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1. Inter-individual differences in cell composition across the ventricular wall may explain variability in ECG response to serum potassium and calcium variations

Author: 'Syed Hassaan Ahmed Bukhari, Carlos Sánchez, Pablo Laguna, Mark Potse, Esther Pueyo\\', Aragón Institute of Engineering Research [Zaragoza] (I3A), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), This work was granted access to the HPC resources of IDRIS under the allocation 2021-A0110307379 made by GENCI., ANR-10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), European Project: 764738,PIC, and European Project: 638284,H2020,ERC-2014-STG,MODELAGE(2015)
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [INFO]Computer Science [cs]
Abstract: International audience; Non-invasive monitoring of serum potassium ([K + ]) and calcium ([Ca 2+ ]) concentration can help to prevent arrhythmia in kidney patients. Current electrocardiogram (ECG) markers, including the T wave width (T w) and its time-warped temporal morphological variability (d U w), correlate significantly with [K + ] and [Ca 2+ ] but these relations vary strongly between patients. We hypothesized that inter-individual differences in cell type distribution across the ventricular wall can explain this variability. We computed T w and d U w in simulated ECGs from a human heart-torso model at different proportions of endo-, mid-, and epicardial cells, while varying [K + ] (3 to 6.2 mM) and [Ca 2+ ] (1.4 to 3.2 mM). Electrical activity was simulated with a reaction-diffusion model with modified Ten Tusscher-Panfilov dynamics. Results were compared to data from 29 patients. T w and d U w correlated strongly with [K + ] (absolute median Pearson coefficient r = 0.70 to 0.93) and [Ca 2+ ] (r = 0.69 to 0.86) in simulations and in patients. Different cell type distributions reproduced inter-patient variability, with the same sign and magnitude of r. In conclusion, the inter-patient variability in the relation between serum electrolytes and their ECG markers can indeed be explained by inter-individual differences in cell type distribution across the ventricular wall.
Published: 2022

2. Rapid On‐Chip Synthesis of Complex Glycomimetics from N‐Glycan Scaffolds for Improved Lectin Targeting

Author: Anna Cioce, Niels-Christian Reichardt, Michel Thépaut, Franck Fieschi, Carbon Bionanotechnology Laboratory (CICbiomaGUNE), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), and Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion
Subjects: Glycan, Glycosylation, Langerin, Oligosaccharides, 010402 general chemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, Immune system, Polysaccharides, Humans, Lectins, C-Type, Binding site, microarrays, Binding selectivity, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, 010405 organic chemistry, Organic Chemistry, Lectin, General Chemistry, Microarray Analysis, lectins, 3. Good health, 0104 chemical sciences, chemistry, Biochemistry, glycomimetics, biology.protein, glycans, DNA microarray
Abstract: International audience; C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines. The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site. Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes. All surface-based reactions were monitored by MALDI-TOF MS to assess conversion and purity of spot compositions. Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
Published: 2020

3. NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies

Author: Miyako Nakano, Alena Wiegandt, Yunli Hu, Viv Lindo, Paulina A. Urbanowicz, Zsuzsanna Lakos, Cassie Caron, Song Klapoetke, Niels Christian Reichardt, Niclas Chiang Tan, Sandra Maier, Rene Hennig, Marton Szigeti, Ju Yeon Lee, Ying Qing Yu, Gregory O. Staples, Sachin Patil, Jolanta Jaworek, Waltraud Evers, Benjamin G. Kremkow, Youngsuk Seo, Kathirvel Alagesan, Yuetian Chen, Gordan Lauc, David L. Duewer, Yang Yang, Daniele Menard, Hyun Joo An, Tim Kelly, Stephen E. Stein, Joseph W. Leone, Anja Wiechmann, Ravi Amunugama, Peng George Wang, Clemens Grunwald-Grube, Maria Lorna A. De Leoz, Göran Larson, Rob Haselberg, Samanta Cajic, Stephanie A. Archer-Hartmann, Maja Pučić-Baković, Edward D. Bodnar, Pauline M. Rudd, Anja Resemann, Daniel Kolarich, Akira Harazono, Jeffrey S. Rohrer, Juan Echevarria Ruiz, Stuart Pengelley, Jong Shin Yoo, Arun V. Everest-Dass, Nicolle H. Packer, Steven W. Mast, William R. Alley, Erika Lattová, Anne Zeck, Corné J.M. Stroop, Radoslaw P. Kozak, Chun Shao, Alain Beck, Joseph Zaia, Erdmann Rapp, Lily Liu, Jennie Truong, Yaojun Wang, Christopher W. Cairo, Roisin O'Flaherty, Radka Saldova, Kudrat Goswami, Emy Komatsu, Jessica Örnros, Taiki Sugiyama, Prachi Bhoskar, Pralima Pradhan, Carlito B. Lebrilla, András Guttman, Christine Merle, Brian Kasper, Oscar G. Potter, Soo Kyung Suh, Li Phing Liew, Ranjan Chakrabarti, Terry D. Cyr, Sohei Funaoka, Masaaki Toyoda, Pui King Amy Leung, Toyin Kasali, Jerko Štambuk, Yanming An, Wolfgang Jabs, Bernd Meyer, Chunxia Zou, John F. Cipollo, Sa Rang Kim, Aaron Shafer, Randy M. Whittal, Jichao Kang, Albert J. R. Heck, Yehia Mechref, Hoi Kei Yau, Guinevere S. M. Lageveen-Kammeijer, Shiwei Sun, Kenichiro Furuki, Richard B. Jones, Béla Reiz, Niclas G. Karlsson, Mohammedazam Lahori, Xu Li, Barbara Adamczyk, Rui Cao, Lauren Wu, Koichi Kato, Detlev Suckau, Paweł Link-Lenczowski, Kelvin H. Lee, Xiaomin Song, Noortje de Haan, Ruth Frenkel, Adam Fung, Friedrich Altmann, Manfred Wuhrer, David Falck, Andreas Bock, Paula Magnelli, Brian Gau, Sachiko Kondo, Robert J. Emery, Chunsheng Jin, Louise Royle, David C. Muddiman, Hélène Perreault, John W. Froehlich, Disha Dadke, Peiqing Zhang, Lara K. Mahal, Takashi Nishikaze, Andrew Saati, Chuncui Huang, Hui Zhang, Carina Sihlbom, Parastoo Azadi, Jonas Nilsson, Yaming Liu, Yannis-Nicolas François, Nassur Said, Jin Young Kim, C. T. Yuen, Shuang Yang, Emmanuelle Leize-Wagner, David Harvey, Xiaofeng Shi, Yan Li, Hirokazu Yagi, Zoran Sosic, Elizabeth M. Hecht, Hua Yuan, Marybeth Creskey, Hyun Kyoung Lee, Sadanori Sekiya, Peter de Vreugd, Len Bell, Sam Tep, BioAnalytical Chemistry, AIMMS, Department of Plant and Microbial Biology, University of California, Laboratory of Infrared Material and Devices, Ningbo University (NBU), University of Natural Resources and Life Sciences (BOKU), Bruker Daltonik GmbH, Bruker Daltonik, Centre d'Immunologie Pierre Fabre, Xinjiang Agriculture University, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Complex Carbohydrate Research Center, University of Georgia [USA], GENOS, Universität Duisburg-Essen [Essen], Max Planck Institute for Dynamics of Complex Technical Systems, Max-Planck-Gesellschaft, Section de mathématiques [Genève], Université de Genève (UNIGE), Department of Computer Science [York] (CS-YORK), University of York [York, UK], State Key Laboratory of Hybrid Rice, Department of Genetics, College of Life Sciences, Wuhan University, LeidenUniversity Medical Center, University College Dublin [Dublin] (UCD), Texas A&M University System, College of Engineering and Computer Science, Australian National University (ANU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Edinburgh, University of Alberta, Department of Biological Sciences, Mass Spectrometry Facility, University of Alberta-Department of Chemistry, Volvo Car Corporation, Centre for Research in Intelligent Systems, Monash University [Clayton], Department of Chemistry [Winnipeg, MB, Canada], University of Manitoba [Winnipeg], Department of Chemistry [Winnipeg, Manitoba, Canada], Université de Strasbourg (UNISTRA), Laboratoire de synthèses métallo-induites, Dynamique et structure moléculaire par spectrométrie de masse (LDSM2), School of Mechanics and Engineering [Chengdu], Southwest Jiaotong University (SWJTU), School of Management and Economics [University of Electronic Science and Technology of China], and University of Electronic Science and Technology of China (UESTC)
Subjects: Proteomics, PROTEIN, fluerescence, Biochemistry, reference antibody, THERAPEUTIC ANTIBODIES, Biopharmaceutics, Analytical Chemistry, chemistry.chemical_compound, Biological sciences, Glycomics, NISTaAb, Analysis method, ComputingMilieux_MISCELLANEOUS, glycoproteins, mass spectrometry, chemistry.chemical_classification, 0303 health sciences, glycan, interlaboratory study, 030302 biochemistry & molecular biology, Glycopeptides, Antibodies, Monoclonal, 3. Good health, glycomics, fluorescence, glycosylation, glycopeptide, NISTmAb, lipids (amino acids, peptides, and proteins), Protein glycosylation, Glycan, Glycosylation, QUANTITATION, medicine.drug_class, Computational biology, Biology, Monoclonal antibody, 03 medical and health sciences, GLYCOMIC ANALYSIS, SDG 3 - Good Health and Well-being, Polysaccharides, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Report, medicine, Humans, LC-MS/MS, Molecular Biology, 030304 developmental biology, Biological Products, IDENTIFICATION, MASS-SPECTROMETRY, PROFILES, QUANTIFICATION, carbohydrates (lipids), chemistry, biology.protein, Laboratories, Glycoprotein, Protein Processing, Post-Translational
Abstract: A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories., Graphical Abstract Highlights A broad-based interlaboratory study of the glycosylation of a reference antibody: NISTmAb. 103 reports were received from 76 diverse laboratories worldwide. Analysis involved two samples, the NISTmAb and an enzymatically modified sample, enabling within-lab separation of random and systematic errors using the “Youden two-sample” method. Consensus values were derived and similar performance across all experimental methods was noted., Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
Published: 2020

4. Estimation of potassium levels in hemodialysis patients by T wave nonlinear dynamics and morphology markers

Author: Hassaan A. Bukhari, Carlos Sánchez, Sabarathinam Srinivasan, Flavio Palmieri, Mark Potse, Pablo Laguna, Esther Pueyo, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Aragón Institute of Engineering Research [Zaragoza] (I3A), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recerca en Enginyeria Biomèdica [Catalunya] (CREB), Universitat Politècnica de Catalunya [Barcelona] (UPC), ANR-10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), European Project: 638284,H2020,ERC-2014-STG,MODELAGE(2015), European Project: 764738,PIC, and Universitat Politècnica de Catalunya. Doctorat en Enginyeria Biomèdica
Subjects: Ronyons -- Malalties, Kidneys -- Diseases, Enginyeria biomèdica [Àrees temàtiques de la UPC], Lyapunov exponents, Health Informatics, Potassi, Hemodiàlisi, 3. Good health, Computer Science Applications, Electrocardiogram, Electrocardiography, Potassium estimation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Electrocardiografia, Hemodialysis, Potassium, T wave morphology, ComputingMilieux_MISCELLANEOUS
Abstract: Objective: Noninvasive screening of hypo- and hyperkalemia can prevent fatal arrhythmia in end-stage renal disease (ESRD) patients, but current methods for monitoring of serum potassium ([K+]) have important limita-tions. We investigated changes in nonlinear dynamics and morphology of the T wave in the electrocardiogram (ECG) of ESRD patients during hemodialysis (HD), assessing their relationship with [K+]and designing a [K+]estimator. Methods: ECG recordings from twenty-nine ESRD patients undergoing HD were processed. T waves in 2-min windows were extracted at each hour during an HD session as well as at 48 h after HD start. T wave nonlinear dynamics were characterized by two indices related to the maximum Lyapunov exponent (¿t, ¿wt) and a divergence-related index (¿). Morphological variability in the T wave was evaluated by three time warping- based indices (dw, reflecting morphological variability in the time domain, and da and dNLa, in the amplitude domain). [K+]was measured from blood samples extracted during and after HD. Stage-specific and patient- specific [K+]estimators were built based on the quantified indices and leave-one-out cross-validation was per-formed separately for each of the estimators. Results: The analyzed indices showed high inter-individual variability in their relationship with [K+]. Never-theless, all of them had higher values at the HD start and 48 h after it, corresponding to the highest [K+]. The indices ¿ and dw were the most strongly correlated with [K+](median Pearson correlation coefficient of 0.78 and 0.83, respectively) and were used in univariable and multivariable linear [K+]estimators. Agreement between actual and estimated [K+]was confirmed, with averaged errors over patients and time points being 0.000 ±0.875 mM and 0.046 ±0.690 mM for stage-specific and patient-specific multivariable [K+]estimators, respectively. Conclusion: ECG descriptors of T wave nonlinear dynamics and morphological variability allow noninvasive monitoring of [K+]in ESRD patients. Significance: ECG markers have the potential to be used for hypo- and hyperkalemia screening in ESRD patients.
Published: 2022

5. The Multiscenario Multienvironment BioSecure Multimodal Database (BMDB)

Author: Lale Akarun, Bernadette Dorizzi, Javier Ortega-Garcia, Joaquin Gonzalez-Rodriguez, Bao Ly-Van, Sonia Garcia-Salicetti, Arman Savran, Harald Ganster, M.R. Freire, Jonas Richiardi, Josef Kittler, Andrezj Drygajlo, Javier Galbally, Massimo Tistarelli, Sri-Kaushik Pavani, Jean Hennebert, J.L. Alba-Castro, Fernando Alonso-Fernandez, Linda Brodo, Thirimachos Bourlai, Lorene Allano, Enrique Otero-Muras, Elisardo González-Agulla, Michael Fairhurst, Alejandro F. Frangi, Ming Ng, Julian Fierrez, Norman Poh, Farzin Deravi, Carmen García-Mateo, Federico M. Sukno, Andreas Humm, Biometric Recognition Group (Universidad Autonoma de Madrid) (ATVS), Departamento de Teoría de la Señal y Comunicaciones (Universidad de Vigo ) (TSC), Département Electronique et Physique (EPH), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), Centre for Vision, Speech and Signal Processing (CVSSP), University of Surrey (UNIS), Lane Department of Computer Science and Electrical Engineering [Virginia] (LCSEE), West Virginia University [Morgantown], School of Engineering and Digital Art (University of Kent) (EDA), Department of Informatics (University of Fribourg), Computer Vision Laboratory (Facoltà di Architettura ad Alghero, Università degli studi di Sassari), Speech Processing and Biometrics Group (Laboratory of IDIAP, Signal Processing Institute, SwissFederal Institute of Technology ) (GTPB), Institute of Digital Image Processing (Joanneum Research) (DIP), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), Department of Computer Engineering [Bogazici], Boǧaziçi üniversitesi = Boğaziçi University [Istanbul], Signal and Image Processing Laboratory (Bogazici University) (BUSIM), Department of Electrical and Electronics Engineering (Bogazici University), Universitat Pompeu Fabra, and Boğaziçi University [Istanbul]
Subjects: Male, FOS: Computer and information sciences, Computer Science - Cryptography and Security, Databases, Factual, Computer science, Performance, Computer Vision and Pattern Recognition (cs.CV), 0211 other engineering and technologies, Fingerprint, Computer Science - Computer Vision and Pattern Recognition, Iris, 02 engineering and technology, computer.software_genre, Benchmark, Signature, Bases de dades, Data acquisition, 0202 electrical engineering, electronic engineering, information engineering, Evaluation, Biometria, Database, Applied Mathematics, ING-INF/05 Sistemi di elaborazione delle informazioni, Speaker, Online Signature Verification, Quality Measures, Fingerprint recognition, Base-Line Corpus, Computational Theory and Mathematics, Biometrics, Biometric Identification, Data Interpretation, Statistical, Female, 020201 artificial intelligence & image processing, The Internet, Computer Vision and Pattern Recognition, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Cryptography and Security (cs.CR), Biometric Database, Mobile computing, Signalbehandling, Iris flower data set, Artificial Intelligence, Humans, Dermatoglyphics, INF/01 Informatica, 021110 strategic, defence & security studies, business.industry, Reproducibility of Results, Hand, Recognition, Multimodal biometrics, Face, Signal Processing, Multimodal, Voice, Database Management Systems, business, computer, Software
Abstract: A new multimodal biometric database designed and acquired within the framework of the European BioSecure Network of Excellence is presented. It is comprised of more than 600 individuals acquired simultaneously in three scenarios: 1) over the Internet, 2) in an office environment with desktop PC, and 3) in indoor/outdoor environments with mobile portable hardware. The three scenarios include a common part of audio/video data. Also, signature and fingerprint data have been acquired both with desktop PC and mobile portable hardware. Additionally, hand and iris data were acquired in the second scenario using desktop PC. Acquisition has been conducted by 11 European institutions. Additional features of the BioSecure Multimodal Database (BMDB) are: two acquisition sessions, several sensors in certain modalities, balanced gender and age distributions, multimodal realistic scenarios with simple and quick tasks per modality, cross-European diversity, availability of demographic data, and compatibility with other multimodal databases. The novel acquisition conditions of the BMDB allow us to perform new challenging research and evaluation of either monomodal or multimodal biometric systems, as in the recent BioSecure Multimodal Evaluation campaign. A description of this campaign including baseline results of individual modalities from the new database is also given. The database is expected to be available for research purposes through the BioSecure Association during 2008, Published at IEEE Transactions on Pattern Analysis and Machine Intelligence journal
Published: 2021

