthropocene epoch. Yet nuanced asymmetries in regional-scale trends suggest that environmental and socioeconomic factors play a key role in shaping observed macro-ecological changes in the plant diversity on agricultural lands.
Published: 2019

42. Biochemical Diversity of Carboxyl Esterases and Lipases from Lake Arreo (Spain): a Metagenomic Approach

Author: Anatoli Tchigvintsev, Julio Polaina, Alexander F. Yakunin, Mónica Martínez-Martínez, María-Eugenia Guazzaroni, Manuel Ferrer, Albert Canet, Eugenio Rico Eguizabal, Francisco Valero, Álvaro Chicote, María del Carmen Guerrero, Rafael Bargiela, María Alcaide, Oleg N. Reva, Ministerio de Economía y Competitividad (España), European Commission, Ontario Genomics Institute, and Ontario Research Fund
Subjects: Models, Molecular, 0106 biological sciences, Oligonucleotides, 01 natural sciences, Applied Microbiology and Biotechnology, 03 medical and health sciences, chemistry.chemical_compound, Hydrolysis, Plasmid, 010608 biotechnology, Proteobacteria, Hydrolase, Cloning, Molecular, Enzymology and Protein Engineering, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Ecology, biology, Oligonucleotide, Temperature, Computational Biology, Lipase, Hydrogen-Ion Concentration, biology.organism_classification, Halophile, Lakes, Enzyme, Biochemistry, chemistry, Spain, 13. Climate action, Metagenome, Metagenomics, Carboxylic Ester Hydrolases, DNA, Food Science, Biotechnology
Abstract: The esterases and lipases from the α/β hydrolase superfamily exhibit an enormous sequence diversity, fold plasticity, and activities. Here, we present the comprehensive sequence and biochemical analyses of seven distinct esterases and lipases from the metagenome of Lake Arreo, an evaporite karstic lake in Spain (42°46=N, 2°59=W; altitude, 655 m). Together with oligonucleotide usage patterns and BLASTP analysis, our study of esterases/lipases mined from Lake Arreo suggests that its sediment contains moderately halophilic and cold-adapted proteobacteria containing DNA fragments of distantly related plasmids or chromosomal genomic islands of plasmid and phage origins. This metagenome encodes esterases/lipases with broad substrate profiles (tested over a set of 101 structurally diverse esters) and habitat-specific characteristics, as they exhibit maximal activity at alkaline pH (8.0 to 8.5) and temperature of 16 to 40°C, and they are stimulated (1.5 to 2.2 times) by chloride ions (0.1 to 1.2 M), reflecting an adaptation to environmental conditions. Our work provides further insights into the potential significance of the Lake Arreo esterases/lipases for biotechnology processes (i.e., production of enantiomers and sugar esters), because these enzymes are salt tolerant and are active at low temperatures and against a broad range of substrates. As an example, the ability of a single protein to hydrolyze triacylglycerols, (non)halogenated alkyl and aryl esters, cinnamoyl and carbohydrate esters, lactones, and chiral epoxides to a similar extent was demonstrated., We gratefully acknowledge the financial support provided by the Spanish Ministry of Economy and Competitiveness (project CSD2007-00005), the European Community project MAGICPAH (FP7-KBBE-2009-245226), the European Regional Development Fund (ERDF), and the Government of Canada through Genome Canada, Ontario Genomics Institute, and Ontario Research Fund (2009-OGI-ABC-1405 and ORF-GL2-01-004). M.-E.G. thanks the CSIC for a JAE fellowship.
Published: 2013
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43. Overview of the interactive task in BioCreative V

