45 results on '"Lees, Jonathan P."'
Search Results
2. Local Change Point Detection and Cleaning of EEMD Signals with Application to Acoustic Shockwaves
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Hoffman, Kentaro, Lees, Jonathan M., and Zhang, Kai
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Electrical Engineering and Systems Science - Signal Processing - Abstract
The Ensemble Empirical Mode Decomposition (EEMD) has become a preferred technique to decompose nonlinear and non-stationary signals due to its ability to create time-varying basis functions. However, current EEMD signal cleaning techniques are unable to deal with situations where a signal only occurs for a portion of the entire recording length. By combining change point detection and statistical hypothesis testing, we demonstrate how to clean a signal to emphasize unique local changes within each basis function. This not only allows us to observe which frequency bands are undergoing a change, but also leads to improved recovery of the underlying information. Using this technique, we demonstrate improved signal cleaning performance for acoustic shockwave signal detection. The technique is implemented in R via the LCDSC package.
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- 2021
3. The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens
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Zhou, Naihui, Jiang, Yuxiang, Bergquist, Timothy R, Lee, Alexandra J, Kacsoh, Balint Z, Crocker, Alex W, Lewis, Kimberley A, Georghiou, George, Nguyen, Huy N, Hamid, Md Nafiz, Davis, Larry, Dogan, Tunca, Atalay, Volkan, Rifaioglu, Ahmet S, Dalkıran, Alperen, Cetin Atalay, Rengul, Zhang, Chengxin, Hurto, Rebecca L, Freddolino, Peter L, Zhang, Yang, Bhat, Prajwal, Supek, Fran, Fernández, José M, Gemovic, Branislava, Perovic, Vladimir R, Davidović, Radoslav S, Sumonja, Neven, Veljkovic, Nevena, Asgari, Ehsaneddin, Mofrad, Mohammad RK, Profiti, Giuseppe, Savojardo, Castrense, Martelli, Pier Luigi, Casadio, Rita, Boecker, Florian, Schoof, Heiko, Kahanda, Indika, Thurlby, Natalie, McHardy, Alice C, Renaux, Alexandre, Saidi, Rabie, Gough, Julian, Freitas, Alex A, Antczak, Magdalena, Fabris, Fabio, Wass, Mark N, Hou, Jie, Cheng, Jianlin, Wang, Zheng, Romero, Alfonso E, Paccanaro, Alberto, Yang, Haixuan, Goldberg, Tatyana, Zhao, Chenguang, Holm, Liisa, Törönen, Petri, Medlar, Alan J, Zosa, Elaine, Borukhov, Itamar, Novikov, Ilya, Wilkins, Angela, Lichtarge, Olivier, Chi, Po-Han, Tseng, Wei-Cheng, Linial, Michal, Rose, Peter W, Dessimoz, Christophe, Vidulin, Vedrana, Dzeroski, Saso, Sillitoe, Ian, Das, Sayoni, Lees, Jonathan Gill, Jones, David T, Wan, Cen, Cozzetto, Domenico, Fa, Rui, Torres, Mateo, Warwick Vesztrocy, Alex, Rodriguez, Jose Manuel, Tress, Michael L, Frasca, Marco, Notaro, Marco, Grossi, Giuliano, Petrini, Alessandro, Re, Matteo, Valentini, Giorgio, Mesiti, Marco, Roche, Daniel B, Reeb, Jonas, Ritchie, David W, Aridhi, Sabeur, Alborzi, Seyed Ziaeddin, Devignes, Marie-Dominique, Koo, Da Chen Emily, Bonneau, Richard, Gligorijević, Vladimir, Barot, Meet, Fang, Hai, Toppo, Stefano, and Lavezzo, Enrico
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Human Genome ,Networking and Information Technology R&D (NITRD) ,Genetics ,Generic health relevance ,Animals ,Biofilms ,Candida albicans ,Drosophila melanogaster ,Genome ,Bacterial ,Genome ,Fungal ,Humans ,Locomotion ,Memory ,Long-Term ,Molecular Sequence Annotation ,Pseudomonas aeruginosa ,Protein function prediction ,Long-term memory ,Biofilm ,Critical assessment ,Community challenge ,Environmental Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.
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- 2019
4. Enhanced HIV SOSIP Envelope yields in plants through transient co-expression of peptidyl-prolyl isomerase B and calreticulin chaperones and ER targeting
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Rosenberg, Yvonne J., Jiang, Xiaoming, Lees, Jonathan P., Urban, Lori A., Mao, Lingjun, and Sack, Markus
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- 2022
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5. Post-exposure treatment with the oxime RS194B rapidly reactivates and reverses advanced symptoms of lethal inhaled paraoxon in macaques
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Rosenberg, Yvonne J, Wang, Jerry, Ooms, Tara, Rajendran, Narayanan, Mao, Lingjun, Jiang, Xiaoming, Lees, Jonathan, Urban, Lori, Momper, Jeremiah D, Sepulveda, Yadira, Shyong, Yan-Jye, and Taylor, Palmer
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Neurosciences ,Prevention ,Biodefense ,Vaccine Related ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Acetamides ,Acetylcholinesterase ,Aerosols ,Animals ,Butyrylcholinesterase ,Chemical Warfare Agents ,Cholinesterase Inhibitors ,Cholinesterase Reactivators ,Female ,Inhalation Exposure ,Insecticides ,Macaca mulatta ,Organophosphate Poisoning ,Oximes ,Paraoxon ,Oxime antidote ,Nebulized paraoxon ,Macaques ,AChE ,BChE ,Reactivation ,IM ,Ma ,OP ,Px ,Reactivation. ,acetylcholinesterase ,butyrylcholinesterase ,intramuscular ,macaque ,organophosphate ,paraoxon ,Environmental Science and Management ,Toxicology ,Pharmacology and pharmaceutical sciences ,Pollution and contamination - Abstract
Fatalities from organophosphate (OP) insecticide result from both occupational and deliberate exposure; significantly impacting human health. Like nerve agents, insecticides are neurotoxins which target and inhibit acetylcholinesterases (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with a pyridinium aldoxime e.g. pralidoxime, to reactivate the OP-inhibited AChE. However, commonly used oximes inefficiently cross the bloodbrain barrier and are rapidly cleared and their benefit is debated. Recent findings have demonstrated the ability of a novel zwitterionic, centrally acting, brain penetrating oxime (RS194B) to reverse severe symptoms and rapidly reactivate sarin-inhibited AChE in macaques, but it has not been tested following OP pesticide poisoning. In the present study, the symptoms following a lethal dose of inhaled paraoxon (100ug/kg), were shown to mimic those in insecticide poisoned individuals and were also rapidly reversed in macaques by post-exposure IM administration of 80mg/kg of RS194B. This occurred with a concomitant reactivation of AChE to 40-100% in
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- 2018
6. Acoustic observations of lava fountain activity during the 2021 Fagradalsfjall eruption, Iceland
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Lamb, Oliver D., Gestrich, Julia E., Barnie, Talfan D., Jónsdóttir, Kristín, Ducrocq, Cécile, Shore, Michael J., Lees, Jonathan M., and Lee, Stephen J.