6. Odorant binding changes the electrical properties of olfactory receptors at the nanoscale

Author: Anna Lagunas, Loïc Briand, Josep Samitier, Pau Gorostiza, Christine Belloir, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institució Catalana de Recerca i Estudis Avançats (ICREA), Universitat de Barcelona (UB), The Biomedical Research Networking Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012, RD16/0011/0022), with the support of the European Regional Development Fund (ERDF). This work was funded by the CERCA Program and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017-SGR-1079, 2017-SGR-1442 and 2017-SGR-00465). This work was supported by grants from the Conseil Régional Bourgogne Franche-Comté (PARI grant) and the FEDER (European Funding for Regional Economical Development). This research also received funding from the European Union Research and Innovation Programme Horizon 2020 (Human Brain Project SGA3 No. 945539), DEEPER (ICT-36-2020-101016787), Agency for Management of University and Research Grants of the Government of Catalonia (CERCA Programme, 2017-SGR-1442 project, AGAUR, Clúster Emergent del Cervell Humà), and Ministry of Economy and Competitiveness (Grant PID2019-111493RB-I00)., and Julien, Sabine
Subjects: Cell signaling, Olfactory receptor, Odorant binding, Chemistry, olfactory receptor, odorant binding, Impedance parameters, law.invention, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, medicine.anatomical_structure, open-circuit voltage, law, electrochemical scanning tunneling microscopy (EC-STM), impedance, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Biophysics, Scanning tunneling microscope, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Receptor, Transduction (physiology), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Electrochemical potential
Abstract: Olfactory receptors (ORs) comprise the largest multigene family in the vertebrates. They belong to the class A (rhodopsin-like) family of G protein-coupled receptors (GPCRs), which are the most abundant membrane proteins, having widespread, significant roles in signal transduction in cells, and therefore, they are a major pharmacological target. Moreover, ORs displayed high selectivity and sensitivity towards odorant detection, a characteristic that raised the interest for developing biohybrid sensors based on ORs for the detection of volatile compounds. The transduction of odorant binding into cellular signaling by ORs is not well understood and knowing its mechanism would enable developing new pharmacology and high performance biohybrid electronic sensors. Recent findings suggest that ligand recognition by ORs is determined by the nanoscale alterations of charge distribution in the receptor structure (Ref). However, the electrical characterization of ORs and their response towards ligand binding in bulk experiments is subjected to microscopic models and assumptions [2]. Here, we have directly determined the nanoscale electrical properties of ORs with unprecedented control over the receptor orientation, and their change upon odorant binding, using electrochemical scanning tunneling microscopy (EC-STM) in near-physiological conditions. Recordings of current versus time, distance, and electrochemical potential allows determining the OR impedance parameters and their dependence with odorant binding. The simultaneous measurement of RC equivalent by means of the open-circuit voltage (VOC) allows increasing the electrical sensitivity at the single receptor level for biosensing applications. Our results allow validating OR structural-electrostatic models and their functional activation processes.
Published: 2021

7. QRS Slopes for Potassium and Calcium Monitoring in End-Stage Renal Disease Patients

Author: Hassaan A Bukhari, Pablo Laguna, Mark Potse, Carlos Sanchez, Esther Pueyo, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Aragón Institute of Engineering Research [Zaragoza] (I3A), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), This work was supported by projects ERC-StG 638284 (ERC), PID2019-105674RB-I00 and PID2019-104881RB-I00 (Ministerio de Ciencia e Innovacion), Marie Skłodowska-Curie grant 764738 (European Commission) and European Social Fund (EU) and Aragon Government through BSICoS group T39 20R and project LMP124-18. Computations were performed by ICTS NANBIOSIS (HPC Unit, Univ. Zaragoza)., ANR-10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), and CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

8. Miniaturized Electrochemical Sensors to Monitor Fetal Hypoxia and Acidosis in a Pregnant Sheep Model

Author: Mònica Mir, Nicole Picard-Hagen, Samuel Dulay, Miriam Illa, Eduard Gratacós, Lourdes Rivas, Sergio Berdún, Josep Samitier, Laura Pla, Elisenda Eixarch, Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Universitat Autònoma de Barcelona (UAB), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Enfermedades Raras (CIBERER), and This research was funded by CELLEX FOUNDATION. This work was financially supported by The Cellex Foundation and the Agencia de Gestio d'Ajuts Universitaris i de Recerca (Grant 2017 SGR 1531). Additionally, E.E. has received support from the Departament de Salut (Grant SLT008/18/00156). The Nanobioengineering group at the Institute of Bioengineering of Catalonia (IBEC) has received support from the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (No. 2017 SGR 1079) and is part of the CERCA Programme/Generalitat de Catalunya and is supported by the Severo Ochoa programme of the Spanish Ministry of Science and Competitiveness (Grant SEV-2014-0425 (2015-2019)). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. L.R. would also like to acknowledge her support within the BEST Postdoctoral Programme, funded by the European Commission under Horizon 2020's Marie Sklodowska-Curie Actions COFUND scheme (Grant Agreement No. 712754).
Subjects: QH301-705.5, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Hemodynamics, Fetal monitoring, Hindlimb, General Biochemistry, Genetics and Molecular Biology, Article, Asphyxia, 03 medical and health sciences, 0302 clinical medicine, Prenatal medicine, medicine, Umbilical Cord Occlusion, Biology (General), Acidosis, umbilical cord occlusion, Asfíxia, Fetus, 030219 obstetrics & reproductive medicine, business.industry, Medicina prenatal, electrochemical sensors, Skeletal muscle, medicine.disease, high-risk pregnancies, Monitoratge fetal, Perinatal asphyxia, Fetal hypoxia, medicine.anatomical_structure, sense organs, medicine.symptom, business, continuous monitoring of acid-base status, 030217 neurology & neurosurgery, Biomedical engineering
Abstract: Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized multiparametric sensor aiming to evaluate tissular oxygen and pH changes continuously in an umbilical cord occlusion (UCO) sheep model. The electrochemical sensors were inserted in fetal hindlimb skeletal muscle and electrochemical signals were recorded. Fetal hemodynamic changes and metabolic status were also monitored during the experiment. Additionally, histological assessment of the tissue surrounding the sensors was performed. Both electrochemical sensors detected the pO2 and pH changes induced by the UCO and these changes were correlated with hemodynamic parameters as well as with pH and oxygen content in the blood. Finally, histological assessment revealed no signs of alteration on the same day of insertion. This study provides the first evidence showing the application of miniaturized multiparametric electrochemical sensors detecting changes in oxygen and pH in skeletal muscular tissue in a fetal sheep model., This research was funded by CELLEX FOUNDATION. This work was financially supported by The Cellex Foundation and the Agència de Gestió d’Ajuts Universitaris i de Recerca (Grant 2017 SGR 1531). Additionally, E.E. has received support from the Departament de Salut (Grant SLT008/18/00156). The Nanobioengineering group at the Institute of Bioengineering of Catalonia (IBEC) has received support from the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (No. 2017 SGR 1079) and is part of the CERCA Programme / Generalitat de Catalunya and is supported by the Severo Ochoa programme of the Spanish Ministry of Science and Competitiveness (Grant SEV-2014-0425 (2015–2019)). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. L.R. would also like to acknowledge her support within the BEST Postdoctoral Programme, funded by the European Commission under Horizon 2020’s Marie Skłodowska-Curie Actions COFUND scheme (Grant Agreement No. 712754).
Published: 2021

9. A unique multidrug nanomedicine made of squalenoyl-gemcitabine and alkyl-lysophospholipid edelfosine

Author: Silvia Irusta, Carlos Rodríguez-Nogales, Didier Desmaële, María J. Blanco-Prieto, Victor Sebastian, Patrick Couvreur, Istituto Italiano di Tecnologia (IIT), Physico-chimie, pharmacotechnie, biopharmacie (PCPB), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Universidad de Navarra [Pamplona] (UNAV), Instituto de Investigacion Sanitaria de Navarra (IdiSNA), Instituto de Nanociencia de Aragón [Saragoza, España] (INA), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institut Galien Paris-Saclay (IGPS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Molécules bioactives, conception, isolement et synthèse (MBCIS), Institut Galien Paris-Sud (IGPS), and Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Squalene, Cell Survival, Dispersity, Supramolecular chemistry, Pharmaceutical Science, Antineoplastic Agents, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 02 engineering and technology, Deoxycytidine, 030226 pharmacology & pharmacy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Microscopy, Electron, Transmission, Dynamic light scattering, Cell Line, Tumor, Amphiphile, medicine, Humans, Prodrugs, Particle Size, ComputingMilieux_MISCELLANEOUS, Chemistry, Phospholipid Ethers, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Prodrug, 021001 nanoscience & nanotechnology, medicine.disease, Gemcitabine, Hemolysis, 3. Good health, Nanomedicine, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Biophysics, Lysophospholipids, 0210 nano-technology, Biotechnology, Edelfosine
Abstract: International audience; Among anticancer nanomedicines, squalenoyl nanocomposites have obtained encouraging outcomes in a great variety of tumors. The prodrug squalenoyl-gemcitabine has been chosen in this study to construct a novel multidrug nanosystem in combination with edelfosine, an alkyl-lysophopholipid with proven anticancer activity. Given their amphiphilic nature, it was hypothesized that both anticancer compounds, with complementary molecular targets, could lead to the formation of a new multitherapy nanomedicine. Nanoassemblies were formulated by the nanoprecipitation method and characterized by dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy. Because free edelfosine is highly hemolytic, hemolysis experiments were performed using human blood erythrocytes and nanoassemblies efficacy was evaluated in a patient-derived metastatic pediatric osteosarcoma cell line. It was observed that these molecules spontaneously self-assembled as stable and monodisperse nanoassemblies of 51 ± 1 nm in a surfactant/polymer free-aqueous suspension. Compared to squalenoyl-gemcitabine nanoassemblies, the combination of squalenoyl-gemcitabine with edelfosine resulted in smaller particle size and a new supramolecular conformation, with higher stability and drug content, and ameliorated antitumor profile.
Published: 2019

10. Detection and Classification of Sleep Apnea and Hypopnea Using PPG and SpO2 Signals

Author: Pablo Laguna, Dries Testelmans, Margot Deviaene, Carolina Varon, Eduardo Gil, Guy Carrault, Bertien Buyse, Remo Lazazzera, Laboratoire Traitement du Signal et de l'Image (LTSI), 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), Department of Electrical Engineering [Leuven] (ESAT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), TU Delft's Circuits and Systems group, Technische Universiteit Delft (TU Delft), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Ecole Doctorale MathSTIC, University of Zaragoza, Spain, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Delft University of Technology (TU Delft), and Jonchère, Laurent
Subjects: medicine.medical_specialty, Central apnea, 0206 medical engineering, Biomedical Engineering, 02 engineering and technology, PRV, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Heart rate variability, Apnea detection, apnea classification, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Sleep apnea, medicine.disease, 020601 biomedical engineering, DAP, respiratory tract diseases, 030228 respiratory system, Cardiology, Obstructive Apnea, Sleep disordered breathing, Classification methods, [SDV.IB]Life Sciences [q-bio]/Bioengineering, PPG, business, Hypopnea, Pulse rate variability
Abstract: In this work, a detection and classification method for sleep apnea and hypopnea, using photopletysmography (PPG) and peripheral oxygen saturation (SpO 2) signals, is proposed. The detector consists of two parts: one that detects reductions in amplitude fluctuation of PPG (DAP)and one that detects oxygen desaturations. To further differentiate among sleep disordered breathing events (SDBE), the pulse rate variability (PRV) was extracted from the PPG signal, and then used to extract features that enhance the sympatho-vagal arousals during apneas and hypopneas. A classification was performed to discriminate between central and obstructive events, apneas and hypopneas. The algorithms were tested on 96 overnight signals recorded at the UZ Leuven hospital, annotated by clinical experts, and from patients without any kind of co-morbidity. An accuracy of 75.1% for the detection of apneas and hypopneas, in one-minute segments,was reached. The classification of the detected events showed 92.6% accuracy in separating central from obstructive apnea, 83.7% for central apnea and central hypopnea and 82.7% for obstructive apnea and obstructive hypopnea. The low implementation cost showed a potential for the proposed method of being used as screening device, in ambulatory scenarios. ispartof: Ieee Transactions On Biomedical Engineering vol:68 issue:5 ispartof: location:United States status: accepted
Published: 2021

11. Minimal epitope for Mannitou IgM on paucimannose-carrying glycoproteins

Author: Ana Gimeno, Jesús Jiménez-Barbero, Stefania Robakiewicz, Sandra Delgado, Clarisse Bridot, Begoña Echeverria, Ann Dansercoer, Nicola G. A. Abrescia, Jérôme de Ruyck, Sonia Serna, Shubham Semwal, Mikel Azkargorta, Ruud H. P. Wilbers, Ana Ardá, Savvas N. Savvides, Diego Charro, Niels C. Reichardt, Kenneth Verstraete, Julie Bouckaert, Kim van Noort, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centro de Investigación Cooperativa en Biomateriales (CIC biomaGUNE), Cell Biology and Stem Cells Unit (CICbioGUNE), Technologic Park of Bizkaia, VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Wageningen University and Research [Wageningen] (WUR), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centro de Investigación Cooperativa en Biomateriales [CIC biomaGUNE], Cell Biology and Stem Cells Unit [CICbioGUNE], VIB-UGent Center for Inflammation Research [Gand, Belgique] [IRC], Wageningen University and Research [Wageningen] [WUR], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], and Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine [CIBER-BBN]
Subjects: [SDV]Life Sciences [q-bio], Mannose, Biochemistry, Epitope, Epitopes, Mice, chemistry.chemical_compound, 0302 clinical medicine, Mannitou, N-linked glycosylation, BINDING, Medicine and Health Sciences, AFFINITY, Mammals, chemistry.chemical_classification, 0303 health sciences, biology, PROLIFERATION, paucimannosidic epitopes, Schistosoma mansoni, N-GLYCOSYLATION, CANCER, 3. Good health, DNA-Binding Proteins, GLYCAN MICROARRAYS, 030220 oncology & carcinogenesis, N-glycan, Antibody, Glycan, core fucose, IgM, CORE FUCOSYLATION, 03 medical and health sciences, Antigen, Polysaccharides, Animals, Humans, Laboratorium voor Nematologie, Fucose, Glycoproteins, 030304 developmental biology, Membrane Proteins, Biology and Life Sciences, IgM binding, Immunoglobulin M, chemistry, ANTIBODIES, biology.protein, Laboratory of Nematology, Glycoprotein, ELASTASE
Abstract: Paucimannosidic glycans are restricted to the core structure [Man1–3GlcNAc2Fuc0–1] of N-glycans and are rarely found in mammalian tissues. Yet, especially [Man2-3GlcNAc2Fuc1] have been found significantly upregulated in tumors, including in colorectal and liver cancer. Mannitou IgM is a murine monoclonal antibody that was previously shown to recognize Man3GlcNAc2 with an almost exclusive selectivity. Here, we have sought the definition of the minimal glycan epitope of Mannitou IgM, initiated by screening on a newly designed paucimannosidic glycan microarray; among the best binders were Man3GlcNAc2 and its α1,6 core-fucosylated variant, Man3GlcNAc2Fuc1. Unexpectedly and in contrast to earlier findings, Man5GlcNAc2-type structures bind equally well and a large tolerance was observed for substitutions on the α1,6 arm. It was confirmed that any substitution on the single α1,3-linked mannose completely abolishes binding. Surface plasmon resonance for kinetic measurements of Mannitou IgM binding, either directly on the glycans or as presented on omega-1 and kappa-5 soluble egg antigens from the helminth parasite Schistosoma mansoni, showed submicromolar affinities. To characterize the epitope in greater and atomic detail, saturation transfer difference nuclear magnetic resonance spectroscopy was performed with the Mannitou antigen-binding fragment. The STD-NMR data demonstrated the strongest interactions with the aliphatic protons H1 and H2 of the α1–3-linked mannose and weaker imprints on its H3, H4 and H5 protons. In conclusion, Mannitou IgM binding requires a nonsubstituted α1,3-linked mannose branch of paucimannose also on proteins, making it a highly specific tool for the distinction of concurrent human tumor-associated carbohydrate antigens.
Published: 2021