Author: Sophia Ananiadou, Laurel Cooper, Socorro Gama-Castro, Lars Juhl Jensen, Peter McQuilton, Raymund Stefancsik, Sérgio Matos, Emiliano Pereira, Matthew Mort, Nicole Vasilevsky, Qinghua Wang, Suresh Subramani, Hamsa D. Tadepally, Andrew Chatr-aryamontri, Georgios V. Gkoutos, David Salgado, Johanna McEntyre, Shruti Rao, Onkar Singh, Sherri Matis-Mitchell, Gabriela Contreras, Karen Rothfels, Jeyakumar Natarajan, S. Jimenez, Evangelos Pafilis, Shabbir Syed Abdul, Juliane Fluck, Cathy H. Wu, Barbra D. Ferrell, Lynette Hirschman, Raul Rodriguez-Esteban, Sangya Pundir, Raquel M. Silva, Xiaodong Wang, Fabio Rinaldi, Hong-Jie Dai, Afroza Khanam Irin, Hui-Jou Chou, Toni Rose Jue, Stanley J. F. Laulederkind, Zhiyong Lu, Riza Theresa Batista-Navarro, David Campos, Nancy George, Marija Milacic, Ingrid M. Keseler, Lucy Chilton, Lara Monteiro Almeida, Chu-Hsien Su, Cecilia N. Arighi, Sandra Orchard, Mary L. Schaeffer, Yalbi I. Balderas-Martínez, Kimberly Van Auken, Sumit Madan, Loukia Tsaprouni, University of Delaware [Newark], Taipei Medical University, Department of Electronics, Telecommunications and Informatics [Aveiro] (DETI), Universidade de Aveiro, National Centre for Text Mining [Manchester] (NaCTeM), University of Manchester [Manchester], Universidad Nacional Autónoma de México (UNAM), Ecology and Evolutionary Biology [Tucson] (EEB), University of Arizona, Newcastle University [Newcastle], Rutgers University [Camden], Rutgers University System (Rutgers), Department of Botany and Plant Pathology, Oregon State University (OSU), Department of Computer Science and Information Engineering, National Taitung University, Fraunhofer Institute for Intelligent Analysis and Information Systems (Fraunhofer IAIS), Fraunhofer (Fraunhofer-Gesellschaft), SourceData - EMBO, University of Birmingham [Birmingham], University of Bonn, University of Copenhagenn, Ecole Polytechnique Fédérale de Lausanne (EPFL), University of New South Wales [Sydney] (UNSW), SRI International [Menlo Park] (SRI), University of Oxford [Oxford], Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Institute of Medical Genetics, Cardiff University-School of Medicine, Bharathiar University, IMBBC, HCMR, Hellenic Centre for Marine Research (HCMR)-Hellenic Centre for Marine Research (HCMR), Laboratorio de Organizacion y Evolucion del Genoma, Universidad de la República [Montevideo] (UCUR), Georgetown University [Washington] (GU), Institute of Computational Linguistics, Universität Zürich [Zürich] = University of Zurich (UZH), Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Genetics, Cambridge University, University of Cambridge [UK] (CAM), Academia Sinica, Freelance scientific curator, University of Bedfordshire, Oregon Health and Science University [Portland] (OHSU), California Institute of Technology (CALTECH), Université de Montréal (UdeM), University of Wisconsin - Milwaukee, Reed Elsevier, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, F. Hoffmann-La Roche [Basel], National Center for Biotechnology Information (NCBI), University of Missouri [Columbia] (Mizzou), University of Missouri System, The MITRE corporation, National Institutes of Health [R13GM109648 to C.N.A., P41HG003751 and U54GM114833 to K.R. and M.M.], Intramural Research Program at National Library of Medicine to Z.L.], National Institutes of Health Office of Director [R24OD011883 to N.V.], the US Department of Energy [DE-SC0010838 to C.H.W. and L.H.], National Science Foundation [#1340112 to L.C., DBI#1356374 for B.F.], Ontario Research Fund, the European Molecular Biology Laboratory, Facultad de Ciencias, UNAM, the post-doctoral program fellowship from DGAPA-UNAM to Y.I.B.-M., Publica, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Universität Bonn = University of Bonn, University of Oxford, Universidad de la República [Montevideo] (UDELAR), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gall, Valérie
Subjects: 0301 basic medicine, Focus (computing), Electronic Data Processing, Information retrieval, business.industry, Computer science, Interface (Java), Usability, R1, Literature searching, General Biochemistry, Genetics and Molecular Biology, Task (project management), 03 medical and health sciences, 030104 developmental biology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Data Mining, Use case, Original Article, User interface, General Agricultural and Biological Sciences, business, Set (psychology), Data Curation, Information Systems
Abstract: Fully automated text mining (TM) systems promote efficient literature searching,\ud retrieval, and review but are not sufficient to produce ready-to-consume curated documents.\ud These systems are not meant to replace biocurators, but instead to assist them in\ud one or more literature curation steps. To do so, the user interface is an important aspect\ud that needs to be considered for tool adoption. The BioCreative Interactive task (IAT) is a\ud track designed for exploring user-system interactions, promoting development of useful\ud TM tools, and providing a communication channel between the biocuration and the TM\ud communities. In BioCreative V, the IAT track followed a format similar to previous interactive\ud tracks, where the utility and usability of TM tools, as well as the generation of use\ud cases, have been the focal points. The proposed curation tasks are user-centric and\ud formally evaluated by biocurators. In BioCreative V IAT, seven TM systems and 43 biocurators\ud participated. Two levels of user participation were offered to broaden curator involvement\ud and obtain more feedback on usability aspects. The full level participation\ud involved training on the system, curation of a set of documents with and without TM\ud assistance, tracking of time-on-task, and completion of a user survey. The partial level\ud participation was designed to focus on usability aspects of the interface and not the performance\ud per se. In this case, biocurators navigated the system by performing predesigned\ud tasks and then were asked whether they were able to achieve the task and the\ud level of difficulty in completing the task. In this manuscript, we describe the development of the interactive task, from planning to execution and discuss major findings for the systems tested.
Published: 2016

44. Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management

Author: M, Avila, D A, Dyment, J V, Sagen, J, St-Onge, U, Moog, B H Y, Chung, S, Mo, S, Mansour, A, Albanese, S, Garcia, D O, Martin, A A, Lopez, T, Claudi, R, König, S M, White, S L, Sawyer, J A, Bernstein, L, Slattery, R K, Jobling, G, Yoon, C J, Curry, M L, Merrer, B L, Luyer, D, Héron, M, Mathieu-Dramard, P, Bitoun, S, Odent, J, Amiel, P, Kuentz, J, Thevenon, M, Laville, Y, Reznik, C, Fagour, M-L, Nunes, D, Delesalle, S, Manouvrier, O, Lascols, F, Huet, C, Binquet, L, Faivre, J-B, Rivière, C, Vigouroux, P R, Njølstad, A M, Innes, C, Thauvin-Robinet, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Children's hospital of Eastern Ontario Research Institute, University of Bergen (UiB), Haukeland University Hospital, Human Genetics Institute, Heidelberg University, Department of Paediatrics and Adolescent Medicine [HKU], The University of Hong Kong (HKU), SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, St George's Hospital, INGEMM, Instituto de Genética Médica y Molecular, IDIPAZ-Hospital Universitario La Paz, Instituto de Salud Carlos III [Madrid] (ISC), Hospital Central de la Cruz Roja San Jose y Santa Adela, University Hospital Puerta de Hierro, Madrid, Bodø University College, Humangenetik, Universitätsklinikum Frankfurt, University of Frankfurt, University of Melbourne, Victorian Clinical Genetics Services, Stanford University, The Hospital for sick children [Toronto] (SickKids), University of California [San Francisco] (UCSF), University of California, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CH Le Havre, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], CHU Amiens-Picardie, Service de Pédiatrie [Jean Verdier], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Bordeaux [Bordeaux], CH Valenciennes, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Calgary, Financial support was from the Regional Council of Burgundy and the Care4Rare Canada Consortium was funded by Genome Canada, the Canadian Institutes of Health Research, the Ontario Genomics Institute, Ontario Research Fund, Genome Quebec, and Children’sHospital of Eastern Ontario Foundation. DAD is the recipient of a CIHR Clinical Investigator award from the Institute of Genetics. PRN was supported in part by grants from the Research Council of Norway, The University of Bergen, an ERC Advanced Grant, Helse Vest and the KG Jebsen Foundation., SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, University of Bergen (UIB), Instituto de Salud Carlos III (ISC), Stanford University [Stanford], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Service de neuropédiatrie [Trousseau], Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Recherche Clinique, Université Joseph Fourier - Grenoble 1 (UJF)-Centre de Recherche en Nutrition Humaine Rhône - Alpes, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, University of Bergen ( UIB ), The University of Hong Kong ( HKU ), Instituto de Salud Carlos III (ISCIII) - Spain RDR - CIBERER, University of California [San Francisco] ( UCSF ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Référence des Déficiences Intellectuelles de Causes Rares, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme ( GRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris 13 ( UP13 ) -Hôpital Jean Verdier, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cardiovasculaire, métabolisme, diabétologie et nutrition ( CarMeN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hospices Civils de Lyon ( HCL ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National de la Recherche Agronomique ( INRA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre de Recherche en Nutrition Humaine Rhône - Alpes, Cancers et préventions, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Bordeaux, Service de Génétique Clinique et Université Lille 2, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN)
Subjects: short stature, lipoatrophy, intrauterine growth restriction, [ SDV ] Life Sciences [q-bio], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], Diabetes, PIK3R1 gene, Insulin Resistance, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, SHORT syndrome
Abstract: International audience; SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.
Published: 2015