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- 2022
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7. Personalized Learning in Wisconsin: FLIGHT Academy. Connect: Making Learning Personal
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Temple University, Center on Innovations in Learning, Taege, Jeffrey, Krauter, Krista, and Lees, Jonathan
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This field report is the third in a series produced by the Center on Innovations in Learning's League of Innovators. The series describes, discusses, and analyzes policies and practices that enable personalization in education. Issues of the series will present either issue briefs or, like this one, field reports on lessons learned by practitioners recounting the successes and obstacles to success encountered in implementing personalized learning. This issue is a field report on the FLIGHT (Facilitating Learning through Integration, Guidance, High expectations, and Technology) Academy in Waukesha, Wisconsin. The FLIGHT Academy is a personalized learning program functioning within a traditional school model. The diversity of students in the program is representative of the school district. The program provides services for students with learning and emotional disabilities, students who are English language learners, and students who are gifted and talented. There is no grade or ability requirement to enroll in FLIGHT; students and their parents only have to fill out an application showing interest. This field report describes the steps that went into the development of the FLIGHT Academy, and the modifications that have been made to the program in response to various challenges that surfaced after the implementation of the program.
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- 2015
8. An expanded evaluation of protein function prediction methods shows an improvement in accuracy
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Jiang, Yuxiang, Oron, Tal Ronnen, Clark, Wyatt T, Bankapur, Asma R, D'Andrea, Daniel, Lepore, Rosalba, Funk, Christopher S, Kahanda, Indika, Verspoor, Karin M, Ben-Hur, Asa, Koo, Emily, Penfold-Brown, Duncan, Shasha, Dennis, Youngs, Noah, Bonneau, Richard, Lin, Alexandra, Sahraeian, Sayed ME, Martelli, Pier Luigi, Profiti, Giuseppe, Casadio, Rita, Cao, Renzhi, Zhong, Zhaolong, Cheng, Jianlin, Altenhoff, Adrian, Skunca, Nives, Dessimoz, Christophe, Dogan, Tunca, Hakala, Kai, Kaewphan, Suwisa, Mehryary, Farrokh, Salakoski, Tapio, Ginter, Filip, Fang, Hai, Smithers, Ben, Oates, Matt, Gough, Julian, Törönen, Petri, Koskinen, Patrik, Holm, Liisa, Chen, Ching-Tai, Hsu, Wen-Lian, Bryson, Kevin, Cozzetto, Domenico, Minneci, Federico, Jones, David T, Chapman, Samuel, C., Dukka B K., Khan, Ishita K, Kihara, Daisuke, Ofer, Dan, Rappoport, Nadav, Stern, Amos, Cibrian-Uhalte, Elena, Denny, Paul, Foulger, Rebecca E, Hieta, Reija, Legge, Duncan, Lovering, Ruth C, Magrane, Michele, Melidoni, Anna N, Mutowo-Meullenet, Prudence, Pichler, Klemens, Shypitsyna, Aleksandra, Li, Biao, Zakeri, Pooya, ElShal, Sarah, Tranchevent, Léon-Charles, Das, Sayoni, Dawson, Natalie L, Lee, David, Lees, Jonathan G, Sillitoe, Ian, Bhat, Prajwal, Nepusz, Tamás, Romero, Alfonso E, Sasidharan, Rajkumar, Yang, Haixuan, Paccanaro, Alberto, Gillis, Jesse, Sedeño-Cortés, Adriana E, Pavlidis, Paul, Feng, Shou, Cejuela, Juan M, Goldberg, Tatyana, Hamp, Tobias, Richter, Lothar, Salamov, Asaf, Gabaldon, Toni, Marcet-Houben, Marina, Supek, Fran, Gong, Qingtian, Ning, Wei, Zhou, Yuanpeng, Tian, Weidong, Falda, Marco, Fontana, Paolo, Lavezzo, Enrico, Toppo, Stefano, Ferrari, Carlo, Giollo, Manuel, Piovesan, Damiano, Tosatto, Silvio, del Pozo, Angela, Fernández, José M, Maietta, Paolo, Valencia, Alfonso, Tress, Michael L, Benso, Alfredo, Di Carlo, Stefano, Politano, Gianfranco, Savino, Alessandro, Rehman, Hafeez Ur, Re, Matteo, Mesiti, Marco, Valentini, Giorgio, Bargsten, Joachim W, van Dijk, Aalt DJ, Gemovic, Branislava, Glisic, Sanja, Perovic, Vladmir, Veljkovic, Veljko, Veljkovic, Nevena, Almeida-e-Silva, Danillo C, Vencio, Ricardo ZN, Sharan, Malvika, Vogel, Jörg, Kansakar, Lakesh, Zhang, Shanshan, Vucetic, Slobodan, Wang, Zheng, Sternberg, Michael JE, Wass, Mark N, Huntley, Rachael P, Martin, Maria J, O'Donovan, Claire, Robinson, Peter N, Moreau, Yves, Tramontano, Anna, Babbitt, Patricia C, Brenner, Steven E, Linial, Michal, Orengo, Christine A, Rost, Burkhard, Greene, Casey S, Mooney, Sean D, Friedberg, Iddo, and Radivojac, Predrag
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Quantitative Biology - Quantitative Methods - Abstract
Background: The increasing volume and variety of genotypic and phenotypic data is a major defining characteristic of modern biomedical sciences. At the same time, the limitations in technology for generating data and the inherently stochastic nature of biomolecular events have led to the discrepancy between the volume of data and the amount of knowledge gleaned from it. A major bottleneck in our ability to understand the molecular underpinnings of life is the assignment of function to biological macromolecules, especially proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, accurately assessing methods for protein function prediction and tracking progress in the field remain challenging. Methodology: We have conducted the second Critical Assessment of Functional Annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. One hundred twenty-six methods from 56 research groups were evaluated for their ability to predict biological functions using the Gene Ontology and gene-disease associations using the Human Phenotype Ontology on a set of 3,681 proteins from 18 species. CAFA2 featured significantly expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis also compared the best methods participating in CAFA1 to those of CAFA2. Conclusions: The top performing methods in CAFA2 outperformed the best methods from CAFA1, demonstrating that computational function prediction is improving. This increased accuracy can be attributed to the combined effect of the growing number of experimental annotations and improved methods for function prediction., Comment: Submitted to Genome Biology
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- 2016
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9. Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor
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Rosenberg, Yvonne J, Mao, Lingjun, Jiang, Xiaoming, Lees, Jonathan, Zhang, Limin, Radic, Zoran, and Taylor, Palmer
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Biochemistry and Cell Biology ,Biological Sciences ,Neurosciences ,Prevention ,Vaccine Related ,Biodefense ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Acetamides ,Acetylcholinesterase ,Animals ,Butyrylcholinesterase ,Chemical Warfare Agents ,Cholinesterase Reactivators ,Gases ,Inhalation ,Macaca ,Models ,Animal ,Oximes ,Paraoxon ,Recombinant Proteins ,Sarin ,Toxicology ,Biochemistry and cell biology - Abstract