12. Harnessing subcellular-resolved organ distribution of cationic copolymer-functionalized fluorescent nanodiamonds for optimal delivery of therapeutic siRNA to a xenografted tumor in mice

Author: Zamira Díaz-Riascos, Patrick Georges, Sandra Claveau, Xavier Délen, Jean-Rémi Bertrand, Petr Cigler, Alexandre Papine, Marek Kindermann, François Treussart, Òscar Tirado Martínez, Ibane Abasolo Olaortua, Roser López-Alemany, Laboratoire Lumière, Matière et Interfaces (LuMIn), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques (METSY), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB / CAS), Czech Academy of Sciences [Prague] (CAS), University of Chemistry and Technology Prague (UCT Prague), IMSTAR, IMSTAR S.A., Vall d’Hebron Research Institute (VHIR), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Laboratoire Charles Fabry / Lasers, Laboratoire Charles Fabry (LCF), Institut d'Optique Graduate School (IOGS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL)
Subjects: Biodistribution, Small interfering RNA, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Quantitative Biology - Quantitative Methods, Fluorescence, Nanodiamonds, Mice, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, In vivo, Neoplasms, Fluorescence microscope, Animals, General Materials Science, Tissue Distribution, RNA, Small Interfering, Nanodiamond, Tissues and Organs (q-bio.TO), biodistribution, Quantitative Methods (q-bio.QM), Oncogene, cationic copolymer, Chemistry, time-delayed epifluorescence, Quantitative Biology - Tissues and Organs, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 3. Good health, 0104 chemical sciences, FOS: Biological sciences, Biophysics, Nanomedicine, fluorescent nanodiamond, 0210 nano-technology, high-throughput quantifications, in vivo siRNA delivery
Abstract: Diamond nanoparticles (nanodiamonds) can transport active drugs in cultured cells as well as in vivo. However, in the latter case, methods allowing to determine their bioavailability accurately are still lacking. Nanodiamond can be made fluorescent with a perfectly stable emission and a lifetime ten times longer than the one of tissue autofluorescence. Taking advantage of these properties, we present an automated quantification method of fluorescent nanodiamonds (FND) in histological sections of mouse organs and tumor, after systemic injection. We use a home-made time-delayed fluorescence microscope comprising a custom pulsed laser source synchronized on the master clock of a gated intensified array detector. This setup allows to obtain ultra-high-resolution images 120 Mpixels of whole mouse organs sections, with subcellular resolution and single-particle sensitivity. As a proof-of-principle experiment, we quantified the biodistribution and aggregation state of new cationic FNDs able to transport small interfering RNA inhibiting the oncogene responsible for Ewing sarcoma. Image analysis showed a low yield of nanodiamonds in the tumor after intravenous injection. Thus, for the in vivo efficacy assay we injected the nanomedicine into the tumor. We achieved a 28-fold inhibition of the oncogene. This method can readily be applied to other nanoemitters with $\approx$100 ns lifetime., Comment: Nanoscale, Royal Society of Chemistry, 2021
Published: 2021
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13. Characterization of t wave amplitude, duration and morphology changes during hemodialysis: Relationship with serum electrolyte levels and heart rate

Author: Julia Ramirez, Carlos Sánchez, José Esteban Ruiz, Esther Pueyo, Dina Ferreira, Pablo Laguna, Mark Potse, Hassaan A. Bukhari, Flavio Palmieri, Aragón Institute of Engineering Research [Zaragoza] (I3A), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Centre de Recerca en Enginyeria Biomèdica [Catalunya] (CREB), Universitat Politècnica de Catalunya [Barcelona] (UPC), William Harvey Research Institute, Barts and the London Medical School, Hospital Clínico Universitario 'Lozano Blesa' [Zaragoza, Spain], Laboratorios Rubió, IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Centro Universitario de la Defensa de Zaragoza (CUD), General Military Academy of Zaragoza, This work was supported by projects ERC-StG 638284(ERC), PID2019-105674RB-I00 and PID2019-104881RB-I00 (Ministerio de Ciencia e Innovacion), Marie Skłodowska-Curie grants 786833 and 764738 (European Commission) and by European Social Fund (EU) and Aragon Government through BSICoS group T3920R and project LMP124-18. Computations were performed by the ICTS NANBIOSIS (HPC Unit at University of Zaragoza)., European Project: 282085,EC:FP7:ERC,ERC-2011-StG_20101109,RETGENTX(2012), Universitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest
Subjects: [SPI.OTHER]Engineering Sciences [physics]/Other, Morphology (linguistics), medicine.medical_treatment, 0206 medical engineering, Heart rate, Biomedical Engineering, 02 engineering and technology, in silico modelling, in silico modeling, T wave amplitude, Electrocardiography, Electrolytes, Nuclear magnetic resonance, Serum electrolyte levels, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Renal Dialysis, medicine, heart rate, T wave morphology, Humans, time warping, calcium, hemodialysis, Chemistry, ECG, potassium, Transmural heterogeneity, Arrhythmias, Cardiac, Time warping, 020601 biomedical engineering, Hemodiàlisi, Serum potassium, Hemodialysis, transmural heterogeneity, Potassium, Kidney Failure, Chronic, Calcium
Abstract: Objective: Chronic kidney disease affects more than 10% of the world population. Changes in serum ion concentrations increase the risk for ventricular arrhythmias and sudden cardiac death, particularly in end-stage renal disease (ESRD) patients. We characterized how T wave amplitude, duration and morphology descriptors change with variations in serum levels of potassium and calcium and in heart rate, both in ESRD patients and in simulated ventricular fibers. Methods: Electrocardiogram (ECG) recordings from twenty ESRD patients undergoing hemodialysis (HD) and pseudo-ECGs (pECGs) calculated from twenty-two simulated ventricular fibers at varying transmural heterogeneity levels were processed to quantify T wave width ( $T_{\mathrm{w}}$ ), T wave slope-to-amplitude ratio ( $T_{\text{S/A}}$ ) and four indices of T wave morphological variability based on time warping ( $d_{\mathrm{w}}$ , $d^{\text{NL}}_{\mathrm{w}}$ , $d_{\mathrm{a}}$ and $d^{\text{NL}}_{\mathrm{a}}$ ). Serum potassium and calcium levels and heart rate were measured along HD. Results: $d^{\text{NL}}_{\mathrm{a}}$ was the marker most strongly correlated with serum potassium, $d_{\mathrm{w}}$ with calcium and $d_{\mathrm{a}}$ with heart rate, after correction for covariates. Median values of partial correlation coefficients were 0.75, $-$ 0.74 and $-$ 0.90, respectively. For all analyzed T wave descriptors, high inter-patient variability was observed in the pattern of such relationships. This variability, accentuated during the first HD time points, was reproduced in the simulations and shown to be influenced by differences in transmural heterogeneity. Conclusion: Changes in serum potassium and calcium levels and in heart rate strongly affect T wave descriptors, particularly those quantifying morphological variability. Significance: ECG markers have the potential to be used for monitoring serum ion concentrations in ESRD patients.
Published: 2021

14. Block copolymer-based magnetic mixed matrix membranes-effect of magnetic field on protein permeation and membrane fouling

Author: Gema Martinez, Suzana Pereira Nunes, Lakshmeesha Upadhyaya, Isabel M. Coelhoso, João G. Crespo, Rodrigo Fernández-Pacheco, Damien Quemener, Carla A.M. Portugal, Mona Semsarilar, Reyes Mallada, European Commission, Fundação para a Ciência e a Tecnologia (Portugal), Ministério da Ciência, Tecnologia e Ensino Superior (Portugal), King Abdullah University of Science and Technology (KAUST), Institut Européen des membranes (IEM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), LAQV@REQUIMTE, DQ - Departamento de Química, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, and Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA)
Subjects: Materials science, Filtration and Separation, 02 engineering and technology, 010501 environmental sciences, lcsh:Chemical technology, Methacrylate, complex mixtures, 01 natural sciences, Article, chemistry.chemical_compound, [CHIM.GENI]Chemical Sciences/Chemical engineering, Copolymer, protein filtration, Chemical Engineering (miscellaneous), lcsh:TP1-1185, lcsh:Chemical engineering, 0105 earth and related environmental sciences, Nanocomposite, Process Chemistry and Technology, Membrane fouling, Superparamagnetic nanoparticles, technology, industry, and agriculture, lcsh:TP155-156, [CHIM.MATE]Chemical Sciences/Material chemistry, Permeation, 021001 nanoscience & nanotechnology, equipment and supplies, superparamagnetic nanoparticles, Block copolymers, block copolymers, Membrane, [CHIM.POLY]Chemical Sciences/Polymers, Methacrylic acid, chemistry, Chemical engineering, Protein filtration, Permeability (electromagnetism), Magneto-responsive membranes, magneto-responsive membranes, 0210 nano-technology, human activities
Abstract: This article belongs to the Special Issue Membrane and Membrane Bioreactors Applied to Health and Life Sciences., In this study, we report the impact of the magnetic field on protein permeability through magnetic-responsive, block copolymer, nanocomposite membranes with hydrophilic and hydrophobic characters. The hydrophilic nanocomposite membranes were composed of spherical polymeric nanoparticles (NPs) synthesized through polymerization-induced self-assembly (PISA) with iron oxide NPs coated with quaternized poly(2-dimethylamino)ethyl methacrylate. The hydrophobic nanocomposite membranes were prepared via nonsolvent-induced phase separation (NIPS) containing poly (methacrylic acid) and meso-2,3-dimercaptosuccinic acid-coated superparamagnetic nanoparticles (SPNPs). The permeation experiments were carried out using bovine serum albumin (BSA) as the model solute, in the absence of the magnetic field and under permanent and cyclic magnetic field conditions OFF/ON (strategy 1) and ON/OFF (strategy 2). It was observed that the magnetic field led to a lower reduction in the permeate fluxes of magnetic-responsive membranes during BSA permeation, regardless of the magnetic field strategy used, than that obtained in the absence of the magnetic field. Nevertheless, a comparative analysis of the effect caused by the two cyclic magnetic field strategies showed that strategy 2 allowed for a lower reduction of the original permeate fluxes during BSA permeation and higher protein sieving coefficients. Overall, these novel magneto-responsive block copolymer nanocomposite membranes proved to be competent in mitigating biofouling phenomena in bioseparation processes., The Doctorate of Lakshmeesha Upadhyaya has been financed by a scholarship of the European Commission—Education, Audiovisual and Culture Executive Agency (EACEA), under the program: Erasmus Mundus Doctorate in Membrane Engineering—EUDIME (FPA N° 2011–0014, Edition III, http:/eudime.unical.it). Furthermore, this work was supported by the project PTDM/EDM-EDM/30828/2017 (FCT/MCTES) and by the Associate Laboratory for Green Chemistry—LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020).
Published: 2021

15. A Scrum-Based Development Process to Support Co-creation with Elders in the eHealth Domain

Author: Cristian Moral, Elena Villalba-Mora, Jose Barambones, Xavier Ferre, Universidad Politécnica de Madrid (UPM), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Regina Bernhaupt, Carmelo Ardito, Stefan Sauer, TC 13, and WG 13.2
Subjects: Process management, Scope (project management), business.industry, Computer science, Process (engineering), Context (language use), Usability, 02 engineering and technology, Scrum, 03 medical and health sciences, 0302 clinical medicine, User experience design, Experience report, 0202 electrical engineering, electronic engineering, information engineering, eHealth, Agile User-Centered Design, 020201 artificial intelligence & image processing, Elder users, [INFO]Computer Science [cs], 030212 general & internal medicine, business, Agile software development
Abstract: Part 2: Model-Based and Model-Driven Approaches; International audience; Since the publication of agile manifesto in 2001, agile methodologies has been gaining significant interest in both software industry and research community. Agile User-Centered Design (AUCD) assesses the challenge of integrating agile development with user experience and usability techniques. Although both methodologies have similarities, their scope and perspective are different and difficult to integrate. The eHealth domain implies additional challenges in terms of usability, due to the differences between healthcare professionals, and lack of knowledge of the day-to-day work carried out in different care tiers. Therefore, the challenge is twofold: to achieve an adequate symbiosis of work between teams, and design a solution adapted to the needs of diverse stakeholders with vast differences in their context of use. We designed a lightweight AUCD process adapted to such situation, and we present our experience in the design and implementation of such development process for the development of a system to monitor frailty in elder patients with support for both community and specialized care. As a result, our UCD process has achieved both iterative and incremental value generation, maintaining a good coordination between developers and UX designers, and resulting on a usable solution with regard to target users.
Published: 2020

16. Electrochemical sensors for cortisol detections: Almost there

Author: Miguel Zea, Abdelhamid Errachid, Nadia Zine, Rosa Villa, Hamdi Ben Halima, Francesca G Bellagambi, Nicole Jaffrezic-Renault, Gemma Gabriel, Instituto de Microelectrònica de Barcelona (IMB-CNM), Centro Nacional de Microelectronica [Spain] (CNM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universitat Autònoma de Barcelona (UAB), Micro & Nanobiotechnologies, Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, M. Zea would like to acknowledge his financial support covered by Fundación Centro de Estudios Interdisciplinarios Básicos y Aplicados (CEIBA)-Gobernación de Bolivar (Colombia). This work was supported by the Spanish government -funded project RTI2018-096786-B-I00 , and RTI2018-102070-B-C21 by Ministerio de Ciencia, Innovación y Universidades (MINECO/FEDER, EU). The authors also want to thank the support of the Generalitat de Catalunya to 2017-SGR-988 , and the SU-8 Unit of the CIBER in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN) at the IMB-CNM (CSIC) of ICTS 'NANBIOSIS.' This work has also made use of the Spanish ICTS Network MICRONANOFABS partially supported by MEINCOM . This work was also partially supported by the EU H2020 research and innovation program KardiaTool with agreement Nº 768686 and from CAMPUS FRANCE program agreement PHC PROCOPE 40544QH ., European Project: 768686,KardiaTool, Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: business.industry, 010401 analytical chemistry, Healthcare, Physiology, Immunosensor, 01 natural sciences, Stress hormone, Hormone, Cortisol, 0104 chemical sciences, 3. Good health, Analytical Chemistry, Human health, Electrochemical sensor, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Medicine, Oral fluid, [CHIM]Chemical Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, business, Cortisol level, hormones, hormone substitutes, and hormone antagonists, Spectroscopy, ComputingMilieux_MISCELLANEOUS
Abstract: Mostly known as “the stress hormone”, cortisol has many essential functions in humans due to its involvement in regulation of blood pressure, immune system, metabolism of protein, carbohydrate, adipose, and anti-inflammatory action. Since a right cortisol balance is essential for human health, many efforts are currently being made to monitor the cortisol level in the human body. Cortisol levels are usually monitored in blood, plasma, serum, oral fluid, sweat, and hair samples through immunochemical and analytical methods, but in the last decade, electrochemical measurements are proving to be reliable techniques for cortisol quantification in biological matrices with the advantages of a fast response by portable and wearable devices. This review gathers the most recent developments and works on electrochemical sensors for cortisol detection, highlighting their high technology maturity and potential for clinical applications.
Published: 2020

