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2,925 results on '"University of California [San Francisco] ( UCSF )"'

1. Stanislaus County Office of Education: 'Project Cal-Well Journey'

Author: WestEd, University of California, San Francisco (UCSF), and California Department of Education
Abstract: This brief outlines how the Stanislaus County Office of Education (SCOE) supports the educational and mental health needs of 25 school districts in the county. SCOE partnered with three school districts--Hughson Unified, Patterson, and Turlock--to enhance their school-based mental health programs for approximately 22,000 students. The brief highlights various initiatives undertaken by SCOE through Project Cal-Well, including: (1) mental health training for staff and students; (2) the creation of wellness spaces based on student input; (3) the implementation of universal mental health screening systems across districts using tools like the Covitality screening tool; and (4) the expansion of National Alliance on Mental Illness (NAMI) On Campus Clubs to promote advocacy and awareness campaigns related to mental health. Additionally, the brief mentions efforts made toward increasing availability and access to school-based mental health services through referral pathways and building partnerships with community organizations, such as Sandy Hook Promise's Start With Hello program at Turlock USD. Overall, SCOE aims to sustain these initiatives beyond the initial funding period through strategic alignment with existing programs focused on children's behavioral health care.
Published: 2024

2. Paradise Unified School District: 'Building School Mental Health Systems to Support Healing and Recovery through Project Cal-Well'

Author: WestEd, University of California, San Francisco (UCSF), and California Department of Education
Abstract: This brief details the significant strides made by the Paradise Unified School District (PUSD) in establishing robust school mental health systems to facilitate healing and recovery. PUSD, which serves the rural communities of Paradise, Magalia, and Stirling City--areas deeply affected by the 2018 Camp Fire--has launched several key initiatives through Project Cal-Well. These initiatives focus on creating supportive school climates, expanding access to mental health services, and fostering partnerships to enhance overall well-being. The brief underscores PUSD's notable achievements in reducing feelings of chronic sadness and hopelessness among its students and in lowering suicide rates. These positive outcomes underscore the district's commitment to the long-term maintenance and improvement of mental health supports. With the aid of grants and the creation of resource centers on each school campus, PUSD is determined to ensure the continuity and growth of these vital programs, demonstrating a sustainable model for fostering student mental health and resilience.
Published: 2024

3. Northern Humboldt Union High School District: 'Aligning Mental Health Initiatives with a Multi-Tiered System of Supports through Project Cal-Well'

Author: WestEd, University of California, San Francisco (UCSF), and California Department of Education
Abstract: Project Cal-Well is a cross-agency mental health initiative led by the California Department of Education focused on building capacity for sustainable school-based mental health systems in local educational agencies (LEAs) throughout California. As part of a series highlighting the work of Project Cal-Well partners in Cohort 2 (2019-2024), this brief summarizes how Northern Humboldt Union High School District leveraged Project Cal-Well funding to shift to a Multi-Tiered System of Support approach to implement a sustainable school mental health system, strengthen connections with community partners, and empower staff to take a proactive approach to supporting students' mental health.
Published: 2024

4. Del Norte Unified School District: 'A Comprehensive Approach to Mental Health Services through Project Cal-Well'

Author: WestEd, University of California, San Francisco (UCSF), and California Department of Education
Abstract: This overview highlights Del Norte Unified School District's (DNUSD) approach to enhancing student mental health services via Project Cal-Well. DNUSD is committed to fostering positive school environments and has expanded its Social and Emotional Learning (SEL) Committee to further this goal. The district has launched various mental health awareness campaigns and employs data-driven methods to refine its decision-making processes. A significant achievement is the establishment of a closed-loop referral system, which ensures that students with unmet mental health needs are able to efficiently access school-based wellness centers. Moreover, DNUSD strategically utilizes funding to bolster support for young people facing significant mental health challenges. These efforts continue to grow, reaching beyond the scope of Project Cal-Well, as the district strives to sustainably improve student well-being within its schools and the broader community.
Published: 2024

5. Project Cal-Well: Building Sustainable School-Based Mental Health Systems

Author: WestEd, University of California, San Francisco (UCSF), and California Department of Education
Abstract: The California Department of Education's Project Cal-Well aims to promote awareness of student mental health and improve access to mental health services for youth, families, and school communities. This brief introduces a series of Project Cal-Well Legacy Briefs that highlight successes achieved by Project Cal-Well partners. WestEd developed the briefs in collaboration with project partners and program evaluators at the University of California, San Francisco.
Published: 2024

6. Sacramento County Office of Education: Transforming Schools into Centers of Wellness

Author: WestEd, California Department of Education, and University of California, San Francisco (UCSF)
Abstract: This brief focuses on the Sacramento County Office of Education (SCOE) and its efforts to transform schools into centers of wellness. SCOE serves 13 school districts with nearly 250,000 students, prioritizing mental health professionals in every school and creating systems for all adults to contribute to supporting a school-community continuum of care. The document highlights various initiatives undertaken by SCOE through Project Cal-Well, including centralizing mental health services, building a mental health career pathway, expanding social-emotional learning (SEL), refining coordination of services teams (COST), developing collaborations and partnerships, sustaining the work through funding strategies, and actively sharing its successful practices statewide.
Published: 2024

7. How Should We Slice up the Executive Function Pie? Striving toward an Ontology of Cognitive Control Processes

Author: University of California, San Francisco (UCSF) and Silvia A. Bunge
Abstract: There is a vast literature on "executive functioning," or the control of one's thoughts and actions in pursuit of a goal. This broad construct is conceptualized as comprising multiple executive functions (EFs) that support academic achievement and other important life outcomes. However, there is a lack of consensus regarding what, exactly, these core EFs are. This commentary briefly reviews a few dominant models of EFs in developmental and cognitive psychology and outlines issues to be addressed; it then illustrates how insights from neuroscience could help us eliminate redundant terminology and identify EFs that have been largely overlooked. Reaching a consensus regarding the core set of EFs will inform efforts to scaffold EF development and improve educational outcomes.
Published: 2024
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8. Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine ( 131 I-MIBG) therapy for neuroblastoma.

Author: Department of Pediatrics, University of Michigan and Mott Children's Hospital, Ann Arbor, Michigan, Department of Pediatrics, UCSF Children's Hospital, University of California, San Francisco, California, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California, Nuclear Medicine Program, Department of Radiology, University of California San Francisco, UCSF Children's Hospital, San Francisco, California, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania ; University of Pennsylvania, Philadelphia, Pennsylvania, Department of Pediatrics, UCSF Children's Hospital, University of California, San Francisco, California ; Department of Pediatrics, University of California San Francisco, 505 Parnassus, M647, San Francisco, CA 94143-0106., Quach, Alekist, Ji, Lingyun, Mishra, Vikash, Sznewajs, Aimee, Veatch, Janet, Huberty, John, Franc, Benjamin, Sposto, Richard, Groshen, Susan, Wei, Denice, Fitzgerald, Paul, Maris, John M., Yanik, Gregory, Hawkins, Randall A., Villablanca, Judith G., Matthay, Katherine K., Department of Pediatrics, University of Michigan and Mott Children's Hospital, Ann Arbor, Michigan, Department of Pediatrics, UCSF Children's Hospital, University of California, San Francisco, California, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California, Nuclear Medicine Program, Department of Radiology, University of California San Francisco, UCSF Children's Hospital, San Francisco, California, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania ; University of Pennsylvania, Philadelphia, Pennsylvania, Department of Pediatrics, UCSF Children's Hospital, University of California, San Francisco, California ; Department of Pediatrics, University of California San Francisco, 505 Parnassus, M647, San Francisco, CA 94143-0106., Quach, Alekist, Ji, Lingyun, Mishra, Vikash, Sznewajs, Aimee, Veatch, Janet, Huberty, John, Franc, Benjamin, Sposto, Richard, Groshen, Susan, Wei, Denice, Fitzgerald, Paul, Maris, John M., Yanik, Gregory, Hawkins, Randall A., Villablanca, Judith G., and Matthay, Katherine K.
Abstract: Background 131 I-Metaiodobenzylguanidine ( 131 I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and 131 I-MIBG is concentrated in the liver after 131 I-MIBG therapy. The aim of our study was to analyze the effects of 131 I-MIBG therapy on thyroid and liver function. Procedure Pre- and post-therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with 131 I-MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow-up, sex, and patient age was examined. Results In patients who presented with Grade 0 or 1 thyroid toxicity at baseline, 12????????4% experienced onset of or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by 2 years after 131 I-MIBG therapy. At 2 years post- 131 I-MIBG therapy, 76????????4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23????????5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies. Conclusion The prophylactic regimen of potassium iodide and potassium perchlorate with 131 I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following 131 I-MIBG therapy were primarily reversible and did not result in late toxicity. 131 I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction. Pediatr Blood Cancer 2011;56:191???201. ?? 2010 Wiley-Liss, Inc.
Published: 2011

9. Making the field of computing more inclusive

Author: John \\'Scooter\\' Morris, Tovi Grossman, Jonathan Lazar, Gerrit C. van der Veer, Jennifer Mankoff, Elizabeth F. Churchill, Philippe Palanque, Towson University [Towson, MD, United States], University of Maryland System, Google Inc., Autodesk Research, University of Twente [Netherlands], Vrije Universiteit Amsterdam [Amsterdam] (VU), Open University of the Netherlands [Heerlen], Dalian Maritime University, Luxun Academy of Fine Arts - LAFA (Shenyang, Chine), Luxun Academy of Fine Arts (Shenyang) (LAFA), Interactive Critical Systems (IRIT-ICS), 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 California [San Francisco] (UCSF), University of California, Carnegie Mellon University [Pittsburgh] (CMU), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université Toulouse - Jean Jaurès - UT2J (FRANCE), Université Toulouse 1 Capitole - UT1 (FRANCE), Dalian Maritime University - DMU (CHINA), Google Inc. (USA), Luxun Academy of Fine Arts - LAFA (CHINA), Open Universiteit - OU (NETHERLANDS), University of California, San Francisco - UCSF (USA), University of Twente (NETHERLANDS), Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), University of California [San Francisco] ( UCSF ), Carnegie Mellon University [Pittsburgh] ( CMU ), Software and Sustainability (S2), Network Institute, Software & Services, and Institut National Polytechnique de Toulouse - INPT (FRANCE)
Subjects: [INFO.INFO-AR]Computer Science [cs]/Hardware Architecture [cs.AR], [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, SDG 16 - Peace, General Computer Science, Computer science, [ INFO.INFO-CR ] Computer Science [cs]/Cryptography and Security [cs.CR], [ INFO.INFO-SE ] Computer Science [cs]/Software Engineering [cs.SE], 02 engineering and technology, [INFO.INFO-SE]Computer Science [cs]/Software Engineering [cs.SE], Interface homme-machine, [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], Lead (geology), [ INFO.INFO-HC ] Computer Science [cs]/Human-Computer Interaction [cs.HC], Human–computer interaction, Architectures Matérielles, 020204 information systems, 0202 electrical engineering, electronic engineering, information engineering, Génie logiciel, 0501 psychology and cognitive sciences, [ INFO.INFO-ES ] Computer Science [cs]/Embedded Systems, [INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC], 050107 human factors, ComputingMilieux_MISCELLANEOUS, ComputingMilieux_THECOMPUTINGPROFESSION, Field (Bourdieu), 05 social sciences, SDG 16 - Peace, Justice and Strong Institutions, Modélisation et simulation, Accessibility, Systèmes embarqués, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Justice and Strong Institutions, Emerging technologies, Human-centered computing, Cryptographie et sécurité, [INFO.INFO-ES]Computer Science [cs]/Embedded Systems, [ INFO.INFO-AR ] Computer Science [cs]/Hardware Architecture [cs.AR]
Abstract: People with disabilities are a potential source of ideas and additional membership for professional computing organizations. Including people with disabilities in the decision-making processes of professional computing organizations ensures the most important barriers are addressed first. SIGCHI is one of ACM's largest special interest groups, with approximately 3,500 members as of 2016. SIGCHI has three goals, underscore the importance of stakeholder engagement; offer broad suggestions for how large SIGs can improve the inclusiveness of physical events and digital content; and underscore that addressing physical and digital accessibility is an ongoing process that takes time, with involvement of many stakeholders. These stakeholders must work together to drive the creation of acceptable and accepted guidelines and resources, find individuals with expertise to work in an advisory capacity, and find volunteers to implement effective strategies and provide feedback regarding the policies and guidelines in action. SIGCHI's hope is that SIGCHI will be a community that is perceived as welcoming for all researchers and practitioners with disabilities. Large SIGs, when they educate others about digital and physical accessibility, can have significant influence on the conference locations they rent and the universities and companies that employ their members. ACM has a leading role to play by ensuring all SIGs strive to be inclusive and by thus being a role model for other professional associations. The best way to handle such responsibility would ultimately be to ensure there are professional staff supporting and centralizing the most vital accessibility needs and accessibility is included in contractual relationships.
Published: 2017
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10. Cross-sectional and longitudinal characterization of SCD patients recruited from the community versus from a memory clinic: subjective cognitive decline, psychoaffective factors, cognitive performances, and atrophy progression over time