45. Digestive proteases in bodies and faeces of the two-spotted spider mite, Tetranychus urticae

Author: Pedro Castañera, Manuel Martinez, Maria Estrella Santamaria, Vojislava Grbic, Joel González-Cabrera, Félix Ortego, Lsabel Díaz, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), Genome Canada, Ontario Genomics Institute, and Ontario Research Fund
Subjects: Proteomics, Proteases, Physiology, Trypsin inhibitor, Gene Expression, Legumain, Feces, Spider mite, parasitic diseases, Mite, Animals, Tetranychus urticae, Plant Proteins, Phytophagous mites, Cathepsin, biology, Serine Endopeptidases, Cystatin, Plants, Protease inhibitors, biology.organism_classification, Cathepsins, Cysteine Endopeptidases, Biochemistry, Insect Science, biology.protein, Female, Tetranychidae, Digestive System, Peptide Hydrolases
Abstract: 31 p.-3 fig.-3 tab.-2 fig. supl.-1 tab. supl., Digestive proteases of the phytophagous mite Tetranychus urticae have been characterised by comparing their activity in body and faecal extracts. Aspartyl, cathepsin B- and L-like and legumain activities were detected in both mite bodies and faeces, with a specific activity of aspartyl and cathepsin L-like proteases about 5- and 2-fold higher, respectively, in mite faeces than in bodies. In general, all these activities were maintained independently of the host plant where the mites were reared (bean, tomato or maize). Remarkably, this is the first report in a phytophagous mite of legumain-like activity, which was characterised for its ability to hydrolyse the specific substrate Z-VAN-AMC, its activation by DTT and inhibition by IAA but not by E-64. Gel free nanoLC–nanoESI-QTOF MS/MS proteomic analysis of mite faeces resulted in the identification of four cathepsins L and one aspartyl protease (from a total of the 29 cathepsins L, 27 cathepsins B, 19 legumains and two aspartyl protease genes identified the genome of this species). Gene expression analysis reveals that four cathepsins L and the aspartyl protease identified in the mite faeces, but also two cathepsins B and two legumains that were not detected in the faeces, were expressed at high levels in the spider mite feeding stages (larvae, nymphs and adults) relative to embryos. Taken together, these results indicate a digestive role for cysteine and aspartyl proteases in T. urticae. The expression of the cathepsins B and L, legumains and aspartyl protease genes analysed in our study increased in female adults after feeding on Arabidopsis plants over-expressing the HvCPI-6 cystatin, that specifically targets cathepsins B and L, or the CMe trypsin inhibitor that targets serine proteases. This unspecific response suggests that in addition to compensation for inhibitor-targeted enzymes, the increase in the expression of digestive proteases in T. urticae may act as a first barrier against ingested plant defensive proteins., This work was supported by a Grant from CSIC (Grant CSIC-201040E049 to F.O), Ministerio de Ciencia e Innovación (Grant AGL11-23650 to I.D.) and the Government of Canada through Genome Canada and the Ontario Genomics Institute (Grant OGI-046 to V.G.), and the Ontario Research Fund-Global Leadership in Genomics and Life Sciences (Grant GL2-01-035 to V.G.).
Published: 2015

46. Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci

Author: Mathieu Lemire, Syed H.E. Zaidi, Maria Ban, Bing Ge, Dylan Aïssi, Marine Germain, Irfahan Kassam, Mike Wang, Brent W. Zanke, France Gagnon, Pierre-Emmanuel Morange, David-Alexandre Trégouët, Philip S. Wells, Stephen Sawcer, Steven Gallinger, Tomi Pastinen, Thomas J. Hudson, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), McGill University = Université McGill [Montréal, Canada], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Dalla Lana School of Public Health, University of Toronto, Department of medecine, University of Ottawa [Ottawa], Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Division of general surgery, Toronto General Hospital, Department of Molecular Genetics [Toronto], Department of Medical Biophysics (MBP), Ontario Research Fund (GL2 competition), Canadian Institutes of Health Research, Ontario Institute for Cancer Research from the Ontario Ministry of Research and Innovation, National Cancer Institute, National Institutes of Health [CA-95-011], Cambridge NIHR Biomedical Research Centre, UK Medical Research Council [G1100125], CIHR, FRSQ (RMGA), Program Hospitalier de Recherche Clinique, GenMed LABEX [ANR-10-LABX-0013], Canadian Institutes of Health Research [MOP 86466, MOP86466], Heart and Stroke Foundation of Canada [T6484], Region Ile de France, Pierre and Marie Curie University, ICAN Institute for Cardiometabolism and Nutrition, [ANR-10-IAHU-05], Region Ile de France (CORDDIM), European Project: 201413,EC:FP7:HEALTH,FP7-HEALTH-2007-A,ENGAGE(2008), Université McGill, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], University of Ottawa [Ottawa] (uOttawa), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'hématologie, Mount Sinai Hospital (MSH), Administateur, HAL Sorbonne Université, European Network for Genetic and Genomic Epidemiology - ENGAGE - - EC:FP7:HEALTH2008-01-01 - 2012-12-31 - 201413 - VALID, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Lemire, Mathieu
Subjects: Genotype, Molecular biology, Quantitative Trait Loci, General Physics and Astronomy, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Autoimmune Diseases, Epigenesis, Genetic, Génétique humaine, Human genetics, Genetic variation, Genetics, Humans, Epigenetics, Lymphocytes, RNA-Directed DNA Methylation, Multidisciplinary, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Chemistry, Methylation, DNA Methylation, Biological sciences, CpG site, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Case-Control Studies, DNA methylation, Expression quantitative trait loci, Colonic Neoplasms, CpG Islands
Abstract: The interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (P1 Mb apart. Over 90% of these pairs are replicated (FDR, There is a functional link between SNPs and epigenetic variations when they are in close range, but the long-range effect is unclear. Here, by analysing methylation quantitative trait loci, the authors demonstrate that methylation levels at CpG sites in lymphocytes are correlated with distal SNPs.
Published: 2015