17. Lipid bilayers: Phase behavior and nanomechanics

Author: Patricia Losada-Pérez, Marina I. Giannotti, Lorena Redondo-Morata, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université libre de Bruxelles (ULB), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Universitat de Barcelona (UB), Irena Levitan, Andreea Trache, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), ANR-16-IDEX-0004,ULNE,ULNE(2016), and REDONDO MORATA, Lorena
Subjects: Phase transition, Materials science, Quartz crystal microbalance with dissipation monitoring (QCM-D), [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 02 engineering and technology, [PHYS.PHYS.PHYS-CHEM-PH] Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Cell membrane, 03 medical and health sciences, Phase (matter), medicine, Lipid bilayer, 030304 developmental biology, 0303 health sciences, Lipid phase behavior, Quartz crystal microbalance, 021001 nanoscience & nanotechnology, Phase coexistence, Nanomechanics, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, medicine.anatomical_structure, Membrane, Membrane protein, Atomic force microscopy (AFM), Biophysics, Thermodynamics, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], 0210 nano-technology, Sciences exactes et naturelles
Abstract: Lipid membranes are involved in many physiological processes like recognition, signaling, fusion or remodeling of the cell membrane or some of its internal compartments. Within the cell, they are the ultimate barrier, while maintaining the fluidity or flexibility required for a myriad of processes, including membrane protein assembly. The physical properties of in vitro model membranes as model cell membranes have been extensively studied with a variety of techniques, from classical thermodynamics to advanced modern microscopies. Here we review the nanomechanics of solid-supported lipid membranes with a focus in their phase behavior. Relevant information obtained by quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force microscopy (AFM) as complementary techniques in the nano/mesoscale interface is presented. Membrane morphological and mechanical characterization will be discussed in the framework of its phase behavior, phase transitions and coexistence, in simple and complex models, and upon the presence of cholesterol., info:eu-repo/semantics/published
Published: 2020

18. Dendrimers toward Translational Nanotherapeutics: Concise Key Step Analysis

Author: Ángeles Muñoz-Fernández, João Rodrigues, Jean-Pierre Majoral, René Roy, Serge Mignani, Xiangyang Shi, Valentín Ceña, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centro de Química da Madeira, Universidade da Madeira (UMA), Glycovax Pharma, State Key Laboratory for Fiber & Material Modification of Donghua University, Donghua University [Shanghai], Northwestern Polytechnical University [Xi'an] (NPU), Hospital General Universitario 'Gregorio Marañón' [Madrid], Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank (SHIVBB), Virtual Institute on Poverty Related Diseases, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Universidad de Castilla-La Mancha (UCLM), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), PRC NSFC-CNRS 2019 (21911530230, 199675), FCT-Fundação para a Ciência e a Tecnologia (Base Fund UIDB/00674/2020 and Programmatic Fund UIDP/00674/2020, Portuguese Government Funds), ARDITI-Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação through Project M1420-01- 0145-FEDER-000005-CQM+ (Madeira 14-20 Program), Transnational EuroNanoMed III (ERANET), Spanish Ministerio de Economía y Competitividad (Project SAF2017-89288-R from MINECO/AEI/FEDER/UE) and JCCM (Project SBPLY/19/180501/000067), RD16/0025/0019 and PI16/01863 projects as part of the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica by ISCIII, Fondos FEDER and CIBER BBN, RIS Cohort (CoRIS) is funded by the ISCIII through the Spanish AIDS Research Network (RIS C03/173 and RD12/0017/0018) Action, COST Action Ca 17140 and NAW European Project, and CNRS
Subjects: Dendrimers, Cancer therapy, Biomedical Engineering, Pharmaceutical Science, Contrast Media, Bioengineering, 02 engineering and technology, 01 natural sciences, Drug Delivery Systems, Animals, Humans, Nanotechnology, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Pharmacology, Dendrons, Drug Carriers, 010405 organic chemistry, Chemistry, Pharmaceutics, Organic Chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, 3. Good health, Clinical Practice, Nanomedicine, Pharmaceutical Preparations, Key (cryptography), Pharmaceuticals, Nanoparticles, Engineering ethics, sense organs, 0210 nano-technology, Biotechnology
Abstract: International audience; The goal of nanomedicine is to address specific clinical problems optimally, to fight human diseases, and to find clinical relevance to change clinical practice. Nanomedicine is poised to revolutionize medicine via the development of more precise diagnostic and therapeutic tools. The field of nanomedicine encompasses numerous features and therapeutic disciplines. A plethora of nanomolecular structures have been engineered and developed for therapeutic applications based on their multitasking abilities and the wide functionalization of their core scaffolds and surface groups. Within nanoparticles used for nanomedicine, dendrimers as well polymers have demonstrated strong potential as nanocarriers, therapeutic agents, and imaging contrast agents. In this review, we present and discuss the different criteria and parameters to be addressed to prepare and develop druggable nanoparticles in general and dendrimers in particular. We also describe the major requirements, included in the preclinical and clinical roadmap, for NPs/dendrimers for the preclinical stage to commercialization. Ultimately, we raise the clinical translation of new nanomedicine issues.
Published: 2020

19. TETRALEC, Artificial Tetrameric Lectins: A Tool to Screen Ligand and Pathogen Interactions

Author: Sabine Mayer-Lambertz, Corinne Vivès, Bernd Lepenies, Franck Fieschi, João T. Monteiro, Christine Ebel, Michel Thépaut, Niels-Christian Reichardt, Aline Le Roy, Sonia Serna, Silvia Achilli, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Immunology Unit and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, CIC biomaGUNE, Glycotechnology Laboratory, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Department of Biomolecular Systems [Potsdam], Max Planck Institute of Colloids and Interfaces, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Subjects: 0301 basic medicine, Glycan, Recombinant Fusion Proteins, glycan array, Ligands, 01 natural sciences, Catalysis, Article, Flow cytometry, law.invention, lcsh:Chemistry, Inorganic Chemistry, 03 medical and health sciences, C-type lectin, Confocal microscopy, law, Candida albicans, medicine, pathogen recognition, Lectins, C-Type, Physical and Theoretical Chemistry, Receptor, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, biology, medicine.diagnostic_test, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 010405 organic chemistry, Chemistry, Organic Chemistry, Lectin, General Medicine, multivalency, Ligand (biochemistry), Flow Cytometry, In vitro, eye diseases, 0104 chemical sciences, Computer Science Applications, Immunoglobulin Fc Fragments, DC-SIGNR, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Biochemistry, biology.protein
Abstract: International audience; C-type lectin receptor (CLR)/carbohydrate recognition occurs through low affinity interactions. Nature compensates that weakness by multivalent display of the lectin carbohydrate recognition domain (CRD) at the cell surface. Mimicking these low affinity interactions in vitro is essential to better understand CLR/glycan interactions. Here, we present a strategy to create a generic construct with a tetrameric presentation of the CRD for any CLR, termed TETRALEC. We applied our strategy to a naturally occurring tetrameric CRD, DC-SIGNR, and compared the TETRALEC ligand binding capacity by synthetic N- and O-glycans microarray using three different DC-SIGNR constructs i) its natural tetrameric counterpart, ii) the monomeric CRD and iii) a dimeric Fc-CRD fusion. DC-SIGNR TETRALEC construct showed a similar binding profile to that of its natural tetrameric counterpart. However, differences observed in recognition of low affinity ligands underlined the importance of the CRD spatial arrangement. Moreover, we further extended the applications of DC-SIGNR TETRALEC to evaluate CLR/pathogens interactions. This construct was able to recognize heat-killed Candida albicans by flow cytometry and confocal microscopy, a so far unreported specificity of DC-SIGNR. In summary, the newly developed DC-SIGNR TETRALEC tool proved to be useful to unravel novel CLR/glycan interactions, an approach which could be applied to other CLRs.
Published: 2020

20. Generation Dependent Effects and Entrance to Mitochondria of Hybrid Dendrimers on Normal and Cancer Neuronal Cells In Vitro

Author: Teresa Gabryelak, Silvia Moreno, Jean-Pierre Majoral, Francisco Javier de la Mata, Dzmitry Shcharbin, Rafael Gomez-Ramirez, Maria Bryszewska, Aleksandra Szwed, Sylwia Michlewska, Katarzyna Milowska, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Alcala (Grant from MINECO CTQ-2014-54004-P), CIBER-BBN (VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program), European Regional Development Fund, Instituto de Salud Carlos III, Polish National Agency for Academic Exchange (grant EUROPARTNER, No. PPI/APM/2018/1/00007/U/00), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Dendrimers, ∆Ψm, δψm, Cytotoxicity, lcsh:QR1-502, Apoptosis, 02 engineering and technology, Mitochondrion, 010402 general chemistry, 01 natural sciences, Biochemistry, Article, lcsh:Microbiology, Membrane Potentials, Mice, Neuroblastoma, Cell Line, Tumor, Cytotoxic T cell, Animals, Carbosilane-viologenphosphorus dendrimers, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Molecular Biology, neoplasms, Membrane potential, Neurons, Chemistry, mHippoE-18, ROS, 021001 nanoscience & nanotechnology, Embryonic stem cell, 0104 chemical sciences, 3. Good health, Cell biology, Mitochondria, N2a, Cell culture, carbosilane–viologen–phosphorus dendrimers, TEM, Nanocarriers, 0210 nano-technology, Reactive Oxygen Species, Immortalised cell line
Abstract: Dendrimers as drug carriers can be utilized for drugs and siRNA delivery in central nervous system (CNS) disorders, including various types of cancers, such as neuroblastomas and gliomas. They have also been considered as drugs per se, for example as anti-Alzheimer&rsquo, s disease (AD), anti-cancer, anti-prion or anti-inflammatory agents. Since the influence of carbosilane&ndash, viologen&ndash, phosphorus dendrimers (SMT1 and SMT2) on the basic cellular processes of nerve cells had not been investigated, we examined the impact of two generations of these hybrid macromolecules on two murine cell lines&mdash, cancer cell line N2a (mouse neuroblastoma) and normal immortalized cell line mHippoE-18 (embryonic mouse hippocampal cell line). We examined alterations in cellular responses including the activity of mitochondrial dehydrogenases, the generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential, and morphological modifications and fractions of apoptotic and dead cells. Our results show that both dendrimers at low concentrations affected the cancer cell line more than the normal one. Also, generation-dependent effects were found: the highest generation induced greater cytotoxic effects and morphological modifications. The most promising is that the changes in mitochondrial membrane potential and transmission electron microscopy (TEM) images indicate that dendrimer SMT1 can reach mitochondria. Thus, SMT1 and SMT2 seem to have potential as nanocarriers to mitochondria or anti-cancer drugs per se in CNS disorders.
Published: 2020

21. The 'Digital Twin' to enable the vision of precision cardiology

Author: Pras Pathmanathan, Liesbet Geris, Yingjing Feng, Francesca Margara, Andrew Gilbert, Espen W. Remme, Alfonso Bueno-Orovio, Joao Filipe Fernandes, Mark Potse, Marta Sitges, Blanca Rodriguez, Viatcheslav Gurev, Tammo Delhaas, Tina M. Morrison, Manuel Villegas Martinez, Pablo Lamata, Ali Wajdan, Ada Doltra, Filip Loncaric, Hassaan A. Bukhari, Richard Cornelussen, Paul Leeson, Paolo DiAchille, Frits W. Prinzen, Peter Mortier, Manuel Mayr, Hongxing Luo, Edward J. Vigmond, Mehrdad Shamohammdi, Esther Pueyo, Kristin McLeod, Philip Westphal, Vicente Grau, Jorge Corral-Acero, Ernesto Zacur, Steven A. Niederer, Mariana Sousa Santos, Maciej Marciniak, Cristobal Rodero, Department of Engineering Science [Oxford], Institute of Biomedical Engineering [Oxford] (IBME), University of Oxford [Oxford]-University of Oxford [Oxford], Department of Computer Science [Oxford], University of Oxford [Oxford], King‘s College London, Universitat de Barcelona (UB), Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Oslo University Hospital [Oslo], Aragón Institute of Engineering Research [Zaragoza] (I3A), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), FEops, Maastricht University [Maastricht], Medtronic Bakken Research Center BV, John Radcliffe Hospital [Oxford University Hospital], IBM Thomas J. Watson Research Center, IBM, Virtual Physiological Human Institute [Leuven] (VPH), U.S. Food and Drug Administration (FDA), Cardiovascular Research Institute Maastricht (CARIM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Oslo (UiO), GE Vingmed Ultrasound AS, IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, This work was supported by the EU’s Horizon 2020 Marie Sklodowska-Curie ITN Projects (g.a. 764738 and 766082), the EU’s Horizon 2020 research and (g.a. 675451 and 823712), the Wellcome/EPSRC Centre for Medical Engineering (WT 203148/Z/16/Z), the National Research Agency (ANR) (g.a. ANR-10-IAHU-04), theNC3RS (NC/P001076/1) and the British Heart Foundation (RE/13/2/30182, RE/13/1/30181, TG/17/3/33406, PG/16/75/32383, FS/17/22/32644, CH/16/3/21406, RG/16/14/32397). E.Pueyo holds an ERC StartingGrant (g.a. 638284). B. Rodriguez and P. Lamata hold Wellcome TrustSenior Research Fellowships (214290/Z/18/Z, 209450/Z/17/Z)., ANR-10-IAHU-04/10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), ANR-10-IAHU-0004,LIRYC,L'Institut de Rythmologie et modélisation Cardiaque(2010), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), University of Oxford-University of Oxford, University of Oxford, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, and Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux]
Subjects: Artificial intelligence, Cardiac & Cardiovascular Systems, INFORMATION, diagnosis, 030204 cardiovascular system & hematology, 0302 clinical medicine, CHANNEL, Medicine, AcademicSubjects/MED00200, RISK, 0303 health sciences, Computational model, ARTIFICIAL-INTELLIGENCE, Precision medicine, twins, 3. Good health, cardiology, HEART, TRIAL, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Algorithms, Digital Health and Innovation, vision, Boosting (machine learning), BIG DATA, Cardiovascular research, MEDLINE, PRESSURE, 03 medical and health sciences, models, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, computer simulation, Extensive data, State of the Art Review, Humans, 030304 developmental biology, Science & Technology, BLOOD-FLOW, business.industry, MEDICINE, Statistical model, PERFORMANCE, CT ANGIOGRAPHY, Data science, Digital twin, Computational modelling, Cardiovascular System & Cardiology, Position paper, precision, business, statistical
Abstract: Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine. ispartof: EUROPEAN HEART JOURNAL vol:41 issue:48 pages:4556-+ ispartof: location:England status: published
Published: 2020

22. Morphosynthesis of porous silica from biocompatible templates

Author: Mélanie Emo, Marie-José Stébé, Claudia Violeta Cervantes-Martinez, M.J. García-Celma, Jean-Luc Blin, Laboratoire Lorrain de Chimie Moléculaire (L2CM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), University of Barcelona, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), and Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion
Subjects: Materials science, Small-angle X-ray scattering, General Chemical Engineering, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Micelle, 0104 chemical sciences, [SPI]Engineering Sciences [physics], Pulmonary surfactant, Chemical engineering, Liquid crystal, Emulsion, Lamellar structure, 0210 nano-technology, Porosity, Mesoporous material
Abstract: International audience; Taking inspiration from morphogenesis, synthetic porous silica materials have been synthesized through rational designs combining the sol–gel process and the surfactant templating method. Materials have been prepared from biocompatible systems using kolliphor as surfactant.The effect of Miglyol and Myristate solubilization in the Kolliphor/water system was first investigated in detail. The phase diagram proved that only a weak fraction of these oils (≈1 wt.%) can be incorporated into the hydrophobic core of the micelles (L1). Results also show that whatever the liquid crystal phases [direct hexagonal (H1) and lamellar (Lα)] the swelling effect take place upon addition of oil. Moreover, at low oil concentration oil-in-water fine emulsions are formulated, while at high oil concentration, oil-in-water concentrated emulsion are formulated.Starting from the various systems, porous silica materials were then synthesized. Results obtained by SAXS and nitrogen adsorption–desorption analysis show that Miglyol and Myristate can expand the mesopore size. The variations of the pore diameter have been related to the solubilization properties of the oil in the surfactant. In addition, macroporous silica could be design by using concentrated emulsions as template.This work demonstrates that synthetic silica materials can be obtained by mimic of natural processes.
Published: 2019

