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99 results on '"University of Dundee"'

1. Communication Exercise

Author: Leverhulme Research Centre for Forensic Science at the University of Dundee, Alda Center for Communicating Science at Stony Brook University, Heather Doran, and Julie Burrill

2. Following the Formation of Synaptonemal Complex Formation in Wheat and Barley by High-Resolution Microscopy

Author: Robbie Waugh, Sybille U. Mittmann, Luke Ramsay, Isabelle Colas, Benoit Darrier, Pierre Sourdille, Mikel Arrieta, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), School of Agriculture, Food and Wine, University of Adelaide, Department of Cell and Molecular Sciences, The James Hutton Institute, Division of Plant Sciences, University of Dundee, University of Dundee, MRC Next Generation Optical Microscopy Award [MR/K015869/1], Scottish Government's Rural and Environment Science and Analytical Services Division Work Program 5.2, INRA, Région Auvergne, INRA-DARESE (Direction de l'Action Regionale, de l'Enseignement Superieur et de l'Europe) in the course of EIR-A (Ecole Internationale de Recherche d'Agreenium), Biotechnology and Biological Science Research Council EASTBIO PhD studentship program, Mónica Pradillo, Stefan Heckmann, European Project: 222883,EC:FP7:KBBE,FP7-KBBE-2007-2A,MEIOSYS(2009), European Project: 669182,H2020,ERC-2014-ADG,SHUFFLE(2015), European Project, and European Project: 606956,EC:FP7:PEOPLE,FP7-PEOPLE-2013-ITN,COMREC(2013)
Subjects: 0106 biological sciences, 0301 basic medicine, Fluorescent Antibody Technique, Biology, 01 natural sciences, Genome, Chromosomal crossover, Chromosome segregation, 03 medical and health sciences, Imaging, Three-Dimensional, Meiosis, Barley, Homologous chromosome, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Triticum, Genomic organization, 2. Zero hunger, Microscopy, Synaptonemal Complex, Synapsis, food and beverages, Hordeum, Sexual reproduction, Chromosome Pairing, 030104 developmental biology, Evolutionary biology, Wheat, 3D microscopy, 010606 plant biology & botany
Abstract: Series Title - Methods in Molecular Biology; International audience; Wheat and barley have large genomes of 15 Gb and 5.1 Gb, respectively, which is much larger than the human genome (3.3 Gb). The release of their respective genomes has been a tremendous advance the understanding of the genome organization and the ability for deeper functional analysis in particular meiosis. Meiosis is the cell division required during sexual reproduction. One major event of meiosis is called recombination, or the formation of crossing over, a tight link between homologous chromosomes, ensuring gene exchange and faithful chromosome segregation. Recombination is a major driver of genetic diversity but in these large genome crops, the vast majority of these events is constrained at the end of their chromosomes. It is estimated that in barley, about 30% of the genes are located within the poor recombining centromeric regions, making important traits, such as resistance to pest and disease for example, difficult to access. Increasing recombination in these crops has the potential to speed up breeding program and requires a good understand of the meiotic mechanism. However, most research on recombination in plant has been carried in Arabidopsis thaliana which despite many of the advantages it brings for plant research, has a small genome and more spread out of recombination compare to barley or wheat. Advance in microscopy and cytological procedures have emerged in the last few years, allowing to follow meiotic events in these crops. This protocol provides the steps required for cytological preparation of barley and wheat pollen mother cells for light microscopy, highlighting some of the differences between the two cereals.
Published: 2019

3. Antiviral polysaccharide and antiviral peptide delivering nanomaterials for prevention and treatment of SARS-CoV-2 caused COVID-19 and other viral diseases

Author: Homaeigohar, Shahin, Liu, Xuan, Elbahri, Mady, University of Dundee, Department of Chemistry and Materials Science, Aalto-yliopisto, and Aalto University
Subjects: Polysaccharides, Virus mimicry, Antiviral peptides, Pharmaceutical Science, Nature-derived, Nanocarriers
Abstract: Publisher Copyright: © 2023 The Authors Antiviral peptides and antiviral polysaccharides can play a major role in the prevention and treatment of emerging viral health problems. These antiviral compounds are biocompatible, environmentally friendly, non-toxic, and cost-effective, yet are poorly water soluble and vulnerable to enzymatic (protease) degradation within the aggressive intercellular microenvironment. Therefore, they should be properly protected and delivered to viruses and host cells by the well-designed nanocarriers that mimic viruses in terms of size, morphology, and smart function. This literature review is meant to introduce the latest advances (mainly within the past five years) in antiviral nano-assemblies comprising antiviral peptides or antiviral polysaccharides. To the best of our knowledge, there is no similar study in the literature that has solely and sufficiently investigated such antiviral nanomaterials partially or totally derived from nature. The rational classification of microorganism-, plant-, and animal-derived antiviral polysaccharide and antiviral peptide delivering nanomaterials and exploration of their relevant applications will clarify the promising capacity of these state-of-the-art materials for a number of technologies developed to inactivate viruses.
Published: 2023

4. Carbonate Disequilibrium in the External Boundary Layer of Freshwater Chrysophytes: Implications for Contaminant Uptake

Author: David J. Kieber, Jérôme F. L. Duval, Warwick F. Vincent, Michel Lavoie, Frédéric Maps, John A. Raven, Béchir Béjaoui, Département de Biologie [Université Laval], Université Laval [Québec] (ULaval), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Division of Plant Sciences, University of Dundee, University of Dundee, Institut National des Sciences et Technologies de la Mer [Salammbô] (INSTM), and State University of New York (SUNY)
Subjects: 010504 meteorology & atmospheric sciences, Nitrogen, Disequilibrium, Carbonates, Fresh Water, 010501 environmental sciences, 01 natural sciences, Chemical reaction, chemistry.chemical_compound, Phytoplankton, Genetic algorithm, medicine, Environmental Chemistry, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Chemistry, fungi, Biological Transport, General Chemistry, 6. Clean water, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Boundary layer, Environmental chemistry, [SDE]Environmental Sciences, Carbonate, medicine.symptom
Abstract: The interplay between biological and chemical reactions in the freshwater phytoplankton phycosphere and the resulting modulations of contaminant speciation and uptake is poorly characterized. Here we modeled the effect of algal C and N uptake on carbonate cycling and speciation of selected contaminants in the phycosphere (external boundary layer) of chrysophytes, a key phytoplankton group in oligotrophic systems. We calculated an enrichment in H
Published: 2018

5. Characteristics and age‐related injury patterns of maxillofacial fractures in children and adolescents: A multicentric and prospective study

Author: Ignasi Segura‐Palleres, Federica Sobrero, Fabio Roccia, Luis Fernando de Oliveira Gorla, Valfrido Antonio Pereira‐Filho, Daniel Gallafassi, Leonardo Perez Faverani, Irene Romeo, Alessandro Bojino, Chiara Copelli, Francesc Duran‐Valles, Coro Bescos, Dimitra Ganasouli, Stelios N. Zanakis, Ahmed Gaber Hassanein, Haider Alalawy, Mohammed Kamel, Sahand Samieirad, Mehul Rajesh Jaisani, Sajjad Abdur Rahman, Tabishur Rahman, Timothy Aladelusi, Kirsten Carlaw, Peter Aquilina, Euan Rae, Sean Laverick, Maximilian Goetzinger, Gian Battista Bottini, University of Turin, Universidade Estadual Paulista (UNESP), Hospital Universitario Vall D’Hebron, Hippocratio General Hospital, Sohag University, Gazi Alhariri Hospital, Mashhad University of Medical Sciences, Aligarh Muslim University, University of Ibadan, Nepean Hospital, University of Dundee, Paracelsus Medical University, Institut Català de la Salut, [Segura-Palleres I, Sobrero F, Roccia F] Division of Maxillofacial Surgery, Città della Salute e della Scienza, University of Turin, Turin, Italy. [de Oliveira Gorla LF, Pereira-Filho VA] Department Diagnosis and Surgery, Araraquara Dental School, São Paulo State University, UNESP, São Paulo, Brazil. [Gallafassi D] Department of Diagnosis and Surgery, Division of Oral and Maxillofacial Surgery, São Paulo State University, UNESP, São Paulo, Brazil. [Duran-Valles F, Bescos C] Servei de Cirurgia Oral i Maxil·lofacial, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Adult, Male, Environment and Public Health::Public Health::Accidents::Accidents, Traffic [HEALTH CARE], Adolescent, personas::Grupos de Edad::niño [DENOMINACIONES DE GRUPOS], heridas y lesiones::fracturas óseas::fracturas craneales::fracturas maxilomandibulares::heridas y lesiones::fracturas mandibulares [ENFERMEDADES], Wounds and Injuries::Fractures, Bone::Skull Fractures::Jaw Fractures::Wounds and Injuries::Mandibular Fractures [DISEASES], children, Mandibular Fractures, Humans, Prospective Studies, Child, Mandíbula - Fractures, Retrospective Studies, Skull Fractures, Accidents, Traffic, Infant, Newborn, Infant, Persons::Age Groups::Child [NAMED GROUPS], ambiente y salud pública::salud pública::accidentes::accidentes de tráfico [ATENCIÓN DE SALUD], prospective, adolescent, epidemiology, maxillofacial fractures, multicentric, Circulació - Accidents, Child, Preschool, Female, Maxillofacial Injuries, Oral Surgery, Infants
Abstract: Made available in DSpace on 2022-04-29T08:39:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Background/Aims: Paediatric maxillofacial trauma accounts for 15% of all maxillofacial trauma but remains a leading cause of mortality. The aim of this prospective, multicentric epidemiological study was to analyse the characteristics of maxillofacial fractures in paediatric patients managed in 14 maxillofacial surgery departments on five continents over a 1-year period. Methods: The following data were collected: age (preschool [0–6 years], school age [7–12 years], and adolescent [13–18 years]), cause and mechanism of the maxillofacial fracture, alcohol and/or drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score, associated injuries, day of the maxillofacial trauma, timing and type of treatment, and length of hospitalization. Statistical analyses were performed using SPSS software. Results: Between 30 September 2019 and 4 October 2020, 322 patients (male:female ratio, 2.3:1) aged 0–18 years (median age, 15 years) were hospitalized with maxillofacial trauma. The most frequent causes of the trauma were road traffic accidents (36%; median age, 15 years), followed by falls (24%; median age, 8 years) and sports (21%; median age, 14 years). Alcohol and/or drug abuse was significantly associated with males (p
Published: 2022

6. Motion estimation-based image enhancement in ultrasound imaging

Author: Adrian Basarab, Stephanie Bidon, Renaud Morin, Denis Kouame, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut Supérieur de l'Aéronautique et de l'Espace - ISAE-SUPAERO (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université Toulouse - Jean Jaurès - UT2J (FRANCE), Université Toulouse 1 Capitole - UT1 (FRANCE), University of Dundee (UNITED KINGDOM), Département d'Electronique, Optronique et Signal - DEOS (Toulouse, France), Traitement et Compréhension d’Images (IRIT-TCI), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, University of Dundee, Université Toulouse III - Paul Sabatier (UT3), Département Electronique, Optronique et Signal (DEOS), Institut Supérieur de l'Aéronautique et de l'Espace (ISAE-SUPAERO), and Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
Subjects: Acoustics and Ultrasonics, Computer science, Iterative reconstruction, Imaging phantom, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Speckle pattern, Traitement des images, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Motion estimation, Traitement du signal et de l'image, Computer vision, Instrumentation (computer programming), Image resolution, Synthèse d'image et réalité virtuelle, Image registration, business.industry, Ultrasound, Resolution (electron density), [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Vision par ordinateur et reconnaissance de formes, Intelligence artificielle, [INFO.INFO-GR]Computer Science [cs]/Graphics [cs.GR], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Super-resolution, Image enhancement, Artificial intelligence, Medical imaging, business, Nuclear medicine
Abstract: International audience; High resolution medical ultrasound (US) imaging is an ongoing challenge in many diagnosis applications and can be achieved either by instrumentation or by post-processing. Though many works have considered the issue of resolution enhancement in optical imaging, very few works have investigated this issue in US imaging. In optics, several algorithms have been proposed to achieve super-resolution (SR) image reconstruction, which consists of merging several low resolution images to create a higher resolution image. However, the straightforward implementation of such techniques for US imaging is unsuccessful, due to the interaction of ultrasound with tissue and speckle. We show how to overcome the limit of SR in this framework by refining the registration part of common multiframe techniques. For this purpose, we investigate motion estimation methods adapted to US imaging. Performance of the proposed technique is evaluated on both realistic simulated US images (providing an estimated best-case performance) and real US sequences of phantom and in-vivo thyroid images. Compared to classical SR methods, our technique brings both quantitative and qualitative improvements. Resolution gain was found to be 1.41 for the phantom sequence and 1.12 for the thyroid sequence and a quantitative study using the phantom further confirmed the spatial resolution enhancement. Furthermore, the contrast-to-noise ratio was increased by 27% and 13% for simulated and experimental US images, respectively.
Published: 2013

7. Retinal Vessel Phenotype in Patients with a History of Retinal Vein Occlusion

Author: Rachel Semecas, Tom MacGillivray, Olivier Gavard, Emmanuel Trucco, Alain M. Bron, Catherine Creuzot-Garcher, Christophe Chiquet, Louis Arnould, Stephen Hogg, Florent Aptel, Thibaud Mautuit, HP2, Pole Biol CHU Grenoble (INSERM, U1042), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), University of Edinburgh, University of Dundee, and Julien, Sabine
Subjects: fractal dimension, medicine.medical_specialty, Retinal Vein, genetic structures, vein diameter, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Text mining, Ophthalmology, Retinal Vein Occlusion, Occlusion, Humans, Medicine, In patient, retinal image analysis, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030304 developmental biology, 0303 health sciences, business.industry, Reproducibility of Results, Retinal Vessels, General Medicine, Phenotype, eye diseases, arterial diameter, Sensory Systems, Retinal vessel, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030221 ophthalmology & optometry, VAMPIRE software, tortuosity, business
Abstract: Introduction: The aim of the study was to estimate the phenotype of retinal vessels using central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), tortuosity, and fractal analysis in the unaffected contralateral eye of patients with central or branch retinal vein occlusion (CRVO or BRVO). Methods: Thirty-four patients suffering from CRVO, 15 suffering from BRVO, and 49 controlled matched subjects had a fundus image analyzed using the VAMPIRE software. The intraclass correlation coefficient and a Bland-Altman plot were done for the reproducibility study. Results: There was a lack of evidence of difference between the control group and the CRVO group for CRAE (p = 0.06), CRVE (p = 0.3), and arterio-venule ratio (AVR, p = 0.6). Contralateral eyes of CRVO exhibited a significantly higher arterial and minimum arterial tortuosity values (p = 0.012), as compared with control eyes. Contralateral eyes of patients with a history of BRVO had a significantly higher CRAE (p = 0.02), AVR (p = 0.006), and minimal arterial tortuosity (p = 0.05). Fractal analysis showed that contralateral eyes of BRVO had higher values of fractal parameters (D0a, p = 0.005). Conclusion: This study suggests that CVRO or BRVO is not triggered by the same retinal vascular phenotypes in the contralateral eye. The morphology of retinal vasculature may be associated with the occurrence of RVO, independently of known risk factors.
Published: 2021

8. Quality of life in men and women with heart failure: association with outcome, and comparison between the Kansas City Cardiomyopathy Questionnaire and the EuroQol 5 dimensions questionnaire