Author: Denis Vivien, Audrey Perrotin, Clémence Tomadesso, Béatrice Desgranges, Alexandre Bejanin, Siya Sherif, Renaud La Joie, Brigitte Landeau, Inès Moulinet, Géraldine Poisnel, Elizabeth Kuhn, Vincent de la Sayette, G. Chételat, Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurology [San Francisco, CA, États-Unis], Memory and Aging Center [San Francisco, CA, États-Unis], University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche clinique [CHU Caen] (CRC), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), The study was supported by Fondation Plan Alzheimer (Alzheimer Plan 2008–2012), Programme Hospitalier de Recherche Clinique (PHRCN 2011-A01493-38 and PHRCN 2012 12-006-0347), Agence Nationale de la Recherche (LONGVIE 2007), Région Basse-Normandie, Association France Alzheimer et maladies apparentées AAP 2013, the Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Caen Normandy., University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Normandie Université (NU)-Normandie Université (NU)-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), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, and Bodescot, Myriam
Subjects: 0301 basic medicine, Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Neocortex, Anxiety, lcsh:RC346-429, 0302 clinical medicine, hemic and lymphatic diseases, Longitudinal Studies, Cognitive decline, Gray Matter, Depression (differential diagnoses), Subclinical infection, Aged, 80 and over, education.field_of_study, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Depression, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Cognition, Middle Aged, Mental Status and Dementia Tests, Magnetic Resonance Imaging, Neurology, Disease Progression, Female, medicine.symptom, Pathological ageing, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Cognitive Neuroscience, Population, Prodromal Symptoms, Neuroimaging, lcsh:RC321-571, 03 medical and health sciences, Diagnostic Self Evaluation, Atrophy, Alzheimer Disease, Internal medicine, medicine, Humans, Cognitive Dysfunction, cardiovascular diseases, education, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Preclinical Alzheimer’s disease, Aged, Memory Disorders, business.industry, Research, Memory clinic, medicine.disease, 030104 developmental biology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Cross-Sectional Studies, Positron-Emission Tomography, Psychoaffective factors, Subjective cognitive decline, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Follow-Up Studies
Abstract: Background Subjective cognitive decline (SCD) defines a heterogeneous population, part of which having Alzheimer’s disease (AD). We aimed at characterizing SCD populations according to whether or not they referred to a memory clinic, by assessing the factors associated with increased AD risk. Methods Seventy-eight cognitively unimpaired older adults from the IMAP+ study (Caen) were included, amongst which 28 healthy controls (HC) and 50 SCD recruited from the community (SCD-community; n = 23) or from a memory clinic (SCD-clinic; n = 27). Participants underwent cognitive, psychoaffective, structural MRI, FDG-PET, and amyloid-PET assessments. They were followed up over a mean period of 2.4 ± 0.8 years. The groups were compared in terms of baseline and follow-up levels of SCD (self- and informant-reported), cognition, subclinical anxiety and depression, and atrophy progression over time. We also investigated SCD substrates within each SCD group through the correlations between self-reported SCD and other psychometric and brain measures. Results Compared to HC, both SCD groups showed similar cognitive performances but higher informant-reported SCD and anxiety. Compared to SCD-community, SCD-clinic showed higher informant-reported SCD, depression score, and atrophy progression over time but similar brain amyloid load. A significant increase over time was found for depression in the SCD-community and for self-reported praxis-domestic activities SCD factor in the SCD-clinic. Higher self-reported SCD correlated with (i) lower grey matter volume and higher anxiety in SCD-community, (ii) greater informant-reported SCD in SCD-clinic, and (iii) lower glucose metabolism in both SCD groups. Conclusions Higher subclinical depression and informant-reported SCD specifically characterize the SCD group that refers to a memory clinic. The same group appears as a frailer population than SCD-community as they show greater atrophy progression over time. Yet, both the SCD groups were quite similar otherwise including for brain amyloid load and the SCD-community showed increased depression score over time. Altogether, our findings highlight the relevance of assessing psychoaffective factors and informant-reported SCD in SCD populations and point to both differences and similarities in SCD populations referring or not to a memory clinic. Electronic supplementary material The online version of this article (10.1186/s13195-019-0514-z) contains supplementary material, which is available to authorized users.
Published: 2019
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11. Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma

Author: Emma Lefrançais, Eugene R. Bleecker, Mark R. Looney, Prescott G. Woodruff, Bruce D. Levy, Brenda R. Phillips, Mario Castro, Michael C. Peters, Wilfred W. Raymond, Eleanor M. Dunican, Marrah E. Lachowicz-Scroggins, Andrea M. Coverstone, Erin D. Gordon, David T. Mauger, Elliot Israel, Merritt L. Fajt, Annette T. Hastie, Serpil C. Erzurum, Nizar N. Jarjour, Mats W. Johansson, Suzy A. A. Comhair, Annabelle R. Charbit, John V. Fahy, Sally E. Wenzel, Division of Pulmonary and Critical Care Medicine [San Francisco, CA, États-Unis], Center for Tuberculosis [San Francisco, CA, États-Unis], University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Male, Inflammasomes, Neutrophils, [SDV]Life Sciences [q-bio], Respiratory System, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Extracellular Traps, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, caspase 1, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], IL-1 beta, 2.1 Biological and endogenous factors, 030212 general & internal medicine, Longitudinal Studies, Aetiology, Lung, ComputingMilieux_MISCELLANEOUS, Blotting, Inflammasome, Middle Aged, 3. Good health, IL-1β, Acute Disease, Respiratory, Female, medicine.symptom, Western, medicine.drug, Pulmonary and Respiratory Medicine, Adult, Blotting, Western, neutrophil extracellular traps, Caspase 1, Glucosephosphate Dehydrogenase, 03 medical and health sciences, Clinical Research, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Secretion, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Asthma, business.industry, Interleukin-6, Inflammatory and immune system, Interleukin-8, Editorials, Neutrophil extracellular traps, DNA, asthma, medicine.disease, In vitro, respiratory tract diseases, Good Health and Well Being, 030228 respiratory system, Case-Control Studies, Immunology, Sputum, Airway, business, extracellular DNA
Abstract: Rationale: Extracellular DNA (eDNA) and neutrophil extracellular traps (NETs) are implicated in multiple inflammatory diseases. NETs mediate inflammasome activation and IL-1β secretion from monocytes and cause airway epithelial cell injury, but the role of eDNA, NETs, and IL-1β in asthma is uncertain. Objectives: To characterize the role of activated neutrophils in severe asthma through measurement of NETs and inflammasome activation. Methods: We measured sputum eDNA in induced sputum from 399 patients with asthma in the Severe Asthma Research Program-3 and in 94 healthy control subjects. We subdivided subjects with asthma into eDNA-low and -high subgroups to compare outcomes of asthma severity and of neutrophil and inflammasome activation. We also examined if NETs cause airway epithelial cell damage that can be prevented by DNase. Measurements and Main Results: We found that 13% of the Severe Asthma Research Program-3 cohort is "eDNA-high," as defined by sputum eDNA concentrations above the upper 95th percentile value in health. Compared with eDNA-low patients with asthma, eDNA-high patients had lower Asthma Control Test scores, frequent history of chronic mucus hypersecretion, and frequent use of oral corticosteroids for maintenance of asthma control (all P values
Published: 2019
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12. Evidence for hormonal control of heart regenerative capacity during endothermy acquisition

Author: Malcom Maden, Michael J. Wolfgang, Guang Hu, Hao Zhang, Rochelle Buffenstein, Guo N. Huang, Emily Wilson, Michael M. Yartsev, Luke I. Szweda, Ellen Gillett, Dominic Lunn, Sandra E Muroy, Stephen Cutie, Frédéric Flamant, Rachel B. Bigley, DeeAnn M. Reeder, Kenneth A. Field, Jeffrey E. Olgin, Tobias A. Schmid, Megan Smith, Kentaro Hirose, Jiajia Wang, Romain Guyot, Thomas S. Scanlan, Alison Hoang, Alexander Y. Payumo, Frank Grützner, Hongyao Yu, Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, Dominican University of California, Department of Medicine, Division of Cardiology, University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences [Durham] (NIEHS-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Calico Life Sciences, School of Biological Sciences, University of South Australia [Adelaide], Department of Molecular and Cell Biology, University of California [Berkeley], Helen Wills Neuroscience Institute and Department of Bioengineering, Department of Biology, Bucknell University, Department of Biology and UF Genetics Institute, University of Florida [Gainesville], Department of Biological Chemistry, Johns Hopkins University School of Medicine [Baltimore], Department of Physiology and Pharmacology, Oregon State University (OSU), University of Texas Southwestern Medical Center, JSPS Overseas Research Fellowships UCSF-IRACDA postdoctoral fellowship NIGMS IMSD fellowship Hillblom fellowship Australian Research Council French National Research Agency (ANR)ANR-15-CE14-0011-01United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS)1ZIAES102745United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAR01HL13845R00HL114738Edward Mallinckrodt Jr. Foundation March of Dimes Basil O'Conner Scholar Award American Heart Association American Federation for Aging Research Life Sciences Research Foundation Program for Breakthrough Biomedical Research UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Seed Grant UCSF Academic Senate Committee on Research REAC Award (Harris Fund) United States Department of Defense Cardiovascular Research Institute, École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of Florida [Gainesville] (UF), University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), University of California [Berkeley] (UC Berkeley), National Institute of Environmental Health Sciences, National Institutes of Health, Life Sciences, University of Adelaide, Johns Hopkins University, School of Medicine, and Oregon Health & Science University
Subjects: 0301 basic medicine, Adult Newt, [SDV]Life Sciences [q-bio], Proliferation, 030204 cardiovascular system & hematology, Cardiovascular, Regenerative Medicine, Mice, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Receptors, Thyroid Hormone, 2.1 Biological and endogenous factors, Myocyte, Myocytes, Cardiac, Aetiology, Receptor, Zebrafish, Phylogeny, Multidisciplinary, Receptors, Thyroid Hormone, Thyroid, Temperature, Heart, Lizards, Cell biology, Cardiovascular physiology, Heart Disease, medicine.anatomical_structure, Signal transduction, Cardiac, Body Temperature Regulation, Signal Transduction, Thyroid Hormones, Consumption, General Science & Technology, Activation, Biology, Energy-expenditure, Article, Polyploidy, 03 medical and health sciences, medicine, Animals, Regeneration, [INFO]Computer Science [cs], Cell Proliferation, Myocytes, Regeneration (biology), Cell Cycle Checkpoints, biology.organism_classification, Diploidy, Recombination, 030104 developmental biology, Metabolic-rate, Hormone
Abstract: The price of staying warm Among vertebrates, zebrafish and salamanders can regenerate their hearts, whereas adult mice and humans cannot. Hirose et al. analyzed diploid cardiomyocyte frequency as a proxy for cardiac regenerative potential across 41 vertebrate species (see the Perspective by Marchianò and Murry). They observed an inverse correlation of these cells with thyroid hormone concentrations during the ectotherm-to-endotherm transition. Mice with defects in thyroid hormone signaling retained significant heart regenerative capacity, whereas zebrafish exposed to excessive thyroid hormones exhibit impaired cardiac repair. Loss of heart regenerative ability in mammals may represent a trade-off for increases in metabolism necessary for the development of endothermy. Science , this issue p. 184 ; see also p. 123
Published: 2019
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13. Development of new TB regimens : harmonizing trial design, product registration requirements, and public health guidance

Author: Payam Nahid, Marco Cavaleri, Christian Lienhardt, Andrew Vernon, Sumati Nambiar, Bodescot, Myriam, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Division of TB Elimination [Atlanta, GA, États-Unis], National Center for HIV, Viral Hepatitis, STD and TB Prevention [Atlanta, GA, États-Unis], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention-Centers for Disease Control and Prevention-Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention-Centers for Disease Control and Prevention, Office of Anti-infective and Vaccines [Amsterdam, Pays-Bas], Human Medicines Evaluation [Amsterdam, Pays-Bas], European Medicines Agency [Amsterdam, Pays-Bas] (EMA)-European Medicines Agency [Amsterdam, Pays-Bas] (EMA), Division of Anti-Infective Products [Silver Spring, MD, États-Unis], Center for Drug Evaluation and Research [Silver Spring, MD, États-Unis], U.S. Food and Drug Administration (FDA)-U.S. Food and Drug Administration (FDA), Division of Pulmonary and Critical Care Medicine [San Francisco, CA, États-Unis], Center for Tuberculosis [San Francisco, CA, États-Unis], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, and Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI)
Subjects: Bacterial Diseases, Research design, Antitubercular Agents, 030204 cardiovascular system & hematology, Medical and Health Sciences, 0302 clinical medicine, Policy decision, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Drug approval, Public and Occupational Health, 030212 general & internal medicine, Policy Making, Drug Approval, Clinical Trials as Topic, Collection Review, Pharmaceutics, General Medicine, Public relations, humanities, 3. Good health, Treatment Outcome, Infectious Diseases, Research Design, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Science policy, Public Health, Infection, medicine.medical_specialty, Drug Research and Development, Science Policy, Endpoint Determination, Clinical Trials and Supportive Activities, MEDLINE, Research and Analysis Methods, 03 medical and health sciences, Rare Diseases, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Drug Therapy, Clinical Research, General & Internal Medicine, medicine, Humans, Tuberculosis, Clinical Trials, Product (category theory), Pharmacology, Health Care Policy, business.industry, Prevention, Public health, Drug Policy, Tropical Diseases, 8.4 Research design and methodologies (health services), Health Care, Clinical trial, Orphan Drug, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, Clinical Medicine, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Biomarkers
Abstract: International audience; • Regulatory approval of new tuberculosis (TB) drugs can be based on data from trial(s) using a surrogate endpoint of treatment efficacy under an accelerated or conditional procedure. In such circumstances, policy makers and TB programs can be hampered in their ability to make recommendations on the optimal use of the drug(s), and consequently , the uptake by national or international public health institutions of such recommendations can be limited. • Based on the essential need to produce high-quality evidence for policy decisions, this paper reflects on specific methodological issues in clinical trial design that need to be addressed to improve compliance with clinical, regulatory, and public health requirements. • Established mechanisms for communication between drug developers and regulators already exist; however, equal engagement with policy makers is also essential for the optimal selection of trial designs, endpoints, and markers of treatment outcome and for giving consideration to public health and program aspects. • The next generation of TB trials should better reconcile the research agenda with the need for global policies on access to TB medicines. Policy decision-makers should establish formal mechanisms for iterative feedback on regimen-development pathways. In this paper, we provide examples of how the need for interactions between regulators, tri-alists, and policy decision-makers can be addressed.
Published: 2019
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14. Quantifying the effects of 16p11.2 copy number variants on brain structure: A multisite genetic-first study