Organophosphate (OP) nerve agents and pesticides trigger a common mechanism of neurotoxicity resulting from critical targeting and inhibition of acetylcholinesterases (AChE) in central and peripheral synapses in the cholinergic nervous system. Therapeutic countermeasures have thus focused on either administering an oxime post-exposure, that can rapidly reactivate OP-inhibited AChE, or by preventing OP poisoning through administering pre-exposure treatments that scavenge OPs before they inhibit their physiological AChE targets. While several pyridinium aldoxime antidotes are currently approved, their utility is impaired due to their inability to cross the blood-brain barrier (BBB) efficiently. The present study utilized a macaque (Ma) model to demonstrate the efficacy of a novel zwitterionic and centrally acting oxime RS194B to reactivate sarin- and paraoxon-inhibited macaque AChE and butyrylcholinesterase (BChE) in vitro and to further assess the capacity of RS194B to effect a reversal of clinical symptoms following sarin inhalation in vivo. In vitro, oxime reactivation of MaAChE and MaBChE was shown to be comparable to their human orthologs, while the macaque studies indicated that IM administration of 62.5 mg/kg of RS194B and 0.28 mg/kg atropine after continuous exposure to 49.6 μg/kg sarin vapor, rapidly reactivated the inhibited AChE and BChE in blood and reversed both early and advanced clinical symptoms of sarin-induced toxicity following pulmonary exposure within 1 h. The rapid cessation of autonomic and central symptoms, including convulsions, observed in macaques bodes well for the use of RS194B as an intra- or post-exposure human treatment and validates the macaque model in generating efficacy and toxicology data required for approval under the FDA Animal rule.
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- 2017
10. Audible acoustics from low-magnitude fluid-induced earthquakes in Finland
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Lamb, Oliver D., Lees, Jonathan M., Malin, Peter E., and Saarno, Tero
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- 2021
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11. Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila
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Scholes, Harry M., Cryar, Adam, Kerr, Fiona, Sutherland, David, Gethings, Lee A., Vissers, Johannes P. C., Lees, Jonathan G., Orengo, Christine A., Partridge, Linda, and Thalassinos, Konstantinos
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- 2020
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12. In situ biomonitoring shows seasonal patterns and environmentally mediated gaping activity in the bivalve, Pinna nobilis
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Garcia-March, Jose R., Jiménez, Santiago, Sanchis, Miguel A., Monleon, Sergio, Lees, Jonathan, Surge, Donna, and Tena-Medialdea, Jose
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- 2016
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13. Earthquake source parameters at the sumatran fault zone: Identification of the activated fault plane
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Kasmolan Madlazim, Santosa Bagus, Lees Jonathan, and Utama Widya
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sumatran fault zone ,three-component local waveform inversion ,earthquake source parameters ,fault plane ,Geology ,QE1-996.5 - Published
- 2010
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14. Myelin Structure and Composition in Zebrafish
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Avila, Robin L., Tevlin, Brian R., Lees, Jonathan P. B., Inouye, Hideyo, and Kirschner, Daniel A.
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- 2007
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15. Source constraints of Tungurahua volcano explosion events
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Ruiz, Mario C., Lees, Jonathan M., and Johnson, Jeffrey B.
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- 2006
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16. Robust estimation of background noise and signal detection in climatic time series
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Mann, Michael E. and Lees, Jonathan M.
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- 1996
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17. Introduction of the YTE mutation into the non-immunogenic HIV bnAb PGT121 induces anti-drug antibodies in macaques
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Rosenberg, Yvonne J., primary, Lewis, George K., additional, Montefiori, David C., additional, LaBranche, Celia C., additional, Lewis, Mark G., additional, Urban, Lori A., additional, Lees, Jonathan P., additional, Mao, Lingjun, additional, and Jiang, Xiaoming, additional
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- 2019
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18. Combining sequence-based prediction methods and circular dichroism and infrared spectroscopic data to improve protein secondary structure determinations
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Lees Jonathan G and Janes Robert W
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background A number of sequence-based methods exist for protein secondary structure prediction. Protein secondary structures can also be determined experimentally from circular dichroism, and infrared spectroscopic data using empirical analysis methods. It has been proposed that comparable accuracy can be obtained from sequence-based predictions as from these biophysical measurements. Here we have examined the secondary structure determination accuracies of sequence prediction methods with the empirically determined values from the spectroscopic data on datasets of proteins for which both crystal structures and spectroscopic data are available. Results In this study we show that the sequence prediction methods have accuracies nearly comparable to those of spectroscopic methods. However, we also demonstrate that combining the spectroscopic and sequences techniques produces significant overall improvements in secondary structure determinations. In addition, combining the extra information content available from synchrotron radiation circular dichroism data with sequence methods also shows improvements. Conclusion Combining sequence prediction with experimentally determined spectroscopic methods for protein secondary structure content significantly enhances the accuracy of the overall results obtained.