Author: Nilesh J. Samani, João Pedro Ferreira, Kenneth Dickstein, Faiez Zannad, Sven Meyer, Marco Metra, John R. Teerlink, Carlo Lombardi, Chim C. Lang, Alice Ravera, Adriaan A. Voors, Iziah E Sama, Bernadet T. Santema, Valentina Carubelli, Stefan D. Anker, Dirk J. van Veldhuisen, University Medical Center Groningen [Groningen] (UMCG), Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia = University of Brescia (UniBs), Carl Von Ossietzky Universität Oldenburg = Carl von Ossietzky University of Oldenburg (OFFIS), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Dundee, Ninewells Hospital and Medical School [Dundee], University of Bergen (UiB), Stavanger University Hospital, Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, University of California [San Francisco] (UC San Francisco), University of California (UC), Veterans Affairs Medical Center, San Francisco, California, European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), Cardiovascular Centre (CVC), BOZEC, Erwan, A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure - BIOSTAT-CHF - - EC:FP7:HEALTH2010-04-01 - 2015-03-31 - 242209 - VALID, Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Heart Center Oldenburg, Department of Cardiology, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, and Department of Cardiovascular Sciences, University of Leicester, NIHR (National Institute for Health Research) Leicester Biomedical Research Centre, Glenfield Hospital
Subjects: Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Heart failure, Outcome, Quality of life, Sex, Women, Female, Humans, Kansas, Quality of Life, Stroke Volume, Surveys and Questionnaires, Cardiomyopathies, Heart Failure, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Medicine, Ejection fraction, business.industry, medicine.disease, Tailored treatment, humanities, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical trial, Kansas City Cardiomyopathy Questionnaire, Cardiology and Cardiovascular Medicine, business
Abstract: Aims: We sought to analyse quality of life (QoL) measures derived from two questionnaires widely used in clinical trials, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQoL 5 dimensions (EQ-5D), and to compare their prognostic value in men and women with heart failure and reduced ejection fraction (HFrEF).Methods and results: From the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) we compared KCCQ and EQ-5D at baseline and after 9 months in 1276 men and 373 women with new-onset or worsening symptoms of HFrEF, who were sub-optimally treated and in whom there was an anticipated up-titration of guideline-derived medical therapies. Women had significantly worse baseline QoL (median) as compared with men, both when assessed with KCCQ overall score (KCCQ-OS, 44 vs. 53, P < 0.001) and EQ-5D utility score (0.62 vs. 0.73, P < 0.001). QoL improved equally in women and men at follow-up. All summary measures of QoL were independently associated with all-cause mortality, with KCCQ-OS showing the most remarkable association with mortality up to 1 year compared to the EQ-5D scores (C-statistic 0.650 for KCCQ-OS vs. 0.633 and 0.599 for EQ-5D utility score and EQ-5D visual analogue scale, respectively). QoL was associated with all outcomes analysed, both in men and women (all P for interaction with sex >0.2).Conclusion: Amongst patients with HFrEF, women reported significantly worse QoL than men. QoL was independently associated with subsequent outcome, similarly in men and women. The KCCQ in general, and the KCCQ-OS in particular, showed the strongest independent association with outcome.
Published: 2021

9. Computational Model of Heterogeneity in Melanoma: Designing Therapies and Predicting Outcomes

Author: Arran Hodgkinson, Dumitru Trucu, Matthieu Lacroix, Laurent Le Cam, Ovidiu Radulescu, University of Exeter, University of Dundee, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Equipe labellisée Ligue contre le Cancer, LPHI - Laboratory of Pathogen Host Interactions (LPHI), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Radulescu, Ovidiu
Subjects: Data, Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Targeted, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Cancer heterogeneity, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mathematical modeling, Single cell, Melanoma, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Cutaneous melanoma is a highly invasive tumor and, despite the development of recent therapies, most patients with advanced metastatic melanoma have a poor clinical outcome. The most frequent mutations in melanoma affect the BRAF oncogene, a protein kinase of the MAPK signaling pathway. Therapies targeting both BRAF and MEK are effective for only 50% of patients and, almost systematically, generate drug resistance. Genetic and non-genetic mechanisms associated with the strong heterogeneity and plasticity of melanoma cells have been suggested to favor drug resistance but are still poorly understood. Recently, we have introduced a novel mathematical formalism allowing the representation of the relation between tumor heterogeneity and drug resistance and proposed several models for the development of resistance of melanoma treated with BRAF/MEK inhibitors. In this paper, we further investigate this relationship by using a new computational model that copes with multiple cell states identified by single cell mRNA sequencing data in melanoma treated with BRAF/MEK inhibitors. We use this model to predict the outcome of different therapeutic strategies. The reference therapy, referred to as “continuous” consists in applying one drug (or several drugs) without disruption. In “combination therapy”, several drugs are used sequentially. In “adaptive therapy” drug application is interrupted when the tumor size is below a lower threshold and resumed when the size goes over an upper threshold. We show that, counter-intuitively, the optimal protocol in combination therapy of BRAF/MEK inhibitors with a hypothetical drug targeting cell states that develop later during the tumor response to kinase inhibitors, is to treat first with this hypothetical drug. Also, even though there is little difference in the timing of emergence of the resistance between continuous and adaptive therapies, the spatial distribution of the different melanoma subpopulations is more zonated in the case of adaptive therapy.
Published: 2022

10. Dynamics of drug response in single mycobacterial cells by microfluidic dose-response assay

Author: Maxime Mistretta, Nicolas Gangneux, Giulia Manina, Individualité microbienne et infection - Microbial Individuality and Infection, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This work was supported by: French Medical Research Foundation grant ING20160435202 (GM), French National Research Agency grant ANR-17-CE11-0007-01 (GM), French National Research Agency grant ANR-10-LABX-62-IBEID (GM), IMI 2 Joint Undertaking grant 853989, receiving support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Global Alliance for TB Drug Development non-profit organization, Bill & Melinda Gates Foundation, University of Dundee (GM), Institut Pasteur core funding (GM), ANR-17-CE11-0007,PersisTB,Lutter contre l'épidémie mondiale de tuberculose: Exploiter la variation cellule à cellule afin d'entraver la persistance adaptative(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and European Project: 853989,H2020-JTI-IMI2-2018-15-two-stage,ERA4TB(2020)
Subjects: [SPI]Engineering Sciences [physics], [SDV]Life Sciences [q-bio]
Abstract: Preclinical analysis of drug efficacy is critical for drug development. However, conventional bulk-cell assays statically assess the mean population behavior, lacking resolution on drugescaping cells. Inaccurate estimation of efficacy can lead to overestimation of compounds, whose efficacy will not be confirmed in the clinic, or lead to rejection of valuable candidates. Time-lapse microfluidic microscopy is a powerful approach to characterize drugs at high spatiotemporal resolution, but hard to apply on a large scale. Here we report the development of a microfluidic platform based on a pneumatic operating principle, which is scalable and compatible with long-term live-cell imaging and with simultaneous analysis of different drug concentrations. We tested the platform with mycobacterial cells, including the tubercular pathogen, providing the first proof of concept of a single-cell dose-response assay. This dynamic in-vitro model will prove useful to probe the fate of drug-stressed cells, providing improved predictions of drug efficacy in the clinic.
Published: 2022

11. Targeted Metabolomics as a Tool in Discriminating Endocrine From Primary Hypertension

Author: Parminder Singh Reel, Anne Blanchard, Casper K Larsen, Paolo Mulatero, Guillaume Assié, Michael Conall Dennedy, Smarti Reel, Zoran Erlic, Cornelia Prehn, Martin Reincke, Anne-Paule Gimenez-Roqueplo, Alessio Pecori, Katharina Langton, Jaap Deinum, Jerzy Adamski, Christina Pamporaki, Felix Beuschlein, Maria-Christina Zennaro, Filippo Ceccato, Livia Lenzini, Laurence Amar, Martina Tetti, Matthias Kroiss, Carla Scaroni, Aleksander Prejbisz, Emily Jefferson, University of Zurich, Beuschlein, Felix, Universitätsspital Zürich (USZ), University of Dundee, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Università degli studi di Torino = University of Turin (UNITO), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Helmholtz Zentrum München = German Research Center for Environmental Health, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), National University of Singapore (NUS), National Institute of Cardiology [Varsovie, Pologne], Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Universitätsklinikum Würzburg, University of Würzburg = Universität Würzburg, Ludwig-Maximilians-Universität München (LMU), National University of Ireland [Galway] (NUI Galway), Radboud University Medical Center [Nijmegen], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and HULOT, Jean-Sébastien
Subjects: Oncology, Male, 1303 Biochemistry, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 10265 Clinic for Endocrinology and Diabetology, Adrenal Gland Neoplasms, 030204 cardiovascular system & hematology, 1308 Clinical Biochemistry, Biochemistry, Cushing syndrome, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Primary aldosteronism, targeted metabolomics, arterial hypertension, pheochromocytoma, primary aldosteronism, screening, Area under the curve, Ornithine, Middle Aged, Hyperaldosteronism, ddc, 3. Good health, 1310 Endocrinology, [SDV] Life Sciences [q-bio], Europe, 2712 Endocrinology, Diabetes and Metabolism, Hypertension, Cushing Syndrome, Arterial Hypertension, Pheochromocytoma, Primary Aldosteronism, Screening, Targeted Metabolomics, Female, Essential Hypertension, AcademicSubjects/MED00250, Adult, medicine.medical_specialty, Context (language use), 030209 endocrinology & metabolism, 610 Medicine & health, 2704 Biochemistry (medical), Endocrine System Diseases, Diagnosis, Differential, Diagnostic Techniques, Endocrine, Paraganglioma, 03 medical and health sciences, Internal medicine, medicine, Endocrine system, Humans, Metabolomics, Clinical Research Articles, Aged, Retrospective Studies, Receiver operating characteristic, business.industry, Biochemistry (medical), medicine.disease, chemistry, business
Abstract: ContextIdentification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL], and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and endocrine conditions associated with hypertension.ObjectiveUse TM to identify distinct metabolic patterns between primary hypertension (PHT) and EHT and test its discriminating ability.MethodsRetrospective analyses of PHT and EHT patients from a European multicenter study (ENSAT-HT). TM was performed on stored blood samples using liquid chromatography mass spectrometry. To identify discriminating metabolites a “classical approach” (CA) (performing a series of univariate and multivariate analyses) and a “machine learning approach” (MLA) (using random forest) were used.The study included 282 adult patients (52% female; mean age 49 years) with proven PHT (n = 59) and EHT (n = 223 with 40 CS, 107 PA, and 76 PPGL), respectively.ResultsFrom 155 metabolites eligible for statistical analyses, 31 were identified discriminating between PHT and EHT using the CA and 27 using the MLA, of which 16 metabolites (C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC16:0, lysoPCaC20:4, lysoPCaC24:0, PCaeC42:0, SM C18:1, SM C20:2) were found by both approaches. The receiver operating characteristic curve built on the top 15 metabolites from the CA provided an area under the curve (AUC) of 0.86, which was similar to the performance of the 15 metabolites from MLA (AUC 0.83).ConclusionTM identifies distinct metabolic pattern between PHT and EHT providing promising discriminating performance.
Published: 2021

12. The evolution of inorganic carbon concentrating mechanisms in photosynthesis

Author: John A. Raven, Charles S. Cockell, Christina L. De La Rocha, Division of Plant Sciences, University of Dundee, University of Dundee, Planetary and Space Sciences Research Institute [Milton Keynes] (PSSRI), Centre for Earth, Planetary, Space and Astronomical Research [Milton Keynes] (CEPSAR), The Open University [Milton Keynes] (OU)-The Open University [Milton Keynes] (OU), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Cyanobacteria, C4 photosynthesis, Lichens, Ribulose-Bisphosphate Carboxylase, Context (language use), Review, Photosynthesis, 01 natural sciences, Models, Biological, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, stromatolites, Magnoliopsida, Total inorganic carbon, Algae, Aquatic plant, Botany, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, 030304 developmental biology, 0303 health sciences, Carbon Isotopes, biology, RuBisCO, food and beverages, Eukaryota, embryophytes, Carbon Dioxide, biology.organism_classification, Biological Evolution, alga, crassulacean acid metabolism, biology.protein, Crassulacean acid metabolism, General Agricultural and Biological Sciences, 010606 plant biology & botany
Abstract: Inorganic carbon concentrating mechanisms (CCMs) catalyse the accumulation of CO 2 around rubisco in all cyanobacteria, most algae and aquatic plants and in C 4 and crassulacean acid metabolism (CAM) vascular plants. CCMs are polyphyletic (more than one evolutionary origin) and involve active transport of , CO 2 and/or H + , or an energized biochemical mechanism as in C 4 and CAM plants. While the CCM in almost all C 4 plants and many CAM plants is constitutive, many CCMs show acclimatory responses to variations in the supply of not only CO 2 but also photosynthetically active radiation, nitrogen, phosphorus and iron. The evolution of CCMs is generally considered in the context of decreased CO 2 availability, with only a secondary role for increasing O 2 . However, the earliest CCMs may have evolved in oxygenic cyanobacteria before the atmosphere became oxygenated in stromatolites with diffusion barriers around the cells related to UV screening. This would decrease CO 2 availability to cells and increase the O 2 concentration within them, inhibiting rubisco and generating reactive oxygen species, including O 3 .
Published: 2008

13. Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO® Trials

Author: James D. Chalmers, Dave Singh, Alberto de la Hoz, Gary T. Ferguson, Jadwiga A. Wedzicha, Ioanna Tsiligianni, Janwillem W. H. Kocks, Wenqiong Xue, Marc Miravitlles, Klaus F. Rabe, Groningen Research Institute for Asthma and COPD (GRIAC), Institut Català de la Salut, [Rabe KF] LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research (DZL), Grosshansdorf, Germany. Christian Albrechts University Kiel, Airway Research Center North, German Center for Lung Research (DZL), Kiel, Germany. [Chalmers JD] Tayside Respiratory Research Group, University of Dundee, Dundee, UK. [Miravitlles M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain. [Kocks JWH] General Practitioners Research Institute, Groningen, The Netherlands. Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Observational and Pragmatic Research Institute, Singapore, Singapore. [Tsiligianni I] Health Planning Unit, Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece. [de la Hoz A] Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 030213 general clinical medicine, Exacerbation, IMPACT, INITIAL MAINTENANCE TREATMENT, Pulmons - Malalties obstructives - Tractament, Other subheadings::Other subheadings::/drug therapy [Other subheadings], chemistry.chemical_compound, 0302 clinical medicine, Bronchodilator, Pharmacology (medical), INDEX, OUTCOMES, COPD, Broncodilatadors - Ús terapèutic, Chronic obstructive pulmonary disease, Olodaterol, Hazard ratio, LAMA, General Medicine, Obstructive lung disease, enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica [ENFERMEDADES], 030220 oncology & carcinogenesis, Cardiology, LAMA/LABA COMBINATION THERAPY, medicine.medical_specialty, Combination therapy, medicine.drug_class, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Health status, LABA/LAMA COMBINATION, Exacerbations, POOLED ANALYSIS, Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Autonomic Agents::Bronchodilator Agents [CHEMICALS AND DRUGS], 03 medical and health sciences, Internal medicine, Post-hoc analysis, medicine, acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::fármacos del sistema nervioso periférico::fármacos del sistema nervioso autónomo::broncodilatadores [COMPUESTOS QUÍMICOS Y DROGAS], DUAL BRONCHODILATION, Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive [DISEASES], business.industry, Tiotropium, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.disease, PREVENTION, Lung function, respiratory tract diseases, chemistry, Avaluació de resultats (Assistència sanitària), business
Abstract: Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy. We compared long-acting muscarinic antagonist/long-acting β2-agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID. CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naive patients with COPD. We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID. Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat®) in two replicate, 52-week, parallel-group, double-blind studies (TONADO® 1/2). CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St. George’s Respiratory Questionnaire score, or moderate/severe exacerbation. Time to first occurrence of one of these events was recorded as time to first CID. Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P
Published: 2020