Author: Sandra Martin-Brevet, Borja Rodríguez-Herreros, Jared A. Nielsen, Clara Moreau, Claudia Modenato, Anne M. Maillard, Aurélie Pain, Sonia Richetin, Aia E. Jønch, Abid Y. Qureshi, Nicole R. Zürcher, Philippe Conus, Wendy K. Chung, Elliott H. Sherr, John E. Spiro, Ferath Kherif, Jacques S. Beckmann, Nouchine Hadjikhani, Alexandre Reymond, Randy L. Buckner, Bogdan Draganski, Sébastien Jacquemont, Marie-Claude Addor, Joris Andrieux, Benoît Arveiler, Geneviève Baujat, Frédérique Sloan-Béna, Marco Belfiore, Dominique Bonneau, Sonia Bouquillon, Odile Boute, Alfredo Brusco, Tiffany Busa, Jean-Hubert Caberg, Dominique Campion, Vanessa Colombert, Marie-Pierre Cordier, Albert David, François-Guillaume Debray, Marie-Ange Delrue, Martine Doco-Fenzy, Ulrike Dunkhase-Heinl, Patrick Edery, Christina Fagerberg, Laurence Faivre, Francesca Forzano, David Genevieve, Marion Gérard, Daniela Giachino, Agnès Guichet, Olivier Guillin, Delphine Héron, Bertrand Isidor, Aurélia Jacquette, Sylvie Jaillard, Hubert Journel, Boris Keren, Didier Lacombe, Sébastien Lebon, Cédric Le Caignec, Marie-Pierre Lemaître, James Lespinasse, Michèle Mathieu-Dramart, Sandra Mercier, Cyril Mignot, Chantal Missirian, Florence Petit, Kristina Pilekær Sørensen, Lucile Pinson, Ghislaine Plessis, Fabienne Prieur, Caroline Rooryck-Thambo, Massimiliano Rossi, Damien Sanlaville, Britta Schlott Kristiansen, Caroline Schluth-Bolard, Marianne Till, Mieke Van Haelst, Lionel Van Maldergem, Hanalore Alupay, Benjamin Aaronson, Sean Ackerman, Katy Ankenman, Ayesha Anwar, Constance Atwell, Alexandra Bowe, Arthur L. Beaudet, Marta Benedetti, Jessica Berg, Jeffrey Berman, Leandra N. Berry, Audrey L. Bibb, Lisa Blaskey, Jonathan Brennan, Christie M. Brewton, Randy Buckner, Polina Bukshpun, Jordan Burko, Phil Cali, Bettina Cerban, Yishin Chang, Maxwell Cheong, Vivian Chow, Zili Chu, Darina Chudnovskaya, Lauren Cornew, Corby Dale, John Dell, Allison G. Dempsey, Trent Deschamps, Rachel Earl, James Edgar, Jenna Elgin, Jennifer Endre Olson, Yolanda L. Evans, Anne Findlay, Gerald D. Fischbach, Charlie Fisk, Brieana Fregeau, Bill Gaetz, Leah Gaetz, Silvia Garza, Jennifer Gerdts, Orit Glenn, Sarah E. Gobuty, Rachel Golembski, Marion Greenup, Kory Heiken, Katherine Hines, Leighton Hinkley, Frank I. Jackson, Julian Jenkins, Rita J. Jeremy, Kelly Johnson, Stephen M. Kanne, Sudha Kessler, Sarah Y. Khan, Matthew Ku, Emily Kuschner, Anna L. Laakman, Peter Lam, Morgan W. Lasala, Hana Lee, Kevin LaGuerre, Susan Levy, Alyss Lian Cavanagh, Ashlie V. Llorens, Katherine Loftus Campe, Tracy L. Luks, Elysa J. Marco, Stephen Martin, Alastair J. Martin, Gabriela Marzano, Christina Masson, Kathleen E. McGovern, Rebecca McNally Keehn, David T. Miller, Fiona K. Miller, Timothy J. Moss, Rebecca Murray, Srikantan S. Nagarajan, Kerri P. Nowell, Julia Owen, Andrea M. Paal, Alan Packer, Patricia Z. Page, Brianna M. Paul, Alana Peters, Danica Peterson, Annapurna Poduri, Nicholas J. Pojman, Ken Porche, Monica B. Proud, Saba Qasmieh, Melissa B. Ramocki, Beau Reilly, Timothy P.L. Roberts, Dennis Shaw, Tuhin Sinha, Bethanny Smith-Packard, Anne Snow Gallagher, Vivek Swarnakar, Tony Thieu, Christina Triantafallou, Roger Vaughan, Mari Wakahiro, Arianne Wallace, Tracey Ward, Julia Wenegrat, Anne Wolken, 16p11.2 European Consortium, Simons Variation in Individuals Project (VIP) Consortium, CSIR-Institute of Microbial Technology [Chandigarh] (IMTech), Council of Scientific and Industrial Research [India] (CSIR), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Human Genetics, Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), The Wellcome Trust Sanger Institute [Cambridge], Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Génétique Humaine, Développement et Cancer, Université Bordeaux Segalen - Bordeaux 2, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Guglielmo Marconi University [Roma], Laboratoire de biomécanique (LBM), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Systèmes de Référence Temps Espace (SYRTE), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medical Sciences, Università degli studi di Torino (UNITO), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Department of Clinical Genetics, Vejle Hospital, Institute of Child Health, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Génétique Médicale, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA)-Hôpital Chubert, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), 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), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), 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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Department of Genomics of Common Disease, Imperial College London, Regional Hospital, Department of Psychiatry and Behavioral Sciences! (UW psychiatry), University of Washington [Seattle], University of California, San Francisco (UCSF), UCSF, Unité de Recherches Zootechniques (URZ), Institut National de la Recherche Agronomique (INRA), University of California [San Francisco] (UCSF), University of California, UCL Institute of Neurology, Biomagnetic Imaging Laboratory - University of California, SFARI219193, Simons Foundation, 31003A160203, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Roger De Spoelberch, Partridge Foundations, Jeanne et Jean Louis Levesque Foundation, 604102, Seventh Framework Programme, Canada Research Chairs, CRSII33-133044, SNSF Sinergia, 32003B_159780, SNSF National Centre of Competence in Research Synapsy, Foundation Parkinson Switzerland, Foundation Synapsis, Université de Lausanne = University of Lausanne (UNIL), CHU Sainte Justine [Montréal], Harvard University [Cambridge], Odense University Hospital (OUH), Department of radiology (Massachusetts General Hospital), Department of Psychiatry Massachusetts General Hospital (MGH), Columbia University [New York], Simons Foundation, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Gothenburg (GU), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vejle Hospital [Danemark], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Harvard University, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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 de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), University of Lausanne (UNIL), Centre de recherche du CHU Sainte-Justine [Montreal], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Human genetics, Institute of Microbial Technology (IMTECH), Intitute of Microbial Technology, Gillberg Neuropsychiatry Centre, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], PSL Research University (PSL)-PSL Research University (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Bretagne Atlantique-Hôpital Chubert, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [APHP], Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Addor, M.C., Andrieux, J., Arveiler, B., Baujat, G., Sloan-Béna, F., Belfiore, M., Bonneau, D., Bouquillon, S., Boute, O., Brusco, A., Busa, T., Caberg, J.H., Campion, D., Colombert, V., Cordier, M.P., David, A., Debray, F.G., Delrue, M.A., Doco-Fenzy, M., Dunkhase-Heinl, U., Edery, P., Fagerberg, C., Faivre, L., Forzano, F., Genevieve, D., Gérard, M., Giachino, D., Guichet, A., Guillin, O., Héron, D., Isidor, B., Jacquette, A., Jaillard, S., Journel, H., Keren, B., Lacombe, D., Lebon, S., Le Caignec, C., Lemaître, M.P., Lespinasse, J., Mathieu-Dramart, M., Mercier, S., Mignot, C., Missirian, C., Petit, F., Pilekær Sørensen, K., Pinson, L., Plessis, G., Prieur, F., Rooryck-Thambo, C., Rossi, M., Sanlaville, D., Schlott Kristiansen, B., Schluth-Bolard, C., Till, M., Van Haelst, M., Van Maldergem, L., Alupay, H., Aaronson, B., Ackerman, S., Ankenman, K., Anwar, A., Atwell, C., Bowe, A., Beaudet, A.L., Benedetti, M., Berg, J., Berman, J., Berry, L.N., Bibb, A.L., Blaskey, L., Brennan, J., Brewton, C.M., Buckner, R., Bukshpun, P., Burko, J., Cali, P., Cerban, B., Chang, Y., Cheong, M., Chow, V., Chu, Z., Chudnovskaya, D., Cornew, L., Dale, C., Dell, J., Dempsey, A.G., Deschamps, T., Earl, R., Edgar, J., Elgin, J., Olson, J.E., Evans, Y.L., Findlay, A., Fischbach, G.D., Fisk, C., Fregeau, B., Gaetz, B., Gaetz, L., Garza, S., Gerdts, J., Glenn, O., Gobuty, S.E., Golembski, R., Greenup, M., Heiken, K., Hines, K., Hinkley, L., Jackson, F.I., Jenkins, J., Jeremy, R.J., Johnson, K., Kanne, S.M., Kessler, S., Khan, S.Y., Ku, M., Kuschner, E., Laakman, A.L., Lam, P., Lasala, M.W., Lee, H., LaGuerre, K., Levy, S., Cavanagh, A.L., Llorens, A.V., Campe, K.L., Luks, T.L., Marco, E.J., Martin, S., Martin, A.J., Marzano, G., Masson, C., McGovern, K.E., McNally Keehn, R., Miller, D.T., Miller, F.K., Moss, T.J., Murray, R., Nagarajan, S.S., Nowell, K.P., Owen, J., Paal, A.M., Packer, A., Page, P.Z., Paul, B.M., Peters, A., Peterson, D., Poduri, A., Pojman, N.J., Porche, K., Proud, M.B., Qasmieh, S., Ramocki, M.B., Reilly, B., Roberts, TPL, Shaw, D., Sinha, T., Smith-Packard, B., Gallagher, A.S., Swarnakar, V., Thieu, T., Triantafallou, C., Vaughan, R., Wakahiro, M., Wallace, A., Ward, T., Wenegrat, J., and Wolken, A.
Subjects: Adult, Male, 0301 basic medicine, Adolescent, DNA Copy Number Variations, [SDV]Life Sciences [q-bio], Autism Spectrum Disorder/diagnostic imaging, Autism Spectrum Disorder/genetics, Brain/pathology, Child, Chromosome Deletion, Chromosome Duplication, Chromosomes, Human, Pair 16/genetics, Cognitive Dysfunction/diagnostic imaging, Cognitive Dysfunction/genetics, Female, Humans, Intellectual Disability/diagnostic imaging, Intellectual Disability/genetics, Language, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders/diagnostic imaging, Neurodevelopmental Disorders/genetics, Schizophrenia/diagnostic imaging, Schizophrenia/genetics, Young Adult, 16p11.2, Autism spectrum disorder, Copy number variant, Genetics, Imaging, Neurodevelopmental disorders, Biology, Biological Psychiatry, 03 medical and health sciences, 0302 clinical medicine, Transverse temporal gyrus, Neuroimaging, Intellectual Disability, medicine, Cognitive Dysfunction, Copy-number variation, ComputingMilieux_MISCELLANEOUS, Brain morphometry, Brain, medicine.disease, 16p112, 030104 developmental biology, Schizophrenia, Williams syndrome, Neuroscience, Insula, Chromosomes, Human, Pair 16, 030217 neurology & neurosurgery
Abstract: BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.
Published: 2018
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15. 2017 publication guidelines for structural modelling of small-angle scattering data from biomolecules in solution: an update

Author: Wayne A. Hendrickson, Lois Pollack, Javier Pérez, Nigel Kirby, Greg L. Hura, Patrice Vachette, Torsten Schwede, Dominique Durand, Jill Trewhella, Ann H. Kwan, John D. Westbrook, Timothy M. Ryan, Dmitri I. Svergun, Andrej Sali, David A. Jacques, Dina Schneidman-Duhovny, Anthony P. Duff, John A. Tainer, J. Mitchell Guss, Masaaki Sugiyama, Andrew E. Whitten, Frank Gabel, School of Molecular and Microbial Biosciences, The University of Sydney [Sydney], Ctr Natl Rech Sci, Inst Biochim & Biophys Mol & Cellulaire, Unite Mixte Rech 8619, Université Paris-Sud - Paris 11 ( UP11 ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), University of Sydney, School od Medicinal Sciences, SWING beamline, Biophysics Group ( SWING ), Synchrotron SOLEIL, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California [San Francisco] ( UCSF ) -California Institute for Quantitative Biosciences, Biozentrum, University of Basel ( Unibas ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Department of Chemistry and Chemical Biology, Center for Integrative Proteomics Research, Rutgers, Rutgers, The State University of New Jersey [New Brunswick] ( RUTGERS ), The University of Sydney, Université Paris-Sud - Paris 11 (UP11), 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), SWING beamline, Biophysics Group (SWING), Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] (UCSF), University of California-University of California, Biozentrum [Basel, Suisse], University of Basel (Unibas), 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), Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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), University of California [San Francisco] (UC San Francisco), and University of California (UC)-University of California (UC)
Subjects: 0301 basic medicine, Models, Molecular, Computer science, MESH : DNA, MESH: Editorial Policies, Biomolecular structure, 01 natural sciences, Field (computer science), small-angle scattering, MESH : Proteins, Data acquisition, X-Ray Diffraction, Structural Biology, MESH : RNA, MESH : Scattering, Small Angle, MESH: Animals, MESH: Proteins, Databases, Protein, integrative structural biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Scope (project management), MESH: DNA, MESH: X-Ray Diffraction, SAXS, Research Papers, 3. Good health, Sample quality, structural modelling, Small-angle scattering, MESH: Models, Molecular, Editorial Policies, MESH: Databases, Protein, MESH : Models, Molecular, 010402 general chemistry, 03 medical and health sciences, MESH : X-Ray Diffraction, MESH: RNA, Scattering, Small Angle, Animals, Humans, publication guidelines, MESH : Databases, Protein, MESH: Scattering, Small Angle, MESH: Humans, Task force, SANS, MESH : Humans, biomolecular structure, Proteins, DNA, Data science, proteins, 0104 chemical sciences, 030104 developmental biology, MESH : Editorial Policies, Data presentation, hybrid structural modelling, RNA, MESH : Animals, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: Updated guidelines are presented for publishing biomolecular small-angle scattering (SAS) experiments so that readers can independently assess the quality of the data and models presented. The focus is on solution scattering experiments with either X-rays (SAXS) or neutrons (SANS), where the primary goal is the generation and testing of three-dimensional models, particularly in the context of integrative/hybrid structural modelling., In 2012, preliminary guidelines were published addressing sample quality, data acquisition and reduction, presentation of scattering data and validation, and modelling for biomolecular small-angle scattering (SAS) experiments. Biomolecular SAS has since continued to grow and authors have increasingly adopted the preliminary guidelines. In parallel, integrative/hybrid determination of biomolecular structures is a rapidly growing field that is expanding the scope of structural biology. For SAS to contribute maximally to this field, it is essential to ensure open access to the information required for evaluation of the quality of SAS samples and data, as well as the validity of SAS-based structural models. To this end, the preliminary guidelines for data presentation in a publication are reviewed and updated, and the deposition of data and associated models in a public archive is recommended. These guidelines and recommendations have been prepared in consultation with the members of the International Union of Crystallography (IUCr) Small-Angle Scattering and Journals Commissions, the Worldwide Protein Data Bank (wwPDB) Small-Angle Scattering Validation Task Force and additional experts in the field.
Published: 2017
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16. Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers

Author: Jeffrey N. Martin, Frederick Hecht, Henri Alexandre Michaud, Christopher D. Pilcher, Devi SenGupta, Miguel de Mulder, Douglas F. Nixon, Jonah B. Sacha, Steven G. Deeks, Department of Microbiology, Immunology & Tropical Medicine [Washington, USA], The George Washington University Medical Center, Department of Clinical Research [Foster City, CA, USA], Gilead Sciences, Inc. [Foster City, CA, USA], Department of Medicine [San Francisco, CA, USA], Division of Experimental Medicine [San Francisco, CA, USA], University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, Department of Medicine [San Francisco, CA, USA] (HIV/AIDS Program), Department of Epidemiology & Biostatistics [San Francisco, CA, USA], University of California, Division of Pathobiology and Immunology [Portland, CA, USA], Oregon Health and Science University [Portland] (OHSU), 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), We gratefully acknowledge reagents supplied from the National Institutes of Health (NIH) AIDS Research and Reference Reagent Program. This work was supported in part by grant number 108248-51-RGRL from amfAR, The Foundation for AIDS Research, The Bill and Melinda Gates Foundation (BMGF:01434000363), the Peter and Shelagh Godsoe Family Foundation thorough the AIDS Research Institute at UCSF, Pfizer Inc. through a sponsored research agreement, and funds from the NIH (R01 AI076059, R56 AI084113, and P51 OD011092). This research was supported in part by a grant from the NIH, University of California, San Francisco-Gladstone Institute of Virology and Immunology Center for AIDS Research (P30 AI027763) and the District of Columbia Developmental Center for AIDS Research (P30 AI087714). The Options study is funded in part by National Institute of Allergy and Infectious Diseases (P01 AI071713). The SCOPE cohort is supported by the NIH (RO1 AI087145, K24 AI069994, U19 AI0961090, UL1 RR024131, and R24 AI067039)., University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), University of California (UC), and BMC, BMC
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], viruses, Peptide, HIV Infections, HIV Antibodies, Epitope, law.invention, Epitopes, 0302 clinical medicine, law, Cells, Cultured, chemistry.chemical_classification, Gag, Cultured, ELISPOT, Recombinant Proteins, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Capsid, 030220 oncology & carcinogenesis, Recombinant DNA, HIV/AIDS, Antibody, Infection, Elite Controllers, gag, Cells, Clinical Sciences, Gene Products, gag, Context (language use), Biology, Peripheral blood mononuclear cell, Antibodies, 03 medical and health sciences, Viral Proteins, Clinical Research, Virology, Gene Products, Humans, Research, Endogenous Retroviruses, HIV, Molecular biology, Peptide Fragments, HERV-K, 030104 developmental biology, Good Health and Well Being, chemistry, biology.protein, HIV-1, Capsid Proteins, Viremic non-controllers
Abstract: Background Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection. Results We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on the matrix (peptides 16 and 31), one on p15 (peptide 85), three on the capsid (peptides 81, 97 and 117), one on the nucleocapsid (peptide 137) and one on the QP1 protein (peptide 157). Four epitopes (peptides 16, 31, 85 and 137) were highly immunogenic. No significant differences in antibody responses were found between HIV infected participants (n = 40) and uninfected donors (n = 40) for 6 out of the 8 epitopes tested. The antibody response against nucleocapsid (peptide 137) was significantly lower (p
Published: 2017
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17. CCR2+ monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice

Author: Florian Sennlaub, Lucie Poupel, Olivier Levy, Noah Saederup, Nico van Rooijen, Shulong J. Hu, Sophie Lavalette, Elisa Dominguez, José-Alain Sahel, William Raoul, Israel F. Charo, Bertrand Calippe, Xavier Guillonneau, Francine Behar-Cohen, Christophe Combadière, Serge Camelo, Elodie Guyon, Emeline F. Nandrot, Constance Auvynet, Jean-Louis Bourges, Molecular cell biology and Immunology, CCA - Immuno-pathogenesis, Raoul, William, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'ophtalmologie [Hôtel-Dieu - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Gladstone Institute of Cardiovascular Disease, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Department of Medicine, University of California (UC)-University of California (UC)-Cardiovascular Research Institute, Department of Molecular Cell Biology, Free University Medical Center [Amsterdam], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), University of California [San Francisco] (UCSF), University of California-University of California, University of California-University of California-Cardiovascular Research Institute, Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), CIC - Quinze-Vingts, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of California [San Francisco] ( UCSF ), University of California [San Francisco] ( UCSF ) -Cardiovascular Research Institute, Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Retinal degeneration, Male, Pathology, CCR2, Chemokine, genetic structures, animal diseases, chemokines, Monocytes, age-related macular disease, neuroinflammation, Macular Degeneration, Mice, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Research Articles, Chemokine CCL2, Mice, Knockout, 0303 health sciences, biology, neurodegeneration, medicine.anatomical_structure, Neutrophil Infiltration, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, monocyte, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Receptors, Chemokine, medicine.symptom, Photoreceptor Cells, Vertebrate, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Receptors, CCR2, CX3C Chemokine Receptor 1, Inflammation, CCL2, 03 medical and health sciences, parasitic diseases, medicine, Animals, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030304 developmental biology, Retina, business.industry, Monocyte, Macular degeneration, medicine.disease, eye diseases, Mice, Inbred C57BL, 030221 ophthalmology & optometry, biology.protein, sense organs, business
Abstract: International audience; Atrophic age-related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal degeneration is unknown. We here show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2(+) inflammatory monocyte infiltration in patients. Using age- and light-induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 knockout mice, we show that subretinal Cx3cr1 deficient MPs overexpress CCL2 and that both the genetic deletion of CCL2 or CCR2 and the pharmacological inhibition of CCR2 prevent inflammatory monocyte recruitment, MP accumulation and photoreceptor degeneration in vivo. Our study shows that contrary to CCR2 and CCL2, CX3CR1 is constitutively expressed in the retina where it represses the expression of CCL2 and the recruitment of neurotoxic inflammatory CCR2(+) monocytes. CCL2/CCR2 inhibition might represent a powerful tool for controlling inflammation and neurodegeneration in AMD.
Published: 2013
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18. Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors

Author: Jeanette E. Eckel-Passow, Mark Lathrop, Stefan Schreiber, Ulrika Andersson, Jonine L. Bernstein, John K. Wiencke, Matthias Simon, Matthew L. Kosel, Marianne Labussière, Elizabeth B. Claus, Faith G. Davis, Francis Ali-Osman, Hugues Sicotte, Rose Lai, Lucie McCoy, Melissa L. Bondy, Preetha Rajaraman, Heinz-Erich Wichmann, Markus M. Nöthen, Margaret Wrensch, Richard S. Houlston, Meredith Yeager, Sarah Fleming, Ben Kinnersley, Georgina Armstrong, Zhaoming Wang, Siegal Sadetzki, Khê Hoang-Xuan, Jean-Yves Delattre, Karim Labreche, Paul A. Decker, Stefanie Heilmann, Karima Mokhtari, Anthony J. Swerdlow, Yanhong Liu, Beatrice Melin, Ahmed Idbaih, Jill S. Barnholtz-Sloan, Christoffer Johansen, Marc Sanson, Terri Rice, Ryan Merrell, Peter Broderick, Joellen Shildkraut, Pilar Galan, Stephen J. Chanock, Christopher I. Amos, Robert B. Jenkins, Ching C. Lau, Sanjay Shete, Yanwen Chen, Sara H. Olson, Dora Il'yasova, Anna Luisa Di Stefano, Martha S. Linet, Quinn T. Ostrom, Minouk J. Schoemaker, Helen M. Hansen, Stefan Herms, Johannes Schramm, Konstantinos Gousias, Dan Lachance, Michael E. Scheurer, Department of Radiation Sciences [Umeå], Umeå University, Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University [Cleveland], Department of Neurological Surgery, School of Medicine, University of California, Institute of Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], Institute of Cancer Epidemiology, The Danish Cancer Society, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Duke Cancer Institute Durham, North Carolina, USA., Duke University Medical Center, School of Public Health [Teheran], University of Tehran, Division of Genetics and Epidemiology, Institute of Cancer Research (ICR), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medecine, Division of Biomedical Statistics anInformatics, Mayo Clinic School Medicine, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Neurosurger, Rheinische Friedrich-Wilhelms-Universität Bonn, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Institute of Epidemiology, Helmholtz Centre Munich, Institute of Medical Statistics and Epidemiology Munich, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), 1st Medical Department, University Clinic Schleswig–Holstein, Division of Breast Cancer Research London, Department of Human Genetics Montreal, McGill University Health Center [Montreal] (MUHC), Genome Québec, Department of Neurosurgery, Institut of Clinical Medicine, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of California [San Francisco] (UCSF), University of California-University of California, Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Geisel School of Medicine at Dartmouth, Department of Epidemiology and Biostatistics, School of Health, Shahrekord University of Medical Sciences, School of Public Health, Imperial College London, Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Department of Pediatrics, Dan L. Duncan Comprehensive Cancer Center, Department of Neurology Evanston, Illinois, USA., NorthShore University HealthSystem, Duke Cancer Institute Durham, Cancer Control and Prevention Program, Department of Community and Family Medicine Durham, Department of Surgery Durham, North, Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Departments of Neurology and Preventive Medicine Keck School of Medicine, University of Southern California (USC), School of Public Health New Haven, Yale University [New Haven], Department of Neurosurgery Boston, Brigham and Women's Hospital [Boston], Department of Laboratory Medicine and Pathology, University of Alberta, Division of Molecular Pathology, Tottori University, Department of Medicine, Dan L. Duncan Comprehensive Cancer Center Baylor Houston, US National Institutes of Health (NIH) [R01CA139020, R01CA52689, P30CA125123], McNair Medical Institute, Population Sciences Biorepository at Baylor College of Medicine, Acta Oncologica through the Royal Swedish Academy of Science, Swedish Research Council, Swedish Cancer Foundation, Cancer Research UK - Bobby Moore Fund [C1298/A8362], Wellcome Trust, DJ Fielding Medical Research Trust, National Cancer Research Network, European Union [QLK4-CT-1999-01563], International Union against Cancer (UICC), Mobile Manufacturers' Forum, GSM Association, UICC, Mobile Telecommunications and Health Research (MTHR) Programme, Health and Safety Executive, Department of Health and Safety Executive, UK Network Operators, Ligue Nationale Contre le Cancer, Fondation ARC, Institut National du Cancer (INCa) [PL046], French Ministry of Higher Education and Research, program 'Investissements d'avenir' [ANR-10-IAIHU-06], Genome Quebec, le Ministere de l'Enseignement superieur, de la Recherche, de la Science et de la Technologie (MESRST) Quebec, McGill University, Deutsche Forschungsgemeinschaft [Si552, Schr285], Deutsche Krebshilfe [70-2385-Wi2, 70-3163-Wi3, 10-6262], BONFOR, Wellcome Trust [076113, 085475], German Federal Ministry of Education and Research (BMBF), Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, German National Genome Research Network (NGFN), Munich Center of Health Sciences (MC Health) as part of LMUinnovativ, German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) - e:Med research and funding concept [01ZX1314A], DFG, Alfried Krupp von Bohlen und Halbach-Stiftung, BONFOR Programme of the University of Bonn, Germany, NIH [R01CA139020, R01CA52689, P50CA097257, R01CA126831, P50CA108961, P30CA15083], Loglio Collective, National Brain Tumor Foundation, Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research, Robert Magnin Newman Endowed Chair in Neuro-oncology, National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, through UCSF-CTSI [UL1 RR024131], National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000140C, HHSN261201000035C, HHSN261201000034C], Centers for Disease Control and Prevention's National Program of Cancer Registries [U58DP003862-01], National Institute of Neurological Disorders and Stroke [RC1NS068222Z], Bernie and Edith Waterman Foundation, Ting Tsung and Wei Fong Chao Family Foundation, Department of Radiation Sciences, University of Umeå, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Sorbonne Universités, Université Pierre et Marie Curie (Paris 6), Groupe Hospitalier Pitié-Salpêtrière, Service de neurologie 2-Mazarin, Assistance Publique - Hôpitaux de Paris, Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Case Western Reserve University, Universität Ulm, Denmark and Rigshospitalet, University of Copenhagen, Department of Epidemiology and Biostatistics, School of Public Health, University of Medical Sciences, Tehran, Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - CHU Pitié-Salpêtrière [APHP] - Centre National de la Recherche Scientifique (CNRS), Baylor College of Medicine, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS), Institut National de la Recherche Agronomique (INRA) - Université Paris Diderot - Paris 7 (UPD7) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris 13 - Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bonn (Rheinische Friedrich-Wilhelms), Technical University of Munich, Research Institute of the McGill University Health Center, National Cancer Institute (NIH), University of California San Francisco (UCSF), Tel-Aviv University, Department of Biostatistics, University of Oslo (UiO), University of Southern California, Yale University, Brigham and Women's Hospital, University of Alberta [Edmonton], University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Tel Aviv University (TAU), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP]
Subjects: 0301 basic medicine, Genotype, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, Genome-wide association study, Quantitative trait locus, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Polymorphism (computer science), Glioma, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Allele, Alleles, Genetic association, Brain Neoplasms, medicine.disease, Molecular biology, 3. Good health, Gene Expression Regulation, Neoplastic, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Glioblastoma, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
Published: 2017
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19. Prediction of homo- and hetero-protein complexes by protein docking and template-based modeling: a CASP-CAPRI experiment