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- 2008
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19. Novel methods for secondary structure determination using low wavelength (VUV) circular dichroism spectroscopic data
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Janes Robert W, Miles Andrew J, Lees Jonathan G, and Wallace B A
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Circular Dichroism (CD) spectroscopy is a widely used method for studying protein structures in solution. Modern synchrotron radiation CD (SRCD) instruments have considerably higher photon fluxes than do conventional lab-based CD instruments, and hence have the ability to routinely measure CD data to much lower wavelengths. Recently a new reference dataset of SRCD spectra of proteins of known structure, designed to cover secondary structure and fold space, has been produced which includes low wavelength (vacuum ultraviolet – VUV) data. However, the existing algorithms used to calculate protein secondary structures from CD data have not been designed to take optimal advantage of the additional information in these low wavelength data. Results In this study, we have optimised secondary structure calculation methods based on the low wavelength CD data by examining existing algorithms and secondary structure assignment schemes, and then developing new methods which have produced clear improvements in prediction accuracy, especially for beta-sheet components. We have further shown that if precise measurements of protein concentrations, and therefore spectral magnitudes, are not available, the inclusion of the low wavelength data will significantly improve the analyses. However, we have also demonstrated that the new reference dataset, methods, and assignments can also improve the analyses of conventional circular dichroism data, even if the low wavelength data is not available. Conclusion VUV CD data include important information on protein structure which can be exploited with the algorithms and methodologies described.
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- 2006
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20. Comparison of Drosophila melanogaster Embryo and Adult Proteome by SWATH-MS Reveals Differential Regulation of Protein Synthesis, Degradation Machinery, and Metabolism Modules.
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Fabre, Bertrand, Korona, Dagmara, Lees, Jonathan G., Lazar, Ikrame, Livneh, Ido, Brunet, Manon, Orengo, Christine A., Russell, Steven, and Lilley, Kathryn S.
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- 2019
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21. Effects of the Iceland plume on Greenland's lithosphere: New insights from ambient noise tomography.
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Antonijevic, Sanja Knezevic and Lees, Jonathan M.
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MANTLE plumes ,LITHOSPHERE ,RAYLEIGH waves ,SEISMIC waves - Abstract
Ambient noise tomography is used to image Greenland's lithosphere, which passed over the Iceland plume between ∼70 and ∼40 Ma. Cross-correlations from 21 stations from GLISN seismic network were used to invert for 2-D Rayleigh wave phase velocity maps for 14 periods between 8 and 40 s. We find that Rayleigh wave phase velocities substantially vary across Greenland, with slow velocities coinciding with NW-SE trending Iceland plume track. In east Greenland the detected velocity reduction at longer periods (33–40s) reflects substantially thinned lithosphere, thermally ablated by the plume. From the east, the reduced velocities shift NW at shorter periods (12–20s), indicating shallowing of the plume-related slow anomaly. In north-central Greenland, the reduced velocities appear in the proximity of the plume ∼60 Ma, reflecting lithospheric weakening in the presence of residual heat that still persists within the lithosphere. Our results provide important new constraints on variations in the seismic velocity structure of Greenland's crust and uppermost mantle, revealing prolonged effects of the mantle plume on the overpassing craton. [ABSTRACT FROM AUTHOR]
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- 2018
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22. Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
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Rosenberg, Yvonne J., primary, Montefiori, David C., additional, LaBranche, Celia C., additional, Lewis, Mark G., additional, Sack, Markus, additional, Lees, Jonathan P., additional, and Jiang, Xiaoming, additional
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- 2016
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23. Lithospheric structure of an incipient rift basin: Results from receiver function analysis of Bransfield Strait, NW Antarctic Peninsula.
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Biryol, C. Berk, Lee, Stephen J., Lees, Jonathan M., and Shore, Michael J.
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LITHOSPHERE ,RIFTS (Geology) ,GEOLOGICAL basins - Abstract
Bransfield Basin (BB), located northwest of the Antarctic Peninsula (AP) and southeast of the South Shetland Islands (SSI), is the most active section of the Antarctic continental margin. The region has long been (50 Ma) a convergent plate boundary where the Phoenix plate was subducting beneath the Antarctic Plate and is characterized by long-lived arc magmatism and accretion. However, the collision of the Antarctic-Phoenix spreading center with the subduction front near SSI (ca. 4 Ma) gave way to the opening of slab windows and dramatic decrease in the subduction rate of the Phoenix plate beneath AP and SSI. Consequently, the Phoenix slab began to rollback slowly along the South Shetland Trench (SST), giving way to slow extension in the back-arc region and rifting along the BB. Although there is consensus on the factors that control the current deformation and extension of the BB, the origin of the BB and the tectonic configuration of the basin are still unclear. Most of the controversy stems from uncertainties regarding the crustal thickness of the BB. Hence, we computed teleseismic receiver functions for 10 broadband stations in the region that belong to existing permanent and temporary deployments in order obtain robust constraints on the lithospheric structure and crustal thickness of the BB, as well as the AP and SSI. Our results indicate that the crust is thinning from 30 km to 26 km from the AP towards the South Shetland trench and Central BB showing the asymmetrical character of the rift basin. The crustal thickness and Vp/Vs variations are less pronounced along the AP but very significant across the SSB indicating the lithospheric scale segmentation of the South Shetland Block (SSB) and the incipient rift basin under the control of the opening of slab window and the roll-back of stalled Phoenix slab. High Vp/Vs ratios (∼1.9) beneath BB and SSI, agree well with the nascent rift character of BB, the presence of a steep Phoenix slab and consequently a wider mantle wedge characterized by the presence of underplating partial melts beneath SSI and BB. [ABSTRACT FROM AUTHOR]
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- 2018
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24. Comparison of Drosophila melanogasterEmbryo and Adult Proteome by SWATH-MS Reveals Differential Regulation of Protein Synthesis, Degradation Machinery, and Metabolism Modules
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Fabre, Bertrand, Korona, Dagmara, Lees, Jonathan G., Lazar, Ikrame, Livneh, Ido, Brunet, Manon, Orengo, Christine A., Russell, Steven, and Lilley, Kathryn S.
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An important area of modern biology consists of understanding the relationship between genotype and phenotype. However, to understand this relationship it is essential to investigate one of the principal links between them: the proteome. With the development of recent mass-spectrometry approaches, it is now possible to quantify entire proteomes and thus relate them to different phenotypes. Here, we present a comparison of the proteome of two extreme developmental states in the well-established model organism Drosophila melanogaster: adult and embryo. Protein modules such as ribosome, proteasome, tricarboxylic acid cycle, glycolysis, or oxidative phosphorylation were found differentially expressed between the two developmental stages. Analysis of post-translation modifications of the proteins identified in this study indicates that they generally follow the same trend as their corresponding protein. Comparison between changes in the proteome and the transcriptome highlighted patterns of post-transcriptional regulation for the subunits of protein complexes such as the ribosome and the proteasome, whereas protein from modules such as TCA cycle, glycolysis, and oxidative phosphorylation seem to be coregulated at the transcriptional level. Finally, the impact of the endosymbiont Wolbachia pipientison the proteome of both developmental states was also investigated.