14. Heart failure treatment up‐titration and outcome and age: an analysis of BIOSTAT‐CHF

Author: Kenneth Dickstein, Faiez Zannad, Adriaan A. Voors, Marco Metra, Ify R. Mordi, John G.F. Cleland, Nilesh J. Samani, Stefan D. Anker, Dirk J. van Veldhuisen, Chim C. Lang, Leong L. Ng, Wouter Ouwerkerk, Ninewells Hospital and Medical School [Dundee], University of Dundee, National Heart Centre Singapore (NHCS), Amsterdam UMC - Amsterdam University Medical Center, Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Imperial College London, University of Bergen (UiB), Stavanger University Hospital, Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, University of Leicester, University Hospitals Leicester, University Medical Center Groningen [Groningen] (UMCG), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), NHS Education for Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship. Grant Number: PCL/17/07, European Commission: FP7-242209-BIOSTAT-CHF, European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), Cardiovascular Centre (CVC), Epidemiology and Data Science, and Dermatology
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, DIAGNOSIS, MORBIDITY, Angiotensin Receptor Antagonists, 03 medical and health sciences, Elderly, Up-titration, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, ACE inhibitor, Internal medicine, Humans, Medicine, ESC GUIDELINES, Beta-blocker, cardiovascular diseases, Angiotensin receptor blocker, ELDERLY-PATIENTS, Beta blocker, Aged, Heart Failure, Ejection fraction, business.industry, BETA-BLOCKERS, MORTALITY, Incidence (epidemiology), Hazard ratio, Stroke Volume, Atrial fibrillation, medicine.disease, RANDOMIZED-TRIAL, Confidence interval, Treatment Outcome, HOSPITALIZATION, Heart failure, SYSTOLIC DYSFUNCTION, ATRIAL-FIBRILLATION, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Aims:\ud Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up‐titration of angiotensin‐converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta‐blockers on outcome across the age spectrum in HFrEF patients.\ud \ud Methods and results:\ud We analysed HFrEF patients on sub‐optimal doses of ACEI/ARB and/or beta‐blockers from the BIOSTAT‐CHF study stratified by age. Patients underwent a 3‐month up‐titration period. We used inverse probability weighting to adjust for the likelihood of successful up‐titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow‐up of 21 months in 1720 HFrEF patients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta‐blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI‐ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91–0.94, P
Published: 2020

15. Introduction

Author: A. Brandenburg, S. Candelaresi, F. A. Gent, NORDITA, University of Dundee, Centre of Excellence Research on Solar Long-Term Variability and Effects, ReSoLVE, Department of Computer Science, Aalto-yliopisto, and Aalto University
Subjects: Geophysics, Geochemistry and Petrology, Mechanics of Materials, education, Computational Mechanics, Astronomy and Astrophysics
Abstract: Non
Published: 2019

16. Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation

Author: Katiuska González-Arzola, Antonio Díaz-Quintana, Noelia Bernardo-García, Jonathan Martínez-Fábregas, Francisco Rivero-Rodríguez, Miguel Á. Casado-Combreras, Carlos A. Elena-Real, Alejandro Velázquez-Cruz, Sergio Gil-Caballero, Adrián Velázquez-Campoy, Elzbieta Szulc, María P. Gavilán, Isabel Ayala, Rocío Arranz, Rosa M. Ríos, Xavier Salvatella, José M. Valpuesta, Juan A. Hermoso, Miguel A. De la Rosa, Irene Díaz-Moreno, Scientific Research Centre 'Isla de la Cartuja' (cicCartuja), Universidad de Sevilla / University of Sevilla, Université Paris-Saclay, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Dundee, 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), Unidad Asociada IQFR-CSIC-BIFI [Zaragoza, Spain], University of Zaragoza - Universidad de Zaragoza [Zaragoza]-Instituto de Biocomputación y Física de Sistemas Complejos - BIFI [Zaragoza, Spain], The Barcelona Institute of Science and Technology, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Consejo Superior de Investigaciones Científicas (CSIC), Institute of Physical Chemistry Rocasolano (IQFR), Instituto de Investigaciones Químicas (IIQ), Universidad de Sevilla / University of Sevilla-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Horizon 2020 program of the European Commission,Cámara Foundation (C.A.E.R.´s fellowship), European Regional Development Fund Regional Development Fund (FEDER), European Project: 648201,H2020,ERC-2014-CoG,CONCERT(2015), Universidad de Sevilla, ALBA Synchrotron, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Junta de Andalucía, European Commission, Fundación Ramón Areces, Ministerio de Educación, Cultura y Deporte (España), Fundación 'la Caixa', Fundación Científica Asociación Española Contra el Cáncer, González-Arzola, Katiuska, Díaz-Quintana, Antonio, Martínez-Fábregas, Jonathan, Casado-Combreras, Miguel Á., Velázquez-Cruz, Alejandro, Velázquez-Campoy, Adrián, Gavilán, María P., Arranz, Rocío, Salvatella, Xavier, Valpuesta, José M., Hermoso, Juan A., Rosa, Miguel A. de la, and Díaz-Moreno, Irene
Subjects: MESH: Caspases, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Mitochondria, Lysine, Tumor Suppressor Proteins, MESH: Arginine, Cytochromes c, Nuclear Proteins, MESH: Nucleophosmin, MESH: Cytochromes c, Arginine, Mitochondria, Structural Biology, Caspases, MESH: Lysine, MESH: Tumor Suppressor Proteins, Molecular Biology, MESH: Nuclear Proteins, Nucleophosmin
Abstract: 32 pags., 17 figs., 1 tab., The regular functioning of the nucleolus and nucleus-mitochondria crosstalk are considered unrelated processes, yet cytochrome c (Cc) migrates to the nucleus and even the nucleolus under stress conditions. Nucleolar liquid-liquid phase separation usually serves the cell as a fast, smart mechanism to control the spatial localization and trafficking of nuclear proteins. Actually, the alternative reading frame (ARF), a tumor suppressor protein sequestered by nucleophosmin (NPM) in the nucleoli, is shifted out from NPM upon DNA damage. DNA damage also triggers early translocation of respiratory Cc to nucleus before cytoplasmic caspase activation. Here, we show that Cc can bind to nucleolar NPM by triggering an extended-to-compact conformational change, driving ARF release. Such a NPM-Cc nucleolar interaction can be extended to a general mechanism for DNA damage in which the lysine-rich regions of Cc-rather than the canonical, arginine-rich stretches of membrane-less organelle components-controls the trafficking and availability of nucleolar proteins., We thank the staf at the NMR facility at CITIUS (University of Seville), the microscopy facility at CABIMER (Seville) and the ALBA Synchrotron (Barcelona). We are grateful to the Spanish Government (grant nos. PID2021-126663NB-I00, PGC2018-096049-B-I00/FEDER, BIO2015-70092-R, BFU2015-71017/BMC, BFU2016-75984/BMC, PID2019-105872GB and BFU2017-90030-P, FEDER/Ministerio de Ciencia e Innovación–Agencia Estatal de Investigación), European Regional Development Fund (FEDER), the Regional Government of Andalusia (grant nos. BIO-198; US-1254317, US-1257019, P18-FR-3487 and P18-HO-4091, US/JUNTA/FEDER, UE), the European Commission: European Regional Development Fund and European Research Council (CONCERT, contract number 648201) and the Ramón Areces Foundation. This work has been supported by Infrastructure for NMR, EM and X-rays for Translational Research (iNEXT, grant no. PID 3407) funded by the Horizon 2020 program of the European Commission, Cámara Foundation (C.A.E.R.´s fellowship), the Spanish Ministry of Education, Culture and Sports (grant nos. FPU18/06577, FPU16/01513 and FPU013/04373; M.A.C.-C., A.V.-C. and F.R.-R.’s fellowships, respectively), La Caixa Foundation (E.S.’s fellowship), Severo Ochoa Award of Excellence from MINECO (Government of Spain, IRB Barcelona and CNB Madrid) and the Spanish Association Against Cancer Scientific Foundation (FC AECC, M.P.G.’s postdoctoral grant)
Published: 2021

17. Towards the sustainable discovery and development of new antibiotics

Author: Ian H. Gilbert, Kenneth Pfarr, Timo Jaeger, Mika Lindvall, Anders Karlén, Philippe Glaser, Jennifer Herrmann, Marco Pieroni, Bertrand Aigle, Evi Stegmann, Heather Graz, Andrea Schiefer, Jean-Luc Pernodet, Thomas Hesterkamp, Rui Moreira, Heike Brötz-Oesterhelt, Andrew W. Truman, Andreas Keller, Ludovic Halby, Alexander Titz, José R. Tormo, Michael Graz, Kira J. Weissman, Olga Genilloud, Marc Stadler, Claus-Michael Lehr, Paola B. Arimondo, Mark Brönstrup, Savithri Ramurthy, Eriko Takano, Frédéric Peyrane, Mathias Winterhalter, Marnix H. Medema, Maarten van Dongen, Anna K. H. Hirsch, Achim Hoerauf, Helge B. Bode, Laurent Fraisse, Laura J. V. Piddock, Martin Empting, Brigitta Loretz, Yanyan Li, Heinz E. Moser, Tilmann Weber, Marcus Miethke, Silke Alt, Stefano Sabatini, Wolfgang Wohlleben, Peter Hammann, Stefano Donadio, Andriy Luzhetskyy, Myriam Seemann, Rolf Müller, Hrvoje Petković, Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Helmholtz-Zentrum für Infektionsforschung GmbH (HZI), Universität des Saarlandes [Saarbrücken], German Centre for Infection Research (DZIF), University of Parma = Università degli studi di Parma [Parme, Italie], Technical University of Denmark [Lyngby] (DTU), Justus-Liebig-Universität Gießen (JLU), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Dynamique des Génomes et Adaptation Microbienne (DynAMic), Université de Lorraine (UL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Goethe-Universität Frankfurt am Main, Max Planck Institute for Terrestrial Microbiology, Max-Planck-Gesellschaft, Universidade de Lisboa (ULISBOA), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Wageningen University and Research [Wageningen] (WUR), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Fundación MEDINA, John Innes Centre [Norwich], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), University of Manchester [Manchester], Università degli Studi di Perugia (UNIPG), University of Tübingen, Jacobs University [Bremen], University Hospital Bonn, Biophys [Usk, UK], University of Bristol [Bristol], Recursion [Salt Lake City, UT], HiberCell [New York], Uppsala Universitet [Uppsala], AMR Insights, University of Ljubljana, BEAM Alliance, Naicons, Drugs for Neglected Diseases Initiative, Global Antibiotic Research and Development Partnership [Geneva, Switzerland] (GARDP), University of Dundee, Novartis Institutes for BioMedical Research (NIBR), The project on PqsR pathoblocker development acknowledges funding through the German Center for Infection Research (DZIF, projects TTU09.908 and TTU09.916), the Helmholtz Association (Helmholtz Validation Fund) and additional contributions by the associated academic institutes (HZI and HIPS). The development of chelocardins is supported by the DZIF (TTU09.814/09.821), the Helmholtz Innovation Fund (Pre-4D), by the Slovenian Research Agency, ARRS, grant no. J4-8226, and in collaboration with AciesBio, Slovenia. The corallopyronin project is funded by the DZIF (TTU09.807/09.816, TTU09.914), the German Federal Ministry of Education and Research (BMBF), the federal state of North Rhine-Westphalia (EFRE.NRW) and EU Horizon 2020. Eriko Takano was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 720793 'TOPCAPI: Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients'., European Project: 720793,H2020-EU.2.1.4.,TOPCAPI(2017), Università degli studi di Parma = University of Parma (UNIPR), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Écologie et Évolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidade de Lisboa = University of Lisbon (ULISBOA), Fundación MEDINA [Granada], Biotechnology and Biological Sciences Research Council (BBSRC), Università degli Studi di Perugia = University of Perugia (UNIPG), and Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, 030306 microbiology, Bioinformatics, General Chemical Engineering, [SDV]Life Sciences [q-bio], General Chemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Investment (macroeconomics), 3. Good health, 03 medical and health sciences, Roadmap, Risk analysis (engineering), 13. Climate action, Order (exchange), Blueprint, ddc:570, Business strategy in drug development, Bioinformatica, Life Science, ddc:610, Business, Drug therapy, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: An ever-increasing demand for novel antimicrobials to treat life-threatening infections caused by the global spread of multidrug-resistant bacterial pathogens stands in stark contrast to the current level of investment in their development, particularly in the fields of natural-product-derived and synthetic small molecules. New agents displaying innovative chemistry and modes of action are desperately needed worldwide to tackle the public health menace posed by antimicrobial resistance. Here, our consortium presents a strategic blueprint to substantially improve our ability to discover and develop new antibiotics. We propose both short-term and long-term solutions to overcome the most urgent limitations in the various sectors of research and funding, aiming to bridge the gap between academic, industrial and political stakeholders, and to unite interdisciplinary expertise in order to efficiently fuel the translational pipeline for the benefit of future generations., Antimicrobial resistance is an increasing threat to public health and encouraging the development of new antimicrobials is one of the most important ways to address the problem. This Roadmap article aims to bring together industrial, academic and political partners, and proposes both short-term and long-term solutions to this challenge.
Published: 2021

18. Collective Cell Migration in a Fibrous Environment: A Hybrid Multiscale Modelling Approach

Author: Szabolcs Suveges, Ibrahim Chamseddine, Katarzyna A. Rejniak, Raluca Eftimie, Dumitru Trucu, University of Dundee, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida [Tampa] (USF), Laboratoire de Mathématiques de Besançon (UMR 6623) (LMB), Université de Bourgogne (UB)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Statistics and Probability, multi-scale hybrid mathematical model, Materials science, cell migration, [SDV.CAN]Life Sciences [q-bio]/Cancer, continuous cell-extracellular matrix interactions, QA273-280, Article, numerical simulations, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Collagen fibres, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [NLIN]Nonlinear Sciences [physics], [MATH]Mathematics [math], T57-57.97, Applied mathematics. Quantitative methods, Applied Mathematics, Collective cell migration, Cell migration, Tumour invasion, Collagen fibre, 030104 developmental biology, orientation of extracellular matrix fibres, agent based discrete cell-cell interactions, Continuous field, Biological system, Probabilities. Mathematical statistics, 030217 neurology & neurosurgery
Abstract: International audience; The specific structure of the extracellular matrix (ECM), and in particular the density and orientation of collagen fibres, plays an important role in the evolution of solid cancers. While many experimental studies discussed the role of ECM in individual and collective cell migration, there are still unanswered questions about the impact of nonlocal cell sensing of other cells on the overall shape of tumour aggregation and its migration type. There are also unanswered questions about the migration and spread of tumour that arises at the boundary between different tissues with different collagen fibre orientations. To address these questions, in this study we develop a hybrid multi-scale model that considers the cells as individual entities and ECM as a continuous field. The numerical simulations obtained through this model match experimental observations, confirming that tumour aggregations are not moving if the ECM fibres are distributed randomly, and they only move when the ECM fibres are highly aligned. Moreover, the stationary tumour aggregations can have circular shapes or irregular shapes (with finger-like protrusions), while the moving tumour aggregations have elongate shapes (resembling to clusters, strands or files). We also show that the cell sensing radius impacts tumour shape only when there is a low ratio of fibre to non-fibre ECM components. Finally, we investigate the impact of different ECM fibre orientations corresponding to different tissues, on the overall tumour invasion of these neighbouring tissues.
Published: 2021

19. Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer

Author: Flora Nguyen Van Long, Audrey Lardy-Cleaud, Dimitri Carène, Caroline Rossoni, Frédéric Catez, Paul Rollet, Nathalie Pion, Déborah Monchiet, Agathe Dolbeau, Marjorie Martin, Valentin Simioni, Susan Bray, Doris Le Beherec, Fernanda Mosele, Ibrahim Bouakka, Amélie Colombe-Vermorel, Laetitia Odeyer, Alexandra Diot, Lee B. Jordan, Alastair M. Thompson, Françoise Jamen, Thierry Dubois, Sylvie Chabaud, Stefan Michiels, Isabelle Treilleux, Jean-Christophe Bourdon, David Pérol, Alain Puisieux, Fabrice André, Jean-Jacques Diaz, Virginie Marcel, Malbec, Odile, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Développement Cancer et Thérapies Ciblées [Lyon] (LabEx DEVweCAN), Université de Lyon, 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), Institut Gustave Roussy (IGR), Ninewells Hospital and Medical School [Dundee], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Dundee, Baylor College of Medicine (BCM), Baylor University, Complexité, Innovation, Activités Motrices et Sportives (CIAMS), Université d'Orléans (UO)-Université Paris-Saclay, Département de Recherche Translationnelle, Institut Curie [Paris], Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Direction de la recherche [Gustave Roussy], Département de médecine oncologique, and CRLCC Paul Strauss
Subjects: Cancer Research, rRNA 2’O-ribose methylation complex, Chromosomal Proteins, Non-Histone, [SDV]Life Sciences [q-bio], Breast Neoplasms, AgNOR, [SDV] Life Sciences [q-bio], Breast cancer, Fibrillarin, Oncology, Ribosome biogenesis, Genetics, Humans, Female, RNA, Messenger, Ribosomes, Biomarkers
Abstract: Background A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated. Methods Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours. Results We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct. Conclusion Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.
Published: 2021