47. Tomato Whole Genome Transcriptional Response to Tetranychus urticae Identifies Divergence of Spider Mite-Induced Responses Between Tomato and Arabidopsis

Author: Nicky Wybouw, Catherine Martel, Marc Cazaux, Vojislava Grbic, Marie Navarro, Maria Navajas, Miodrag Grbic, Vladimir Zhurov, Isabel Diaz, M. Estrella Santamaria, Thomas Van Leeuwen, Alain Migeon, Philippe Auger, Manuel Martinez, Evolutionary Biology (IBED, FNWI), Department of Biology, Northern Arizona University [Flagstaff], Instituto de Ciencias de la Vid y el Vino - Institute of Grapevine and Wine Sciences, Partenaires INRAE, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), University of Western Ontario (UWO), Department of Crop Protection, Universiteit Gent = Ghent University [Belgium] (UGENT), Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam [Amsterdam] (UvA), Government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-046) (to M. Grbic and V. Grbic), Ontario Research Fund–Global Leadership in Genomics and Life Sciences GL2-01-0 35 (to M. Grbic and V. Grbic), ANR 2010 BLAN 1715 02) (to M. Navajas), FWO Grants 3G061011 and 3G009312, and Institute for the Promotion of Innovation by Science and Technology
Subjects: Arabidopsis thaliana, genetic structures, Physiology, Propanols, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Arabidopsis, Cyclopentanes, Biology, Host-Parasite Interactions, spider mite, chemistry.chemical_compound, Solanum lycopersicum, Plant Growth Regulators, Spider mite, Botany, Mite, Animals, Wild tomato, Tetranychus urticae, Herbivory, Oxylipins, transcriptional responses, Oligonucleotide Array Sequence Analysis, Plant Diseases, Flavonoids, Terpenes, Jasmonic acid, Gene Expression Profiling, fungi, food and beverages, General Medicine, biology.organism_classification, Gene Ontology, chemistry, Solanum, Tetranychidae, Agronomy and Crop Science, Signal Transduction
Abstract: International audience; The two-spotted spider mite Tetranychus urticae is one of the most significant mite pests in agriculture, feeding on more than 1,100 plant hosts, including model plants Arabidopsis thaliana and tomato, Solanum lycopersicum. Here, we describe timecourse tomato transcriptional responses to spider mite feeding and compare them with Arabidopsis in order to determine conserved and divergent defense responses to this pest. To refine the involvement of jasmonic acid (JA) in mite-induced responses and to improve tomato Gene Ontology annotations, we analyzed transcriptional changes in the tomato JA-signaling mutant defenseless1 (def-1) upon JA treatment and spider mite herbivory. Overlay of differentially expressed genes (DEG) identified in def-1 onto those from the timecourse experiment established that JA controls expression of the majority of genes differentially regulated by herbivory. Comparison of defense responses between tomato and Arabidopsis highlighted 96 orthologous genes (of 2,133 DEG) that were recruited for defense against spider mites in both species. These genes, involved in biosynthesis of JA, phenylpropanoids, flavonoids, and terpenoids, represent the conserved core of induced defenses. The remaining tomato DEG support the establishment of tomato-specific defenses, indicating profound divergence of spider mite–induced responses between tomato and Arabidopsis.
Published: 2015