Author: Eichiro Ichiishi, Dmitri Beglov, Bernard Maigret, Gyu Rie Lee, Artem B. Mamonov, Shoshana J. Wodak, Jonathan C. Fuller, Dima Kozakov, Jong Young Joung, Petr Popov, Xiaofeng Yu, Keehyoung Joo, João P. G. L. M. Rodrigues, Anna Vangone, Koen M. Visscher, Xiaoqin Zou, Paul A. Bates, Andriy Kryshtafovych, Shourya S. Roy Burman, Daisuke Kihara, Romina Oliva, Efrat Ben-Zeev, Jeffrey J. Gray, Yang Shen, Li C. Xue, Sameer Velankar, Emilie Neveu, Shruthi Viswanath, Dina Schneidman-Duhovny, Juan Esquivel-Rodríguez, Mieczyslaw Torchala, Amit Roy, Alexandre M. J. J. Bonvin, David R. Hall, Tanggis Bohnuud, Xusi Han, David W. Ritchie, Ron Elber, Daisuke Kuroda, Zhiwei Ma, Joan Segura, Carlos A. Del Carpio, Nicholas A. Marze, Jong Yun Kim, Andrej Sali, Petras J. Kundrotas, Ezgi Karaca, Neil J. Bruce, Chaok Seok, Panagiotis L. Kastritis, Shen You Huang, Ilya A. Vakser, Lim Heo, Sanbo Qin, Raphael A. G. Chaleil, Adrien S. J. Melquiond, Miguel Romero-Durana, Anisah W. Ghoorah, Surendra S. Negi, Andrey Tovchigrechko, Françoise Ochsenbein, Narcis Fernandez-Fuentes, Liming Qiu, Miriam Eisenstein, Mehdi Nellen, Marie-Dominique Devignes, Lenna X. Peterson, Jinchao Yu, Minkyung Baek, Brian G. Pierce, Hasup Lee, Toshiyuki Oda, Rebecca C. Wade, Raphael Guerois, Juan Fernández-Recio, Iain H. Moal, Edrisse Chermak, Sergei Grudinin, Sangwoo Park, Ivan Anishchenko, Chengfei Yan, Thom Vreven, Kentaro Tomii, Bing Xia, Hyung Rae Kim, Chiara Pallara, Jooyoung Lee, Kazunori D. Yamada, Xianjin Xu, Kenichiro Imai, Zhiping Weng, Luigi Cavallo, Tyler M. Borrman, Jianlin Cheng, Marc F. Lensink, Huan-Xiang Zhou, Jilong Li, Gydo C. P. van Zundert, Brian Jiménez-García, Tsukasa Nakamura, Scott E. Mottarella, Sandor Vajda, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] ( IRI ), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), European Molecular Biology Laboratory, European Bioinformatics Institute, Genome Center [UC Davis], University of California at Davis, Research Support Computing [Columbia], University of Missouri-Columbia, Bioinformatics Consortium and Department of Computer Science [Columbia], Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] ( UCSF ), Department of Pharmaceutical Chemistry, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California [San Francisco] ( UCSF ) -California Institute for Quantitative Biosciences, GN7 of the National Institute for Bioinformatics (INB) and Biocomputing Unit, Centro Nacional de Biotecnología (CSIC), Institute of Biological, Environmental and Rural Sciences ( IBERS ), Institute for Computational Engineering and Sciences [Austin] ( ICES ), University of Texas at Austin [Austin], Department of Computer Science, Department of Chemistry, Algorithms for Modeling and Simulation of Nanosystems ( NANO-D ), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Laboratoire Jean Kuntzmann ( LJK ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Institut National Polytechnique de Grenoble ( INPG ), Moscow Institute of Physics and Technology [Moscow] ( MIPT ), Seoul National University [Seoul], Florida State University [Tallahassee] ( FSU ), Computational Algorithms for Protein Structures and Interactions ( CAPSID ), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Department of Complex Systems, Artificial Intelligence & Robotics ( LORIA - AIS ), Laboratoire Lorrain de Recherche en Informatique et ses Applications ( LORIA ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ) -Laboratoire Lorrain de Recherche en Informatique et ses Applications ( LORIA ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), University of Mauritius, Biomolecular Modelling Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, G-INCPM, Weizmann Institute of Science, Chemical Research Support [Rehovot], Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch ( UTMB ), Program in Bioinformatics and Integrative Biology [Worcester], University of Massachusetts Medical School [Worcester] ( UMASS ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Bijvoet Center for Biomolecular Research [Utrecht], Utrecht University [Utrecht], Dalton Cardiovascular Research Center [Columbia], Department of Computer Science [Columbia], Informatics Intitute, Department of Biochemistry, University of Missouri, UNIVERSITY OF MISSOURI, Toyota Technological Institute at Chicago [Chicago] ( TTIC ), Department of Biological Sciences, Purdue University, Purdue University [West Lafayette], Department of Computer Science [Purdue], Bioinformatics and Computational Biosciences Branch, Rocky Mountain Laboratories, Molecular and Cellular Modeling Group, Heidelberg Institute of Theoretical Studies, Center for Molecular Biology ( ZMBH ), Universität Heidelberg [Heidelberg], Interdisciplinary Center for Scientiﬁc Computing ( IWR ), Department of Molecular Biosciences [Lawrence], University of Kansas [Lawrence] ( KU ), Computational Biology Research Center ( CBRC ), National Institute of Advanced Industrial Science and Technology ( AIST ), Graduate School of Frontier Sciences, The University of Tokyo, Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center - Centro Nacional de Supercomputacion ( BSC - CNS ), Center for In-Silico Protein Science, Korea Institute for Advanced Study ( KIAS ), Center for Advanced Computation, Department of Biomedical Engineering [Boston], Boston University [Boston] ( BU ), Institute of Biological Diversity, International Pacific Institute of Indiana, Drosophila Genetic Resource Center, Kyoto Institute of Technology, International University of Health and Welfare Hospital ( IUHW Hospital ), International University of Health and Welfare Hospital, Department of Chemical and Biomolecular Engineering [Baltimore], Johns Hopkins University ( JHU ), Program in Molecular Biophysics [Baltimore], King Abdullah University of Science and Technology ( KAUST ), University of Naples, J Craig Venter Institute, Structural Biology Research Center, VIB, 1050 Brussels, Belgium, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), University of Missouri [Columbia] (Mizzou), University of Missouri System, University of California [San Francisco] (UC San Francisco), Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institute of Biological, Environmental and Rural Sciences (IBERS), Institute for Computational Engineering and Sciences [Austin] (ICES), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Moscow Institute of Physics and Technology [Moscow] (MIPT), Seoul National University [Seoul] (SNU), Florida State University [Tallahassee] (FSU), Computational Algorithms for Protein Structures and Interactions (CAPSID), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Biomolecular Modelling Laboratory [London], The Francis Crick Institute [London], Weizmann Institute of Science [Rehovot, Israël], The University of Texas Medical Branch (UTMB), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), 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), Assemblage moléculaire et intégrité du génome (AMIG), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Missouri System-University of Missouri System, Toyota Technological Institute at Chicago [Chicago] (TTIC), Department of Biological Sciences [Lafayette IN], Heidelberg Institute for Theoretical Studies (HITS ), Center for Molecular Biology (ZMBH), Universität Heidelberg [Heidelberg] = Heidelberg University, Interdisciplinary Center for Scientiﬁc Computing (IWR), University of Kansas [Lawrence] (KU), Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), The University of Tokyo (UTokyo), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Korea Institute for Advanced Study (KIAS), Boston University [Boston] (BU), International University of Health and Welfare Hospital (IUHW Hospital), Johns Hopkins University (JHU), King Abdullah University of Science and Technology (KAUST), University of Naples Federico II = Università degli studi di Napoli Federico II, J. Craig Venter Institute, VIB-VUB Center for Structural Biology [Bruxelles], VIB [Belgium], Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, University of California-University of California, University of California [San Francisco] (UCSF), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), University of Naples Federico II, Barcelona Supercomputing Center, NMR Spectroscopy, and Sub NMR Spectroscopy
Subjects: 0301 basic medicine, Protein Conformation, alpha-Helical, Protein Folding, Computer science, International Cooperation, Amino Acid Motifs, Oligomer state, Homoprotein, DATA-BANK, computer.software_genre, Molecular Docking Simulation, Biochemistry, CAPRI Round 30, DESIGN, Structural Biology, ALIGN, Blind prediction, AFFINITY, Protein interaction, Enginyeria biomèdica [Àrees temàtiques de la UPC], ZDOCK, Oligomer State, computer.file_format, Articles, Protein structure prediction, Proteïnes--Investigació, 3. Good health, WEB SERVER, CASP, Thermodynamics, Data mining, CAPRI, Protein docking, Molecular Biology, Algorithms, INTERFACES, Protein Binding, [ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation, Bioinformatics, STRUCTURAL BIOLOGY, Computational biology, Molecular Dynamics Simulation, Article, 03 medical and health sciences, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Heteroprotein, Humans, Protein binding, Macromolecular docking, Protein Interaction Domains and Motifs, Homology modeling, ALGORITHM, Protein-protein docking, Internet, Binding Sites, Models, Statistical, 030102 biochemistry & molecular biology, Bacteria, Sequence Homology, Amino Acid, Computational Biology, Proteins, Protein Data Bank, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Protein Structure, Tertiary, 030104 developmental biology, Structural biology, Docking (molecular), Protein structure, Protein Conformation, beta-Strand, Protein Multimerization, oligomer state, blind prediction, protein interaction, protein docking, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], computer, Software
Abstract: We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein–protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. We are most grateful to the PDBe at the European Bioinformatics Institute in Hinxton, UK, for hosting the CAPRI website. Our deepest thanks go to all the structural biologists and to the following structural genomics initiatives: Northeast Structural Genomics Consortium, Joint Center for Structural Genomics, NatPro PSI:Biology, New York Structural Genomics Research Center, Midwest Center for Structural Genomics, Structural Genomics Consortium, for contributing the targets for this joint CASP-CAPRI experiment. MFL acknowledges support from the FRABio FR3688 Research Federation “Structural & Functional Biochemistry of Biomolecular Assemblies.”
Published: 2016
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20. Power estimation for non-standardized multisite studies

Author: Till Sprenger, Massimo Filippi, David A. Hafler, Sara Llufriu, Gina Kirkish, Mona K. Beyer, Pablo Villoslada, Xavier Montalban, Sandra D'Alfonso, Anisha Keshavan, Philippe Demaerel, Claus Zimmer, Pradip M. Pattany, Mike P. Wattjes, Christiane Graetz, Ludwig Kappos, Alessandro Carriero, Jorge R. Oksenberg, Jacob L. McCauley, Roland G. Henry, Alyssa H. Zhu, Adriane Gröger, Michael Amann, An Goris, Laura Gaetano, Antje Bischof, Filippo Martinelli-Boneschi, Hanne F. Harbo, Sergiu Groppa, Alessandro Stecco, Stefano Magon, Margaret A. Pericak-Vance, Daniel Pelletier, Frauke Zipp, Regina Schlaeger, Alex Rovira, Nico Papinutto, Friedemann Paul, Albert Saiz, Maria A. Rocca, Isabelle Cournu-Rebeix, William A. Stern, Howard L. Weiner, Bernhard Hemmer, Russell T. Shinohara, Manuel Comabella, Bénédicte Dubois, Rohit Bakshi, Jason C. Crane, Vinzenz Fleischer, Bernard M. J. Uitdehaag, Jens Wuerfel, Stephen L. Hauser, Mark Mühlau, Kesshi M. Jordan, Bertrand Fontaine, Keshavan, A, Paul, F, Beyer, Mk, Zhu, Ah, Papinutto, N, Shinohara, Rt, Stern, W, Amann, M, Bakshi, R, Bischof, A, Carriero, A, Comabella, M, Crane, Jc, D'Alfonso, S, Demaerel, P, Dubois, B, Filippi, M, Fleischer, V, Fontaine, B, Gaetano, L, Goris, A, Graetz, C, Gröger, A, Groppa, S, Hafler, Da, Harbo, Hf, Hemmer, B, Jordan, K, Kappos, L, Kirkish, G, Llufriu, S, Magon, S, Martinelli-Boneschi, F, Mccauley, J, Montalban, X, Muhlau, M, Pelletier, D, Pattany, Pm, Pericak-Vance, M, Rebeix, I, Rocca, M, Rovira, A, Schlaeger, R, Saiz, A, Sprenger, T, Stecco, A, Uitdehaag, Bm, Villoslada, P, Wattjes, Mp, Weiner, H, Wuerfel, J, Zimmer, C, Zipp, F, International Multiple Sclerosis Genetics, Consortium, Hauser, S, Oksenberg, Jr, Henry, Rg, Bioengineering Graduate Program (joint degree with UCSF), Department of Bioengineering [Berkeley], University of California [Berkeley], University of California-University of California-University of California [Berkeley], University of California-University of California-University of California [San Francisco] (UCSF), University of California, Department of Neurology [San Francisco], University of California [San Francisco] (UCSF), University of California-University of California, Max Delbrueck Centre for Molecular Medicine, NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Radiology and Nuclear Medicine, Oslo University Hospital [Oslo], Department of Biostatistics and Epidemiology [Philadelphia], Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Department of Neurology [Suisse], University Hospital Basel [Basel], Medical Image Analysis Center (MIAC AG), Brigham and Women's Hospital [Boston], Clinical Immunology, Department of Translational Medicine, UPO University, Vall d'Hebron University Hospital [Barcelona], Department of Radiology and Biomedical Imaging [San Francisco], Department of Health Sciences, UPO University, Department of Radiology[Leuven], University Hospitals Leuven [Leuven], Department of Neurosciences Leuven, University of Leuven K.U.Leuven, Institute of Experimental Neurology, Milan, University Medical Centre of the Johannes Gutenberg University Mainz, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), University Medical Centre of the Johannes Gutenberg-University Mainz, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Departments of Neurology and Immunobiology [Yale], Yale University School of Medicine, Department of Neurology [Oslo], Akershus University Hospital [Lørenskog], Department Neurology of the Klinikum rechts der Isar, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Munich Cluster of Systems Neurology (SyNery), Center for Neuroimmunology, Service of Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Neuroimaging Research Unit, Scientific Institute and University Hospital San Raffaele, Milan, John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), TUM–Neuroimaging Center, Department of Radiology [Miami], DKD Helios Klinik Wiesbaden, Section of Neuroradiology [Novara], Maggiore Hospital, VU University Medical Center [Amsterdam], Dept Neuroradiology [Munich], Klinikums rechts der Isar, University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC)-University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), University of Pennsylvania-University of Pennsylvania, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Yale School of Medicine [New Haven, Connecticut] (YSM), Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Radiology and nuclear medicine
Subjects: Computer science, Cognitive Neuroscience, computer.software_genre, Sensitivity and Specificity, 050105 experimental psychology, Imaging phantom, Article, Set (abstract data type), 03 medical and health sciences, 0302 clinical medicine, Distortion, Image Interpretation, Computer-Assisted, Calibration, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, 0501 psychology and cognitive sciences, Segmentation, Computer Simulation, 10. No inequality, Scaling, Models, Statistical, medicine.diagnostic_test, 05 social sciences, Contrast (statistics), Brain, Reproducibility of Results, Magnetic resonance imaging, Equipment Design, Scale factor, Image Enhancement, Magnetic Resonance Imaging, United States, Equipment Failure Analysis, Europe, Neurology, Ordinary least squares, Data mining, Function and Dysfunction of the Nervous System, Artifacts, computer, 030217 neurology & neurosurgery, Algorithms
Abstract: A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this assumption, we provide a new statistical framework and derive a power equation to define inclusion criteria for a set of sites based on the variability of their scaling factors. We estimated the scaling factors of 20 scanners with heterogeneous hardware and sequence parameters by scanning a single set of 12 subjects at sites across the United States and Europe. Regional volumes and their scaling factors were estimated for each site using Freesurfer's segmentation algorithm and ordinary least squares, respectively. The scaling factors were validated by comparing the theoretical and simulated power curves, performing a leave-one-out calibration of regional volumes, and evaluating the absolute agreement of all regional volumes between sites before and after calibration. Using our derived power equation, we were able to define the conditions under which harmonization is not necessary to achieve 80% power. This approach can inform choice of processing pipelines and outcome metrics for multisite studies based on scaling factor variability across sites, enabling collaboration between clinical and research institutions. publisher: Elsevier articletitle: Power estimation for non-standardized multisite studies journaltitle: NeuroImage articlelink: http://dx.doi.org/10.1016/j.neuroimage.2016.03.051 content_type: article copyright: © 2016 The Authors. Published by Elsevier Inc. ispartof: NeuroImage vol:134 pages:281-294 ispartof: location:United States status: published
Published: 2016
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21. Data publication with the structural biology data grid supports live analysis