23. Tri-mannose grafting of chitosan nanocarriers remodels the macrophage response to bacterial infection

Author: Laura De Matteis, Anne Biton, Jesús M. de la Fuente, Brigitte Gicquel, Inés Serrano-Sevilla, Alexandre Giraud-Gatineau, Anne Danckaert, Ludovic Tailleux, Marie-Agnès Dillies, Juan Manuel Coya, Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), Instituto de Nanociencia de Aragón [Saragoza, España] (INA), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), This research project was co-financed by the Institut Pasteur and the European Commission as part of the European Seventh Framework Program Nanotherapeutics against Resistant Emerging Bacterial Pathogens (NAREB Project 604237), public funding from the Fondo Social de la DGA (grupos DGA), Ministerio de Economía y Competitividad del Gobierno de España for the public founding of the Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad. The text represents the authors’ views and does not necessarily represent the position of the Commission who are not liable for the publication of this information. The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript., European Project: 604237,EC:FP7:NMP,FP7-NMP-2013-LARGE-7,NAREB(2014), European Commission, Institut Pasteur, Diputación General de Aragón, Ministerio de Economía y Competitividad (España), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pharmaceutical Science, Medicine (miscellaneous), Mannose, 02 engineering and technology, Drug resistance, 01 natural sciences, Applied Microbiology and Biotechnology, chemistry.chemical_compound, Drug Delivery Systems, Macrophage, Cells, Cultured, Drug Carriers, Chemistry, Bacterial Infections, 021001 nanoscience & nanotechnology, 3. Good health, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:R855-855.5, Drug delivery, Host-Pathogen Interactions, Molecular Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Metabolic Networks and Pathways, lcsh:Medical technology, lcsh:Biotechnology, Biomedical Engineering, Bioengineering, 010402 general chemistry, Immune system, Phagocytosis, lcsh:TP248.13-248.65, Host response, Humans, Surface grafting, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Chitosan, Innate immune system, Research, Macrophages, Mycobacterium tuberculosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, 0104 chemical sciences, MRNA Sequencing, Chitosan nanocarriers, Nanoparticles, Nanocarriers, Transcriptome
Abstract: [Background]: Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs and strategies are thus urgently needed to improve treatment efficacy and limit drug-associated side effects. Nanotechnology-based drug delivery systems are promising approaches, offering hope in the fight against drug resistant bacteria. However, how nanocarriers influence the response of innate immune cells to bacterial infection is mostly unknown., [Results]: Here, we used Mycobacterium tuberculosis as a model of bacterial infection to examine the impact of mannose functionalization of chitosan nanocarriers (CS-NCs) on the human macrophage response. Both ungrafted and grafted CS-NCs were similarly internalized by macrophages, via an actin cytoskeleton-dependent process. Although tri-mannose ligands did not modify the capacity of CS-NCs to escape lysosomal degradation, they profoundly remodeled the response of M. tuberculosis-infected macrophages. mRNA sequencing showed nearly 900 genes to be differentially expressed due to tri-mannose grafting. Unexpectedly, the set of modulated genes was enriched for pathways involved in cell metabolism, particularly oxidative phosphorylation and sugar metabolism., [Conclusions]: The ability to modulate cell metabolism by grafting ligands at the surface of nanoparticles may thus be a promising strategy to reprogram immune cells and improve the efficacy of encapsulated drugs., This research project was co-financed by the Institut Pasteur and the European Commission as part of the European Seventh Framework Program Nanotherapeutics against Resistant Emerging Bacterial Pathogens (NAREB Project 604237), public funding from the Fondo Social de la DGA (grupos DGA), Ministerio de Economía y Competitividad del Gobierno de España for the public founding of the Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad.
Published: 2019

24. New active formulations against M. tuberculosis: Bedaquiline encapsulation in lipid nanoparticles and chitosan nanocapsules

Author: Fabrice Navarro, José A. Aínsa, Sonia García-Embid, Inés Serrano-Sevilla, Dorothée Jary, J. M. de la Fuente, L. De Matteis, D. Pérez, Ainhoa Lucía, Diputación General de Aragón, Ministerio de Economía y Competitividad (España), Ministerio de Educación, Cultura y Deporte (España), European Commission, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and European Project: 604237,EC:FP7:NMP,FP7-NMP-2013-LARGE-7,NAREB(2014)
Subjects: 0301 basic medicine, Drug, Tuberculosis, medicine.drug_class, Bedaquiline, General Chemical Engineering, media_common.quotation_subject, Cytotoxicity, Antibiotics, 02 engineering and technology, Pharmacology, Industrial and Manufacturing Engineering, Nanocapsules, [SPI]Engineering Sciences [physics], 03 medical and health sciences, chemistry.chemical_compound, In vivo, Electron microscopy, Environmental Chemistry, Medicine, media_common, business.industry, General Chemistry, Mycobacterium tuberculosis, 021001 nanoscience & nanotechnology, medicine.disease, Antimicrobial, 3. Good health, 030104 developmental biology, chemistry, Nanocarriers, 0210 nano-technology, business
Abstract: In the last years, the increase in antimicrobial resistance, together with a lack of new drugs for the treatment of bacterial infections resistant to classical antibiotics are of growing concern. Moreover, some of current therapies induce severe side effects and are often difficult to administer. In 2012 the FDA approved the use of bedaquiline, as the first new very effective drug against TB in the last 40 years. Despite its effectiveness, unfortunately bedaquiline side effects can be so dangerous that at present it is to be prescribed only when no other treatment options are available. The development of effective and safe nanotechnology-based methods can be particularly relevant to increase antimicrobial concentration at the site of infection, to reduce doses in the general circulation, which in turn reduces adverse effects. In this work bedaquiline was encapsulated in two types of nanocarriers, lipid nanoparticles and chitosan-based nanocapsules with high encapsulation efficiency and drug loading values. The efficacy of the drug-encapsulating nanocarriers has been demonstrated in vitro against Mycobacterium tuberculosis, together with the excellent compatibility of both carriers with animal cells. The obtained results open the way for further studies on multi-drug resistant strains of M. tuberculosis and for in vivo studies of the optimized nanocarriers. The promising behaviour of drug-loaded nanocarriers will hopefully lead to a reduction of the administered doses of a quite dangerous drug as bedaquiline, tuning its biodistribution and so decreasing its adverse effects, finally allowing its use in a higher number of patients., Authors would like to acknowledge the public funding from Fondo Social de la DGA (grupos DGA), Ministerio de la Economía y Competitividad del Gobierno de España for the public founding of ProyectosI + D + i – ProgramaEstatal de Investigación, Desarrollo e InnovaciónOrientada a los Retos de la Sociedad (project n. SAF2014-54763-C2-2-R), the European Seventh Framework Program (NAREB Project 604237) and Ministerio de Educación Cultura y Deporte for SGE fellowship.
Published: 2019

25. Transmural Ventricular Heterogeneities Play a Major Role in Determining T-Wave Morphology at Different Extracellular Potassium Levels

Author: Bukhari, H.A., Palmieri, F., Ferreira, D., Potse, M., Ramírez, J., Laguna, P., Sánchez, C., Pueyo, E., Aragón Institute of Engineering Research [Zaragoza] (I3A), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Laboratorios Rubió, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Queen Mary University of London (QMUL), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), This work was supported by projects ERC-2014-StG 638284 (ERC), DPI2016-75458-R (MINECO), MarieSkłodowska-Curie grant 764738 and Aragón Government, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 0206 medical engineering, 02 engineering and technology, [MATH]Mathematics [math], 020601 biomedical engineering
Abstract: International audience; End-stage renal disease (ESRD) affects more than 10% of the world population. ESRD patients present impaired potassium homeostasis, which increases the risk for ventricular arrhythmias and sudden cardiac death. Noninvasive estimation of serum potassium, [K+], before the patient experiences serious consequences is of major importance. In this study, we investigated the relationship of [K+] with three T-wave morphological descriptors: the T-wave width (Tw), slope-to-amplitude ratio (TSA) and temporal morphological variability (dw) from ECGs of 12 ESRD patients undergoing hemodialysis and from simulated ECGs. Spearman’s correlation coefficients between the descriptors Tw, TSA and dw and [K+] were -0.5, 0.8 and 0.65, respectively. These associations were, however, highly patient-dependent. The high inter-individual variability in T-wave morphology, particularly observed at high [K+], was reproduced in the simulations and could be explained by differences in transmural heterogeneities, with 10% variations in the proportion of midmyocardial cells leading to changes larger than 15% in T-wave morphology. In conclusion, T-wave morphological descriptors have the potential to be used as predictors of [K+] in ESRD patients, but their associated inter-individual variability should be taken into account, especially under hyperkalemic conditions.
Published: 2019

26. pH-Sensitive Dendrimersomes of Hybrid Triazine-Carbosilane Dendritic Amphiphiles-Smart Vehicles for Drug Delivery

Author: Francisco Javier de la Mata, Nadezhda Knauer, Ekaterina Pashkina, Valeria Arkhipova, Rafael Gómez, Julia Poletaeva, Javier Sánchez-Nieves, Evgeny K. Apartsin, Alina Aktanova, Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia] (ICBFM SB RAS), Siberian Branch of the Russian Academy of Sciences (SB RAS), Novosibirsk State University (NSU), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Research Institute of Fundamental and Clinical Immunology, Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Russian Foundation for Basic Research grant No. 18-33-20109, Grant of the President of the Russian Federation No. MK-2278.2019.4, MINECO grant CTQ-2017-85224-P, and Consortium NANODENDMED-II-CM (B2017/BMD-3703) and IMMUNOTHERCAN-CM (B2017/BMD3733)
Subjects: Drug, General Chemical Engineering, media_common.quotation_subject, dendron, Supramolecular chemistry, amphiphile, carbosilane, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 02 engineering and technology, 010402 general chemistry, doxorubicin, 01 natural sciences, Article, methotrexate, lcsh:Chemistry, chemistry.chemical_compound, Dendrimer, Amphiphile, medicine, General Materials Science, Doxorubicin, Triazine, media_common, vesicles, Chemistry, pH-sensitive, self-assembly, 021001 nanoscience & nanotechnology, Combinatorial chemistry, 3. Good health, 0104 chemical sciences, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, lcsh:QD1-999, leukaemia, Drug delivery, triazine, 0210 nano-technology, Drug carrier, medicine.drug
Abstract: Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species&mdash, triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy.
Published: 2020

27. Exploring the Gas-Permeation Properties of Proton-Conducting Membranes Based on Protic Imidazolium Ionic Liquids: Application in Natural Gas Processing

Author: Kallem, Parashuram, Charmette, Christophe, Drobek, Martin, Julbe, Anne, Mallada, Reyes, Pina, Maria, Institut Européen des membranes (IEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, and Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: protic imidazolium ionic liquids, nanoporous polybenzimidazole membranes, CH4 solubility, photo-assisted polymerization, [CHIM]Chemical Sciences, CH4 selective membranes, lcsh:TP155-156, lcsh:TP1-1185, supported ionic liquid membranes, lcsh:Chemical engineering, lcsh:Chemical technology
Abstract: This experimental study explores the potential of supported ionic liquid membranes (SILMs) based on protic imidazolium ionic liquids (ILs) and randomly nanoporous polybenzimidazole (PBI) supports for CH4/N2 separation. In particular, three classes of SILMs have been prepared by the infiltration of porous PBI membranes with different protic moieties: 1-H-3-methylimidazolium bis (trifluoromethane sulfonyl)imide, 1-H-3-vinylimidazolium bis(trifluoromethane sulfonyl)imide followed by in situ ultraviolet (UV) polymerization to poly[1-(3H-imidazolium)ethylene] bis(trifluoromethanesulfonyl)imide. The polymerization process has been monitored by Fourier transform infrared (FTIR) spectroscopy and the concentration of the protic entities in the SILMs has been evaluated by thermogravimetric analysis (TGA). Single gas permeability values of N2 and CH4 at 313 K, 333 K and 363 K were obtained from a series of experiments conducted in a batch gas permeance system. The results obtained were assessed in terms of the preferential cavity formation and favorable solvation of methane in the apolar domains of the protic ionic network. The most attractive behavior exhibited poly[1-(3H-imidazolium)ethylene]bis(trifluoromethanesulfonyl)imide polymeric ionic liquid (PIL) cross-linked with 1% divinylbenzene supported membranes, showing stable performance when increasing the upstream pressure. The CH4/N2 permselectivity value of 2.1 with CH4 permeability of 156 Barrer at 363 K suggests that the transport mechanism of the as-prepared SILMs is solubility-dominated.
Published: 2018

28. Chemoenzymatic Synthesis of N-glycan Positional Isomers and Evidence for Branch Selective Binding by Monoclonal Antibodies and Human C-type Lectin Receptors

Author: Michel Thépaut, Cornelis H. Hokke, Begoña Echeverria, Niels-Christian Reichardt, Julie Pham, Silvia Achilli, Sonia Serna, Corinne Vivès, Franck Fieschi, CIC biomaGUNE, Glycotechnology Laboratory, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Parasitology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Glycan, medicine.drug_class, Receptors, Cell Surface, Monoclonal antibody, 01 natural sciences, Biochemistry, 03 medical and health sciences, Mice, Isomerism, C-type lectin, Polysaccharides, Structural isomer, medicine, Animals, Humans, Lectins, C-Type, Receptor, Innate immune system, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 010405 organic chemistry, Chemistry, Lectin, Antibodies, Monoclonal, General Medicine, 0104 chemical sciences, carbohydrates (lipids), 030104 developmental biology, Receptors, Mitogen, biology.protein, Biocatalysis, Molecular Medicine, Antibody, Cell Adhesion Molecules
Abstract: Here, we describe a strategy for the rapid preparation of pure positional isomers of complex N-glycans to complement an existing array comprising a larger number of N-glycans and smaller glycan structures. The expanded array was then employed to study context-dependent binding of structural glycan fragments by monoclonal antibodies and C-type lectins. A partial enzymatic elongation of semiprotected core structures was combined with the protecting-group-aided separation of positional isomers by preparative HPLC. This methodology, which avoids the laborious chemical differentiation of antennae, was employed for the preparation of eight biantennary N-glycans with Galβ1,4GlcNAc (LN), GalNAcβ1,4GlcNAc (LDN), and GalNAcβ1,4[Fucα1,3]GlcNAc (LDNF) motifs presented on either one or both antennae. Screening of the binding specificities of three anti-LeX monoclonal IgM antibodies raised against S. mansoni glycans and three C-type lectin receptors of the innate immune system, namely DC-SIGN, DC-SIGNR, and LSECtin, revealed a surprising context-dependent fine specificity for the recognition of the glycan motifs. Moreover, we observed a striking selection of one individual positional isomer over the other by the C-type lectins tested, underscoring the biological relevance of the structural context of glycan elements in molecular recognition.
Published: 2018

29. Phosphorus Dendrimers as Vectors for Gene Therapy in Cancer

Author: Vladimir A. Kulchitsky, Dzmitry Shcharbin, E. Pedziwiatr-Werbicka, Natallia Shcharbina, Serge Mignani, Rafael Gomez-Ramirez, M. A. Muñoz-Fernández, Jean-Pierre Majoral, J. Mata, Anne-Marie Caminade, Maria Bryszewska, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Republican Research and Practical Center of Neurology and Neurosurgery, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISC)-ministerio de ciencia e innovacion, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Institute of Physiology of NASB, Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario 'Gregorio Marañón'-Instituto de Investigación Sanitaria Gregorio Marañón, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Caminade, A.-M. and Turrin, C.-O. and Majoral, J.-P., Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Chemistry, Genetic enhancement, Phosphorus, Cancer, chemistry.chemical_element, 02 engineering and technology, 021001 nanoscience & nanotechnology, medicine.disease, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Dendrimer, Cancer research, medicine, [CHIM.COOR]Chemical Sciences/Coordination chemistry, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

30. Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (A). Mechanisms of interaction