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- 2019
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25. Detecting Lightning Infrasound Using a High‐Altitude Balloon
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Lamb, Oliver D., Lees, Jonathan M., and Bowman, Daniel C.
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Acoustic waves with a wide range of frequencies are generated by lightning strokes during thunderstorms, including infrasonic waves (0.1 to 20 Hz). The source mechanism for these low‐frequency acoustic waves is still debated, and studies have so far been limited to ground‐based instruments. Here we report the first confirmed detection of lightning‐generated infrasound with acoustic instruments suspended at stratospheric altitudes using a free‐flying balloon. We observe high‐amplitude signals generated by lightning strokes located within 100 km of the balloon as it flew over the Tasman Sea on 17 May 2016. The signals share many characteristics with waveforms recorded previously by ground‐based instruments near thunderstorms. The ability to measure lightning activity with high‐altitude infrasound instruments has demonstrated the potential for using these platforms to image the full acoustic wavefield in the atmosphere. Furthermore, it validates the use of these platforms for recording and characterizing infrasonic sources located beyond the detection range of ground‐based instruments. Lightning generates sound waves across a wide range of frequencies, including below the threshold for human hearing at 20 Hz. How these waves at less than 20 Hz, also known as infrasound waves, are generated during a lightning stroke is currently an area for debate. So far, measurements of lightning infrasound waves have been limited to microphones fixed to the ground, and models have shown that only a small section of sound waves actually reach the ground. Here we show lightning infrasound that has been detected using microphones suspended over a thunderstorm using a balloon flying at 32 km height. This opens up the possibility of using balloons in future studies to make better measurements of infrasound waves generated by lightning activity and, in turn, give a better idea of how they are generated. It also shows how balloons can be used to record infrasound waves far away from land and therefore beyond the detection limit of ground‐based microphones. First lightning infrasound was detected using free‐flying balloon at stratospheric altitudes over Tasman Sea in May 2016Infrasonic signals matched with a few lightning strokes within 100 km range of balloon as it flew over at least two thundercloudsOnly a fraction of the expected infrasound signals were detected, and the cause of this remains unclear
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- 2018
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26. Acoustic and Seismic Fields of Hydraulic Jumps at Varying Froude Numbers
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Ronan, Timothy J., Lees, Jonathan M., Mikesell, T. Dylan, Anderson, Jacob F., and Johnson, Jeffrey B.
- Abstract
Mechanisms that produce seismic and acoustic wavefields near rivers are poorly understood because of a lack of observations relating temporally dependent river conditions to the near‐river seismoacoustic fields. This controlled study at the Harry W. Morrison Dam (HWMD) on the Boise River, Idaho, explores how temporal variation in fluvial systems affects surrounding acoustic and seismic fields. Adjusting the configuration of the HWMD changed the river bathymetry and therefore the form of the standing wave below the dam. The HWMD was adjusted to generate four distinct wave regimes that were parameterized through their dimensionless Froude numbers (Fr) and observations of the ambient seismic and acoustic wavefields at the study site. To generate detectable and coherent signals, a standing wave must exceed a threshold Frvalue of 1.7, where a nonbreaking undular jump turns into a breaking weak hydraulic jump. Hydrodynamic processes may partially control the spectral content of the seismic and acoustic energies. Furthermore, spectra related to reproducible wave conditions can be used to calibrate and verify fluvial seismic and acoustic models. For detectable and coherent seismoacoustic energies to be generated, a standing wave must exceed a threshold Frvalue of approximately 1.7Hydrodynamic processes may partially control the spectral content of the seismic and acoustic energiesVariations in the width and amplitude of seismoacoustic spectral peaks may be explained by horizontal variations across a hydraulic jump
- Published
- 2017
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27. The 1.75 Å resolution structure of fission protein Fis1 fromSaccharomyces cerevisiaereveals elusive interactions of the autoinhibitory domain
- Author
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Tooley, James E., primary, Khangulov, Victor, additional, Lees, Jonathan P. B., additional, Schlessman, Jamie L., additional, Bewley, Maria C., additional, Heroux, Annie, additional, Bosch, Jürgen, additional, and Hill, R. Blake, additional
- Published
- 2011
- Full Text
- View/download PDF
28. Myelin Structure and Composition in Zebrafish
- Author
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Avila, Robin L., primary, Tevlin, Brian R., additional, Lees, Jonathan P. B., additional, Inouye, Hideyo, additional, and Kirschner, Daniel A., additional
- Published
- 2006
- Full Text
- View/download PDF
29. Three‐dimensional attenuation model of Sierra Negra Volcano, Galápagos Archipelago
- Author
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Rodd, Rebecca L., Lees, Jonathan M., and Tepp, Gabrielle
- Abstract
The shallow magma system beneath Sierra Negra was imaged using attenuation tomographic methods. The t∗spectral decay method for Pwave phases was used to highlight regions of high Qp−1which suggest the presence of magma melt. High‐ Qp−1anomalies ranging from 0.005 to 0.04 are concentrated below the caldera from 0.5 to 10.5 km depths. Attenuation is sensitive to temperature and fluid presence; thus, this high attenuation is interpreted as possible zones of magma accumulation. An imaged shallow body is consistent with geodetic studies on caldera deformation that modeled a magma sill or flattopped diapir of unknown thickness at ∼1 km depth below sea level. t* spectral decay method was used to obtain attenuation structure beneath Sierra NegraHigh‐attenuation anomaly from 0.5 to 10.5 km depth interpreted as possible magma accumulation zonesResults support a shallow magma body described and modeled in caldera deformation studies
- Published
- 2016
- Full Text
- View/download PDF
30. Acoustic source inversion to estimate volume flux from volcanic explosions
- Author
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Kim, Keehoon, Fee, David, Yokoo, Akihiko, and Lees, Jonathan M.