Author: Pa, Meyer, Socias S, Key J, Ransey E, Ec, Tjon, Alejandro Buschiazzo, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Ks, Anderson, Rh, Baxter, Sc, Blacklow, Tj, Boggon, Am, Bonvin, Borek D, Tj, Brett, Caflisch A, Ci, Chang, Department of Biological Chemistry and Molecular Pharmacology [Boston] (DBCMP), Harvard Medical School [Boston] (HMS), Molecular and structural microbiology = Microbiología Molecular y Estructural [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Shanghai Institutes for Biological Sciences (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences [Beijing] (CAS), NE-CAT and department of chemistry and chemical biology [Argonne], Cornell University, Departments of pharmacology and molecular biophysics and biochemistry [New Haven], Yale University School of Medicine, Department of Chemistry and Molecular Biophysics & Biochemistry [New Haven], Yale University [New Haven], Bijovet center [Utrecht], Utrecht University [Utrecht], Department of Biophysics and Biochemistry [Dallas], University of Texas Southwestern Medical Center [Dallas], Department of Internal Medicine [St Louis], Washington University School of Medicine, Department of Biochemistry [Zurich], University of Zürich [Zürich] (UZH), Institute of Biological Chemistry (IBC Sinica), Academia Sinica, Departments of biochemistry and chemistry [Nashville], Vanderbilt University [Nashville], Ludwig Institute for Cancer Research, University of California [San Diego] (UC San Diego), University of California, SUNY Upstate Medical University, State University of New York (SUNY), University of Chicago, Dana-Farber Cancer Institute [Boston], Saint Louis University School of Medicine [St Louis], Massachusetts Institute of Technology (MIT), Department of Biological Chemistry and Molecular Pharmacology (DBCMP), Columbia University [New York], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Weill Institute for Cell and Molecular Biology, Howard Hughes Medical Institute [Stanford], Stanford University School of Medicine [CA, USA], Harvard University [Cambridge], Wuhan Institute of Virology, Howard Hughes Medical Institute [Boston], Tufts University School of Medicine [Boston], Queen's University [Kingston], La Trobe University [Melbourne], Geisel School of Medicine at Dartmouth, University of Cambridge [UK] (CAM), University of Texas at Dallas [Richardson] (UT Dallas), Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Instituto de Biologia Molecular e Celular (IBMC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), University of Maryland [Baltimore County] (UMBC), University of Maryland System, National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch (UTMB), Rice University [Houston], University of Washington School of Medicine, University of Kentucky, Boston Children's Hospital, Department of Computer Science, University of Chicago, University of California [San Francisco] (UCSF), Uppsala University, Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Howard Hughes Medical Institute [Ashburn], Fachbereich Biologie, University of Konstanz, Institute for Quantitative Social Sciences, Development of the Structural Biology Data Grid is funded by The Leona M. and Harry B. Helmsley Charitable Trust 2016PG-BRI002 to PS and MC. Development of citation workflows is supported NSF 1448069 (to PS). DAA is being developed as a pilot project of the National Data Service, with additional funds to support storage and technology development, including NIH P41 GM103403 (NE-CAT) and 1S10RR028832 (HMS) and DOE DE-AC02-06CH11357, NIH 1U54EB020406-01, Big Data for Discovery Science Center, and NIST 60NANB15D077 (Globus Project), Department of Biological Chemistry and Molecular Pharmacology [Boston] ( DBCMP ), Harvard Medical School [Boston] ( HMS ), Laboratory of molecular and structural microbiology, Institut Pasteur Montevideo-Réseau International des Instituts Pasteur ( RIIP ), Shanghai Institutes for Biological Sciences ( Institute of Biochemistry and Cell Biology ), Chinese Academy of Sciences [Beijing] ( CAS ), Yale University, Faculty of Science, Utrecht University, University of Zürich [Zürich] ( UZH ), Institute of Biological Chemistry ( IBC Sinica ), Vanderbilt University of Nashville, University of California [San Diego] ( UC San Diego ), Massachusetts Institute of Technology ( MIT ), Department of Biological Chemistry and Molecular Pharmacology ( DBCMP ), National Heart, Lung, and Blood Institute [Bethesda] ( NHLBI ), Stanford University School of Medicine, Havard Medical School, University of Cambridge [UK] ( CAM ), University of Texas at Dallas [Richardson] ( UT Dallas ), Instituto de Biologia Molecular e Celular ( IBMC ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), University of Maryland Baltimore County [Baltimore] ( UMBC ), National Institute of Neurological Disorders and Stroke [Bethesda] ( NINDS ), National Institutes of Health [Bethesda] ( NIH ), The University of Texas Medical Branch ( UTMB ), Yale School of Medicine, University of California [San Francisco] ( UCSF ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Drennan, Catherine L., Schwartz, Thomas, 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)-Centre National de la Recherche Scientifique (CNRS), and Instituto de Investigação e Inovação em Saúde
Subjects: Data set, Data quality, General Physics and Astronomy, Experimental data, General Chemistry, Data grid, General Biochemistry, Genetics and Molecular Biology, Data science, Genetics, Paradigm shift, Data access, Data mining, Biology, The Internet
Abstract: The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community., Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
Published: 2016
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22. MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone

Author: Julie Kennedy, Chunmei Li, Marta Romani, Enza Maria Valente, Victor L. Jensen, Jean Baptiste Rivière, Michel R. Leroux, Jeremy F. Reiter, Estelle Lopez, Kwangjin Park, Francesc R. Garcia-Gonzalo, Laurence Faivre, Bérénice Doray, Oliver E. Blacque, Christel Thauvin-Robinet, Roberta De Mori, Ange Line Bruel, Dominique Gaillard, Department of Molecular Biology and Biochemistry ( MBB ), Simon Fraser University ( SFU.ca ), School of Biology & Environmental Science and Conway Institute of Biomolecular & Biomedical Research, University College Dublin, University College Dublin [Dublin] ( UCD ), Cardiovascular Research Institute ( CVRI ), Univerisity of California ( UCSF ), IRCCS 'Casa Sollievo della Sofferenza', Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Service de Génétique, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), Service de Génétique Médicale, Hôpital Civil, Strasbourg, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), voestalpine Stahl Donawitz GmbH, Department of Biochemistry & Biophysics, University of California [San Francisco] ( UCSF ), Canadian Institutes of Health Research (CIHR) MOP 142243 March of Dimes Michael Smith Foundation for Health Research (MSFHR) European Research Council (ERC) 260888 Telethon Foundation Italy GGP13146 Science Foundation Ireland SFI-111037 European Community's Seventh Framework Programme (SYSCILIA) 241955 NIH AR054396 GM095941 Burroughs Wellcome Fund Packard Foundation Sandler Family Supporting Foundation GIS-Institut des Maladies Rares French Fondation for Rare Disease French Ministry of Health (PHRC) 2010-A01014-35 Regional Council of Burgundy Vanier Canada Graduate Scholarship MSFHR postdoctoral fellowship KRESCENT postdoctoral fellowship, Department of Molecular Biology and Biochemistry (MBB), Simon Fraser University (SFU.ca), University College Dublin [Dublin] (UCD), Cardiovascular Research Institute (CVRI), University of California [San Francisco] (UCSF), University of California-University of California, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: 0301 basic medicine, Nematoda, Cell Membranes, Peripheral Membrane Proteins, Gene Identification and Analysis, syndrome type vi, Animal Cells, Medicine and Health Sciences, Biology (General), Caenorhabditis elegans, Connective Tissue Cells, Genetics, biology, General Neuroscience, Cilium, Ciliary transition zone, joubert syndrome, Animal Models, Orofaciodigital Syndromes, Cyclin-Dependent Kinases, 3. Good health, Cell biology, Phenotypes, Connective Tissue, RPGRIP1L, c-elegans, flagella, Cellular Structures and Organelles, Cellular Types, Anatomy, General Agricultural and Biological Sciences, Microtubule-Associated Proteins, primary cilium, Research Article, Microtubule-associated protein, QH301-705.5, Molecular Sequence Data, Research and Analysis Methods, General Biochemistry, Genetics and Molecular Biology, meckel syndrome, 03 medical and health sciences, Model Organisms, Intraflagellar transport, Ciliogenesis, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Animals, Humans, Cilia, Amino Acid Sequence, Caenorhabditis elegans Proteins, Mutation Detection, intraflagellar transport, General Immunology and Microbiology, Organisms, Biology and Life Sciences, Membrane Proteins, Cell Biology, Fibroblasts, biology.organism_classification, Invertebrates, caenorhabditis-elegans, 030104 developmental biology, Biological Tissue, Membrane protein, Genetic Interactions, membrane-proteins, Caenorhabditis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ciliogenesis
Abstract: Cilia have a unique diffusion barrier (“gate”) within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease are not completely understood. Here, we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation. Consistent with a critical role in ciliary gate function, CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and keeps ARL-13 (Arl13b) from leaking out of cilia via the TZ. We identify a novel MKS module component, TMEM-218 (Tmem218), that requires CEP-290 and other MKS module components for TZ localisation and functions together with the NPHP module to facilitate ciliogenesis. We show that TZ localisation of TMEM-138 (Tmem138) and CDKL-1 (Cdkl1/Cdkl2/Cdkl3/Cdlk4 related), not previously linked to a specific TZ module, similarly depends on CEP-290; surprisingly, neither TMEM-138 or CDKL-1 exhibit interdependent localisation or genetic interactions with core MKS or NPHP module components, suggesting they are part of a distinct, CEP-290-associated module. Lastly, we show that families presenting with Oral-Facial-Digital syndrome type 6 (OFD6) have likely pathogenic mutations in CEP-290-dependent TZ proteins, namely Tmem17, Tmem138, and Tmem231. Notably, patient fibroblasts harbouring mutated Tmem17, a protein not yet ciliopathy-associated, display ciliogenesis defects. Together, our findings expand the repertoire of MKS module-associated proteins—including the previously uncharacterised mammalian Tmem80—and suggest an MKS-5 and CEP-290-dependent assembly pathway for building a functional TZ., The transition zone is a barrier structure required to maintain the dynamic composition and functional integrity of the cilium. This study describes the pathway by which the transition zone is assembled during cilium formation., Author Summary The primary cilium is a structure found in most animal cell types. Much like an antenna, it is responsible for sensing extracellular signals, including light and small molecules, and conveying this information to the receiving cell and respective tissue or organ. At the base of the cilium is the transition zone (TZ), which acts as a “gate” to regulate the entry and exit of ciliary proteins required for signal transduction. Here, we use the nematode Caenorhabditis elegans as a model system to dissect how different proteins within the TZ assemble to form a functional barrier. We find that the TZ protein MKS-5 (Rpgrip1/Rpgrip1L orthologue) forms the foundation for two different assembly pathways involving two distinct modules: Nephronophthisis (NPHP) and Meckel syndrome (MKS). We show that at the base of the MKS module is CEP-290, another TZ protein that assembles MKS module proteins, including a novel TZ protein we identify as TMEM-218. CEP-290 also helps assemble a potentially separate submodule containing TMEM-138 and CDKL-1. Notably, we provide evidence that the MKS module protein TMEM-17 facilitates cilium formation and is disrupted in the human disorder (ciliopathy) Oral-Facial-Digital Syndrome type 6 (OFD6). Together, our findings provide essential insights into the assembly pathway of the ciliary TZ and suggest further connections between the transition zone and human health.
Published: 2016
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23. Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study

Author: Marti-Aguado, David, Gougol, Amir, Gómez-Medina, Concepción, Jamali, Arsia, Abo-Zed, Abdelrhman, Morales-Arraez, Dalia, Villagrasa Vilella, Ares Aurora, Ventura Cots, Meritxell, Institut Català de la Salut, [Marti-Aguado D] Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain. [Gougol A] Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. University of California, San Francisco (UCSF), San Francisco, CA, USA. [Gomez-Medina] Digestive Disease Department, Clinic University Hospital, Biomedical Research Institute (INCLIVA), Valencia, Spain. [Jamali A, Abo-Zed A] Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Morales-Arraez D] Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain. [Villagrasa A] Unitat Hepàtica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ventura-Cots M] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Unitat Hepàtica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], trastornos mentales::trastornos relacionados con sustancias::síndrome de abstinencia de sustancias [PSIQUIATRÍA Y PSICOLOGÍA], Alcoholisme, Síndrome d'abstinència, enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis alcohólica [ENFERMEDADES], Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Alcoholic [DISEASES], Mental Disorders::Substance-Related Disorders::Substance Withdrawal Syndrome [PSYCHIATRY AND PSYCHOLOGY], Hepatitis C - Complicacions, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract: Alcohol withdrawal syndrome; Alcohol-associated hepatitis; Benzodiazepines Síndrome de abstinencia alcohólica; Hepatitis asociada al alcohol; Benzodiazepinas Síndrome d'abstinència d'alcohol; Hepatitis associada a l'alcohol; Benzodiazepines Background The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3–27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05–2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31–3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36–0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02–4.64) and phenobarbital (HR = 2.99, 95% CI 1.07–8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44–3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38–4.49), and ICU admission (OR = 1.96, 95% CI 1.19–3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40–3.82), 90-day (HR = 1.78, 95% CI 1.18–2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06–2.24). Interpretation AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH.
Published: 2023