48. A proteome-scale map of the human interactome network

Author: Mike Jin, Julie M. Sahalie, Andrew MacWilliams, Jean-Claude Twizere, Patrick Aloy, Patrick Reichert, Lilia M. Iakoucheva, Song Yi, Martin P. Broly, Roberto Mosca, John Rasla, Stanley Tam, Yu Xia, Amélie Dricot, Marc Vidal, Bryan J. Gutierrez, Viviana Romero, Annemarie Scholz, David E. Hill, Shuli Kang, Irma Lemmens, Michael A. Calderwood, Roser Corominas, Yun Shen, Murat Tasan, Javier De Las Rivas, Pascal Braun, Kerstin Spirohn, Shelly A. Trigg, Guan Ning Lin, Elizabeth Dann, Xinping Yang, Michael E. Cusick, Amitabh Sharma, Nidhi Sahni, Xavier Rambout, Kerwin Vega, Fana Gebreab, Dan Convery-Zupan, Ryan R. Murray, Akash A. Shah, Bridget E. Begg, Eric A. Franzosa, Alexander O. Tejeda, Jasmin Coulombe-Huntington, Anne-Ruxandra Carvunis, Madeleine F. Hardy, Atanas Kamburov, Dawit Balcha, Ruth Kiros, Matthew M. Poulin, Elien Ruyssinck, Alexandre Palagi, Thomas Rolland, Susan Dina Ghiassian, Celia Fontanillo, Lila Ghamsari, Jan Tavernier, Samuel J. Pevzner, Katja Luck, Jörg Menche, Frederick P. Roth, Benoit Charloteaux, Matija Dreze, Tong Hao, Albert-László Barabási, Marc Brehme, Jennifer M. Walsh, Quan Zhong, Changyu Fan, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Ontario Research Fund, Avon Foundation for Women, Government of Canada, Krembil Foundation, European Commission, Research Foundation - Flanders, European Research Council, Ghent University, EMBO, Dana Foundation, Fonds de la Recherche Scientifique (Fédération Wallonie-Bruxelles), Celgene, National Cancer Institute (US), National Institutes of Health (US), National Science Foundation (US), and National Human Genome Research Institute (US)
Subjects: Proteome, Computational biology, Biology, Interactome, General Biochemistry, Genetics and Molecular Biology, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Human interactome, Neoplasms, Animals, Humans, Protein Interaction Maps, Databases, Protein, 030304 developmental biology, Genetics, 0303 health sciences, Biochemistry, Genetics and Molecular Biology(all), Human genetics, Homogeneous, Cancer gene, 030217 neurology & neurosurgery, Protein Interaction Map, Genome-Wide Association Study, Reference genome
Abstract: PMCID: PMC4266588.-- et al., Just as reference genome sequences revolutionized human genetics, reference maps of interactome networks will be critical to fully understand genotype-phenotype relationships. Here, we describe a systematic map of ∼14,000 high-quality human binary protein-protein interactions. At equal quality, this map is ∼30% larger than what is available from small-scale studies published in the literature in the last few decades. While currently available information is highly biased and only covers a relatively small portion of the proteome, our systematic map appears strikingly more homogeneous, revealing a >broader> human interactome network than currently appreciated. The map also uncovers significant interconnectivity between known and candidate cancer gene products, providing unbiased evidence for an expanded functional cancer landscape, while demonstrating how high-quality interactome models will help >connect the dots> of the genomic revolution., This work was supported primarily by NHGRI grant R01/U01HG001715 awarded to M.V., D.E.H., F.P.R., and J.T. and in part by the following grants and agencies: NHGRI P50HG004233 to M.V., F.P.R., and A.-L.B.; NHLBI U01HL098166 subaward to M.V.; NHLBI U01HL108630 subaward to A.-L.B.; NCI U54CA112962 subaward to M.V.; NCI R33CA132073 to M.V.; NIH RC4HG006066 to M.V., D.E.H., and T.H.; NICHD ARRA R01HD065288, R21MH104766, and R01MH105524 to L.M.I.; NIMH R01MH091350 to L.M.I. and T.H.; NSF CCF-1219007 and NSERC RGPIN-2014-03892 to Y.X.; Canada Excellence Research Chair, Krembil Foundation, Ontario Research Fund–Research Excellence Award, Avon Foundation, grant CSI07A09 from Junta de Castilla y Leon (Valladolid, Spain), grant PI12/00624 from Ministerio de Economia y Competitividad (AES 2012, ISCiii, Madrid, Spain), and grant i-Link0398 from Consejo Superior de Investigaciones Científicas (CSIC, Madrid, Spain) to J.D.L.R.; Spanish Ministerio de Ciencia e Innovación (BIO2010-22073) and the European Commission through the FP7 project SyStemAge grant agreement n: 306240 to P.A.; Group-ID Multidisciplinary Research Partnerships of Ghent University, grant FWO-V G.0864.10 from the Fund for Scientific Research-Flanders and ERC Advanced Grant N° 340941 to J.T.; EMBO long-term fellowship to A.K.; Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative to M.V. I.L. is a postdoctoral fellow with the FWO-V. M.V. is a “Chercheur Qualifié Honoraire” from the Fonds de la Recherche Scientifique (FRS-FNRS, Wallonia-Brussels Federation, Belgium). Since performing the work described, C. Fontanillo has become an employee of Celgene Research SL, part of the Celgene Corporation.
Published: 2014