- Abstract
We present an acoustic waveform inversion technique for infrasound data to estimate volume fluxes from volcanic eruptions. Previous inversion techniques have been limited by the use of a 1‐D Green's function in a free space or half space, which depends only on the source‐receiver distance and neglects volcanic topography. Our method exploits full 3‐D Green's functions computed by a numerical method that takes into account realistic topographic scattering. We apply this method to vulcanian eruptions at Sakurajima Volcano, Japan. Our inversion results produce excellent waveform fits to field observations and demonstrate that full 3‐D Green's functions are necessary for accurate volume flux inversion. Conventional inversions without consideration of topographic propagation effects may lead to large errors in the source parameter estimate. The presented inversion technique will substantially improve the accuracy of eruption source parameter estimation (cf. mass eruption rate) during volcanic eruptions and provide critical constraints for volcanic eruption dynamics and ash dispersal forecasting for aviation safety. Application of this approach to chemical and nuclear explosions will also provide valuable source information (e.g., the amount of energy released) previously unavailable. First waveform inversion of volcano infrasound using a 3‐D Green's functionStrong topographic scattering must be considered for source inversionThe method substantially improves the accuracy of eruption source parameter estimation
- Published
- 2015
- Full Text
- View/download PDF
31. Optimization of a Nucleic Acid-Based Reporter System To Detect Mycobacterium tuberculosisAntibiotic Sensitivity
- Author
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Mulvey, Matthew C., Lemmon, Margaret, Rotter, Stephanie, Lees, Jonathan, Einck, Leo, and Nacy, Carol A.
- Abstract
ABSTRACTWe previously reported the development of a prototype antibiotic sensitivity assay to detect drug-resistant Mycobacterium tuberculosisusing infection by mycobacteriophage to create a novel nucleic acid transcript, a surrogate marker of mycobacterial viability, detected by reverse transcriptase PCR (M. C. Mulvey et al., mBio 3:e00312-11, 2012). This assay detects antibiotic resistance to all drugs, even drugs for which the resistance mechanism is unknown or complex: it is a phenotypic readout using nucleic acid detection. In this report, we describe development and characteristics of an optimized reporter system that directed expression of the RNA cyclase ribozyme, which generated circular RNA through an intramolecular splicing reaction and led to accumulation of a new nucleic acid sequence in phage-infected bacteria. These modifications simplified the assay, increased the limit of detection from 104to <102M. tuberculosiscells, and correctly identified the susceptibility profile of M. tuberculosisstrains exposed for 16 h to either first-line or second-line antitubercular drugs. In addition to phenotypic drug resistance or susceptibility, the assay reported streptomycin MICs and clearly detected 10% drug-resistant cells in an otherwise drug-susceptible population.
- Published
- 2014
- Full Text
- View/download PDF
32. The 1.75 Å resolution structure of fission protein Fis1 from Saccharomyces cerevisiae reveals elusive interactions of the autoinhibitory domain.
- Author
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Tooley, James E., Khangulov, Victor, Lees, Jonathan P. B., Schlessman, Jamie L., Bewley, Maria C., Heroux, Annie, Bosch, Jürgen, and Hill, R. Blake
- Subjects
PROTEIN structure ,SACCHAROMYCES cerevisiae ,FISSION (Asexual reproduction) ,CRYSTALLIZATION ,X-ray crystallography ,NUCLEAR magnetic resonance - Abstract
Fis1 mediates mitochondrial and peroxisomal fission. It is tail-anchored to these organelles by a transmembrane domain, exposing a soluble cytoplasmic domain. Previous studies suggested that Fis1 is autoinhibited by its N-terminal region. Here, a 1.75 Å resolution crystal structure of the Fis1 cytoplasmic domain from Saccharomyces cerevisiae is reported which adopts a tetratricopeptide-repeat fold. It is observed that this fold creates a concave surface important for fission, but is sterically occluded by its N-terminal region. Thus, this structure provides a physical basis for autoinhibition and allows a detailed examination of the interactions that stabilize the inhibited state of this molecule. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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33. A Study of the Regional Variation of Low-Frequency QLg-1 around the Korean Peninsula.
- Author
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Tae Woong Chung, Myung-Hyun Noh, Junk-Kyong Kim, Yun-Kyong Park, Hyun-Jae Yoo, and Lees, Jonathan M.
- Subjects
EARTHQUAKE hazard analysis ,EARTHQUAKES ,EARTHQUAKE magnitude ,SEISMIC event location ,SEISMOLOGY - Abstract
We studied regional Q
Lg -1 at 1 Hz (Q0 -1 ) around the Korean Peninsula based on broadband vertical component seismic records of six Incorporated Research Institutions for Seismology (IRIS) Global Seismographic Network stations and 19 Korean stations of the Korea Institute of Geoscience and Mineral Resources (KIGAM). Using 177 seismic events with magnitudes between 5.3 and 5.7 and depths less than 50 km, the reversed two station method was applied, and 94 high quality interstation paths were selected from 869 possible pairs. These results show high Q0 -1 paths around the Sea of Japan (East Sea) reflecting the typical oceanic structure and low Q0 -1 paths around northeastern China related to inactive seismicity. Assigning these path values into 193 cells around South Korea with a size of 1° by 1°, we observed that the regional Q0 -1 decreased gradually from east to west between 2 and 1 x 10-3 . [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
- View/download PDF
34. Systems biology approaches to finding novel pain mediators
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Antunes‐Martins, Ana, Perkins, James R., Lees, Jonathan, Hildebrandt, Tobias, Orengo, Christine, and Bennett, David L.H.
- Abstract
Chronic pain represents a major health burden; this maladaptive pain state occurs as a consequence of hypersensitivity within the peripheral and central components of the somatosensory system. High throughput technologies (genomics, transciptomics, lipidomics, and proteomics) are now being applied to tissue derived from pain patients as well as experimental pain models to discover novel pain mediators. The use of clustering, meta‐analysis and other techniques can help refine potential candidates. Of particular importance are systems biology methods, such as co‐expression network generating algorithms, which infer potential associations/interactions between molecules and build networks based on these interactions. Protein–protein interaction networks allow the lists of potential targets generated by these different platforms to be analyzed in their biological context. Outputs from these different methods must also be related to the clinical pain phenotype. The improved and standardized phenotyping of pain symptoms and sensory signs enables much better subject stratification. Our hope is that, in the future, the use of computational approaches to integrate datasets including sensory phenotype as well as the outputs of high throughput technologies will help define novel pain mediators and provide insights into the pathogenesis of chronic pain. WIREs Syst Biol Med2013, 5:11–35. doi: 10.1002/wsbm.1192
- Published
- 2013
- Full Text
- View/download PDF
35. Earthquake source parameters at the sumatran fault zone: Identification of the activated fault plane
- Author
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Kasmolan, Madlazim, Santosa, Bagus, Lees, Jonathan, and Utama, Widya
- Abstract
Abstract: Fifteen earthquakes (M
w 4.1–6.4) occurring at ten major segments of the Sumatran Fault Zone (SFZ) were analyzed to identify their respective fault planes. The events were relocated in order to assess hypocenter uncertainty. Earthquake source parameters were determined from three-component local waveforms recorded by IRIS-DMC and GEOFON broadband lA networks. Epicentral distances of all stations were less than 10°. Moment tensor solutions of the events were calculated, along with simultaneous determination of centroid position. Joint analysis of hypocenter position, centroid position, and nodal planes produced clear outlines of the Sumatran fault planes. The preferable seismotectonic interpretation is that the events activated the SFZ at a depth of approximately 14–210 km, corresponding to the interplate Sumatran fault boundary. The identification of this seismic fault zone is significant to the investigation of seismic hazards in the region.- Published
- 2010
- Full Text
- View/download PDF
36. Travel‐time tomography in the northern Coachella Valley using aftershocks of the 1986 ML5.9 North Palm Springs Earthquake
- Author
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Nicholson, Craig and Lees, Jonathan M.