24. Radial derivatives of the mouse ventral pallium traced with Dbx1-LacZ reporters

Author: Anne Teissier, Alessandra Pierani, John L.R. Rubenstein, Loreta Medina, Luis Puelles, Isabel Legaz, Ugo Borello, Department of Human Anatomy and Psychobiology, Medical School, University of Murcia, Murcia E30071, Spain, Universidad de Murcia, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA., UCSF, University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, MINECO grant BFU2014-57516-P - grant BFU2012-33029 - (including ERDF European Funds co-funding), DGICYT-FEDER grants BFU2005-09378, C01-C02/BFI - BFU2008-04156/BFI - BFI2003-06453-C02-02 - BFU2006-14804-C02-02/BFI, NAAR, NINDS R01 NS34661-01A1, NIMH R37 MH049428-16A1 grants, Human Frontiers grants, ANR-05-NEUR-0007,CRDEVO,Contrôle Moléculaire de la différenciation et de la fonction des cellules de Cajal-Retzius par l' homéoprotéine Dbx1 au cours du développement du cortex cérébral chez la souris(2005), European Project: 28771,INTERDEVO, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), and University of California (UC)-University of California (UC)
Subjects: 0301 basic medicine, Olfactory system, External capsule, Basal Forebrain, Neurogenesis, Hypothalamus, Mice, Transgenic, Ventral pallium, Biology, Piriform cortex, Amygdala, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neural Stem Cells, Pallial extended amygdala, medicine, Animals, Lateral pallium, ComputingMilieux_MISCELLANEOUS, Entorhinal cortex, Homeodomain Proteins, Endopiriform nuclei, Olfactory bulb, 030104 developmental biology, medicine.anatomical_structure, Lac Operon, DBX1, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Preoptic area, Neuroscience, Biomarkers, 030217 neurology & neurosurgery
Abstract: The progeny of Dbx1-expressing progenitors was studied in the developing mouse pallium, using two transgenic mouse lines: (1) Dbx1(nlslacZ) mice, in which the gene of the β-galactosidase reporter (LacZ) is inserted directly under the control of the Dbx1 promoter, allowing short-term lineage tracing of Dbx1-derived cells; and (2) Dbx1(CRE) mice crossed with a Cre-dependent reporter strain (ROSA26(loxP-stop-loxP-LacZ)), in which the Dbx1-derived cells result permanently labeled (Bielle et al., 2005). We thus examined in detail the derivatives of the postulated longitudinal ventral pallium (VPall) sector, which has been defined among other features by its selective ventricular zone expression of Dbx1 (the recent ascription by Puelles, 2014 of the whole olfactory cortex primordium to the VPall was tested). Earlier notions about a gradiental caudorostral reduction of Dbx1 signal were corroborated, so that virtually no signal was found at the olfactory bulb and the anterior olfactory area. The piriform cortex was increasingly labeled caudalwards. The only endopiriform grisea labeled were the ventral endopiriform nucleus and the bed nucleus of the external capsule. Anterior and basolateral parts of the whole pallial amygdala also were densely marked, in contrast to the negative posterior parts of these pallial amygdalar nuclei (leaving apart medial amygdalar parts ascribed to subpallial or extratelencephalic sources of Dbx1-derived GABAergic and non-GABAergic neurons). Alternative tentative interpretations are discussed to explain the partial labeling obtained of both olfactory and amygdaloid structures. This includes the hypothesis of an as yet undefined part of the pallium, potentially responsible for the posterior amygdala, or the hypothesis that the VPall may not be wholly characterized by Dbx1 expression (this gene not being necessary for VPall molecular distinctness and histogenetic potency), which would leave a dorsal Dbx1-negative VPall subdomain of variable size that might contribute partially to olfactory and posterior amygdalar structures.
Published: 2015
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25. Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

Author: Joanne Nithitham, Gaetane Nocturne, Karine Briot, Christian Roux, Kimberly E. Taylor, Lindsey A. Criswell, Francis Berenbaum, Xavier Mariette, Antoine Feydy, Maxime Dougados, Pascal Claudepierre, Corinne Miceli-Richard, Floris A. van Gaalen, Philippe Goupille, Philippe Chanson, Saida Boudaoud, Raphaèle Seror, Stephan Pavy, Philippe Dieudé, Désirée van der Heijde, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de rhumatologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Francois Rabelais [Tours], Service d'endocrinologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Universiteit Leiden [Leiden], CHU Saint-Antoine [APHP], Service de rhumatologie B, Université Paris Descartes - Paris 5 (UPD5), Service de radiologie, CHU Cochin [AP-HP], Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor, Service de rhumatologie [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), University of California [San Francisco] (UCSF), University of California, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Universiteit Leiden, University of California [San Francisco] (UC San Francisco), University of California (UC), Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -APHP-CHU Saint-Antoine [APHP], Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), and University of California [San Francisco] ( UCSF )
Subjects: Adult, Genetic Markers, Male, medicine.medical_specialty, Multivariate analysis, Genotype, Cross-sectional study, lcsh:Medicine, Single-nucleotide polymorphism, Gastroenterology, Polymorphism, Single Nucleotide, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, Spondylarthritis, medicine, Humans, lcsh:Science, Wnt Signaling Pathway, 030304 developmental biology, Adaptor Proteins, Signal Transducing, 030203 arthritis & rheumatology, 0303 health sciences, Ankylosing spondylitis, Multidisciplinary, business.industry, lcsh:R, Desir cohort, Sacroiliitis, medicine.disease, 3. Good health, Cross-Sectional Studies, Back Pain, Cohort, Immunology, Bone Morphogenetic Proteins, Intercellular Signaling Peptides and Proteins, lcsh:Q, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study, Research Article
Abstract: International audience; Objectives : To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.Methods : The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and
Published: 2015
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26. Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management

Author: M, Avila, D A, Dyment, J V, Sagen, J, St-Onge, U, Moog, B H Y, Chung, S, Mo, S, Mansour, A, Albanese, S, Garcia, D O, Martin, A A, Lopez, T, Claudi, R, König, S M, White, S L, Sawyer, J A, Bernstein, L, Slattery, R K, Jobling, G, Yoon, C J, Curry, M L, Merrer, B L, Luyer, D, Héron, M, Mathieu-Dramard, P, Bitoun, S, Odent, J, Amiel, P, Kuentz, J, Thevenon, M, Laville, Y, Reznik, C, Fagour, M-L, Nunes, D, Delesalle, S, Manouvrier, O, Lascols, F, Huet, C, Binquet, L, Faivre, J-B, Rivière, C, Vigouroux, P R, Njølstad, A M, Innes, C, Thauvin-Robinet, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Children's hospital of Eastern Ontario Research Institute, University of Bergen (UiB), Haukeland University Hospital, Human Genetics Institute, Heidelberg University, Department of Paediatrics and Adolescent Medicine [HKU], The University of Hong Kong (HKU), SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, St George's Hospital, INGEMM, Instituto de Genética Médica y Molecular, IDIPAZ-Hospital Universitario La Paz, Instituto de Salud Carlos III [Madrid] (ISC), Hospital Central de la Cruz Roja San Jose y Santa Adela, University Hospital Puerta de Hierro, Madrid, Bodø University College, Humangenetik, Universitätsklinikum Frankfurt, University of Frankfurt, University of Melbourne, Victorian Clinical Genetics Services, Stanford University, The Hospital for sick children [Toronto] (SickKids), University of California [San Francisco] (UCSF), University of California, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CH Le Havre, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], CHU Amiens-Picardie, Service de Pédiatrie [Jean Verdier], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Bordeaux [Bordeaux], CH Valenciennes, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Calgary, Financial support was from the Regional Council of Burgundy and the Care4Rare Canada Consortium was funded by Genome Canada, the Canadian Institutes of Health Research, the Ontario Genomics Institute, Ontario Research Fund, Genome Quebec, and Children’sHospital of Eastern Ontario Foundation. DAD is the recipient of a CIHR Clinical Investigator award from the Institute of Genetics. PRN was supported in part by grants from the Research Council of Norway, The University of Bergen, an ERC Advanced Grant, Helse Vest and the KG Jebsen Foundation., SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, University of Bergen (UIB), Instituto de Salud Carlos III (ISC), Stanford University [Stanford], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Service de neuropédiatrie [Trousseau], Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Recherche Clinique, Université Joseph Fourier - Grenoble 1 (UJF)-Centre de Recherche en Nutrition Humaine Rhône - Alpes, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, University of Bergen ( UIB ), The University of Hong Kong ( HKU ), Instituto de Salud Carlos III (ISCIII) - Spain RDR - CIBERER, University of California [San Francisco] ( UCSF ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Référence des Déficiences Intellectuelles de Causes Rares, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme ( GRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris 13 ( UP13 ) -Hôpital Jean Verdier, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cardiovasculaire, métabolisme, diabétologie et nutrition ( CarMeN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hospices Civils de Lyon ( HCL ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National de la Recherche Agronomique ( INRA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre de Recherche en Nutrition Humaine Rhône - Alpes, Cancers et préventions, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Bordeaux, Service de Génétique Clinique et Université Lille 2, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN)
Subjects: short stature, lipoatrophy, intrauterine growth restriction, [ SDV ] Life Sciences [q-bio], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], Diabetes, PIK3R1 gene, Insulin Resistance, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, SHORT syndrome
Abstract: International audience; SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.
Published: 2015
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27. Genotypic and Phenotypic Characterization of P23H Line 1 Rat Model

Author: Orhan, Elise, Dalkara, Deniz, Neuillé, Marion, Lechauve, Christophe, Michiels, Christelle, Picaud, Serge, Léveillard, Thierry, Sahel, José-Alain, Naash, Muna I., Lavail, Matthew M., Zeitz, Christina, Audo, Isabelle, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM-DHOS CIC 1423, University College of London [London] (UCL), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Académie des Sciences [Paris], Institut de France, University of Oklahoma (OU), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Fondation Ophtalmologique Adolphe de Rothschild, Académie des Sciences, University of California [San Francisco] (UCSF), University of California, Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), CIC Quinze-Vingts, Assistance publique - Hôpitaux de Paris (AP-HP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, University College of London [London], Fondation Ophtalmologique Adolphe de Rotschild, Academie des Sciences, University of Oklahoma, and University of California San Francisco (UCSF)
Subjects: Rhodopsin, genetic structures, Science, Molecular Sequence Data, Gene Dosage, Retina, Rats, Sprague-Dawley, Electroretinography, Animals, Amino Acid Sequence, Transgenes, Hemizygote, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Base Sequence, Color Vision, Sequence Analysis, DNA, eye diseases, Disease Models, Animal, Phenotype, Mutation, Medicine, sense organs, Rats, Transgenic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Retinitis Pigmentosa, Tomography, Optical Coherence, Research Article
Abstract: International audience; Rod-cone dystrophy, also known as retinitis pigmentosa (RP), is the most common inherited degenerative photoreceptor disease, for which no therapy is currently available. The P23H rat is one of the most commonly used autosomal dominant RP models. It has been created by incorporation of a mutated mouse rhodopsin (Rho) transgene in the wild-type (WT) Sprague Dawley rat. Detailed genetic characterization of this transgenic animal has however never been fully reported. Here we filled this knowledge gap on P23H Line 1 rat (P23H-1) and provide additional phenotypic information applying non-invasive and state-of-the-art in vivo techniques that are relevant for preclinical therapeutic evaluations. Trans-gene sequence was analyzed by Sanger sequencing. Using quantitative PCR, transgene copy number was calculated and its expression measured in retinal tissue. Full field electro-retinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were performed at 1-, 2-, 3-and 6-months of age. Sanger sequencing revealed that P23H-1 rat carries the mutated mouse genomic Rho sequence from the promoter to the 3' UTR. Trans-gene copy numbers were estimated at 9 and 18 copies in the hemizygous and homozygous rats respectively. In 1-month-old hemizygous P23H-1 rats, transgene expression represented 43% of all Rho expressed alleles. ERG showed a progressive rod-cone dysfunction peaking at 6 months-of-age. SD-OCT confirmed a progressive thinning of the photoreceptor cell layer leading to the disappearance of the outer retina by 6 months with additional morphological changes in the inner retinal cell layers in hemizygous P23H-1 rats. These results provide precise genotypic information of the P23H-1 rat with additional phenotypic characterization that will serve basis for therapeutic interventions, especially for those aiming at gene editing.
Published: 2015
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28. Renal Artery Variations in Patients With Mild-to-Moderate Hypertension From the RADIANCE-HTN SOLO Trial

Author: Felix Mahfoud, Terry Levy, Ajay J. Kirtane, Marc Sapoval, Jeremy Sayer, Andreas M. Loening, Leslie Coleman, Ronald J. Zagoria, Ajay N. Jain, Anthony Mathur, Yale Wang, Meital Horesh-Bar, Joost Daemen, Philipp Lurz, Suhail Dohad, Kintur Sanghvi, David Craig, Michel Azizi, Abbott Northwestern Hospital, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Queen Mary University of London (QMUL), Cedars-Sinai Medical Center, Université Paris Descartes - Paris 5 (UPD5), 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 (UPC), 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), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), 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), Saarland University Hospital (UKS), Leipzig University, Royal Bournemouth Hospital, University of California [San Francisco] (UCSF), University of California, Stanford University, Columbia University Medical Center (CUMC), Columbia University [New York], and Cardiology
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Blood Pressure, Fibromuscular dysplasia, Kidney, Imaging, Renal Artery, medicine.artery, medicine, Humans, Sympathectomy, Renal artery, Antihypertensive Agents, Denervation, medicine.diagnostic_test, business.industry, Ultrasound, Angiography, General Medicine, medicine.disease, Clinical trial, Stenosis, medicine.anatomical_structure, Hypertension, Renal denervation, Radiology, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Purpose: To assess the variability of renal artery (RA) anatomy and presence of RA-pathology in patients with mild-to-moderate hypertension enrolled in the RADIANCE-HTN SOLO trial.Background: RADIANCE-HTN SOLO was a multicenter, international, blinded, randomized, sham-controlled trial evaluating ultrasound-based endovascular renal denervation (RDN) in patients with mild-to-moderate hypertension while off antihypertensive medications.Methods: Eligible subjects had pre-randomization renal CT- or MR- angiography (CTA, MRA) to confirm anatomic suitability and to define RA ablation sites. All images were sent for independent review for evaluation of RA anatomy and other vascular pathology.Results: A total of 324 patients underwent RA imaging (282 CTA and 42 MRA). Of those, 178 had simple anatomy with a single left and single right RA with mean diameters of 5.4 ± 0.9 and 5.1 ± 0.8 mm and mean lengths of 40.0 ± 12.9 and 52.0 ± 13.1 mm, respectively. Twenty-seven patients (8.3%) had unilateral or bilateral dual RAs with mean diameters of 4.0 ± 0.9 mm on the left and 3.9 ± 0.9 mm on the right. Forty percent (129/324) of patients had at least 1 accessory RA, with mean accessory diameters of 2.4 ± 0.8 mm on the left and 2.3 ± 0.8 mm on the right. Twenty-eight patients (8.6%) had at least 1 short (
Published: 2022
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29. Long-term side effects of radiotherapy for pediatric localized neuroblastoma