20. ONTOLOGY-BASED WEB TOOLS FOR RETRIEVING PHOTOGRAMMETRIC CULTURAL HERITAGE MODELS

Author: Erica Nocerino, Filipe Castro, Odile Papini, Jean-Philip Royer, Timmy Gambin, Kari Hyttinen, Djamal Merad, Mohamad Motasem Nawaf, Pierre Drap, M. Ben Ellefi, Jean-Christophe Sourisseau, Laboratoire d'Informatique et Systèmes (LIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles (I&M), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Centre Camille Jullian - Histoire et archéologie de la Méditerranée et de l'Afrique du Nord de la protohistoire à la fin de l'Antiquité (CCJ), Aix Marseille Université (AMU)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), University of Dundee, University of Malta [Malta], and Texas A&M University System
Subjects: lcsh:Applied optics. Photonics, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Domain Knowledge, Computer science, Interoperability, Cultural Heritage, 02 engineering and technology, Ontology (information science), lcsh:Technology, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], World Wide Web, Software, Ontologies, 0202 electrical engineering, electronic engineering, information engineering, [INFO]Computer Science [cs], [SHS.CLASS]Humanities and Social Sciences/Classical studies, Semantic Web, ComputingMilieux_MISCELLANEOUS, lcsh:T, business.industry, 05 social sciences, lcsh:TA1501-1820, 020207 software engineering, [SHS.ART]Humanities and Social Sciences/Art and art history, Visualization, Cultural heritage, Photogrammetry, lcsh:TA1-2040, Ontology, Domain knowledge, 0509 other social sciences, lcsh:Engineering (General). Civil engineering (General), [SHS.HIST]Humanities and Social Sciences/History, 050904 information & library sciences, business
Abstract: A key challenge in cultural heritage (CH) sites visualization is to provide models and tools that effectively integrate the content of a CH data with domain-specific knowledge so that the users can query, interpret and consume the visualized information. Moreover, it is important that the intelligent visualization systems are interoperable in the semantic web environment and thus, capable of establishing a methodology to acquire, integrate, analyze, generate and share numeric contents and associated knowledge in human and machine-readable Web. In this paper, we present a model, a methodology and a software Web-tools that support the coupling of the 2D/3D Web representation with the knowledge graph database of Xlendi shipwreck. The Web visualization tools and the knowledge-based techniques are married into a photogrammetry driven ontological model while at the same time, user-friendly web tools for querying and semantic consumption of the shipwreck information are introduced.
Published: 2019

21. Spatio-Genetic and phenotypic modelling elucidates resistance and re-sensitisation to treatment in heterogeneous melanoma

Author: Ovidiu Radulescu, Dumitru Trucu, Laurent Le Cam, Arran Hodgkinson, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and University of Dundee
Subjects: 0301 basic medicine, Statistics and Probability, Drug, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Systems biology, media_common.quotation_subject, Cell, Population, Context (language use), Drug resistance, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, education, Melanoma, Protein Kinase Inhibitors, 030304 developmental biology, media_common, 0303 health sciences, education.field_of_study, General Immunology and Microbiology, Applied Mathematics, General Medicine, Immunotherapy, medicine.disease, Phenotype, 3. Good health, medicine.anatomical_structure, 030104 developmental biology, 030220 oncology & carcinogenesis, Modeling and Simulation, Mutation, Cancer research, Neoplasm Recurrence, Local, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery
Abstract: Although novel targeted therapies have significantly improved the overall survival of patients with advanced melanoma, understanding and combatting drug resistance remains a major clinical challenge. Using partial differential equations, we describe the evolution of a cellular population through time, space, and phenotype dimensions, in the presence of various drug species. We then use this framework to explore models in which resistance is attained by either mutations (irreversible) or plasticity (reversible). Numerical results suggest that punctuated evolutionary assumptions are more consistent with results obtained from murine melanoma models than gradual evolution. Furthermore, in the context of an evolving tumour cell population, sequencing the treatment, for instance applying immunotherapy before BRAF inhibitors, can increase treatment effectiveness. However, drug strategies which showed success within a spatially homogeneous tumour environment were unsuccessful under heterogeneous conditions, suggesting that spatio-environmental heterogeneity may be the greatest challenge to tumour therapies. Plastic metabolic models are additionally capable of reproducing the characteristic resistant tumour volume curves and predicting re-sensitisation to secondary waves of treatment observed in patient derived xenograft (PDX) melanomas treated with MEK and BRAF inhibitors. Nevertheless, secondary relapse due to a pre-adapted subpopulation, remaining after the first wave of treatment, results in a more rapid development of resistance. Our model provides a framework through which tumour resistance can be understood and would suggest that carefully phased treatments may be able to overcome the development of long-term resistance in melanoma.
Published: 2019

22. Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability

Author: Philippe M. Campeau, Katherine Agre, Vernon R. Sutton, Kirsty McWalter, Bertrand Isidor, Øystein L. Holla, Anna Lehman, Megha Desai, Jonathan Berg, Stéphane Bézieau, Rolph Pfundt, Jennifer Tarpinian, Jennifer B. Humberson, Holly A.F. Stessman, Madeleine R. Geisheker, Emma Bedoukian, Shalini N. Jhangiani, Marine I. Murphree, Annapurna Poduri, Anne-Sophie Denommé-Pichon, Christian Gilissen, Yaping Yang, Eliane Beauregard-Lacroix, Claude Férec, Francesca Filippini, Anne Guimier, Daryl A. Scott, Stephen Sanders, Julie C. Sapp, Ralitza H. Gavrilova, Slavé Petrovski, Ann Nordgren, Sylvia Redon, Ernie M.H.F. Bongers, Shelagh Joss, Jill A. Rosenfeld, Wallid Deb, Ingrid M. Wentzensen, Usha Kini, Vandana Shashi, Mindy H. Li, Stanislas Lyonnet, Thomas Garcia, Øyvind L. Busk, Christoffer Nellåker, Amber Begtrup, Brigitte Gilbert-Dussardier, Thomas Besnard, Francois V. Bolduc, Patrick R. Blackburn, Justine Rousseau, Frédéric Bilan, Eric W. Klee, Christopher T. Gordon, Pavel N. Pichurin, Peggy Kulch, Kevin P. Lally, Laurie Robak, Arnaud Picard, Kristian Tveten, Meredith Park, Sébastien Küry, Jaya Punetha, Moira Blyth, Asbjørg Stray-Pedersen, Jacqueline Harris, Erin L. Heinzen, Nicholas Stong, Cara M. Skraban, Julie S. Cohen, Aida Telegrafi, Xenia Latypova, Zeynep Coban Akdemir, Jacob Zyskind, Caitlin Troyer, Xiang-Jiao Yang, Tuula Rinne, Leslie G. Biesecker, Jennifer E. Posey, Kyle Retterer, Jeanne Amiel, Rui Xiao, Magnus Nordenskjöld, Tammie Dewan, Jennifer A. Sullivan, Charlotte von der Lippe, Evan E. Eichler, Anna Lindstrand, Dominique Bonneau, Yuri A. Zarate, Elaine H. Zackai, Fayth M. Kalb, Daniel H. Lowenstein, Shiri Avni, Benjamin Cogné, Jennifer J. Johnston, Kerri H. Whitlock, Catherine Shain, Séverine Audebert-Bellanger, Malin Kvarnung, Oana Caluseriu, David Goldstein, Annick Toutain, Andres Hernandez-Garcia, Brina Daniels, Sophie Ehresmann, James R. Lupski, Julie McGaughran, Ashley H Ebanks, Kévin Uguen, Marine Legendre, Sylvie Odent, Richard Redon, Erica H. Gerkes, Xiaofei Song, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Sainte Justine [Montréal], Université du Québec à Montréal = University of Québec in Montréal (UQAM), University of Oxford [Oxford], GeneDx [Gaithersburg, MD, USA], Mayo Clinic [Rochester], University of California [San Francisco] (UCSF), University of California, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang Bretagne, EFS, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Johns Hopkins University School of Medicine [Baltimore], Kennedy Krieger Institute [Baltimore], Chapel Allerton Hospital, University of British Columbia (UBC), University of Dundee, Rush University Medical Center [Chicago], Oxford University Hospitals NHS Trust, Queen Elizabeth University Hospital (Glasgow), Trondheim University, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Virginia [Charlottesville], Texas Children's Hospital [Houston, USA], Baylor College of Medicine (BCM), Baylor University, University of Pennsylvania [Philadelphia], National Human Genome Research Institute (NHGRI), Harvard Medical School [Boston] (HMS), Karolinska University Hospital [Stockholm], Duke University Medical Center, University of Groningen [Groningen], University of Arkansas for Medical Sciences (UAMS), McGovern Medical School [Houston, Texas], The University of Texas Health Science Center at Houston (UTHealth), Phoenix Children's Hospital, Columbia University [New York], University of Southern Queensland (USQ), Telemark Hospital Trust [Skien, Norway], University of Washington [Seattle], Oslo University Hospital [Oslo], Children’s Hospital of Philadelphia (CHOP ), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud University Medical Center [Nijmegen], Ann & Robert H. Lurie Children's Hospital of Chicago, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Centre de référence Maladies Rares CLAD-Ouest [Rennes], Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of Alberta, Boston Children's Hospital, McGill University Health Center [Montreal] (MUHC), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Creighton University Medical School [Omaha, NE, USA], Howard Hughes Medical Institute [Boston] (HHMI), Howard Hughes Medical Institute (HHMI)-Harvard Medical School [Boston] (HMS), National Institute of Neurological Disorders and Stroke, K08 HG008986, National Human Genome Research Institute, BC Children’s Hospital Foundation, Genome British Columbia, Fonds de Recherche du Québec - Santé, Canadian Institutes of Health Research, Center for Individualized Medicine, Mayo Clinic, Health Regional Agency from Poitou-Charentes, French Ministry of Health, RC14_0107, HUGODIMS, NS053998, The Epilepsy Phenome/Genome Project, NS077303, Epi4K, Duke Genome Sequencing Clinic, NINDS R35 NS105078, National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, HG200328 12, intramural research program of the NHGRI, Dart NeuroScience, Kids Brain Health Network, Mining for Miracles, UM1 HG006542, National Heart, Lung, and Blood Institute, CIM Investigative and Functional Genomics Program, R01MH101221, National Institute of Mental Health, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Virginia, University of Pennsylvania, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), CCSD, Accord Elsevier, Faculteit Medische Wetenschappen/UMCG, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: CHROMATIN, Male, 0301 basic medicine, Autism, Sequence Homology, [SDV.GEN] Life Sciences [q-bio]/Genetics, Medical and Health Sciences, 0302 clinical medicine, SCHIZOPHRENIA, Gene expression, 2.1 Biological and endogenous factors, Missense mutation, Aetiology, Child, de novo variants, Genetics (clinical), Pediatric, Genetics & Heredity, Genetics, biology, neurodevelopmental disorders, histone acetylation, Adaptor Proteins, Nuclear Proteins, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Syndrome, Biological Sciences, Prognosis, Phenotype, Chromatin, Mental Health, Histone, intellectual disability, Child, Preschool, Female, REGULATOR, congenital malformations, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], BRAIN-DEVELOPMENT, Adult, Adolescent, Histone acetyltransferase complex, Intellectual and Developmental Disabilities (IDD), Mutation, Missense, Deciphering Developmental Disorders study, autism spectrum disorder, KAT6B, RNAI SCREEN, Young Adult, 03 medical and health sciences, CAUSES Study, Rare Diseases, Intellectual Disability, Report, COFACTOR, medicine, RUBINSTEIN-TAYBI-SYNDROME, Humans, Amino Acid Sequence, Autistic Disorder, Preschool, Gene, Genetic Association Studies, Adaptor Proteins, Signal Transducing, [SDV.GEN]Life Sciences [q-bio]/Genetics, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Rubinstein–Taybi syndrome, Signal Transducing, Neurosciences, Infant, medicine.disease, TRRAP, Brain Disorders, SELF-RENEWAL, 030104 developmental biology, DE-NOVO MUTATIONS, Mutation, biology.protein, Missense, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 202928.pdf (Publisher’s version ) (Open Access) Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.
Published: 2019

23. Photochemistry and Photobiology

Author: Farley S.J., Salassa L., Pizarro A.M., Sadler P.J. and 'We thank the MRC (grant number G0701062), EPSRC (grant numbers EP/G006792 and EP/F034210/1) and EU FP7 (grant number 20377',' MC fellowship for LS). LS acknowledges the Severo Ochoa Centres of Excellence Program of the Spanish State Research Agency (grant number CEX2018‐000867‐S',' DIPC) for funding and the Spanish Multi‐MetDrugs network (RED2018‐102471‐T) for fruitful discussion. AMP acknowledges funding from the MINECO of Spain (SEV‐2016‐0686 and CTQ2017‐84932‐P). We also thank Dr Julie Woods and Kim Robinson (University of Dundee) for phototoxicity testing, and Dr Lijiang Song and Dr Ivan Prokes (University of Warwick) for help with MS and NMR, respectively.'
Published: 2021

24. What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?

Author: Louisa Flander, Evelien Dekker, Berit Andersen, Mette Bach Larsen, Robert J Steele, Nea Malila, Tytti Sarkeala, Manon van der Vlugt, Clasine de Klerk, Bart Knottnerus, Lucinda Bertels, Anke Woudstra, Manon C.W. Spaander, Mirjam Fransen, Sirpa Heinavaara, Mary Dillon, Driss Ait Ouakrim, Mark Jenkins, University of Melbourne, Amsterdam UMC, Aarhus University, University of Dundee, Finnish Cancer Registry, Netherlands Institute for Health Services Research, Erasmus University Rotterdam, Vrije Universiteit Amsterdam, University of Amsterdam, Department of Information and Service Management, Aalto-yliopisto, Aalto University, Gastroenterology and hepatology, Public and occupational health, Gastroenterology and Hepatology, CCA - Cancer Treatment and Quality of Life, CCA - Imaging and biomarkers, Amsterdam Gastroenterology Endocrinology Metabolism, General practice, ACS - Heart failure & arrhythmias, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Quality of Care, APH - Global Health, Socio-Medical Sciences (SMS), and Gastroenterology & Hepatology
Subjects: Male, screening, Australia, population, colorectal cancer, Hematology, General Medicine, SDG 3 - Good Health and Well-being, Oncology, Occult Blood, Humans, Mass Screening, Female, epidemiology, helth care, Colorectal Neoplasms, Early Detection of Cancer
Abstract: Funding Information: This work was supported by the University of Melbourne, Melbourne School of Population and Global Health, Human Ethics Advisory Group. Project title: “Consultation to understand international differences in bowel cancer screening participation,” ID 2057312.1 Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Engagement Research Funding from the Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia. Publisher Copyright: © The Author(s) 2022. Background: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia’s CRC incidence and mortality are among the world’s highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation. Methods: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening. Results: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features. Conclusions: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation. Impact: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.
Published: 2022

25. Discovery of a new sialic acid binding region that regulates Siglec-7

Author: Gérard Vergoten, Chihiro Sato, Atsushi Yoshimura, Kana Matsumoto, Yu Yasuda, Paul R. Crocker, Shinya Hanashima, Yuji Nishiura, Ami Goshima, Ken Kitajima, Takashi Takahashi, Nao Yamakawa, Yoshiki Yamaguchi, Hiroshi Tanaka, Nagoya University, 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), University of Dundee, Tokyo Institute of Technology [Tokyo] (TITECH), Osaka University [Osaka], Nagoya Institute of Technology (NIT), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Tokyo Institute of Technology [Tokyo] [TITECH], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Glycoconjugate, [SDV]Life Sciences [q-bio], In silico, Sialic Acid Binding Ig-like Lectin 3, Molecular Conformation, Glycobiology, Antigens, Differentiation, Myelomonocytic, lcsh:Medicine, Sialic acid binding, Monocytes, Article, 03 medical and health sciences, 0302 clinical medicine, Gangliosides, Lectins, Humans, Amino Acid Sequence, lcsh:Science, chemistry.chemical_classification, Binding Sites, Multidisciplinary, Ganglioside, lcsh:R, Mutagenesis, SIGLEC, respiratory system, 3. Good health, Cell biology, Killer Cells, Natural, Molecular Docking Simulation, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Mutagenesis, Site-Directed, Sialic Acids, lcsh:Q, Glycoconjugates, Function (biology)
Abstract: Siglec-7 is a human CD33-like siglec, and is localised predominantly on human natural killer (NK) cells and monocytes. Siglec-7 is considered to function as an immunoreceptor in a sialic acid-dependent manner. However, the underlying mechanisms linking sialic acid-binding and function remain unknown. Here, to gain new insights into the ligand-binding properties of Siglec-7, we carried out in silico analysis and site-directed mutagenesis, and found a new sialic acid-binding region (site 2 containing R67) in addition to the well-known primary ligand-binding region (site 1 containing R124). This was supported by equilibrium dialysis, STD-NMR experiments, and inhibition analysis of GD3-binding toward Siglec-7 using synthetic sialoglycoconjugates and a comprehensive set of ganglioside-based glycoconjugates. Our results suggest that the two ligand-binding sites are potentially controlled by each other due to the flexible conformation of the C-C′ loop of Siglec-7.
Published: 2020