- Abstract
Tomographic inversion is applied to delay times from aftershocks of the 1986 ML5.9 North Palm Springs (NPS) earthquake to image 3‐D velocity variations within the northern Coachella Valley. P‐wave arrival times from 1074 earthquakes, with depths ranging from 3 to 20 km, were used as sources recorded by 12 portable and 4 permanent stations. Preliminary results show well‐defined high‐ and low‐velocity anomalies (2–7%) that correlate with the rupture distribution of the 1986 mainshock. At depths less than 8 km, a low‐velocity anomaly predominates between the two NE‐dipping Banning and Mission Creek faults. From 8 to 12 km in depth, where the NPS mainshock and most of the aftershocks occur, a high‐velocity anomaly is observed. This high‐velocity feature is interpreted as imaging the asperity responsible for the 1986 rupture; and suggests that velocity information may help to define important elements, such as asperities, that control fault rupture, and thus, may help to predict the location and size of future events.
- Published
- 1992
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- View/download PDF
37. The South Fossa Magna, Japan, revealed by high-resolution P- and S-wave travel time tomography
- Author
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Lees, Jonathan M. and Ukawa, Motoo
- Abstract
Detailed tomographic images of the collision zone between the northern edge of the Philippine Sea and the Eurasian plates reveal a high correlation between tectonic features inferred from seismicity and P- and S-wave velocity structures. The linear tomographic inversion covered a 150 × 150 × 60 km region in the South Fossa Magna centered on the northern Izu Peninsula. Thirty-three three-component stations were located in the target region and 3823 high-quality earthquakes were selected from the catalogues of the NRIESDP, giving rise to 53,593 P- and 50,059 S-wave phase arrivals used in the inversion. The model was parameterized by 60 × 60 × 10 rectilinear blocks, measuring 2.5 km per side horizontally and 5–10 km varying thicknesses in depth. Three-dimensional perturbations from the one-dimensional, NRIESDP, layered model were derived by minimizing the squared misfit of the travel-time residuals. Regularization was employed to reduce the effects of noisy data by constraining the two-dimensional Laplacian of the model, within horizontal layers, to be small. The large sparse matrix was solved using the conjugate gradient algorithm LSQR. Reduction of misfit was 50% for the P-wave inversion and 57% for the S-wave inversion.
- Published
- 1992
- Full Text
- View/download PDF
38. Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
- Author
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Rosenberg, Yvonne J., Montefiori, David C., LaBranche, Celia C., Lewis, Mark G., Sack, Markus, Lees, Jonathan P., and Jiang, Xiaoming
- Subjects
3. Good health - Abstract
PLoS one 11(3), e0152760 (2016). doi:10.1371/journal.pone.0152760, Published by PLoS, Lawrence, Kan.
39. An autonomous structural health monitoring solution
- Author
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Schmid, Ulrich, Sánchez de Rojas Aldavero, José Luis, Leester-Schaedel, Monika, Featherston, Carol A., Holford, Karen M., Pullin, Rhys, Lees, Jonathan, Eaton, Mark, and Pearson, Matthew
- Published
- 2013
- Full Text
- View/download PDF
40. Molecular Mechanisms Behind Mitochondrial Fission
- Author
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Hill, Blake, Koppenol-Raab, Marijke, Lees, Jonathan P.B., Marie Manlandro, Cara, Picton, Lora K., Posey, Ammon, and Wells, Robert C.
- Published
- 2012
- Full Text
- View/download PDF
41. A reference database for circular dichroism spectroscopy covering fold and secondary structure space
- Author
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Lees, Jonathan G., Miles, Andrew J., Wien, Frank, and Wallace, B. A.
- Abstract
Motivation: Circular Dichroism (CD) spectroscopy is a long-established technique for studying protein secondary structures in solution. Empirical analyses of CD data rely on the availability of reference datasets comprised of far-UV CD spectra of proteins whose crystal structures have been determined. This article reports on the creation of a new reference dataset which effectively covers both secondary structure and fold space, and uses the higher information content available in synchrotron radiation circular dichroism (SRCD) spectra to more accurately predict secondary structure than has been possible with existing reference datasets. It also examines the effects of wavelength range, structural redundancy and different means of categorizing secondary structures on the accuracy of the analyses. In addition, it describes a novel use of hierarchical cluster analyses to identify protein relatedness based on spectral properties alone. The databases are shown to be applicable in both conventional CD and SRCD spectroscopic analyses of proteins. Hence, by combining new bioinformatics and biophysical methods, a database has been produced that should have wide applicability as a tool for structural molecular biology. Contact:
b.wallace@mail.cryst.bbk.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.- Published
- 2006
- Full Text
- View/download PDF
42. Calibration and standardisation of synchrotron radiation and conventional circular dichroism spectrometers. Part 2: Factors affecting magnitude and wavelength
- Author
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J. Miles, Andrew, Wien, Frank, G. Lees, Jonathan, and Wallace, B.A.