Author: Rafael Gomez-Ramirez, Francisco Javier de la Mata, Svetlana Loznikova, Alya G. Venyaminova, Inessa Halets, Jean-Pierre Majoral, Dzmitry Shcharbin, Katarzyna Milowska, D. S. Novopashina, Volha Dzmitruk, Maksim Ionov, Joanna Lazniewska, Olga A. Krasheninina, Maria Bryszewska, Evgeny K. Apartsin, Olga Nowacka, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Institute of of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Ionov, Maksim, Lazniewska, Joanna, Dzmitruk, Volha, Halets, Inessa, Loznikova, Svetlana, Novopashina, Darya, Apartsin, Evgeny, Krasheninina, Olga, Venyaminova, Alya, Milowska, Katarzyna, Nowacka, Olga, Gomez-Ramirez, Rafael, Javier de la Mata, Francisco, Majoral, Jean-Pierre, Shcharbin, Dzmitry, and Bryszewska, Maria
Subjects: Dendrimers, Small interfering RNA, Circular dichroism, Light, RNase P, Stereochemistry, anticancer siRNA, biophysical characteristics, bcl-X Protein, Pharmaceutical Science, 02 engineering and technology, dendrimer, Transfection, 03 medical and health sciences, Microscopy, Electron, Transmission, complex formation, Neoplasms, Dendrimer, Zeta potential, Humans, Scattering, Radiation, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Pharmacology & Pharmacy, Particle Size, RNA, Small Interfering, 030304 developmental biology, Electrophoresis, Agar Gel, 0303 health sciences, Heparin, Chemistry, Circular Dichroism, Phosphorus, Silanes, 021001 nanoscience & nanotechnology, 3. Good health, Gene Expression Regulation, Neoplastic, RNAi Therapeutics, Spectrometry, Fluorescence, Proto-Oncogene Proteins c-bcl-2, Cell culture, Cancer cell, Biophysics, Myeloid Cell Leukemia Sequence 1 Protein, Nucleic Acid Conformation, Nanocarriers, 0210 nano-technology, nano-drug-delivery
Abstract: International audience; This paper examines a perspective on the use of newly engineered nanomaterials as effective and safe carriers of genes for the therapy of cancer. Three different groups of cationic dendrimers (PAMAM, phosphorus and carbosilane) were complexed with anticancer siRNA and their biophysical properties of the dendriplexes analyzed. The potential of the dendrimers as nanocarriers for anticancer siBcl-xl, siBcl-2, siMcl-1 siRNAs and a siScrambled sequence was explored. Dendrimer/siRNA complexes were characterized by methods including fluorescence, zeta potential, dynamic light scattering, circular dichroism, gel electrophoresis and transmission electron microscopy. Some of the experiments were done with heparin to check if siRNA can be easily disassociated from the complexes, and whether released siRNA maintains its structure after interaction with the dendrimer. The results indicate that siRNAs form complexes with all the dendrimers tested. Oligoribonucleotide duplexes can be released from dendriplexes after heparin treatment and the structure of siRNA is maintained in the case of PAMAM or carbosilane dendrimers. The dendrimers were also effective in protecting siRNA from RNase A activity. The selection of the best siRNA carrier will be made based on cell culture studies (Part B).
Published: 2015

31. Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

Author: Svetlana Loznikova, Evgeny K. Apartsin, María Ángeles Muñoz-Fernández, Katarzyna Milowska, Alya G. Venyaminova, Maksim Ionov, Maria Bryszewska, Serge Mignani, Jean-Pierre Majoral, Olga A. Krasheninina, Aliaksei Ihnatsyeu-Kachan, Dzmitry Shcharbin, Volha Dzmitruk, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Institute of Chemical Biology and Fundamental Medicine [Novosibirsk, Russia] (ICBFM SB RAS), Siberian Branch of the Russian Academy of Sciences (SB RAS), Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centro de Química da Madeira, Universidade da Madeira (UMA), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISC)-ministerio de ciencia e innovacion, Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario 'Gregorio Marañón'-Instituto de Investigación Sanitaria Gregorio Marañón, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Small interfering RNA, phosphorus dendrimers, siRNA, 5-fluorouracil, cancer, combination therapy, 02 engineering and technology, Biology, 010402 general chemistry, 01 natural sciences, HeLa, lcsh:Chemistry, Colloid and Surface Chemistry, RNA interference, Gene silencing, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Transfection, 021001 nanoscience & nanotechnology, biology.organism_classification, Molecular biology, 0104 chemical sciences, 3. Good health, lcsh:QD1-999, Chemistry (miscellaneous), Lipofectamine, Cell culture, Cancer cell, Cancer research, 0210 nano-technology
Abstract: Currently, RNAi based approaches for cancer treatment involving short double stranded RNA molecules (siRNA) are under vigorous scrutinization. Due to numerous biological obstacles, siRNA delivery into target cells requires protective escort. On the other hand, combining of siRNA-mediated gene silencing and action of conventional chemotherapeutics can propose additional enhancement of anticancer activity. In the present study, we investigated a siRNA cocktail able to downregulate anti-apoptotic genes (BCL-xL,BCL-2,MCL-1) and the chemotherapeutic agent 5-fluorouracil (5-FU) to evaluate multi-target cytotoxic effect on human cervical carcinoma cells (HeLa cell line). Novel phosphorus containing dendrimers of 3rd and 4th generations (namely AE2G3 and AE2G4) with voluminous piperidine terminal cationic groups were designed and tested as siRNA carriers. Dendrimers of both generations showed remarkable ability to bind pro-apoptotic siRNAs and provided 80–100% siRNA uptake by HeLa cells in the serum containing medium, while the widespread transfection agent Lipofectamine showed only ~40% uptake. SiRNA cocktail (in low concentrations 50 and 100 nM) delivered by AE2G3 dendrimer caused almost complete elimination of cancer cells. We have discovered considerable increase of 5-FU cytotoxic effect by addition of AE2G3/siRNA cocktail complexes in low doses. Thus, we demonstrated the effectiveness of combined multi-target siRNA anticancer approach and described new highly effective serum stable nanomaterial vehicle for gene-based drugs.
Published: 2017
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32. Dendrimer-protein interactions versus dendrimer-based nanomedicine

Author: Elzbieta Pedziwiatr-Werbicka, Maksim Ionov, Jean-Pierre Majoral, María Ángeles Muñoz-Fernández, Maria Bryszewska, Volha Dzmitruk, Dzmitry Shcharbin, Natallia Shcharbina, Serge Mignani, F. Javier de la Mata, Rafael Gómez, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Clinics at the MAZ Company, Minsk, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISC)-ministerio de ciencia e innovacion, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank (SHIVBB), Virtual Institute on Poverty Related Diseases, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Dendrimers, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Protein Structure, Secondary, Protein–protein interaction, Hydrophobic effect, symbols.namesake, Colloid and Surface Chemistry, Protein structure, Dendrimer, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Surface charge, Amino Acids, Physical and Theoretical Chemistry, Protein secondary structure, Chemistry, Proteins, Surfaces and Interfaces, General Medicine, Hydrogen-Ion Concentration, 021001 nanoscience & nanotechnology, 3. Good health, 0104 chemical sciences, Nanomedicine, Biophysics, symbols, van der Waals force, 0210 nano-technology, Hydrophobic and Hydrophilic Interactions, Biotechnology
Abstract: Dendrimers are hyperbranched polymers belonging to the huge class of nanomedical devices. Their wide application in biology and medicine requires understanding of the fundamental mechanisms of their interactions with biological systems. Summarizing, electrostatic force plays the predominant role in dendrimer-protein interactions, especially with charged dendrimers. Other kinds of interactions have been proven, such as H-bonding, van der Waals forces, and even hydrophobic interactions. These interactions depend on the characteristics of both participants: flexibility and surface charge of a dendrimer, rigidity of protein structure and the localization of charged amino acids at its surface. pH and ionic strength of solutions can significantly modulate interactions. Ligands and cofactors attached to a protein can also change dendrimer-protein interactions. Binding of dendrimers to a protein can change its secondary structure, conformation, intramolecular mobility and functional activity. However, this strongly depends on rigidityversusflexibility of a protein’s structure. In addition, the potential applications of dendrimers to nanomedicine are reviwed related to dendrimer-protein interactions.
Published: 2017

33. Binding of poly(amidoamine), carbosilane, phosphorus and hybrid dendrimers to thrombin-Constants and mechanisms

Author: Maksim Ionov, Aliaksandra Vcherashniaya, Jean-Pierre Majoral, Viktar Abashkin, Elzbieta Pedziwiatr-Werbicka, Rafael Gomez-Ramirez, Dzmitry Shcharbin, Anna Janaszewska, Barbara Klajnert-Maculewicz, Aliaksei Ihnatsyeu-Kachan, Maria Bryszewska, F. Javier de la Mata, Piotr Goska, Paula Ortega, Monika Marcinkowska, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Department of Biophysics, Belarusian State University, Belarusian State University, Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Dendrimers, Static Electricity, Nanoparticle, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Fibrin, Protein Structure, Secondary, Colloid and Surface Chemistry, Thrombin, Dendrimer, medicine, Organic chemistry, Molecule, Humans, Nanotechnology, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Surface charge, Physical and Theoretical Chemistry, Blood Coagulation, Binding Sites, biology, Chemistry, Viologen, Phosphorus, Surfaces and Interfaces, General Medicine, Poly(amidoamine), Silanes, 021001 nanoscience & nanotechnology, Combinatorial chemistry, 0104 chemical sciences, Solutions, Kinetics, biology.protein, Nanoparticles, 0210 nano-technology, Biotechnology, medicine.drug, Protein Binding
Abstract: Thrombin is an essential part of the blood coagulation system; it is a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, and catalyzes many other coagulation-related reactions. Absorption at its surface of small nanoparticles can completely change the biological properties of thrombin. We have analyzed the influence on thrombin of 3 different kinds of small nanoparticles: dendrimers (phosphorus-based, carbosilane based and polyamidoamine) and 2 hybrid systems containing carbosilane, viologen and phosphorus dendritic scaffolds in one single molecule, bearing different flexibility, size and surface charge. There was significant alteration in the rigidity of the rigid dendrimers in contrast to flexible dendrimers. These differences in their action are important in understanding interactions taking place at a bio-nanointerface.
Published: 2017

34. Modular bioink for 3D printing of biocompatible hydrogels: sol-gel polymerization of hybrid peptides and polymers

Author: Gilles Subra, Xavier Garric, Cécile Echalier, Stéphane Dejean, Miguel A. Mateos-Timoneda, Jean Martinez, Ahmad Mehdi, Coline Pinese, Oscar Castaño, Danièle Noël, Elisabeth Engel, Riccardo Levato, Mehdi, Ahmad, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica, Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Materials science, Biocompatibility, Chemistry(all), Polymers, General Chemical Engineering, Biocompatible Materials, 02 engineering and technology, 010402 general chemistry, Enginyeria dels materials [Àrees temàtiques de la UPC], 01 natural sciences, chemistry.chemical_compound, Polymer chemistry, Sol-gel, chemistry.chemical_classification, [CHIM.MATE] Chemical Sciences/Material chemistry, Materials biocompatibles, Enginyeria biomèdica [Àrees temàtiques de la UPC], General Chemistry, Polymer, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Polímers, Chemical engineering, chemistry, Polymerization, Reagent, Siloxane, Network covalent bonding, Self-healing hydrogels, Chemical Engineering(all), 0210 nano-technology, Hydrogels--chemistry
Abstract: International audience; An unprecedented generic system allowing the 3D printing of peptide-functionalized hydrogels by soft sol-gel inorganic polymerization is presented. Hybrid silylated inorganic/bioorganic blocks are mixed in biological buffer in an appropriate ratio, to yield a multicomponent bioink that can be printed as a hydrogel without using any photochemical or organic reagent. Hydrolysis and condensation of the silylated precursors occur during the printing process and result in a covalent network in which molecules are linked through siloxane bonds. The viscosity of the colloidal solution used as bioink was monitored in order to set up the optimal conditions for extrusion printing. Grid-patterned hydrogel scaffolds containing a hybrid integrin ligand were printed using a pressure-driven rapid prototyping machine. Finally, they were seeded with mesenchymal stem cells, demonstrating their suitability for cell culture. The versatility of the sol-gel process and its biocompatibility makes this approach highly promising for the preparation of tailor-made cell-laden scaffolds.
Published: 2017

35. The proangiogenic potential of a novel calcium releasing composite biomaterial: Orthotopic in vivo evaluation

Author: Hugo Oliveira, J.A. Planell, Marc Batista, Reine Bareille, Joan Marti-Munoz, Douglas A. Clift, Robin Siadous, Elisabeth Engel, Oscar Castaño, Sylvie Rey, Joëlle Amédée, Sylvain Catros, Chassande, Olivier, Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Universitat Autònoma de Barcelona (UAB), Universitat Politècnica de Catalunya [Barcelona] (UPC), Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica, and Universitat Politècnica de Catalunya. IMEM-BRT- Innovation in Materials and Molecular Engineering - Biomaterials for Regenerative Therapies
Subjects: Angiogenesis, [SDV]Life Sciences [q-bio], Drug Evaluation, Preclinical, 02 engineering and technology, Bone tissue, Biochemistry, Mice, Osteogenesis, Endothelial Progenitor Cells, Biomaterial, General Medicine, 021001 nanoscience & nanotechnology, 3. Good health, Bone regeneration, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Enginyeria de teixits, Materials biomèdics, Heterografts, 0210 nano-technology, Biotechnology, Materials science, Polyesters, Ossos -- Regeneració, 0206 medical engineering, Biomedical Engineering, chemistry.chemical_element, Neovascularization, Physiologic, Bone healing, Calcium, Enginyeria dels materials [Àrees temàtiques de la UPC], Biomaterials, In vivo, medicine, Animals, Humans, Tissue engineering, Rats, Wistar, Molecular Biology, Calcium phosphate ormoglasses, Regeneration (biology), 020601 biomedical engineering, Rats, chemistry, Delayed-Action Preparations, Ciments ossis, Biophysics, Biomedical materials, Biomedical engineering
Abstract: Insufficient angiogenesis remains a major hurdle in current bone tissue engineering strategies. An extensive body of work has focused on the use of angiogenic factors or endothelial progenitor cells. However, these approaches are inherently complex, in terms of regulatory and methodologic implementation, and present a high cost. We have recently demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber-based membranes, containing calcium phosphate (CaP) ormoglass particles, to elicit angiogenesis in vivo , in a subcutaneous model in mice. Here we have devised an injectable composite, containing CaP glass-ceramic particles, dispersed within a (Hydroxypropyl)methyl cellulose (HPMC) matrix, with the capacity to release calcium in a more sustained fashion. We show that by tuning the release of calcium in vivo , in a rat bone defect model, we could improve both bone formation and increase angiogenesis. The bone regeneration kinetics was dependent on the Ca 2+ release rate, with the faster Ca 2+ release composite gel showing improved bone repair at 3 weeks, in relation to control. In the same line, improved angiogenesis could be observed for the same gel formulation at 6 weeks post implantation. This methodology allows to integrate two fundamental processes for bone tissue regeneration while using a simple, cost effective, and safe approach. Statement of Significance In current bone tissue engineering approaches the achievement of sufficient angiogenesis, during tissue regeneration, is a major limitation in order to attain full tissue functionality. Recently, we have shown that calcium ions, released by the degradation of calcium phosphate ormoglasses (CaP), are effective angiogenic promoters, in both in vitro and in a subcutaneous implantation model. Here, we devised an injectable composite, containing CaP glass-ceramic particles, dispersed within a HPMC matrix, enabling the release of calcium in a more sustained fashion. We show that by tuning the release of calcium in vivo , in a rat bone defect model, we could improve both bone formation and increase angiogenesis. This simple and cost effective approach holds great promise to translate to the clinics.
Published: 2017

36. Interference of cationic polymeric nanoparticles with clinical chemistry tests—Clinical relevance

Author: Maria Bryszewska, Francisco Javier de la Mata, Jean-Pierre Majoral, Natallia Shcharbina, Rafael Gomez-Ramirez, Serge Mignani, Katarzyna Milowska, María Ángeles Muñoz-Fernández, Dzmitry Shcharbin, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Republican Research and Practical Center of Neurology and Neurosurgery, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISC)-ministerio de ciencia e innovacion, Hospital General Universitario 'Gregorio Marañón' [Madrid], Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Serum, Dendrimers, Clinical chemistry, Amidoamine, Pharmaceutical Science, Nanoparticle, Clinical Chemistry Tests, Nanotechnology, 02 engineering and technology, Carbon nanotube, Nanomaterials, law.invention, 03 medical and health sciences, chemistry.chemical_compound, In vivo, law, Dendrimer, [CHIM.COOR]Chemical Sciences/Coordination chemistry, 030304 developmental biology, 0303 health sciences, Cationic polymerization, food and beverages, Phosphorus, Silanes, 021001 nanoscience & nanotechnology, 3. Good health, chemistry, Nanoparticles, 0210 nano-technology
Abstract: International audience; The development of medical nanosystems requires knowledge of their behavior in vivo. Clinical chemistry tests are widely used to estimate the systemic toxicity of nanoparticles. In this paper we have explored the impact of small positively charged nanoparticles-poly(amidoamine), phosphorous and carbosilane dendrimers-on biochemical parameters of standardized serum in vitro. All the dendrimers could shift the main biochemical parameters. Thus, in the case of patients having the normal, but 'boundary', values of biochemical parameters, nanoparticle-induced changes can be wrongly interpreted as evidence of some dysfunctions (hepatic, renal, etc.). Moreover, the effects of nanoparticles of metals, carbon nanotubes, quantum dots, fullerenes, dendrimers having been sized up to 4000 nm and the hundreds of reactive groups, can be significantly higher. Thus, preliminary evaluation of any nanomaterial in vitro is required in clinical chemistry tests before its application in vivo to draw the correct conclusions and benefit animals. (C) 2014 Elsevier B.V. All rights reserved.
Published: 2014