26. Psychosocial risk factors for suicidality in children and adolescents

Author: Celso Arango, David Coghill, Juan J. Carballo, Diane Purper-Ouakil, Kate Lievesley, Alessandro Zuddas, Paramala Santosh, Ralf W. Dittmann, Itziar Flamarique, Josefina Castro-Fornieles, Cloe Llorente, L. Kehrmann, Jan K. Buitelaar, Pieter J. Hoekstra, U. Schulze, Hospital General Universitario 'Gregorio Marañón' [Madrid], Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain., Universita degli Studi di Cagliari [Cagliari], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Groningen [Groningen], Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, Murdoch Children's Research Institute (MCRI), University of Dundee, Universitätsklinikum Ulm - University Hospital of Ulm, Medical Faculty [Mannheim], Radboud University Nijmegen Medical Centre and Karakter, Child and Adolescent Psychiatry University Centre Nijmegen, Child and Adolescent Psychiatry and Psychology Department, Neurosciences Institute, Hospital Clinic Barcelona, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, NHS Foundation Trust [London], The Royal Marsden, HealthTracker Ltd, Centre for Interventional Paediatric Psychopharmacology, and Great Ormond Street Hospital for Children [London] (GOSH)
Subjects: Male, SYMPTOMS, Youth, Poison control, Review, Suicidality, Adolescents, Suicide prevention, Resiliència (Tret de la personalitat), 0302 clinical medicine, Risk Factors, Developmental and Educational Psychology, Child and adolescent psychiatry, Psychology, Prospective Studies, Suïcidi, PREDICTORS, Child, Children, ASSOCIATIONS, 05 social sciences, DELIBERATE SELF-HARM, Human factors and ergonomics, General Medicine, DEPRESSION, Neuroticism, 3. Good health, Psychiatry and Mental health, Suicide, [SCCO.PSYC]Cognitive science/Psychology, Anxiety, ATTEMPTERS, Female, medicine.symptom, Resilience (Personality trait), Psychosocial, 050104 developmental & child psychology, Clinical psychology, Risk, medicine.medical_specialty, Adolescent, MESH: Prospective studies, Suicide / psychology, BEHAVIORS, Teenagers, EVENTS, 03 medical and health sciences, medicine, Humans, 0501 psychology and cognitive sciences, IDEATION, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Suicide attempt, Resilience, Questionnaire, [SCCO.NEUR]Cognitive science/Neuroscience, 030227 psychiatry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Pediatrics, Perinatology and Child Health, Web-based
Abstract: Suicidality in childhood and adolescence is of increasing concern. The aim of this paper was to review the published literature identifying key psychosocial risk factors for suicidality in the paediatric population. A systematic two-step search was carried out following the PRISMA statement guidelines, using the terms ‘suicidality, suicide, and self-harm’ combined with terms ‘infant, child, adolescent’ according to the US National Library of Medicine and the National Institutes of Health classification of ages. Forty-four studies were included in the qualitative synthesis. The review identified three main factors that appear to increase the risk of suicidality: psychological factors (depression, anxiety, previous suicide attempt, drug and alcohol use, and other comorbid psychiatric disorders); stressful life events (family problems and peer conflicts); and personality traits (such as neuroticism and impulsivity). The evidence highlights the complexity of suicidality and points towards an interaction of factors contributing to suicidal behaviour. More information is needed to understand the complex relationship between risk factors for suicidality. Prospective studies with adequate sample sizes are needed to investigate these multiple variables of risk concurrently and over time.
Published: 2020

27. Mild Stress Conditions during Laboratory Culture Promote the Proliferation of Mutations That Negatively Affect Sigma B Activity in Listeria monocytogenes

Author: Teresa Tiensuu, Diana Gudynaite, Aoife Boyd, Francisco García-del Portillo, Duarte N. Guerreiro, Jialun Wu, Catarina M. Marinho, Jörgen Johansson, Ana H. Oliveira, Charlotte Dessaux, Conor P. O'Byrne, Bacterial Stress Response Group, Microbiology, School of Natural Sciences, National University of Ireland Galway, H91 TK33, Ireland, Laboratory of Intracellular Bacterial Pathogens, National Center for Biotechnology (CNB)-CSIC, Madrid-Spain, Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå Centre of Microbial Research, Umeå, Sweden, Molecular Microbiology Department, School of Life Sciences, University of Dundee, Agroécologie [Dijon], Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pathogenic Mechanisms Research Group, National University of Ireland Galway, Ireland, European Commission, and Department of Agriculture, Food and Marine (Ireland)
Subjects: Transposable element, Operon, Mutant, Population, Sigma Factor, Biology, Stress, Microbiology, 03 medical and health sciences, Bacterial Proteins, Stress, Physiological, sigma B, Sigma factor, education, sigB, Molecular Biology, Gene, 030304 developmental biology, 2. Zero hunger, Genetics, 0303 health sciences, education.field_of_study, Competition, 030306 microbiology, Wild type, Gene Expression Regulation, Bacterial, Listeria monocytogenes, Stop codon, Kinetics, Mutation, [SDE]Environmental Sciences, rsbU, rsbT, rsbS, Mutations, Research Article
Abstract: In Listeria monocytogenes, the full details of how stress signals are integrated into the σB regulatory pathway are not yet available. To help shed light on this question, we investigated a collection of transposon mutants that were predicted to have compromised activity of the alternative sigma factor B (σB). These mutants were tested for acid tolerance, a trait that is known to be under σB regulation, and they were found to display increased acid sensitivity, similar to a mutant lacking σB (ΔsigB). The transposon insertions were confirmed by whole-genome sequencing, but in each case, the strains were also found to carry a frameshift mutation in the sigB operon. The changes were predicted to result in premature stop codons, with negative consequences for σB activation, independently of the transposon location. Reduced σB activation in these mutants was confirmed. Growth measurements under conditions similar to those used during the construction of the transposon library revealed that the frameshifted sigB operon alleles conferred a growth advantage at higher temperatures, during late exponential phase. Mixed-culture experiments at 42°C demonstrated that the loss of σB activity allowed mutants to take over a population of parental bacteria. Together, our results suggest that mutations affecting σB activity can arise during laboratory culture because of the growth advantage conferred by these mutations under mild stress conditions. The data highlight the significant cost of stress protection in this foodborne pathogen and emphasize the need for whole-genome sequence analysis of newly constructed strains to confirm the expected genotype., This project has received funding from the European Union’s Horizon 2020 research-and-innovation program under Marie Skłodowska-Curie grant agreement no. 721456. Jialun Wu was funded by the Department of Agriculture, Food and the Marine (17/F/244).
Published: 2020
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28. Reflective Coloration from Structural Plasmonic to Disordered Polarizonic

Author: Shahin Homaeigohar, Mhd Adel Assad, Mady Elbahri, Nanochemistry and Nanoengineering, University of Dundee, Department of Chemistry and Materials Science, Aalto-yliopisto, and Aalto University
Subjects: Materials science, metallic nanostructures, Metallic nanostructures, reflective coloration, Nanotechnology, QC350-467, General Medicine, Optics. Light, TA1501-1820, polarizonic, Applied optics. Photonics, metallic nanocomposites, Plasmon, plasmonic
Abstract: M.E. and MA.A. thank the School of Chemical Engineering at the Aalto University, Finland, for the starting fund; in addition, M.E. gratefully acknowledges the Nanochromic ASCI project funded by Aalto University and the Bioshell project funded by the Academy of Finland (Decision No. 296636). The authors gratefully acknowledge Prof. Mehdi Hedayati for his fruitful discussions and comments. Correction added after publication, 7 July 2021: The order of the authors was corrected. The generation of pigment-free colors by nanostructures and subwavelength patterns has evolved in the last decade and outperformed the conventional paints in terms of durability, recyclability, and environmental friendliness. The recent progress in the field of structural coloration, particularly reflective coloration, offering a full-color gamut, has realized high-resolution printing, not attainable by the pigment paints. Herein, an overview of the various systems able to offer reflective coloration for a variety of optical applications with static and dynamic responses is presented. Specifically, an emphasis is given to recent works of the article's authors on the cooperative action of the disordered particles and dipoles that can generate specular reflective colors. In addition, further developments of reflective color nanosystems are discussed. In the first section, an overview of the recent progress in the field of plasmonic reflective structural coloration is provided. The second part of the article deals with the authors’ latest findings with respect to polarizonic color generation and its implementation in various areas ranging from environmental detection and biosensing to colored solar perfect absorbers. The report is wrapped up with an outlook and summary.
Published: 2021

29. Rewards that are near increase impulsive action

Author: Anael Belle, Jan Peters, David A. O'Connor, Jean-Claude Dreher, Benjamin T. Vincent, Brice Corgnet, Valentin Guigon, Remi Janet, Uli Bromberg, business school, emlyon, emlyon business school, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Dundee, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Cologne, Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), DREHER, JEAN-CLAUDE, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), and ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016)
Subjects: 0301 basic medicine, Science, 02 engineering and technology, Space (commercial competition), Behavioral neuroscience, Article, Behavioral Neuroscience, [SCCO]Cognitive science, 03 medical and health sciences, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, Biological sciences, Multidisciplinary, [SCCO] Cognitive science, Biological Sciences, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 021001 nanoscience & nanotechnology, Neuroeconomics, 030104 developmental biology, Action (philosophy), [SHS.GESTION]Humanities and Social Sciences/Business administration, [SHS.GESTION] Humanities and Social Sciences/Business administration, 0210 nano-technology, Psychology, Neuroscience, Cognitive psychology
Abstract: Summary In modern society, the natural drive to behave impulsively in order to obtain rewards must often be curbed. A continued failure to do so is associated with a range of outcomes including drug abuse, pathological gambling, and obesity. Here, we used virtual reality technology to investigate whether spatial proximity to rewards has the power to exacerbate the drive to behave impulsively toward them. We embedded two behavioral tasks measuring distinct forms of impulsive behavior, impulsive action, and impulsive choice, within an environment rendered in virtual reality. Participants responded to three-dimensional cues representing food rewards located in either near or far space. Bayesian analyses revealed that participants were significantly less able to stop motor actions when rewarding cues were near compared with when they were far. Since factors normally associated with proximity were controlled for, these results suggest that proximity plays a distinctive role in driving impulsive actions for rewards., Graphical abstract, Highlights • Proximity to rewarding cues can alter human behavior • Humans are less able to stop motor actions when rewarding cues are within reach • Results highlight the adverse role of environmental factors on impulsivity • Factors that change as objects move closer in the real world were controlled using VR, Biological Sciences; Neuroscience; Behavioral Neuroscience
Published: 2021

30. Siglec-H is a microglia-specific marker that discriminates microglia from CNS-associated macrophages and CNS-infiltrating monocytes

Author: Masaaki Kobayashi, Paul R. Crocker, Kenta Imai, Katsuaki Sato, Hiroshi Kiyama, Taikan Kunisawa, Akira Sayo, Bernard Malissen, Hiroyuki Konishi, Department of Functional Anatomy and Neuroscience, Nagoya University, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Dundee, Miyazaki University, and Dou Goarin, Carine
Subjects: Central Nervous System, Male, 0301 basic medicine, Nervous system, Perivascular spaces, Choroid plexus, Mice, Meninges, 0302 clinical medicine, Lectins, Perivascular space, DAP12, Microglia, respiratory system, 3. Good health, medicine.anatomical_structure, Neutrophil Infiltration, Neurology, Integrin alpha M, Myeloid cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Encephalomyelitis, Autoimmune, Experimental, [SDV.IMM] Life Sciences [q-bio]/Immunology, Receptors, CCR2, Pain, Mice, Transgenic, Receptors, Cell Surface, Inflammation, Biology, Allodynia, 03 medical and health sciences, Cellular and Molecular Neuroscience, Parenchyma, medicine, Animals, Macrophages, SIGLEC, Embryo, Mammalian, Peptide Fragments, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Animals, Newborn, Gene Expression Regulation, Pertussis Toxin, nervous system, Immunology, biology.protein, Neuralgia, Myelin-Oligodendrocyte Glycoprotein, 030217 neurology & neurosurgery
Abstract: International audience; Several types of myeloid cell are resident in the CNS. In the steady state, microglia are present in the CNS parenchyma, whereas macrophages reside in boundary regions of the CNS, such as perivascular spaces, the meninges and choroid plexus. In addition, monocytes infiltrate into the CNS parenchyma from circulation upon blood-brain barrier breakdown after CNS injury and inflammation. Although several markers, such as CD11b and ionized calcium-binding adapter molecule 1 (Iba1), are frequently used as microglial markers, they are also expressed by other types of myeloid cell and microglia-specific markers were not defined until recently. Previous transcriptome analyses of isolated microglia identified a transmembrane lectin, sialic acid-binding immunoglobulin-like lectin H (Siglec-H), as a molecular signature for microglia; however, this was not confirmed by histological studies in the nervous system and the reliability of Siglec-H as a microglial marker remained unclear. Here, we demonstrate that Siglec-H is an authentic marker for microglia in mice by immunohistochemistry using a Siglec-H-specific antibody. Siglec-H was expressed by parenchymal microglia from developmental stages to adulthood, and the expression was maintained in activated microglia under injury or inflammatory condition. However, Siglec-H expression was absent from CNS-associated macrophages and CNS-infiltrating monocytes, except for a minor subset of cells. We also show that the Siglech gene locus is a feasible site for specific targeting of microglia in the nervous system. In conclusion, Siglec-H is a reliable marker for microglia that will allow histological identification of microglia and microglia-specific gene manipulation in the nervous system.
Published: 2017

31. Poly(fluoroacrylate)s with tunable surface hydrophobicity via radical copolymerization of 2,2,2-trifluoroethyl α-fluoroacrylate and 2-(trifluoromethyl)acrylic acid

Author: Lionel X. Dupuy, Vincent Ladmiral, Bhausaheb V. Tawade, Bruno Ameduri, Michael P. MacDonald, Sanjib Banerjee, 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), The James Hutton Institute, Electronic Engineering and Physics Division, University of Dundee, Dundee, DD1 4HN, United Kingdom, affiliation inconnue, Consolated Grant EU (projet SENSOILS), European Project: ERC SENSOILS-647857,SENSOILS, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), and 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: Polymers and Plastics, Radical polymerization, Bioengineering, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Polymer chemistry, Copolymer, Thermal stability, radical copolymerization, Acrylic acid, Poly(fluoroacrylate), Trifluoromethyl, Chemistry, Comonomer, Organic Chemistry, 021001 nanoscience & nanotechnology, NMR, 0104 chemical sciences, [CHIM.POLY]Chemical Sciences/Polymers, Monomer, surface properties, fluoropolymers, 0210 nano-technology, Glass transition
Abstract: International audience; The synthesis of poly(fluoroacrylate)s with tunable wettability and improved adhesion for potential applicationas functional coatings was achieved via radical copolymerization of 2,2,2-trifluoroethylα-fluoroacrylate (FATRIFE) with 2-(trifluoromethyl)acrylic acid (MAF), an adhesion-promoting monomer.These copolymerizations, initiated by tert-butyl peroxypivalate at varying comonomer feed ([FATRIFE]0/[MAF]0) ratios led to a series of poly(FATRIFE-co-MAF) copolymers with different molar compositions infair to good conversions (32–87%) depending on the MAF feed content. The microstructures of the synthesizedpoly(FATRIFE-co-MAF) copolymers were determined by 19F NMR spectroscopy. Even at MAFfeed contents higher than 50%, MAF incorporation into the copolymers was lower than 50%, since MAFdoes not undergo any homopolymerization under radical polymerization conditions. The reactivity ratiosof the (FATRIFE; MAF) monomer pair were also determined (rFATRIFE = 1.65 ± 0.07 and rMAF = 0 at 56 °C)evidencing the formation of statistical copolymers. Initiation involving a highly branched perfluorinatedradical that released a •CF3 radical enabled the demonstration of the regioselective attack of the latterradical onto the CH2 of FATRIFE. The resulting poly(FATRIFE-co-MAF) copolymers exhibited various glasstransition temperatures (Tgs) depending on their compositions. Tg values increased with increasing MAFcontents in the copolymer. In addition, their thermal stability (the temperature for 10% weight loss in air,Td10%) increased with increasing FATRIFE content in the copolymer and reached 348 °C (for that containing93 mol% FATRIFE). Finally, a high copolymer MAF content led to both a good adhesion onto metalsubstrates and to improved hydrophilicity, as revealed by the decrease of the water contact angle from107° (for a reference PFATRIFE homopolymer) to 81° (for a copolymer containing 42 mol% MAF).
Published: 2017