- Abstract
Circular dichroism (CD) spectroscopy is an important tool in structural biology, especially for protein secondary structure analyses. Synchrotron radiation circular dichroism (SRCD) spectroscopy is a modified version of the technique that uses the intense light from a synchrotron source to enable the collection of data to much lower wavelengths than possible on conventional circular dichroism (cCD) instruments. There is a need for standardization of calibration methods amongst and between cCD and SRCD instruments to ensure consistency and the ability to use common reference databases for empirical secondary structural analyses. In a previous study (Spectroscopy17 (2003), 653–661), we compared optical rotation measurements on several cCD and SRCD instruments, whilst holding constant other experimental factors. In this study, other experimental parameters which contribute to the spectral magnitude, such as cell pathlength and protein concentration determinations, are examined. In addition, the extent of wavelength calibration variations between instruments and their effects on secondary structure calculations have been examined. Hence, this paper provides additional practical guidance for “good practice” in the measurement of CD data.
- Published
- 2005
- Full Text
- View/download PDF
43. Calibration and Standardisation of Synchrotron Radiation Circular Dichroism and Conventional Circular Dichroism Spectrophotometers
- Author
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J. Miles, Andrew, Wien, Frank, G. Lees, Jonathan, Rodger, A., W. Janes, Robert, and A. Wallace, B.
- Abstract
Synchrotron radiation circular dichroism (SRCD) is an emerging technique in structural biology with particular value in protein secondary structure analyses since it permits the collection of data down to much lower wavelengths than conventional circular dichroism (cCD) instruments. Reference database spectra collected on different SRCD instruments in the future as well as current reference datasets derived from cCD spectra must be compatible. Therefore there is a need for standardization of calibration methods to ensure quality control. In this study, magnitude and optical rotation measurements on four cCD and three SRCD instruments were compared at 192.5, 219, 290 and 490 nm. At high wavelengths, all gave comparable results, however, at the lower wavelengths, some variations were observable. The consequences of these differences on the spectrum, and the calculated secondary structure, of a representative protein (myoglobin) are demonstrated. A method is proposed for standardising spectra obtained on any CD instrument, conventional or synchrotron‒based, with respect to existing and future databases.
- Published
- 2003
- Full Text
- View/download PDF
44. A designed point mutant in Fis1 disrupts dimerization and mitochondrial fission.
- Author
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Lees JP, Manlandro CM, Picton LK, Tan AZ, Casares S, Flanagan JM, Fleming KG, and Hill RB
- Subjects
- Binding Sites, Dimerization, Protein Conformation, Protein Multimerization, Mitochondria metabolism, Mitochondrial Dynamics genetics, Mitochondrial Proteins chemistry, Mitochondrial Proteins genetics, Point Mutation, Saccharomyces cerevisiae Proteins chemistry, Saccharomyces cerevisiae Proteins genetics
- Abstract
Mitochondrial and peroxisomal fission are essential processes with defects resulting in cardiomyopathy and neonatal lethality. Central to organelle fission is Fis1, a monomeric tetratricopeptide repeat (TPR)-like protein whose role in assembly of the fission machinery remains obscure. Two nonfunctional, Saccharomyces cerevisiae Fis1 mutants (L80P or E78D/I85T/Y88H) were previously identified in genetic screens. Here, we find that these two variants in the cytosolic domain of Fis1 (Fis1ΔTM) are unexpectedly dimeric. A truncation variant of Fis1ΔTM that lacks an N-terminal regulatory domain is also found to be dimeric. The ability to dimerize is a property innate to the native Fis1ΔTM amino acid sequence as we find this domain is dimeric after transient exposure to elevated temperature or chemical denaturants and is kinetically trapped at room temperature. This is the first demonstration of a specific self-association in solution for the Fis1 cytoplasmic domain. We propose a three-dimensional domain-swapped model for dimerization that is validated by a designed mutation, A72P, which potently disrupts dimerization of wild-type Fis1. A72P also disrupts dimerization of nonfunctional variants, indicating a common structural basis for dimerization. The obligate monomer variant A72P, like the dimer-promoting variants, is nonfunctional in fission, consistent with a model in which Fis1 activity depends on its ability to interconvert between monomer and dimer species. These studies suggest a new functionally important manner in which TPR-containing proteins may reversibly self-associate., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
45. Peripheral myelin of Xenopus laevis: role of electrostatic and hydrophobic interactions in membrane compaction.
- Author
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Luo X, Cerullo J, Dawli T, Priest C, Haddadin Z, Kim A, Inouye H, Suffoletto BP, Avila RL, Lees JP, Sharma D, Xie B, Costello CE, and Kirschner DA
- Subjects
- Amino Acid Sequence, Animals, Anura, Base Sequence, Computer Simulation, Detergents pharmacology, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Hydroxylamine pharmacology, Molecular Sequence Data, Myelin P0 Protein genetics, Myelin Sheath drug effects, Osmolar Concentration, Sequence Homology, Amino Acid, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Static Electricity, X-Ray Diffraction, Xenopus laevis, Myelin P0 Protein chemistry, Myelin Sheath chemistry
- Abstract
P0 glycoprotein is the major structural protein of peripheral nerve myelin where it is thought to modulate inter-membrane adhesion at both the extracellular apposition, which is labile upon changes in pH and ionic strength, and the cytoplasmic apposition, which is resistant to such changes. Most studies on P0 have focused on structure-function correlates in higher vertebrates. Here, we focused on its role in the structure and interactions of frog (Xenopus laevis) myelin, where it exists primarily in a dimeric form. As part of our study, we deduced the full sequence of X. laevis P0 (xP0) from its cDNA. The xP0 sequence was found to be similar to P0 sequences of higher vertebrates, suggesting that a common mechanism of PNS myelin compaction via P0 interaction might have emerged through evolution. As previously reported for mouse PNS myelin, a similar change of extracellular apposition in frog PNS myelin as a function of pH and ionic strength was observed, which can be explained by a conformational change of P0 due to protonation-deprotonation of His52 at P0's putative adhesive interface. On the other hand, the cytoplasmic apposition in frog PNS myelin, like that in the mouse, remained unchanged at different pH and ionic strength. The contribution of hydrophobic interactions to stabilizing the cytoplasmic apposition was tested by incubating sciatic nerves with detergents. Dramatic expansion at the cytoplasmic apposition was observed for both frog and mouse, indicating a common hydrophobic nature at this apposition. Urea also expanded the cytoplasmic apposition of frog myelin likely owing to denaturation of P0. Removal of the fatty acids that attached to the single Cys residue in the cytoplasmic domain of P0 did not change PNS myelin structure of either frog or mouse, suggesting that the P0-attached fatty acyl chain does not play a significant role in PNS myelin compaction and stability. These results help clarify the present understanding of P0's adhesion role and the role of its acylation in compact PNS myelin.
- Published
- 2008
- Full Text
- View/download PDF
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