37. Cyr61 silencing reduces vascularization and dissemination of osteosarcoma tumors

Author: O Fromigué, O Bawa, Marta Vilalta, P Opolon, Jerónimo Blanco, N Habel, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, and FROMIGUE, OLIVIA
Subjects: Cancer Research, Cell, Down-Regulation, Mice, Nude, Bone Neoplasms, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Neovascularization, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, RNA interference, Tumor Cells, Cultured, Genetics, medicine, Animals, Humans, Gene silencing, Neoplasm Invasiveness, Neoplasm Metastasis, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Cell Proliferation, Regulation of gene expression, Mice, Inbred BALB C, Osteosarcoma, Neovascularization, Pathologic, medicine.disease, Primary tumor, 3. Good health, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, CYR61, Immunology, Cancer research, RNA Interference, medicine.symptom, Cysteine-Rich Protein 61
Abstract: International audience; Osteosarcoma is the most prevalent primary pediatric cancer-related bone disease. These tumors frequently develop resistance to chemotherapy and are highly metastatic, leading to poor outcome. Thus, there is a need for new therapeutic strategies that can prevent cell dissemination. We previously showed that CYR61/CCN1 expression in osteosarcoma cells is correlated to aggressiveness both in vitro and in vivo in mouse models, as well as in patients. In this study, we found that CYR61 is a critical contributor to the vascularization of primary tumor. We demonstrate that silencing CYR61, using lentiviral transduction, leads to a significant reduction in expression level of pro-angiogenic markers such as VEGF, FGF2, PECAM and angiopoietins concomitantly to an increased expression of major anti-angiogenic markers such as thrombospondin-1 and SPARC. Matrix metalloproteinase-2 family member expression, a key pathway in osteosarcoma metastatic capacity was also downregulated when CYR61 was downregulated in osteosarcoma cells. Using a metastatic murine model, we show that CYR61 silencing in osteosarcoma cells results in reduced tumor vasculature and slows tumor growth compared with control. We also find that microvessel density correlates with lung metastasis occurrence and that CYR61 silencing in osteosarcoma cells limits the number of metastases. Taken together, our data indicate that CYR61 silencing can blunt the malignant behavior of osteosarcoma tumor cells by limiting primary tumor growth and dissemination process. INTRODUCTION Osteosarcoma is a highly vascular and extremely destructive bone malignancy that mainly affects children and young adults. It represents the most frequent pediatric cancer-related disease. Despite the introduction, during the 70 s, of aggressive multi-agent chemotherapy in addition to tumor ablation surgery, the long-term survival (45 years) increased from 10-60% for patients with localized primary tumors, but to o 30% for patients presenting metastases at initial diagnosis. Nowadays, knowledge of the mechanisms underlying osteosarcoma metastasis is quite limited. Thus, in order to improve the clinical outcomes for patients with poor prognosis and to manage primary osteosar-coma by preventing development of metastatic disease, it is imperative to find new approaches to block the metastasis process. Degradation of the extracellular matrix, facilitated by the action of matrix metalloproteinases (MMPs), is a prerequisite of tumor invasion and metastasis in a variety of cancers including osteosarcoma. MMP-2 and MMP-9 have been repetitively implicated in osteosarcoma cell invasion, 1-3 and increased expression of membrane type-1 MMP correlated with decreased overall survival. 4 A correlation was recently reported between the expression of the extracellular MMP inducer EMMPRIN (CD147) and vascular endothelial growth factor (VEGF) in osteosarcoma
Published: 2014

38. Positron emission tomography with α-[11C]methyl-<scp>l</scp>-tryptophan in tuberous sclerosis complex-related epilepsy

Author: Karine Ostrowsky, Sandrine Bouvard, Julien Jung, Keiko Hino, Alexander Hammers, Berta Marti Fuster, Didier Le Bars, Hélène Catenoix, François Liger, Rolf A. Heckemann, S. Rubí, Nicolas Costes, Xavier Setoain, Alexandra Montavont, Philippe Ryvlin, Nuclear Medicine Department, Hospital Clinic, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Division of Experimental Medicine, Imperial College London, Fondation neurodis, Fondation Neurodis, Translational and integrative group in epilepsy research, Lyon Neuroscience Research center, Biophysics and Bioengineering Unit, University of Barcelona, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Department of Functional Neurology and Epileptology and IDEE, and Hospices Civils de Lyon (HCL)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Adolescent, Neuroimaging, Fluid-attenuated inversion recovery, 030218 nuclear medicine & medical imaging, Young Adult, 03 medical and health sciences, Tuberous sclerosis, Epilepsy, 0302 clinical medicine, Tuberous Sclerosis, medicine, Humans, Ictal, Epilepsy surgery, Carbon Radioisotopes, Child, medicine.diagnostic_test, business.industry, fungi, Tryptophan, Brain, food and beverages, Electroencephalography, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Neurology, Positron emission tomography, Child, Preschool, Positron-Emission Tomography, Female, Neurology (clinical), business, Nuclear medicine, 030217 neurology & neurosurgery
Abstract: Summary Objective Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[11C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity. Methods We included 12 patients (six male, 4–53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[11C]methyl-l-tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG recording. AMT uptake in each tuber was visually evaluated on PET coregistered with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also calculated. Sensitivity and specificity values of AMT-PET in the detection of epileptogenic lesions were obtained, using the available electroclinical and neuroimaging evidence as the gold standard for epileptogenicity. Results A total of 126 tubers were identified. Two of 12 patients demonstrated a tuber with clearly increased AMT uptake, one of whom also showed a subtle increased AMT uptake in another contralateral tuber. Four other patients showed only subtle increased AMT uptake. The only two tubers with clearly increased AMT uptake proved to be epileptogenic based on intracerebral EEG data, whereas none of the tubers associated with subtle increased AMT uptake were involved at ictal onset. In a per-patient approach, this yielded a sensitivity of clearly increased AMT uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3–34%) and 100% (95% CI: 97–100%), respectively. Significance AMT-PET is a specific neuroimaging technique in the identification of epileptogenic tubers in TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still deserves to be considered according to the challenging complexity of epilepsy surgery in tuberous sclerosis.
Published: 2013

39. Understanding the mechanisms amenable to CRT response: from pre-operative multimodal image data to patient-specific computational models

Author: Reza Razavi, Oscar Camara, M. Steghofer, Jatin Relan, Stephanie Marchesseau, Ali Pashaei, Pablo Lamata, Mireille Garreau, Catalina Tobon-Gomez, Alfredo Hernandez, Maxime Sermesant, Hervé Delingette, Simon G. Duckett, Erwan Donal, K. S. Rhode, Christophe Leclercq, Nicholas Ayache, Alejandro F. Frangi, Rafael Sebastian, M. De Craene, Nicolas P. Smith, Nicolas Duchateau, Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Computational Multi-Scale Physiology Lab [Valencia], Universitat de València (UV), Analysis and Simulation of Biomedical Images (ASCLEPIOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), MedisysResearch Lab (Medisys), Philips Research, School of Biomedical Engineering & Imaging Sciences [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Department of Computer Science [Oxford], University of Oxford [Oxford], Division of Imaging Sciences, King‘s College London, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Oxford
Subjects: Adult, Computer science, medicine.medical_treatment, 0206 medical engineering, Biomedical Engineering, Cardiac resynchronization therapy, 02 engineering and technology, 030204 cardiovascular system & hematology, Machine learning, computer.software_genre, Cardiac Resynchronization Therapy, Electrocardiography, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Computer Simulation, Computer vision, Precision Medicine, Aged, Computational model, business.industry, Patient Selection, Models, Cardiovascular, Middle Aged, Patient specific, Precision medicine, Magnetic Resonance Imaging, 020601 biomedical engineering, Pipeline (software), Pre operative, 3. Good health, Computer Science Applications, Multimodal image, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Fully automatic, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, computer
Abstract: International audience; This manuscript describes our recent developments towards better understanding of the mechanisms amenable to cardiac resynchronization therapy response. We report the results from a full multimodal dataset corresponding to eight patients from the euHeart project. The datasets include echocardiography, MRI and electrophysiological studies. We investigate two aspects. The first one focuses on pre-operative multimodal image data. From 2D echocardiography and 3D tagged MRI images, we compute atlas based dyssynchrony indices. We complement these indices with presence and extent of scar tissue and correlate them with CRT response. The second one focuses on computational models. We use pre-operative imaging to generate a patient-specific computational model. We show results of a fully automatic personalized electromechanical simulation. By case-per-case discussion of the results, we highlight the potential and key issues of this multimodal pipeline for the understanding of the mechanisms of CRT response and a better patient selection.
Published: 2013

40. A High-Resolution Atlas and Statistical Model of the Human Heart From Multislice CT

Author: Corné Hoogendoorn, Mathieu De Craene, Karim Lekadir, Nicolas Duchateau, Federico M. Sukno, Alejandro F. Frangi, Damián Sánchez-Quintana, Tristan Whitmarsh, Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), Cardiology Department, Thorax Clinic Institute, Hospital Cliınic, Institut d'Investigacions Biomèdiques [Barcelona], Universitat de Barcelona (UB), MedisysResearch Lab (Medisys), Philips Research, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), and Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion
Subjects: Computer science, Image registration, Computed tomography, Image processing, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Atlases as Topic, 0302 clinical medicine, Atlas (anatomy), Image Processing, Computer-Assisted, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Computer vision, Electrical and Electronic Engineering, Retrospective Studies, Models, Statistical, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Atlas (topology), Models, Cardiovascular, Reproducibility of Results, Heart, Pattern recognition, Statistical model, Computer Science Applications, medicine.anatomical_structure, Spatial normalization, Artificial intelligence, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery, Software, Level of detail
Abstract: Atlases and statistical models play important roles in the personalization and simulation of cardiac physiology. For the study of the heart, however, the construction of comprehensive atlases and spatio-temporal models is faced with a number of challenges, in particular the need to handle large and highly variable image datasets, the multi-region nature of the heart, and the presence of complex as well as small cardiovascular structures. In this paper, we present a detailed atlas and spatio-temporal statistical model of the human heart based on a large population of 3D+time multi-slice computed tomography sequences, and the framework for its construction. It uses spatial normalization based on nonrigid image registration to synthesize a population mean image and establish the spatial relationships between the mean and the subjects in the population. Temporal image registration is then applied to resolve each subject-specific cardiac motion and the resulting transformations are used to warp a surface mesh representation of the atlas to fit the images of the remaining cardiac phases in each subject. Subsequently, we demonstrate the construction of a spatio-temporal statistical model of shape such that the inter-subject and dynamic sources of variation are suitably separated. The framework is applied to a 3D+time data set of 138 subjects. The data is drawn from a variety of pathologies, which benefits its generalization to new subjects and physiological studies. The obtained level of detail and the extendability of the atlas present an advantage over most cardiac models published previously.
Published: 2013

41. P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

Author: Agustí Brugués, Cédric Plutoni, Maïlys Le Borgne-Rochet, Stéphane Bodin, Elsa Bazellieres, Franck Comunale, Xavier Trepat, Martial Séveno, Sylvie Thuault, Nathalie Morin, Damien Planchon, Cécile Gauthier-Rouvière, BOUBLIK, Yvan, Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioCampus (BCM), Institució Catalana de Recerca i Estudis Avançats (ICREA), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ICREA Institute for Bioengineering of Catalonia (ICREA), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Instituto de Salud Carlos III (ISC)-ministerio de ciencia e innovacion, Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille-Luminy (IBDML), and Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Motility, CDC42, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, Myoblasts, Mice, 03 medical and health sciences, Cell Movement, Cell polarity, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Myocyte, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, cdc42 GTP-Binding Protein, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Research Articles, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Cadherin, Cell adhesion molecule, Cell Polarity, Cell Biology, Cadherins, Biomechanical Phenomena, Cell biology, 030104 developmental biology, Cdc42 GTP-Binding Protein, Wound healing, Rho Guanine Nucleotide Exchange Factors
Abstract: P-cadherin induces polarization and collective cell migration through an increase in the strength and anisotropy of mechanical forces, which is mediated by the P-cadherin/β-PIX/Cdc42 axis., Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.
Published: 2016

42. Interaction between dendrimers and regulatory proteins. Comparison of effects of carbosilane and carbosilane-viologen-phosphorus dendrimers

Author: Teresa Gabryelak, Aleksandra Szwed, Maksim Ionov, Rafael Gomez-Ramirez, Dzmitry Shcharbin, F. J. de la Mata, Katarzyna Milowska, Silvia Moreno, Jean-Pierre Majoral, Maria Bryszewska, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Circular dichroism, Chemistry, Stereochemistry, General Chemical Engineering, Nanoparticle, Viologen, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Dendrimer, Biological property, medicine, Zeta potential, Biophysics, Alkaline phosphatase, [CHIM.COOR]Chemical Sciences/Coordination chemistry, 0210 nano-technology, medicine.drug, Macromolecule
Abstract: International audience; For nanoparticles to be used successfully in biomedical application, their interactions with biological fluids need to be investigated, in which they will react with proteins and other macromolecules. In this case, dendrimers might change their biological properties. Thus, the interaction of 2 generations of carbosilane-viologen-phosphorus and 2 types of carbosilane dendrimers with the 3 proteins - alkaline phosphatase from E. coli, human aspartate transaminase and l-lactate dehydrogenase from rabbit muscles, will be discussed. The techniques used included circular dichroism, zeta potential measurement, fluorescence quenching and transmission electron microscopy. The results show that positively charged hybrid and carbosilane dendrimers can interact with negatively charged regulatory proteins, and are able to form complexes. However, the spatial structure and the flexibility of dendrimer are as important as the protein configuration in complex formation.
Published: 2016

43. The proangiogenic potential of a novel calcium releasing biomaterial: Impact on cell recruitment

Author: Joan Marti-Munoz, Joëlle Amédée, Claudine Boiziau, Sylvain Catros, Robin Siadous, Sylvie Rey, Elisabeth Engel, Oscar Castaño, Hugo Oliveira, Reine Bareille, J.A. Planell, Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Universitat Autònoma de Barcelona (UAB), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Universitat Politècnica de Catalunya [Barcelona] (UPC), Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica, Universitat Politècnica de Catalunya. IMEM-BRT- Innovation in Materials and Molecular Engineering - Biomaterials for Regenerative Therapies, and Chassande, Olivier
Subjects: Calcium Phosphates, Male, Angiogenesis, Polymers, [SDV]Life Sciences [q-bio], Drug Evaluation, Preclinical, 02 engineering and technology, Biochemistry, Mice, Ossos, Biomaterial, General Medicine, 021001 nanoscience & nanotechnology, Cell biology, Bone regeneration, [SDV] Life Sciences [q-bio], Regeneration (Biology), Membrane, Enginyeria de teixits, Materials biomèdics, Female, 0210 nano-technology, Biotechnology, Adult, Materials science, Ossos -- Regeneració, Polyesters, 0206 medical engineering, Biomedical Engineering, Calcium phosphate ormoglass, chemistry.chemical_element, Neovascularization, Physiologic, Calcium, Enginyeria dels materials [Àrees temàtiques de la UPC], Biomaterials, In vivo, Animals, Humans, Tissue engineering, Lactic Acid, Progenitor cell, Molecular Biology, Bones, Regeneració (Biologia), Chemotaxis, Membranes, Artificial, 020601 biomedical engineering, chemistry, Delayed-Action Preparations, Ciments ossis, Biomedical materials, Biomedical engineering
Abstract: International audience; In current bone tissue engineering strategies the achievement of sufficient angiogenesis during tissue regeneration is still a major limitation in order to attain full functionality. Several strategies have been described to tackle this problem, mainly by the use of angiogenic factors or endothelial progenitor cells. However, when facing a clinical scenario these approaches are inherently complex and present a high cost. As such, more cost effective alternatives are awaited. Here, we demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber-based membranes, containing calcium phosphate ormoglass (CaP) particles, to elicit angiogenesis in vivo, in a subcutaneous model in mice. We show that the current approach elicited the local expression of angiogenic factors, associated to a chemotactic effect on macrophages, and sustained angiogenesis into the biomaterial. As both PLA and CaP are currently accepted for clinical application these off-the-shelf novel membranes have great potential for guided bone regeneration applications.Statement of significance: In current bone tissue engineering approaches the achievement of sufficient angiogenesis, during tissue regeneration, is a major limitation in order to attain full tissue functionality. Recently, our group has found that calcium ions released by the degradation of calcium phosphate ormoglasses (CaP) are effective angiogenic promoters. Based on this, in this work we successfully produced hybrid fibrous mats with different contents of CaP nanoparticles and thus with different calcium ion release rates, using an ormoglass - poly(lactic acid) blend approach. We show that these matrices, upon implantation in a subcutaneous site, could elicit the local expression of angiogenic factors, associated to a chemotactic effect on macrophages, and sustained angiogenesis into the biomaterial, in a CaP dose dependent manner. This off-the-shelf cost effective approach presents great potential to translate to the clinics.
Published: 2016