32. Plasma proteomic approach in patients with heart failure: insights into pathogenesis of disease progression and potential novel treatment targets

Author: Cao, Thong, Jones, Donald, Voors, Adriaan, Quinn, Paulene, Sandhu, Jatinderpal, Chan, Daniel, Parry, Helen, Mohan, Mohapradeep, Mordi, Ify, Sama, Iziah, Anker, Stefan, Cleland, John, Dickstein, Kenneth, Filippatos, Gerasimos, Hillege, Hans, Metra, Marco, Ponikowski, Piotr, Samani, Nilesh J, van Veldhuisen, Dirk, Zannad, Faiez, Lang, Chim, Ng, Leong L, University of Leicester, Glenfield Hospital, University Medical Center Groningen [Groningen] (UMCG), Ninewells Hospital and Medical School [Dundee], University of Dundee, Berlin-Brandenburg Center for Regenerative Therapies, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Centre for Cardiovascular Research (DZHK) partner site Berlin, Institute of Health and Wellbeing [Glasgow, UK], Stavanger University Hospital, National and Kapodistrian University of Athens (NKUA), University of Brescia, Wroclaw Medical University [Wrocław, Pologne], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), This work was funded by the European Union FP7 Project [FP7-242209-BIOSTAT-CHF, EudraCT 2010-020808-29] and supported by the John and Lucille van Geest Foundation, the British Heart Foundation (FS/15/10/31223) and the National Institute for Health Research Leicester Biomedical Research Centre., European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), European Project, Wrocław Medical University, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), BOZEC, Erwan, A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure - BIOSTAT-CHF - - EC:FP7:HEALTH2010-04-01 - 2015-03-31 - 242209 - VALID, and EudraCT 2010–020808–29 - INCOMING
Subjects: Male, Proteomics, Proteome, Angiotensin-Converting Enzyme Inhibitors, Pathogenesis, Heart failure, Mass spectrometry, Metabolism, Treatment target, Pathophysiology, Ventricular Function, Left, Angiotensin Receptor Antagonists, Plasma, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Tandem Mass Spectrometry, Humans, Research Articles, Aged, Aged, 80 and over, Heart Failure, Stroke Volume, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Disease Progression, Female, Research Article
Abstract: International audience; Aims: To provide insights into pathogenesis of disease progression and potential novel treatment targets for patients with heart failure by investigation of the plasma proteome using network analysis.Methods and results: The plasma proteome of 50 patients with heart failure who died or were rehospitalised were compared with 50 patients with heart failure, matched for age and sex, who did not have an event. Peptides were analysed on two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC ESI-MS/MS) in high definition mode (HDMSE). We identified and quantified 3001 proteins, of which 51 were significantly up-regulated and 46 down-regulated with more than two-fold expression changes in those who experienced death or rehospitalisation. Gene ontology enrichment analysis and protein-protein interaction networks of significant differentially expressed proteins discovered the central role of metabolic processes in clinical outcomes of patients with heart failure. The findings revealed that a cluster of proteins related to glutathione metabolism, arginine and proline metabolism, and pyruvate metabolism in the pathogenesis of poor outcome in patients with heart failure who died or were rehospitalised.Conclusions: Our findings show that in patients with heart failure who died or were rehospitalised, the glutathione, arginine and proline, and pyruvate pathways were activated. These pathways might be potential targets for therapies to improve poor outcomes in patients with heart failure.
Published: 2019

33. The future of Blue Carbon science

Author: Iris E. Hendriks, Bayden D. Russell, Peter I. Macreadie, Kenta Watanabe, Paul S. Lavery, James W. Fourqurean, Jeff Baldock, Tomohiro Kuwae, Dan A. Smale, Daniel Murdiyarso, Rod M. Connolly, Brian R. Silliman, Catherine E. Lovelock, Oscar Serrano, Rui Santos, Karen J. McGlathery, Trisha B. Atwood, Gail L. Chmura, Pere Masqué, Nicola Beaumont, Carlos M. Duarte, Tiziana Luisetti, John A. Raven, Hilary Kennedy, Thomas S. Bianchi, Jason M. Hall-Spencer, Dorte Krause-Jensen, Eugenia T. Apostolaki, Dan Laffoley, Jeffrey J. Kelleway, Daniel A. Friess, Núria Marbà, J. Patrick Megonigal, Bradley D. Eyre, Andrea Anton, Mark Huxham, Nature Publishing Group, Australian Research Council, King Abdullah University of Science and Technology, Ministry of Environment (Japan), Natural Environment Research Council (UK), Independent Research Fund Denmark, Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), National Science Foundation (US), University of Dundee, Smithsonian Institution, and Fundação para a Ciência e a Tecnologia (Portugal)
Subjects: 0301 basic medicine, General Physics and Astronomy, SEA-LEVEL RISE, 02 engineering and technology, Carbon sequestration, 7. Clean energy, VEGETATED COASTAL HABITATS, MARINE MACROPHYTES, Environmental protection, lcsh:Science, 2. Zero hunger, CLIMATE-CHANGE, Multidisciplinary, sequestration, Biogeochemistry, 021001 nanoscience & nanotechnology, coastal ecosystems, climate change, Perspective, GB Physical geography, 0210 nano-technology, ecosystems, Animal and Plant Science Research Group, MANGROVE FORESTS, Science, Culture and Communities, Climate change, Biodiversity and conservation, Microbiology, General Biochemistry, Genetics and Molecular Biology, Education, LITTER DECOMPOSITION, ZOSTERA-NOLTII, 03 medical and health sciences, Blue carbon, ORGANIC-CARBON, blue carbon, Ecosystem, ATMOSPHERIC CO2, Carbon accumulation, General Chemistry, 15. Life on land, 030104 developmental biology, Climate change mitigation, Disturbance (ecology), 13. Climate action, 551.457 Coasts & Beaches, Greenhouse gas, Other Life Sciences, Environmental science, lcsh:Q, SEAGRASS MEADOWS, Plant sciences
Abstract: The term Blue Carbon (BC) was first coined a decade ago to describe the disproportionately large contribution of coastal vegetated ecosystems to global carbon sequestration. The role of BC in climate change mitigation and adaptation has now reached international prominence. To help prioritise future research, we assembled leading experts in the field to agree upon the top-ten pending questions in BC science. Understanding how climate change affects carbon accumulation in mature BC ecosystems and during their restoration was a high priority. Controversial questions included the role of carbonate and macroalgae in BC cycling, and the degree to which greenhouse gases are released following disturbance of BC ecosystems. Scientists seek improved precision of the extent of BC ecosystems; techniques to determine BC provenance; understanding of the factors that influence sequestration in BC ecosystems, with the corresponding value of BC; and the management actions that are effective in enhancing this value. Overall this overview provides a comprehensive road map for the coming decades on future research in BC science., P.I.M. and C.E.L. were supported by an Australian Research Council Linkage Project (LP160100242). C.M.D. was supported by baseline funding from King Abdullah University of Science and Technology. T.K. and K.W. were supported by JSPS KAKENHI (18H04156) and the Environment Research and Technology Development Fund (S-14) of the Ministry of the Environment, Japan. B.D.E. was supported by Australian Research Council grants DP160100248 and LP150100519. D.A.S. was supported by the UK Natural Environment Research Council (NE/K008439/1), and D.K.J. was supported by the CARMA project (8021-00222B), funded by the Independent Research Fund Denmark. Funding was provided to P.M. by the Generalitat de Catalunya (MERS, 2017SGR 1588) and an Australian Research Council LIEF Project (LE170100219). This work is contributing to the ICTA ‘Unit of Excellence’ (MinECo, MDM2015-0552). O.S. was supported by an ARC DECRA (DE170101524). N.M. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MedShift project). N.B. was supported by the UK Research Councils under Natural Environment Research Council award NE/N013573/1. J.W.F. was supported by the US National Science Foundation through the Florida Coastal Everglades Long-Term Ecological Research program under Grant No. DEB-1237517. R.S. had the support of FCT, project FCT UID/MAR/00350/2018. I.E.H. was supported by Ramon y Cajal Fellowship RYC2014-14970, co-funded by the Conselleria d’Innovació, Recerca i Turisme of the Balearic Government and the Spanish Ministry of Economy, Industry and Competitiveness. The University of Dundee is a registered Scottish charity, no. 015096. J.P.M. was supported by the Smithsonian Institution and the National Science Foundation Long-Term Research in Environmental Biology Program (DEB-0950080, DEB-1457100, DEB-1557009).
Published: 2019

34. The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

Author: D. Dumas, A. Diot, N. de Freitas Caires, Michael W.H. Coughtrie, Isabelle Bertin-Jung, A. M. Thompson, Xianqing Mao, Sandrine Gulberti, Caroline Gauche, F. Merhi-Soussi, J-C Bourdon, Catherine Bui, Mohamed Ouzzine, Sylvie Fournel-Gigleux, Nick Ramalanjaona, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Luxembourg Institute of Health, University of Dundee, University of British Columbia (UBC), Institut National de la Santé et de la Recherche Médicale (INSERM), MD Anderson Cancer Center [Houston], and The University of Texas Health Science Center at Houston (UTHealth)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, Breast Neoplasms, Biology, medicine.disease_cause, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Growth factor receptor, Internal medicine, Biomarkers, Tumor, Genetics, medicine, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], skin and connective tissue diseases, Molecular Biology, Cancer, Heparan sulfate, DNA Methylation, Cell cycle, Prognosis, medicine.disease, Xenograft Model Antitumor Assays, 3. Good health, 030104 developmental biology, Endocrinology, chemistry, SKBR3, 030220 oncology & carcinogenesis, Cancer cell, MCF-7 Cells, Cancer research, Female, Heparitin Sulfate, Sulfotransferases, Carcinogenesis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: International audience; Heparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumorigenesis, albeit mechanisms remain mostly obscure. HS function is mainly controlled by sulfotransferases, and here we report a novel cellular and pathophysiological significance for the 3-O-sulfotransferase 3-OST3A (HS3ST3A), catalyzing the final maturation step of HS, in breast cancer. We show that 3-OST3A is epigenetically repressed in all breast cancer cell lines of a panel representative of distinct molecular subgroups, except in human epidermal growth factor receptor 2-positive (HER2+) sloan-kettering breast cancer (SKBR3) cells. Epigenetic mechanisms involved both DNA methylation and histone modifications, producing different repressive chromatin environments depending on the cell molecular signature. Gain and loss of function experiments by cDNA and siRNA transfection revealed profound effects of 3-OST3A expression on cell behavior including apoptosis, proliferation, response to trastuzumab in vitro and tumor growth in xenografted mice. 3-OST3A exerted dual activities acting as tumor-suppressor in lumA-michigan cancer foundation (MCF)-7 and triple negative-MD Anderson (MDA) metastatic breast (MB)-231 cells, or as an oncogenic factor in HER2+-SKBR3 cells. Mechanistically, fluorescence-resonance energy transfer-fluorescence-lifetime imaging microscopy experiments indicated that the effects of 3-OST3A in MCF-7 cells were mediated by altered interactions between HS and fibroblast growth factor-7 (FGF-7). Further, this interplay between HS and FGF-7 modulated downstream ERK, AKT and p38 cascades, suggesting that altering 3-O-sulfation affects FGFR2IIIb-mediated signaling. Corroborating our cellular data, a clinical study conducted in a cohort of breast cancer patients uncovered that, in HER2+ patients, high level expression of 3-OST3A in tumors was associated with reduced relapse-free survival. Our findings define 3-OST3A as a novel regulator of breast cancer pathogenicity, displaying tumor-suppressive or oncogenic activities in a cell-and tumor-dependent context, and demonstrate the clinical value of the HS-O-sulfotransferase 3-OST3A as a prognostic marker in HER2+ patients.
Published: 2016

35. Localizing the lipid products of PI3Kγ in neutrophils

Author: Arnaud Deladeriere, Hervé Guillou, Sabine Suire, Oliver Rausch, G. John Ferguson, Simon Andrews, Simon Walker, Tamara Chessa, Till Bretschneider, Cheng-Jin Du, Laura J. Norton, Anne Segonds-Pichon, Len R. Stephens, Takehiko Sasaki, Peter Finan, Yvonne E. Lindsay, Phillip T. Hawkins, John M. Lucocq, Signalling Department, Babraham Institute, College of Life Sciences, Division of Molecular Physiology, University of Dundee, College of Life Sciences, Division of Cell Biology and Immunology, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), The Imaging Facility, Bioinformatics Group, Wageningen University, UCB, Novartis Institutes for BioMedical Research (NIBR), School of Medicine, University of Patras [Greece], Warwick Systems Biology Centre, University of Warwick, Stephens, Len, University of St Andrews. School of Medicine, and University of St Andrews. Biomedical Sciences Research Complex
Subjects: 0301 basic medicine, Cancer Research, phosphoinositide 3 kinase, neutrophile, Neutrophils, QH301 Biology, [SDV]Life Sciences [q-bio], Stimulation, PI3K, Green fluorescent protein, Mice, PH, Pleckstrin homology, Phosphatidylinositol Phosphates, Polarization, PI3K, Phosphoinositide 3-kinase, Class Ib Phosphatidylinositol 3-Kinase, Cells, Cultured, fMLP, formylated-Met-Leu-Phe, biology, Neutrophil, TAPP-1, TAndem PH domain containing Protein-1, neutrophil, microscopie électronique, Cell biology, Transport protein, Protein Transport, Biochemistry, Molecular Medicine, polarization, GPCR, G-Protein Coupled Receptor, NDAS, polarisation, R Medicine, eGFP, enhanced Green Fluorescent Protein, Article, QH301, 03 medical and health sciences, Genetics, Animals, Molecular Biology, PI3K/AKT/mTOR pathway, G protein-coupled receptor, EM, Electron Microscopy, Phosphoinositide 3-kinase, electron microscopy, Chemotaxis, 030104 developmental biology, PKB, Protein Kinase B (also called Akt), biology.protein
Abstract: Class I phosphoinositide 3-kinases (PI3Ks) are important regulators of neutrophil migration in response to a range of chemoattractants. Their primary lipid products PtdIns(3,4,5)P3 and PtdIns(3,4)P2 preferentially accumulate near to the leading edge of migrating cells and are thought to act as an important cue organizing molecular and morphological polarization. We have investigated the distribution and accumulation of these lipids independently in mouse neutrophils using eGFP-PH reporters and electron microscopy (EM). We found that authentic mouse neutrophils rapidly polarized their Class I PI3K signalling, as read-out by eGFP-PH reporters, both at the up-gradient leading edge in response to local stimulation with fMLP as well as spontaneously and randomly in response to uniform stimulation. EM studies revealed these events occurred at the plasma membrane, were dominated by accumulation of PtdIns(3,4,5)P3, but not PtdIns(3,4)P2, and were dependent on PI3Kγ and its upstream activation by both Ras and Gβγs. Publisher PDF
Published: 2016
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36. Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes

Author: Kabbara, Samar, Herivaux, Anais, Dugé de Bernonville, Thomas, Courdavault, Vincent, Clastre, Marc, Gastebois, Amandine, Osman, Marwan, Hamzé, Monzer, Cock, J Mark, Schaap, Pauline, Papon, Nicolas, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Biomolécules et biotechnologies végétales (BBV EA 2106), Université de Tours (UT), 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), Centre AZM pour la Recherche en Biotechnologie et ses Applications, Université Libanaise, Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), School of Life Sciences, University of Dundee, Gestionnaire, HAL Sorbonne Université 5, 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), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université de Tours
Subjects: Evolution, Molecular, eukaryotes, Histidine Kinase, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], phylogenetic analysis, histidine kinases, two-component systems, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Eukaryota, cell signaling, Phylogeny, Signal Transduction, Research Article
Abstract: International audience; Histidine kinases (HKs) are primary sensor proteins that act in cell signaling pathways generically referred to as “two-component systems” (TCSs). TCSs are among the most widely distributed transduction systems used by both prokaryotic and eukaryotic organisms to detect and respond to a broad range of environmental cues. The structure and distribution of HK proteins are now well documented in prokaryotes, but information is still fragmentary for eukaryotes. Here, we have taken advantage of recent genomic resources to explore the structural diversity and the phylogenetic distribution of HKs in the prominent eukaryotic supergroups. Searches of the genomes of 67 eukaryotic species spread evenly throughout the phylogenetic tree of life identified 748 predicted HK proteins. Independent phylogenetic analyses of predicted HK proteins were carried out for each of the major eukaryotic supergroups. This allowed most of the compiled sequences to be categorized into previously described HK groups. Beyond the phylogenetic analysis of eukaryotic HKs, this study revealed some interesting findings: 1) characterization of some previously undescribed eukaryotic HK groups with predicted functions putatively related to physiological traits; 2) discovery of HK groups that were previously believed to be restricted to a single kingdom in additional supergroups, and 3) indications that some evolutionary paths have led to the appearance, transfer, duplication, and loss of HK genes in some phylogenetic lineages. This study provides an unprecedented overview of the structure and distribution of HKs in the Eukaryota and represents a first step toward deciphering the evolution of TCS signaling in living organisms.
Published: 2018

37. Merging in-solution X-ray and neutron scattering data allows fine structural analysis of membrane-protein detergent complexes

Author: Giulia Tamburrino, Frank Gabel, Jochen S. Hub, Olwyn Byron, Tim Rasmussen, Ulrich Zachariae, Miloš T. Ivanović, Arnaud Javelle, Felix M. Strnad, Paul A. Hoskisson, Gaëtan Dias Mirandela, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Physics, School of Science and Engineering, University of Dundee, Theoretical Physics, Saarland University [Saarbrücken], Institute for Microbiology and Genetics [Göttingen], Georg-August-University [Göttingen], ePlant Science Group, School of Life Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, School of Chemical Sciences and Pharmacy, University of East Anglia [Norwich] (UEA), Division of Physics, School of Engineering, Institut de biologie structurale (IBS - UMR 5075 ), 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)-Centre National de la Recherche Scientifique (CNRS), Georg-August-University = Georg-August-Universität Göttingen, Centre National de la Recherche Scientifique (CNRS)-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)
Subjects: Materials science, Detergents, Ab initio, Molecular Dynamics Simulation, Neutron scattering, 010402 general chemistry, 01 natural sciences, Chemistry Techniques, Analytical, Turn (biochemistry), 03 medical and health sciences, X-Ray Diffraction, Molecule, MESH: Molecular Dynamics Simulation, 030304 developmental biology, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Small-angle X-ray scattering, MESH: X-Ray Diffraction, X-ray, Membrane Proteins, MESH: Chemistry Techniques, Analytical, MESH: Neutron Diffraction, 0104 chemical sciences, QD450, MESH: Solubility, Neutron Diffraction, Crystallography, Solubility, Membrane protein, Membrane protein complex, MESH: Membrane Proteins, MESH: Detergents
Abstract: International audience; In-solution small-angle X-ray and neutron scattering (SAXS/SANS) have become popular methods to characterize the structure of membrane proteins, solubilized by either detergents or nanodiscs. SANS studies of protein-detergent complexes usually require deuterium-labeled proteins or detergents, which in turn often lead to problems in their expression or purification. Here, we report an approach whose novelty is the combined analysis of SAXS and SANS data from an unlabeled membrane protein complex in solution in two complementary ways. First, an explicit atomic analysis, including both protein and detergent molecules, using the program WAXSiS, which has been adapted to predict SANS data. Second, the use of MONSA which allows one to discriminate between detergent head- and tail-groups in an ab initio approach. Our approach is readily applicable to any detergent-solubilized protein and provides more detailed structural information on protein-detergent complexes from unlabeled samples than SAXS or SANS alone.
Published: 2018

38. Phenformin, But Not Metformin, Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation

Author: Vara-Ciruelos, Diana, Dandapani, Madhumita, Russell, Fiona, Grzes, Katarzyna, Atrih, Abdelmadjid, Foretz, Marc, Viollet, Benoit, Lamont, Douglas, Cantrell, Doreen, Hardie, D Grahame, Hardie, D. Grahame, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Immunology & Cell Biology, University of Dundee, and College of Life Sciences
Subjects: AMPK, Male, Administration, Oral, AMP-Activated Protein Kinases, Mechanistic Target of Rapamycin Complex 1, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, T cell acute lymphoblastic leukemia/lymphoma, Disease-Free Survival, Article, Mice, Phenformin, Animals, Hypoglycemic Agents, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cell Proliferation, Mice, Knockout, Sirolimus, AMP-activated protein kinase, PTEN Phosphohydrolase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Metformin, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Mice, Inbred C57BL, Disease Models, Animal, biguanides, Female, T-ALL, Glycolysis, Signal Transduction
Abstract: International audience; AMPK acts downstream of the tumor suppressor LKB1, yet its role in cancer has been controversial. AMPK is activated by biguanides, such as metformin and phenformin, and metformin use in diabetics has been associated with reduced cancer risk. However, whether this is mediated by cell-autonomous AMPK activation within tumor progenitor cells has been unclear. We report that T-cell-specific loss of AMPK-α1 caused accelerated growth of T cell acute lymphoblastic leukemia/lymphoma (T-ALL) induced by PTEN loss in thymic T cell progenitors. Oral administration of phenformin, but not metformin, delayed onset and growth of lymphomas, but only when T cells expressed AMPK-α1. This differential effect of biguanides correlated with detection of phenformin, but not metformin, in thymus. Phenformin also enhanced apoptosis in T-ALL cells both in vivo and in vitro. Thus, AMPK-α1 can be a cell-autonomous tumor suppressor in the context of T-ALL, and phenformin may have potential for the prevention of some cancers.
Published: 2018

39. Chem. Sci

Author: Ievgen Mazurenko, Luciano A. Abriata, Sophie Lecomte, Romain Clement, Marianne Ilbert, Xie Wang, Marie-Thérèse Giudici-Orticoni, Elisabeth Lojou, Pascal Mansuelle, Magali Roger, Frédéric Biaso, Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Dundee, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Ecole Polytechnique Fédérale de Lausanne (EPFL), Plateforme Protéomique [Marseille], Institut de Microbiologie de la Méditerranée (IMM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Leeds, ANR-16-CE05-0024,Enzymor,Bases moléculaires de l'immobilisation fonctionnelle d'enzymes pour des biopiles performantes(2016), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Centre National de la Recherche Scientifique (CNRS), and Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, chemistry.chemical_classification, Cytochrome, biology, Copper protein, Intermolecular force, Respiratory chain, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, Electrochemistry, 03 medical and health sciences, chemistry.chemical_compound, Electron transfer, 030104 developmental biology, chemistry, biology.protein, Biophysics, Metalloprotein, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Heme
Abstract: International audience; Acidithiobacillus ferrooxidans, a chemolithoautotrophic Gram-negative bacterium, has a remarkable ability to obtain energy from ferrous iron oxidation at pH 2. Several metalloproteins have been described as being involved in this respiratory chain coupling iron oxidation with oxygen reduction. However, their properties and physiological functions remain largely unknown, preventing a clear understanding of the global mechanism. In this work, we focus on two metalloproteins of this respiratory pathway, a diheme cytochrome c 4 (Cyt c 4) and a green copper protein (AcoP) of unknown function. We first demonstrate the formation of a complex between these two purified proteins, which allows homogeneous intermolecular electron-transfer in solution. We then mimic the physiological interaction between the two partners by replacing one at a time with electrodes displaying different chemical functionalities. From the electrochemical behavior of individual proteins, we show that, while electron transfer on AcoP requires weak electrostatic interaction, electron transfer on Cyt c 4 tolerates different charge and hydrophobicity conditions, suggesting a pivotal role of this protein in the metabolic chain. The electrochemical study of the proteins incubated together demonstrates an intermolecular electron transfer involving the protein complex, in which AcoP is reduced through the high potential heme of Cyt c 4. Modelling of the electrochemical signals at different scan rates allows us to estimate the rate constant of this intermolecular electron transfer in the range of a few s À1. Possible routes for electron transfer in the acidophilic bacterium are deduced.
Published: 2018

40. Editorial

Author: Jonathan Knappett, Luc Thorel, University of Dundee, Géomatériaux et Modèles Géotechniques (IFSTTAR/GERS/GMG), and Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-PRES Université Nantes Angers Le Mans (UNAM)
Subjects: [SPI]Engineering Sciences [physics], 0211 other engineering and technologies, 02 engineering and technology, Geotechnical Engineering and Engineering Geology, MODELISATION PHYSIQUE, GEOTECHNIQUE, 021102 mining & metallurgy, 021101 geological & geomatics engineering
Abstract: Editorial of the Focus EUROFUGE 2016, 3rd European Conference on Physical Modelling in Geotechnics, 1st-3rd June 2016 at IFSTTAR in Nantes; Editorial du Focus EUROFUGE 2016, 3e conférence européenne de modélisation physique en géotechnique, 1-3 juin 2016, à l'IFSTTAR (Nantes)
Published: 2019

41. Micromechanics of root development in soil

Author: Vincent Ladmiral, Daniel Patko, Mariya Ptashnyk, Michael P. MacDonald, Lionel X. Dupuy, Bruno Ameduri, M. Mimault, The James Hutton Institute, 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), University of Dundee, and Heriot-Watt University [Edinburgh] (HWU)
Subjects: 0301 basic medicine, Root growth, Root (linguistics), particle, Earth science, [SDV]Life Sciences [q-bio], Granular media, Biology, Plant Roots, biomechanics, 03 medical and health sciences, Mechanobiology, Genetic Heterogeneity, Soil, Granular matter, Genetics, Mechanical Phenomena, 2. Zero hunger, granular media, Rhizosphere, Plant roots, 15. Life on land, 030104 developmental biology, 13. Climate action, Developmental Biology
Abstract: International audience; Our understanding of how root develop in soil may be at the eve of significant transformations. The formidable expansion of imaging technologies enables live observations of the rhizosphere micropore architecture at unprecedented resolution. Granular matter physics provides ways to understand the microscopic fluctuations of forces in soils, and the increasing knowledge of pressure sensitive ion channels in plants may shed light on how roots perceive soil heterogeneity. This opinion paper exposes how recent scientific achievements may contribute to design a new theory for root growth in heterogeneous environments.
Published: 2017

42. The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway

Author: Joost C. B. M. Zomerdijk, L J Bou Malhab, Mark Larance, Dimitris P. Xirodimas, P G Smith, Aurélien Perrin, P-E Gleizes, Aymeric P. Bailly, M Nagala, Angus I. Lamond, Emmanuelle Pion, M-F O'Donohue, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre for Gene Regulation and Expression, School of Life Sciences Dundee, University of Dundee, University of Cambridge [UK] (CAM), Millennium Pharmaceuticals, Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Ribosomal Proteins, 0301 basic medicine, Cancer Research, NEDD8 Protein, Nucleolus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cyclopentanes, Biology, NEDD8, Cell Line, 03 medical and health sciences, Transcription (biology), Genetics, RNA polymerase I, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Ribosome profiling, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Ubiquitins, Molecular Biology, ComputingMilieux_MISCELLANEOUS, RNA, Proto-Oncogene Proteins c-mdm2, Genes, p53, Mice, Mutant Strains, Cell biology, Nucleolar fragmentation, Pyrimidines, 030104 developmental biology, MCF-7 Cells, Neddylation, Ribosomes, Cell Nucleolus, Metabolic Networks and Pathways
Abstract: The ubiquitin-like molecule NEDD8 is essential for viability, growth and development, and is a potential target for therapeutic intervention. We found that the small molecule inhibitor of NEDDylation, MLN4924, alters the morphology and increases the surface size of the nucleolus in human and germline cells of Caenorhabditis elegans in the absence of nucleolar fragmentation. SILAC proteomics and monitoring of rRNA production, processing and ribosome profiling shows that MLN4924 changes the composition of the nucleolar proteome but does not inhibit RNA Pol I transcription. Further analysis demonstrates that MLN4924 activates the p53 tumour suppressor through the RPL11/RPL5-Mdm2 pathway, with characteristics of nucleolar stress. The study identifies the nucleolus as a target of inhibitors of NEDDylation and provides a mechanism for p53 activation upon NEDD8 inhibition. It also indicates that targeting the nucleolar proteome without affecting nucleolar transcription initiates the required signalling events for the control of cell cycle regulators.
Published: 2015

43. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei

Author: Shameer, Sanu, Logan-Klumpler, Flora J, Vinson, Florence, Cottret, Ludovic, Merlet, Benjamin, Achcar, Fiona, Boshart, Michael, Berriman, Matthew, Breitling, Rainer, Bringaud, Frédéric, Bütikofer, Peter, Cattanach, Amy M, Bannerman-Chukualim, Bridget, Creek, Darren J, Crouch, Kathryn, de Koning, Harry P, Denise, Hubert, Ebikeme, Charles, Fairlamb, Alan H, Ferguson, Michael A J, Ginger, Michael L, Hertz-Fowler, Christiane, Kerkhoven, Eduard J, Mäser, Pascal, Michels, Paul A M, Nayak, Archana, Nes, David W, Nolan, Derek P, Olsen, Christian, Silva-Franco, Fatima, Smith, Terry K, Taylor, Martin C, Tielens, Aloysius G M, Urbaniak, Michael D, van Hellemond, Jaap J, Vincent, Isabel M, Wilkinson, Shane R, Wyllie, Susan, Opperdoes, Fred R, Barrett, Michael P, Jourdan, Fabien, LS Biochemie van parasieten, B&C BRC-SIB-TR, Regenerative Medicine, Stem Cells & Cancer, Medical Microbiology & Infectious Diseases, LS Biochemie van parasieten, B&C BRC-SIB-TR, Regenerative Medicine, Stem Cells & Cancer, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), The Wellcome Trust Sanger Institute [Cambridge], Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Laboratoire des interactions plantes micro-organismes (LIPM), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), University of Glasgow, Ludwig Maximilians University of Munich, University of Manchester [Manchester], Centre National de la Recherche Scientifique (CNRS), University of Bern, Monash University, European Molecular Biology Laboratory European Bioinformatics Institute, United Nations Educational, Scientific and Cultural Organization (UNESCO), University of Dundee, Lancaster University, University of Liverpool, Chalmers University of Technology [Gothenburg, Sweden], Swiss Tropical and Public Health Institute [Basel], University of Edinburgh, TexasTech University, Trinity College Dublin, Biomatters Inc, Partenaires INRAE, University of St Andrews [Scotland], London School of Hygiene and Tropical Medicine (LSHTM), Utrecht University [Utrecht], Erasmus University Rotterdam, Queen Mary University of London (QMUL), Université Catholique de Louvain = Catholic University of Louvain (UCL), ANR project, European Project: 290080,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,PARAMET(2012), University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Ludwig-Maximilians University [Munich] (LMU)
Subjects: Proteomics, Anabolism, QH301 Biology, [SDV]Life Sciences [q-bio], Trypanosoma brucei brucei, Metabolic network, 610 Medicine & health, Biology, Trypanosoma brucei, computer.software_genre, 03 medical and health sciences, QH301, Metabolomics, Metabolome, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Database Issue, Data Mining, 030304 developmental biology, base de données, 0303 health sciences, Internet, Database, Catabolism, 030302 biochemistry & molecular biology, DAS, métabolisme cellulaire, biology.organism_classification, maladie parasitaire, QR, Metabolic pathway, 570 Life sciences, biology, computer, trypanosoma brucei, Databases, Chemical, Metabolic Networks and Pathways
Abstract: European Commission FP7 Marie Curie Initial Training Network ‘ParaMet’ [290080 to S.S.]; ANR project MetaboHub [ANR-11-INBS-0010 to B.M.]; Wellcome Trust [085349]; The work of Fiona Achcar was part of the SysMO SilicoTryp project coordinated by R.B. Funding for open access charge: European Commission FP7 Marie Curie Initial Training Network ‘ParaMet’ [290080]. The metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individual metabolic networks is increasing as we learn more about the enzymes that are active in particular cells under particular conditions and as technologies advance to allow detailed measurements of the cellular metabolome. Metabolic network databases are of increasing importance in allowing us to contextualise data sets emerging from transcriptomic, proteomic and metabolomic experiments. Here we present a dynamic database, TrypanoCyc (http://www.metexplore.fr/trypanocyc/), which describes the generic and condition-specific metabolic network of Trypanosoma brucei, a parasitic protozoan responsible for human and animal African trypanosomiasis. In addition to enabling navigation through the BioCyc-based TrypanoCyc interface, we have also implemented a network-based representation of the information through MetExplore, yielding a novel environment in which to visualise the metabolism of this important parasite. Publisher PDF
Published: 2015