49. The influence of landscape on gene flow in the eastern massasauga rattlesnake (Sistrurus c. catenatus): insight from computer simulations

Author: Jeremy D. Rouse, Stephen C. Lougheed, Michelle F. DiLeo, José A. Dávila, Natural Sciences and Engineering Research Council of Canada, University of Guelph, U.S. Fisheries and Wildlife Service, Ontario Ministry of Natural Resources and Forestry, World Wildlife Fund, National Geographic Society, and Ontario Research Fund
Subjects: Gene Flow, Simulations, Population, Population genetics, Landscape genetics, Gene flow, Genetics, Animals, Cluster Analysis, Computer Simulation, education, Ecosystem, Ecology, Evolution, Behavior and Systematics, Ontario, education.field_of_study, Geography, Models, Genetic, Resistance (ecology), biology, Ecology, Sistrurus, Crotalus, Bayes Theorem, Anthropogenic disturbances, biology.organism_classification, Genetics, Population, DNA microsatellites, Massasauga rattlesnake, Genetic structure, Biological dispersal, CDPOP, Replicate landscapes
Abstract: Understanding how gene flow shapes contemporary population structure requires the explicit consideration of landscape composition and configuration. New landscape genetic approaches allow us to link such heterogeneity to gene flow within and among populations. However, the attribution of cause is difficult when landscape features are spatially correlated, or when genetic patterns reflect past events. We use spatial Bayesian clustering and landscape resistance analysis to identify the landscape features that influence gene flow across two regional populations of the eastern massasauga rattlesnake, Sistrurus c. catenatus. Based on spatially explicit simulations, we inferred how habitat distribution modulates gene flow and attempted to disentangle the effects of spatially confounded landscape features. We found genetic clustering across one regional landscape but not the other, and also local differences in the effect of landscape on gene flow. Beyond the effects of isolation-by-distance, water bodies appear to underlie genetic differentiation among individuals in one regional population. Significant effects of roads were additionally detected locally, but these effects are possibly confounded with the signal of water bodies. In contrast, we found no signal of isolation-by-distance or landscape effects on genetic structure in the other regional population. Our simulations imply that these local differences have arisen as a result of differences in population density or tendencies for juvenile rather than adult dispersal. Importantly, our simulations also demonstrate that the ability to detect the consequences of contemporary anthropogenic landscape features (e.g. roads) on gene flow may be compromised when long-standing natural features (e.g. water bodies) co-exist on the landscape., This work was supported by an NSERC Discovery Grant (SCL), a postgraduate scholarship (MFD), Sigma-Xi Grants-in-Aid-of-Research (MFD), a National Geographic Young Explorers Grant (MFD) and Parks Canada. We gratefully acknowledge the support of WWF-Canada, Environment Canada and the Ontario Ministry of Natural Resources through the Endangered Species Recovery Fund and Species at Risk Research Fund for Ontario.
Published: 2013

50. Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk

Author: Rik Vandenberghe, Maria Mattheijssens, Kristel Sleegers, Nathalie Brouwers, Nathalie Le Bastard, Ekaterina Rogaeva, Richard Mayeux, Jean-Charles Lambert, Sebastiaan Engelborghs, Peter St George-Hyslop, Peter Paul De Deyn, Christine Van Broeckhoven, Steven Vermeulen, Karolien Bettens, Philippe Amouyel, Florence Pasquier, Karin Peeters, Jasper Van Dongen, St George-Hyslop, Peter [0000-0003-0796-7209], Apollo - University of Cambridge Repository, Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Institute Born-Bunge, University of Antwerp (UA), Department of Neurology and Memory Clinic, Hospital Network Antwerp Middelheim and Hoge Beuken, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, 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, Droit et Santé, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medicine (Neurology), University of Toronto-Centre for Research in Neurodegenerative Diseases, Department of Neurology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospitals Leuven [Leuven], Gertrude H. Sergievsky Center, Columbia University [New York], Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), The research at the Antwerp site was in part supported by the Interuniversity Attraction Poles program P6/43 of the Belgian Science Policy Office (BELSPO, http://www.belspo.be/), the Foundation for Alzheimer Research (SAO/FRMA, http://alzh.org/), a Methusalem Excellence Grant of the Flemish Government (EWI, http://www.ewi-vlaanderen.be/), the Research Foundation Flanders (FWO, http://www.fwo.be/), the Special Research Fund of the University of Antwerp (UA, http://www.ua.ac.be/), the Antwerp Medical Research Foundation and Neurosearch, Belgium. KB, NB and KS are postdoctoral fellows, and RV a senior clinical investigator of the FWO. The Lille site was funded in part by the National Foundation for Alzheimer's disease and related disorders, the Institute Pasteur de Lille and INSERM. The Toronto site was supported by grants from the Canadian Institutes of Health Research, Ontario Research Fund, Weston foundation (PSH), the Howard Hughes Medical Institute, The Wellcome Trust, the Alzheimer Society of Ontario (PSH)., BMC, Ed., Clinical sciences, and Neurology
Subjects: Male, Genome-wide association study, lcsh:Geriatrics, lcsh:RC346-429, Cohort Studies, clusterin gene (CLU), 0302 clinical medicine, Gene Frequency, Risk Factors, b?β?-chain domain, European Continental Ancestry Group/genetics, genomic resequencing, Sequence Deletion, Medicine(all), Aged, 80 and over, Genetics, 0303 health sciences, biology, Alzheimer's disease--Research, Chromosome Mapping, Exons, Middle Aged, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Research Article, Canada, Genotype, Clinical Neurology, Single-nucleotide polymorphism, Locus (genetics), Medical sciences, Polymorphism, Single Nucleotide, White People, Amino acid sequence, 03 medical and health sciences, Cellular and Molecular Neuroscience, Alzheimer Disease, insertions/deletions, Humans, SNP, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Allele, Molecular Biology, Allele frequency, lcsh:Neurology. Diseases of the nervous system, Alleles, Aged, 030304 developmental biology, Genetic association, Alzheimer Disease/genetics, Clusterin, FOS: Clinical medicine, Neurosciences, Genetic Variation, β-chain domain, meta-analysis, lcsh:RC952-954.6, non-synonymous substitutions, Mutagenesis, Insertional, Nervous system--Degeneration--Genetic aspects, FOS: Biological sciences, insertions/ deletions, biology.protein, Human medicine, Neurology (clinical), Clusterin/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Background We have followed-up on the recent genome-wide association (GWA) of the clusterin gene (CLU) with increased risk for Alzheimer disease (AD), by performing an unbiased resequencing of all CLU coding exons and regulatory regions in an extended Flanders-Belgian cohort of Caucasian AD patients and control individuals (n = 1930). Moreover, we have replicated genetic findings by targeted resequencing in independent Caucasian cohorts of French (n = 2182) and Canadian (n = 573) origin and by performing meta-analysis combining our data with previous genetic CLU screenings. Results In the Flanders-Belgian cohort, we identified significant clustering in exons 5-8 of rare genetic variations leading to non-synonymous substitutions and a 9-bp insertion/deletion affecting the CLU β-chain (p = 0.02). Replicating this observation by targeted resequencing of CLU exons 5-8 in 2 independent Caucasian cohorts of French and Canadian origin identified identical as well as novel non-synonymous substitutions and small insertion/deletions. A meta-analysis, combining the datasets of the 3 cohorts with published CLU sequencing data, confirmed that rare coding variations in the CLU β-chain were significantly enriched in AD patients (ORMH = 1.96 [95% CI = 1.18-3.25]; p = 0.009). Single nucleotide polymorphisms (SNPs) association analysis indicated the common AD risk association (GWA SNP rs11136000, p = 0.013) in the 3 combined datasets could not be explained by the presence of the rare coding variations we identified. Further, high-density SNP mapping in the CLU locus mapped the common association signal to a more 5' CLU region. Conclusions We identified a new genetic risk association of AD with rare coding CLU variations that is independent of the 5' common association signal identified in the GWA studies. At this stage the role of these coding variations and their likely effect on the β-chain domain and CLU protein functioning remains unclear and requires further studies.
Published: 2012

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