44. euHeart: personalized and integrated cardiac care using patient-specific cardiovascular modelling

Author: Walther H. W. Schulze, Jatin Relan, Dominique Chapelle, Matt McCormick, Helko Lehmann, Philipp Beerbaum, Maxime Sermesant, David Nordsletten, Jos A. E. Spaan, Alejandro F. Frangi, Israel Valverde, Peter Hunter, Reza Rezavi, Rod Hose, Nicholas Ayache, Juergen Weese, Cristina Staicu, Maria Siebes, Hervé Delingette, Oscar Camara, Nic Smith, Adelaide de Vecchi, Martin W. Krueger, Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Computing Laboratory (OUCL), University of Oxford, Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institució Catalana de Recerca i Estudis Avançats (ICREA), Institute of Simulation and Graphics [Magdeburg], Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Analysis and Simulation of Biomedical Images (ASCLEPIOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institute of Biomedical Engineering [Karlsruhe], Karlsruhe Institute of Technology (KIT), Department of Cardiovascular Science [Sheffield], University of Sheffield [Sheffield], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Auckland Bioengineering Institute, University of Auckland [Auckland], Philips Research Laboratories [Eindhoven], Philips Research [Nederlands], Philips Research, Modeling, analysis and control in computational structural dynamics (MACS), Inria Paris-Rocquencourt, Division of Imaging Sciences, King‘s College London, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University of Oxford [Oxford], Otto-von-Guericke University [Magdeburg] (OVGU), ACS - Amsterdam Cardiovascular Sciences, Biomedical Engineering and Physics, and Other Research
Subjects: Cardiac function curve, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 0206 medical engineering, Population, Biomedical Engineering, Biophysics, Pump function, Bioengineering, 02 engineering and technology, Disease, 030204 cardiovascular system & hematology, Bioinformatics, Biochemistry, Biomaterials, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Clinical imaging, education, Intensive care medicine, education.field_of_study, business.industry, Virtual Physiological Human, Articles, Patient specific, 020601 biomedical engineering, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 3. Good health, Lifetime risk, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Biotechnology
Abstract: International audience; The loss of cardiac pump function accounts for a significant increase in both mortality and morbidity in Western society, where there is currently a one in four lifetime risk, and costs associated with acute and long-term hospital treatments are accelerating. The significance of cardiac disease has motivated the application of state-of-the-art clinical imaging techniques and functional signal analysis to aid diagnosis and clinical planning. Measurements of cardiac function currently provide high-resolution datasets for characterizing cardiac patients. However, the clinical practice of using population-based metrics derived from separate image or signal-based datasets often indicates contradictory treatments plans owing to inter-individual variability in pathophysiology. To address this issue, the goal of our work, demonstrated in this study through four specific clinical applications, is to integrate multiple types of functional data into a consistent framework using multi-scale computational modelling.
Published: 2011

45. Estimation of the viscoelastic properties of vessel walls using a computational model and Doppler ultrasound

Author: Alejandro F. Frangi, Piero Tortoli, Enrico Boni, Guy Courbebaisse, Olivier Basset, Christian Cachard, Simone Balocco, Computer Vision Center (Centre de visio per computador) (CVC), Universitat Autònoma de Barcelona (UAB), Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Microelectronic Systems Design Laboratory - Università di Firenze, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institució Catalana de Recerca i Estudis Avançats (ICREA), Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Universitat Pompeu Fabra
Subjects: Sistema cardiovascular -- Malalties, Artèries -- Malalties, Physics::Medical Physics, Constitutive equation, Reference data (financial markets), 030204 cardiovascular system & hematology, 01 natural sciences, Physics::Fluid Dynamics, Viscosity, 0302 clinical medicine, ARMA parameter fitting, 010301 acoustics, ComputingMilieux_MISCELLANEOUS, Espagne, Radiological and Ultrasound Technology, Phantoms, Imaging, Mechanics, Imagerie Ultrasonore, reseau_international, categₘixte, France, Standard linear solid model, Materials science, Quantitative Biology::Tissues and Organs, imagerie_ultrasonore, Models, Biological, Terms—Viscoelasticity, Imaging phantom, Viscoelasticity, 03 medical and health sciences, Approximation error, 0103 physical sciences, categₛt2i, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Computer Simulation, Radiology, Nuclear Medicine and imaging, Sensitivity (control systems), Simulation, Arterial wall model, Italie, Computational Biology, Ultrasonography, Doppler, Elasticity, Regional Blood Flow, Noninvasive measurement, Blood Vessels, Aterosclerosi
Abstract: Human arteries affected by atherosclerosis are characterized by altered wall viscoelastic properties. The possibility of noninvasively assessing arterial viscoelasticity in vivo would significantly contribute to the early diagnosis and prevention of this disease. This paper presents a noniterative technique to estimate the viscoelastic parameters of a vascular wall Zener model. The approach requires the simultaneous measurement of flow variations and wall displacements, which can be provided by suitable ultrasound Doppler instruments. Viscoelastic parameters are estimated by fitting the theoretical constitutive equations to the experimental measurements using an ARMA parameter approach. The accuracy and sensitivity of the proposed method are tested using reference data generated by numerical simulations of arterial pulsation in which the physiological conditions and the viscoelastic parameters of the model can be suitably varied. The estimated values quantitatively agree with the reference values, showing that the only parameter affected by changing the physiological conditions is viscosity, whose relative error was about 27% even when a poor signal-to-noise ratio is simulated. Finally, the feasibility of the method is illustrated through three measurements made at different flow regimes on a cylindrical vessel phantom, yielding a parameter mean estimation error of 25%. This work has been partially funded by the Industrial and Technological Development Centre (CDTI) within the CENIT Programme (CDTEAM Project), the EC @neurIST (IST-FP6-2004-027703) projects, by BQR INSA-Lyon and by the Italian/nMinistry of University & Research (COFIN-PRIN 2005).
Published: 2010

46. Generation of ultra-realistic synthetic echocardiographic sequences to facilitate standardization of deformation imaging

Author: Olivier Bernard, Maxime Sermesant, Martino Alessandrini, M. De Craene, Jan D'hooge, Pascal Allain, Sophie Giffard-Roisin, Brecht Heyde, Hervé Delingette, Laboratory of Cardiovascular Imaging and Dynamics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Analysis and Simulation of Biomedical Images (ASCLEPIOS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), GIP Cyceron (Cyceron), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Computational Imaging and Simulation Technologies in Biomedicine (CISTIB), Universitat Pompeu Fabra [Barcelona] (UPF), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Université Jean Monnet [Saint-Étienne] (UJM)-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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Standardization, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, business.industry, Computer science, Ultrasound, 030204 cardiovascular system & hematology, Pipeline (software), 030218 nuclear medicine & medical imaging, Ultrasonic imaging, 03 medical and health sciences, 0302 clinical medicine, 2d echocardiography, Computer engineering, Computer vision, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS
Abstract: © 2015 IEEE. Despite the overwhelming availability of techniques for computation of cardiac deformation and strain with 2D echocardiography, their widespread dissemination in clinical practice is still held back by the reported low reproducibility between different solutions. This can in part be attributed to the lack of a solid and open quality assurance framework to assess and compare their performance. Building upon our previous work, we present here a new pipeline for the benchmarking of such algorithms making use of realistic 2D synthetic sequences. While the synthetic motion is fully controlled by a computational heart model, the visual appearance is extremely similar to a real ultrasound recording. The pipeline is used to generate an initial library of four sequences. ispartof: pages:756-759 ispartof: IEEE International Symposium on Biomedical Imaging vol:2015-July pages:756-759 ispartof: IEEE International Symposium on Biomedical Imaging location:New York City. US date:May - May 2015 status: published
Published: 2015

47. Synthesis, characterization and biological properties of new hybrid carbosilane-viologen-phosphorus dendrimers

Author: Maria Bryszewska, Aleksandra Szwed, Joanna Kurowska, Anne-Marie Caminade, Elzbieta Pedziwiatr-Werbicka, Elena Fuentes-Paniagua, Katarzyna Milowska, Jean-Pierre Majoral, Rafael Gomez-Ramirez, F. Javier de la Mata, Silvia Moreno, Nadia Katir, Teresa Gabryelak, Nabil El Brahmi, Ma Ángeles Muñoz-Fernández, Departamento Química Orgánica y Química Inorgánica, Universidad de Alcalá, Alcalá de Henares, Universidad de Alcalá - University of Alcalá (UAH), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Euromed Research Center, Engineering Division, Université Euro Méditerranéenne de Fès (UEMF), and Hospital General Universitario 'Gregorio Marañón' [Madrid]
Subjects: Chemistry, General Chemical Engineering, Cationic polymerization, Viologen, General Chemistry, Alkylation, Condensation reaction, Human serum albumin, Combinatorial chemistry, Reagent, Dendrimer, medicine, Organic chemistry, Molecule, [CHIM.COOR]Chemical Sciences/Coordination chemistry, medicine.drug
Abstract: International audience; A series of hybrid carbosilane-viologen-phosphorus dendrimers was prepared, as a new example of the synthetic "onion peel" approach. This is based on a convergent strategy by combination of double alkylation of 4,4-bipyridine units with two different halogenated reagents, one of them as a carbosilane dendron, and their subsequent ligation to a hexafunctionalized phosphorus core through amine-aldehyde condensation reactions. In these systems two kinds of cationic groups were included: those located at the branches due to viologen quaternized units and those related to the ammonium groups at the surface of carbosilane wedges. This feature constitutes a novel situation to be explored in the search for new physical-chemical and biological properties, respecting traditional dendritic architectures. The biological properties of two of these hybrid molecules have been studied, focusing the investigation on their interactions with plasma proteins like human serum albumin (HSA), cytotoxicity and hemotoxicity experiments. Although the observed biological behaviors were mainly related to the presence of outer positive charges, in some cases the inner positive charges acted as fine tuning factors.
Published: 2015

48. HIV-antigens charged on phosphorus dendrimers as tools for tolerogenic dendritic cells-based immunotherapy

Author: Maksim Ionov, M. A. Muñoz-Fernández, Aurélien Hameau, Jean-Pierre Majoral, Marjorie Pion, Enrique Vacas-Córdoba, Anne-Marie Caminade, Hugo Bastida, Maria Bryszewska, Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario 'Gregorio Marañón'-Instituto de Investigación Sanitaria Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, and University of Lódź
Subjects: Dendrimers, HIV Antigens, medicine.medical_treatment, Inflammation, 02 engineering and technology, Biochemistry, Flow cytometry, 03 medical and health sciences, Immune system, Cell Movement, Dendrimer, Drug Discovery, medicine, Humans, [CHIM.COOR]Chemical Sciences/Coordination chemistry, 030304 developmental biology, Pharmacology, 0303 health sciences, medicine.diagnostic_test, Chemistry, Organic Chemistry, Phosphorus, Immunotherapy, Dendritic Cells, 021001 nanoscience & nanotechnology, In vitro, 3. Good health, Immunology, Cancer research, Molecular Medicine, Cytokines, medicine.symptom, 0210 nano-technology, Adjuvant, Chemotaxis assay
Abstract: International audience; The objective was to study if cationic phosphorus dendrimers can be used as DC-based vaccine or adjuvant in anti-HIV-1 vaccine development when associated with HIV-1 derived peptides. Materials & Methods: The HIVderived peptides uptake in DC and the phenotype of iDC and mDC were studied using Flow Cytometry analysis. Migration of mDC was evaluated by an in vitro chemotaxis assay. Allogenic T-cells proliferative response induced by DC was studied using Flow Cytometry assays. Cytokines production was analysed by Diaclon DIAplex Th1/Th2/Inflammation kit. Results: All phosphorus dendrimers showed the ability to deliver HIV-derived peptides in DC. The phosphorus dendrimers from second and third generations induced important changes in phenotype. Moreover, the treatment of mDC with the second generation dendrimer and derivated dendriplexes modified cellular migratory properties, altered their capacity to stimulate allogenic naïve T cells in vitro and impeded the production of pro-inflammatory cytokines. Conclusions: The phosphorus dendrimers cannot be used as vaccines because they would not have the ability to induce an immune response. The cationic phosphorus dendrimers associated with HIV-derived peptides have the ability to deliver peptides as non-viral vectors. However, there are other potential therapeutic applications of these compounds, for instance as topical antiinflammatory agents, as compounds for allograft rejection or autoimmune diseases and as agents inducing specific tolerance with antigen-loaded DC against allergy reaction. Nevertheless, these applications need to be evaluated.
Published: 2014

49. Radical dendrimers: A family of five generations of phosphorus dendrimers functionalized with TEMPO radicals

Author: Badetti, Elena, Lloveras, Vega, Muñoz Gómez, José L, Sebastián, Rosa M., Caminade, Anne M., Majoral, Jean P., Veciana, Jaume, Vidal Gancedo, José, Institut de Ciència de Materials de Barcelona (ICMAB), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Universitat Autònoma de Barcelona (UAB), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials Chemistry2506 Metals and Alloys, Polymers and Plastics, Chemistry, Radical, Organic Chemistry, Settore CHIM/06 - Chimica Organica, Molar absorptivity, Photochemistry, 7. Clean energy, law.invention, Inorganic Chemistry, Paramagnetism, law, Dendrimer, Intramolecular force, Polymer chemistry, Materials Chemistry, Proton NMR, Settore CHIM/01 - Chimica Analitica, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Spectroscopy, Electron paramagnetic resonance
Abstract: © 2014 American Chemical Society. Five novel generations of phosphorus dendrimers based on a cyclotriphosphazene core with stable TEMPO radicals end groups have been synthesized and studied by EPR, SQUID, 1H NMR, 31P NMR, FT-IR, and UV-vis spectroscopy. The nitroxyl radicals exhibit a strong exchange interaction, which depends on the dendrimer generation and the temperature. An |fms| = 2 transition has been observed in each generation in dilution conditions demonstrating the intramolecular origin of the radicals interaction. There exists a direct proportionality between the EPR |Δms| = 2 transition intensity and the number of radicals by generation; consequently, the utility of EPR for the determination of the substitution efficiency on dendrimers by paramagnetic species is quite good. From the UV-vis characterization, we have observed that the molar extinction coefficient value is also proportional to the number of TEMPO groups. The magnetic properties of the zero, first and fourth generation dendrimers studied by SQUID magnetometry show antiferromagnetic interaction between radicals., This work was supported by the DGI grant CONSOLIDERC (CTQ2006-06333), CSIC-PIF RAPCAM (PIF-08-017-3), AGAUR (2009-SGR-00516) and DGI grant POMAs (CTQ2010-19501). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.
Published: 2014

50. Influence of ligand presentation density on the molecular recognition of mannose-functionalised glyconanoparticles by bacterial lectin BC2L-A

Author: Reynolds, M., MARRADI, M., Imberty, A., Penades, S., Perez, S., Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), European Synchrotron Radiation Facility (ESRF), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, inconnu, Inconnu, and Carret, Michèle
Subjects: [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Polyvalent carbohydrate-protein interactions play a key role in bio- and pathological processes, including cell-cell communication and pathogen invasion. In order to study, control and manipulate these interactions gold nanoparticles have been employed as a 3D scaffold, presenting carbohydrate ligands in a multivalent fashion for use as high affinity binding partners and a model system for oligosaccharide presentation at biomacromolecular surfaces. In this study, the binding of a series of mannose-functionalised gold nanoparticles to the dimeric BC2L-A lectin from Burkholderia cenocepacia has been evaluated. BC2L-A is known to exhibit a high specificity for (oligo)mannosides. Due to the unique structure and binding nature of this lectin, it provides a useful tool to study (oligo)saccharides presented on multivalent scaffolds. Surface plasmon resonance and isothermal titration calorimetric assays were used to investigate the effect of ligand presentation density towards binding to the bacterial lectin. We show how a combination of structural complementarities between ligand presentation and lectin architecture and statistical re-binding effects are important for increasing the avidity of multivalent ligands for recognition by their protein receptors; further demonstrating the application of glyconanotechnology towards fundamental glycobiology research as well as a potential towards biomedical diagnostics and therapeutic treatments.
Published: 2013

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