44. Sensitivity to morpheme units in English as L2 word recognition

Author: Séverine Casalis, Eva Commissaire, Lynne G. Duncan, Unité de Recherche en Sciences Cognitives et Affectives (URECA), Université de Lille, Sciences Humaines et Sociales-PRES Université Lille Nord de France, Laboratoire de Psychologie des Cognitions (LPC), Université de Strasbourg (UNISTRA), University of Dundee, Université de Lille, CNRS, CHU Lille, Unité de Recherche en Sciences Cognitives et Affectives [URECA], Laboratoire de Psychologie des Cognitions [LPC], and Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193
Subjects: Second language, Morphology, Linguistics and Language, 4. Education, 05 social sciences, Word processing, [SCCO.LING]Cognitive science/Linguistics, 050105 experimental psychology, Language and Linguistics, Linguistics, Pseudoword, 03 medical and health sciences, Word lists by frequency, 0302 clinical medicine, Morpheme, Word recognition, Lexical decision task, 0501 psychology and cognitive sciences, Suffix, Psychology, 030217 neurology & neurosurgery, Word (group theory)
Abstract: International audience; Little is yet known about how L2 learners process morphology during visual word recognition. Two points of view may be contrasted: the first one suggests that L2 learners, as less proficient speakers, may be less sensitive to the computational aspects of word processing such as the morphological structure of complex words, relying more on lexical information; whereas, the second one suggests that word processing is constrained mainly by linguistic aspects, making L2 learners as sensitive to word structure as native speakers. While previous studies have mainly focused on proficient to highly proficient L2 speakers, the present study compared L2 learners of low proficiency with those of intermediate to high levels of proficiency. The role of morphological structure in word recognition and pseudoword processing was examined by manipulating the presence of embedded words and suffixes in items presented for L2 lexical decision. Contrasting patterns in L2 word recognition were observed between groups as the low-proficiency group was more sensitive to the presence of an embedded word than the higher proficiency group in both accuracy and speed. However, pseudowords made up of an embedded word and suffix were significantly more likely to be wrongly accepted as words than other pseudowords by both groups. Furthermore, correct rejection of these items as words induced longer latencies in both groups, indicating a morphological analysis of these pseudowords. Together, the results show that L2 learners, including those who are low in proficiency, are sensitive to the morphological structure of written L2 words.
Published: 2014

45. Grapheme coding in L2: How do L2 learners process new graphemes?

Author: Séverine Casalis, Eva Commissaire, Lynne G. Duncan, Unité de Recherche en Sciences Cognitives et Affectives (URECA), Université de Lille, Sciences Humaines et Sociales-PRES Université Lille Nord de France, University of Dundee, Université de Lille, CNRS, CHU Lille, and Unité de Recherche en Sciences Cognitives et Affectives [URECA]
Subjects: Second language, Visual word recognition, business.industry, [SDV]Life Sciences [q-bio], Grapheme, Sub-lexical processing, Experimental and Cognitive Psychology, computer.software_genre, Linguistics, English as a second language, Word recognition, L2 learners, Artificial intelligence, Psychology, business, computer, Natural language processing, Coding (social sciences)
Abstract: International audience; Grapheme coding was examined in French Grade 6 and Grade 8 children and adults who learned English as a second language (L2). In Experiments 1 and 2, three conditions were compared in a letter detection task in L2: (1) simple grapheme (i.e., detect “a” in black); (2) complex language-shared grapheme (i.e., “a” in brain) and (3) complex L2-specific grapheme (i.e., “a” in beach). The data indicated that graphemes in L2 words were functional sub-lexical orthographic units for these L2 learners. Moreover, L2-specific graphemes took longer to process than language-shared complex graphemes. Using the same task, Experiment 3 examined phonological influences by manipulating the cross-language congruency of grapheme-to-phoneme mappings (detect “a” in have [congruent] vs. take [incongruent]). The outcome of this study offers preliminary evidence of graphemic coding during L2 word recognition both at the orthographic and the orthography-to-phonology mapping levels.
Published: 2014

46. The TRANSFoRm project: Experience and lessons learned regarding functional and interoperability requirements to support primary care

Author: Adrien Barton, Anne-Marie Cloutier, Brendan Delaney, Anita Burgun, Mark McGilchrist, Vasa Curcin, Jean-François Ethier, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Sherbrooke (UdeS), University of Dundee, MEthodes et ingénierie des Langues, des Ontologies et du DIscours (IRIT-MELODI), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS), King‘s College London, Imperial College London, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)
Subjects: Service (systems architecture), Decision support system, Engineering, Knowledge management, 020205 medical informatics, Interoperability, Health Informatics, Context (language use), interoperability, 02 engineering and technology, computer.software_genre, 03 medical and health sciences, primary care, 0302 clinical medicine, Health Information Management, learning health system, 0202 electrical engineering, electronic engineering, information engineering, Relevance (information retrieval), [INFO]Computer Science [cs], TRANSFoRm project, 030212 general & internal medicine, requirements, Experience Report, business.industry, Public Health, Environmental and Occupational Health, Functional requirement, Informatics, business, Experience Reports, computer, Data integration
Abstract: International audience; Introduction The current model of medical knowledge production, transfer, and application suffers from serious shortcomings. Learning health systems (LHS) have recently emerged as a potential solution—systems in which health information generated from patients is continuously analyzed to improve knowledge that will be transferred to patient care. Method Various approaches of data integration already exist and could be considered for the implementation of a LHS. We discuss what are the possible informatics approaches to address the functional requirements of LHS, in the specific context of primary care, and present the experience and lessons learned from the TRANSFoRm project. Result Implemented in 4 countries around 5 systems, TRANSFoRm is based on a local-as-view data mediation approach integrating the structural and terminological models in the same framework. It clearly demonstrated that it has the potential to address the requirements for a LHS in primary care, by dealing with data fragmented across multiple points of service. Also, it has the potential to support the generation of hypotheses from the context of clinical care, retrospective and prospective research, and decision support systems that improve the relevance of medical decisions. Conclusion The LHS approach embodies a shift from an institution-centered to a patient-centered perspective in knowledge production and transfer and can address important challenges in the primary care setting.
Published: 2016

47. Is there a left-handed magnetic field in the solar neighborhood?

Author: F. Del Sordo, Andrea Bracco, Simon Candelaresi, Axel Brandenburg, Royal Institute of Technology [Stockholm] (KTH ), and University of Dundee
Subjects: ISM: structure, Extinction (astronomy), Cosmic background radiation, FOS: Physical sciences, Context (language use), Astrophysics::Cosmology and Extragalactic Astrophysics, cosmic background radiation, Astrophysics, 01 natural sciences, Local interstellar matter, Spectral line, symbols.namesake, ISM Structure, 0103 physical sciences, Planck, 010306 general physics, 010303 astronomy & astrophysics, Astrophysics::Galaxy Astrophysics, Physics, extinction, Dust, Astronomy and Astrophysics, Polarization (waves), Astrophysics - Astrophysics of Galaxies, Magnetic field, Interstellar medium, 13. Climate action, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), symbols, ISM: magnetic fields, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], local insterstellar matter
Abstract: The full-sky Planck polarization data at 850um revealed unexpected properties of the E and B mode power spectra of dust emission in the interstellar medium (ISM). The positive cross-correlation between the total dust intensity, T, with the B modes has raised new questions about the physical mechanisms that affect dust polarization, such as the Galactic magnetic-field structure. This is key both to better understanding ISM dynamics and to accurately describing Galactic foregrounds to the polarization of the Cosmic Microwave Background (CMB). In this theoretical paper we investigate the possibility that the observed cross-correlations in the dust polarization power spectra, and specifically between T and B, can be related to a parity-odd quantity in the ISM such as the magnetic helicity. We produce synthetic dust polarization data, derived from 3D analytical toy models of density structures and helical magnetic fields, to compare with the E and B modes of observations. Focusing on the observed T-B correlation, we propose a new line of interpretation of the Planck observations based on a large-scale helical component of the Galactic magnetic field in the solar neighborhood. Our analysis shows that: I) the sign of magnetic helicity does not affect E and B modes for isotropic magnetic-field configurations; II) helical magnetic fields threading interstellar filaments cannot reproduce the Planck results; III) a weak helical left-handed magnetic field structure in the solar neighborhood may explain the T-B correlation seen in the Planck data. This work suggests a new perspective for the interpretation of the dust polarization power spectra, which strongly supports the imprint of a large-scale structure of the Galactic magnetic field in the solar neighborhood., Accepted by Astronomy & Astrophysics on November 24, 2018
Published: 2019

48. Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

Author: Sara Jaber, Ming Fang, Michel Huerre, Boris Bardot, Laure Charbonnier, Claire Soudais, Franck Toledo, Rachida Bouarich-Bourimi, Jean-Christophe Bourdon, Iva Simeonova, Irena Draskovic, Vincent Lejour, Arturo Londoño-Vallejo, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CD4+T-Lymphocytes and Anti-Tumour Response, University of Dundee, Département de Pathologie [Curie], Institut Curie [Paris], HAL UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Dynamique de l'information génétique : bases fondamentales et cancer ( DIG CANCER ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ), Telomeres and Cancer Laboratory, INSTITUT CURIE, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Curie, and Institut Curie
Subjects: Male, Telomere-Binding Proteins, Mutant, Gene Expression, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, TINF2, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Dyskerin, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pulmonary fibrosis, medicine, Animals, Humans, Aplastic anemia, lcsh:QH301-705.5, 030304 developmental biology, 0303 health sciences, Mutation, Syndrome, Telomere, medicine.disease, Mice, Mutant Strains, Protein Structure, Tertiary, 3. Good health, Disease Models, Animal, lcsh:Biology (General), [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, Cancer research, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Tumor Suppressor Protein p53, Dyskeratosis congenita
Abstract: International audience; Mutations in p53, although frequent in human cancers , have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53 D31 , a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis, hallmarks of syndromes caused by short telomeres. Indeed, p53 D31/D31 mice had short telomeres and other phenotypic traits associated with the telomere disease dyskeratosis congenita and its severe variant the Hoyeraal-Hreidarsson syndrome. Hetero-zygous p53 +/D31 mice were only mildly affected, but decreased levels of Mdm4, a negative regulator of p53, led to a dramatic aggravation of their symptoms. Importantly, several genes involved in telomere metabolism were downregulated in p53 D31/D31 cells, including Dyskerin, Rtel1, and Tinf2, which are mutated in dyskeratosis congenita, and Terf1, which is implicated in aplastic anemia. Together, these data reveal that a truncating mutation can activate p53 and that p53 plays a major role in the regulation of telomere metabolism.
Published: 2013
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49. The impact and mode of action of phenolic compounds extracted from brown seaweed on mixed anaerobic microbial cultures

Author: Phillip J. Collier, Lucile Chatellard, Martin Kierans, Anthony Hierholtzer, Joseph C. Akunna, Abertay University (Abertay University), Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), University of Dundee, and University of Abertay Dundee
Subjects: Cell Membrane Permeability, [SDV]Life Sciences [q-bio], 020209 energy, Phloroglucinol, 02 engineering and technology, biodegradation, 7. Clean energy, Applied Microbiology and Biotechnology, Phlorotannin, antimicrobials, Polymerization, Microbiology, Cell membrane, 03 medical and health sciences, chemistry.chemical_compound, Phenols, 0202 electrical engineering, electronic engineering, information engineering, medicine, Anaerobiosis, Food science, Mode of action, membrane, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Bacteria, biology, Cell Membrane, General Medicine, Fatty Acids, Volatile, Seaweed, biology.organism_classification, Laminaria digitata, Anti-Bacterial Agents, medicine.anatomical_structure, chemistry, [SDE]Environmental Sciences, Laminaria, Methane, Tannins, Intracellular, cell injury, mechanism of action, Biotechnology
Abstract: Aims This study discusses the effect of phenolic compounds extracted from brown seaweed (phlorotannins) on mixed microbial cultures found in anaerobic systems. Methods and Results Assays were conducted with phloroglucinol as the nonpolymerized form of phlorotannin and with phlorotannins extracted from the brown seaweed Laminaria digitata. Electron micrographs revealed that phlorotannins induce significant extra- and intracellular effects upon cells, with the disruption of cell membranes observed with most micro-organisms. Microscopy results were further confirmed by cell membrane leakage assays demonstrating that phloroglucinol strongly affects cell membrane permeability. However, cell membrane leakage could not be observed with phlorotannins as the cell suspension immediately started to coagulate and impaired spectrophotometric measurements. Conclusions Results suggest that the bactericidal activity of phlorotannins is a function of the level of polymerization of the compounds. By monitoring intermediary compounds during the anaerobic digestion of phlorotannins, it was also found that higher energy consumption is required by micro-organisms for survival under stress induced by phlorotannins. Significance and Impact of the Study The successful anaerobic degradation of brown seaweed is thus likely to be dependant on the concentration of phenolic compounds present and their bactericidal effect on micro-organisms. This is the first article to posit a probable mode of action for the antimicrobial effect of phlorotannins.
Published: 2013

50. Introduction: Supranational governance and European Union security after the Lisbon Treaty - Exogenous shocks, policy entrepreneurs and 11 September 2001

Author: Christian Kaunert, Sarah Léonard, Centre d'études européennes et de politique comparée (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), and University of Dundee
Subjects: Security governance, Common Foreign and Security Policy (CFSP), 0211 other engineering and technologies, 02 engineering and technology, security governance, Political science, Realm, counter-terrorism, 050602 political science & public administration, media_common.cataloged_instance, European union, Treaty, media_common, EU institutions, 021110 strategic, defence & security studies, Corporate governance, 05 social sciences, terrorism, supranational governance, 16. Peace & justice, [SHS.SCIPO]Humanities and Social Sciences/Political science, 0506 political science, Economy, Political economy, Political Science and International Relations, Terrorism, Counter terrorism, European Union (EU)
Abstract: The EU has been making strong inroads into the realm of security over the last few years. This is a remarkable development, since security matters used to be the preserve of states. The articles presented in this special issue all testify to the breadth of the EU security agenda, as they all try to capture some aspects of the EU’s fast-changing security policies following the entry into force of the Lisbon Treaty on 1 December 2009. In parallel with a broadening of the EU’s security agenda, an increase in supranational security governance in the EU can also be observed. The transition to supranational governance is reached in two ways. First, cross-border security threats generate demand for EU laws, which supranational organisations then supply. Reasons for changes in the EU polity are exogenous shocks, the fact that rule innovations are endogenous to politics, the diffusion of organisational behaviour and models of action, and policy entrepreneurship, whereby institutional entrepreneurs construct and revise ‘policy frames’, which engage other actors and define new relationships between them and chart courses of action. As the articles in this special issue demonstrate, 11 September 2001 provided such a major exogenous shock required for a change in the EU polity, which EU institutions exploited by providing increasing EU legislation, and even, as a by-product, stabilising a European legal order.
Published: 2012

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