Author: Ducassou , Anne, Gambart , Marion, Munzer , Caroline, Padovani , Laetitia, Carrie , Christian, Haas-Kogan , Daphne, Bernier-Chastagner , Valérie, Demoor , Charlotte, Claude , Line, Helfre , Sylvie, Bolle , Stéphanie, Leseur , Julie, Huchet , Aymeri, Rubié , Hervé, Valteau-Couanet , Dominique, Schleiermacher , Gudrun, Coze , Carole, Defachelles , Anne-Sophie, Marabelle , Aurelien, Ducassou , Stéphane, Devalck , Christine, Gandemer , Virginie, Munzer , Martine, Laprie , Anne, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiothérapie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Léon Bérard [Lyon], Dept. of Radiation Oncology, UCSF, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, CRLCC Eugène Marquis (CRLCC), CHU Bordeaux [Bordeaux], Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Hématogoie pédiatrique, Institut Jean Godinot [Reims], Imagerie cérébrale et handicaps neurologiques (ICHN), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital des Enfants, CHU Toulouse [Toulouse], University of California [San Francisco] (UCSF), University of California-University of California, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Unité d'Hémato-Oncologie, Hôpital des Enfants, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Institut Jean Godinot, CRLCC Jean Godinot, Imagerie cérébrale et handicaps neurologiques, Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hôpital des enfants, Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), University of California [San Francisco] ( UCSF ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CRLCC Eugène Marquis ( CRLCC ), Institut Gustave Roussy ( IGR ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Université Toulouse III - Paul Sabatier ( UPS ), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: [ SDV ] Life Sciences [q-bio], Radiotherapy, Neoplasien, Late effects, [SDV]Life Sciences [q-bio], Musculoskeletal abnormalities, Skoliose, Strahlentherapie, Radiation therapy, second primary, Scoliosis, Oncology, Spätfolgen, Neoplasms, Muskel-Skelett-Anomalien, zweite primäre, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Introduction - Neuroblastoma (NB) is the most frequent indication for extracranial pediatric radiotherapy. As long-term survival of high-risk localized NB has greatly improved, we reviewed treatment-related late toxicities in pediatric patients who received postoperative radiotherapy (RT) for localized NB within two French prospective clinical trials: NB90 and NB94. Patients and methods - From 1990-2000, 610 children were enrolled. Among these, 35 were treated with induction chemotherapy, surgery, and RT. The recommended RT dose was 24 Gy at ≤ 2 years, 34 Gy at > 2 years, ± a 5 Gy boost in both age groups. Results - The 22 patients still alive after 5 years were analyzed. The median follow-up time was 14 years (range 5-21 years). Late effects after therapy occurred in 73 % of patients (16/22), within the RT field for 50 % (11/22). The most frequent in-field effects were musculoskeletal abnormalities (n = 7) that occurred only with doses > 31 Gy/1.5 Gy fraction (p = 0.037). Other effects were endocrine in 3 patients and second malignancies in 2 patients. Four patients presented with multiple in-field late effects only with doses > 31 Gy. Conclusion - After a median follow-up of 14 years, late effects with multimodality treatment were frequent. The most frequent effects were musculoskeletal abnormalities and the threshold for their occurrence was 31 Gy.
Published: 2015
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30. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Author: Ruth Dobson, P. Kleinova, Tessel F. Runia, H.-P. Hartung, Maria Trojano, A.D. Martinez, Viviana Annibali, Sreeram V. Ramagopalan, Florian Deisenhammer, Mohsen Khademi, Jens Kuhle, Jan Lycke, Mar Tintoré, Ludwig Kappos, Pietro Iaffaldano, Antonio Uccelli, Dana Horakova, Kjell-Morten Myhr, Cecilia Rajda, Konrad Rejdak, Stig Wergeland, Monica Marta, Roberto Furlan, Florian Lauda, Jean Pelletier, Romain Marignier, G. Comi, Giulio Disanto, Romy Roesler, Vita Direnzo, Özgür Yaldizli, N. Moll, Silvia Romano, Sergey V. Lapin, Sylvain Lehmann, Irena Dujmovic, Elio Scarpini, Tomas Olsson, Rogier Q. Hintzen, Raija L.P. Lindberg, E. P. Evdoshenko, Siegrid Fuchs, B. C. Kieseier, Henrik Larsson, Eric Thouvenot, Jonathan P. Bestwick, Maurizio Leone, László Vécsei, S. Saip, Pablo Villoslada, Roberto Bergamaschi, Xavier Montalban, Øivind Torkildsen, José C. Álvarez-Cermeño, Joanne Topping, Albert Saiz, Isabel Bosca, Hayrettin Tumani, Adriana Carrá, Joep Killestein, Sara Llufriu, N. Barizzone, Ute-Christiane Meier, Diego Franciotta, David Brassat, Christian Enzinger, Michael Khalil, Gavin Giovannoni, Timucin Avsar, Scott L. Rauch, Aksel Siva, N. Lazareva, Clas Malmeström, Jette L. Frederiksen, Harald Hegen, Ugur Uygunoglu, Luisa M. Villar, Lucia Bianchi, Marco Salvetti, Tobias Derfuss, Giovanni Castelnovo, Ayse Altintas, Rocco Adiutori, E. Colombo, G. Dalla Costa, Daniela Galimberti, Madeleine H. Sombekke, Vittorio Martinelli, Sandra D'Alfonso, Manuel Comabella, Eva Havrdova, Fredrik Piehl, Charlotte E. Teunissen, Til Menge, Jelena Drulovic, C. Picard, Alice Laroni, Christian Confavreux, Chiara Fenoglio, Neurology, Laboratory Medicine, NCA - Neuroinflamation, Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), National Oceanography Centre (NOC), Department of Anatomy and Structural Biology Albert Einstein College of Medicine, Albert Einstein College of Medicine [New York], Department of public health, University of Turin, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Water Environment Technology, Chalmers University of Technology [Göteborg], Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara, Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB), Leibniz Association, Department of Neurology, University of California [San Francisco] (UCSF), University of California-University of California, Center for Neuroimmunology, Service of Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Université européenne de Bretagne - European University of Brittany (UEB), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Azm Center for Biotechnology Research, Agence universitaire de la Francophonie (Beyrouth, Lebanon)-Lebanese University [Beirut] (LU), FOI, Linköping University (LIU), Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, IRMP-Louvain, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Dipartimento Ingegneria Aerospaziale 'Lucio Lazzarino' (DIA), University of Pisa - Università di Pisa, International Centre for Hydrology 'Dino Tonini' and Dipartimento IMAGE, Universita degli Studi di Padova, Dept. of Neurology, University Hospital Rigshospitalet, University of California [Berkeley], University of California, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology, The Weizmann Institute, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Laboratory of Neuroimmunology, IRCCS, Neurological Institute 'C. Mondino', University of Pavia, Pa, University of Pavia, Department of Neurology, Albert Szent-Gyorgyi Clinical Centre, University of Szeged [Szeged], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Universitat de Barcelona (UB)-Hospital Clinic, University of Ulm, Department of Neurology, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], University of Eastern Piedmont, Department of Medical Sciences, IRCAD, Novara, Vall d'Hebron University Hospital [Barcelona], Department of Public Health and Clinical Medicine, Umeå University, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Universitaire de Bâle, Laboratory of Molecular Virology, Université libre de Bruxelles (ULB), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Department of Atmospheric, Oceanic and Planetary Physics [Oxford] (AOPP), University of Oxford [Oxford], Blizard Institute of Cell and Molecular Science, Università degli studi di Torino = University of Turin (UNITO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), University of California [Berkeley] (UC Berkeley), University of California (UC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Pavia = University of Pavia (UNIPV), University of Oxford, Direction des Applications Militaires ( DAM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), National Oceanography Centre, University of Southampton [Southampton], Albert Einstein College of Medicine, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Neuropsychiatrie : recherche épidémiologique et clinique, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Leibniz-Institute, University of California [San Francisco] ( UCSF ), Université européenne de Bretagne ( UEB ), Laboratoire de l'intégration, du matériau au système ( IMS ), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique ( CNRS ), Agence universitaire de la Francophonie (Beyrouth, Lebanon)-Lebanese University [Beirut], Linköping University ( LIU ), Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy, Università di Bologna [Bologna] ( UNIBO ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Dipartimento Ingegneria Aerospaziale 'Lucio Lazzarino' ( DIA ), Università di Pisa, Universita degli Studi di Padova = University of Padua = Université de Padoue, Educational Testing Service, Graduate School of Education, University of California at Berkeley, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Centre de résonance magnétique biologique et médicale ( CRMBM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Centre National de la Recherche Scientifique ( CNRS ), Universitat de Barcelona ( UB ) -Hospital Clinic, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Institut de recherche en biothérapie ( IRB ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Université de Montpellier ( UM ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Department of Atmospheric, Oceanic and Planetary Physics [Oxford] ( AOPP ), Kuhle, J., Disanto, G., Dobson, R., Adiutori, R., Bianchi, L., Topping, J., Bestwick, J. P., Meier, U. -C., Marta, M., Dalla Costa, G, Runia, T., Evdoshenko, E., Lazareva, N., Thouvenot, E., Iaffaldano, P., Direnzo, V., Khademi, M., Piehl, F., Comabella, M., Sombekke, M., Killestein, J., Hegen, H., Rauch, S., Dalfonso, S., Alvarez-Cermeno, J. C., Kleinova, P., Horakova, D., Roesler, R., Lauda, F., Llufriu, S., Avsar, T., Uygunoglu, U., Altintas, A., Saip, S., Menge, T., Rajda, C., Bergamaschi, R., Moll, N., Khalil, M., Marignier, R., Dujmovic, I., Larsson, H., Malmestrom, C., Scarpini, E., Fenoglio, C., Wergeland, S., Laroni, A., Annibali, V., Romano, S., Martinez, A. D., Carra, A., Salvetti, M., Uccelli, A., Torkildsen, O., Myhr, K. M., Galimberti, D., Rejdak, K., Lycke, J., Frederiksen, J. L., Drulovic, J., Confavreux, C., Brassat, D., Enzinger, C., Fuchs, S., Bosca, I., Pelletier, J., Picard, C., Colombo, E., Franciotta, D., Derfuss, T., Lindberg, R. L. P., Yaldizli, O., Vecsei, L., Kieseier, B. C., Hartung, H. P., Villoslada, P., Siva, A., Saiz, A., Tumani, H., Havrdova, E., Villar, L. M., Leone, M., Barizzone, N., Deisenhammer, F., Teunissen, C., Montalban, X., Tintore, M., Olsson, T., Trojano, M., Lehmann, S., Castelnovo, G., Lapin, S., Hintzen, R., Kappos, L., Furlan, R., Martinelli, V., Comi, G., Ramagopalan, S. V., and Giovannoni, G.
Subjects: Male, Pathology, serum 25-hydroxyvitamin D3 (25-OH-D), [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Gastroenterology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, sclerosis, clinically isolated syndrome (CIS), Vitamin D, 0303 health sciences, Clinically isolated syndrome, Nuclear Proteins, Prognosis, Magnetic Resonance Imaging, Neurology, Clinically definite multiple sclerosis (CDMS), Epstein-Barr nuclear antigen 1 (EBNA-1), oligoclonal bands (OCBs), Predictive value of tests, Cohort, Disease Progression, Female, Cohort study, Adult, medicine.medical_specialty, Multiple Sclerosis, clinic study, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Vitamin D and neurology, Humans, Survival analysis, 030304 developmental biology, business.industry, Multiple sclerosis, Oligoclonal Bands, Endonucleases, medicine.disease, Survival Analysis, chemistry, Immunoglobulin G, [ SHS.ANTHRO-BIO ] Humanities and Social Sciences/Biological anthropology, Neurology (clinical), business, Cotinine, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
Published: 2015
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31. Classification of current anticancer immunotherapies

Author: Chiara Castelli, Axel Hoos, Anna Karolina Palucka, Aitziber Buqué, Kenneth J. Pienta, Aled Clayton, Daniel E. Speiser, Jean-Pierre Mach, Klas Kärre, Richard G. Vile, Maha Ayyoub, Norma Bloy, Theresa L. Whiteside, Eli Gilboa, Naiyer A. Rizvi, Cornelis J. M. Melief, Alexander Knuth, Bruno Silva-Santos, Lisa M. Coussens, James E. Talmadge, Jean-Yves Blay, Rolf Kiessling, Lorenzo Moretta, Alexander M.M. Eggermont, Estaban Celis, Anne Caignard, Mario P. Colombo, Abhishek D. Garg, José Manuel Bravo-San Pedro, Pramod K. Srivastava, Dmitry I. Gabrilovich, Wolf H. Fridman, Catherine Sautès-Fridman, Eric Tartour, Fabrizio Mattei, Patrizia Agostinis, Philipp Beckhove, Laura Bracci, Vincenzo Cerundolo, Giuseppe Giaccone, Fernando Aranda, Angel Porgador, Elisa E. Baracco, Radek Spisek, Jean Pierre Abastado, Michael T. Lotze, Ron N. Apte, Federica Cavallo, Benoît Van den Eynde, Weiping Zou, François Ghiringhelli, Hans Schreiber, Jitka Fucikova, Lorenzo Galluzzi, Adekunke Odunsi, Erika Vacchelli, Roland S. Liblau, Hideho Okada, Hiroshi Shiku, Laurence Zitvogel, Pawel Kalinski, Guido Kroemer, Oliver Kepp, George C. Prendergast, Eva Klein, Francesca Castoldi, Enrico Lugli, Jedd D. Wolchok, Anne Hosmalin, Sjoerd H. van der Burg, Hermann Wagner, Mark J. Smyth, Nicholas P. Restifo, Dirk Jäger, John M. Kirkwood, Gabriel A. Rabinovich, Sacha Gnjatic, Madhav V. Dhodapkar, E. A. Mittendorf, Douglas T. Fearon, Ignacio Melero, Marcus E. Peter, Jérôme Galon, Domenico Mavilio, Laura Senovilla, Claire E. Lewis, Barbara Seliger, Jeffrey S. Weber, UCL - SSS/DDUV - Institut de Duve, Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Paris-Sud - Paris 11 (UP11), Sotio a.c., Pole d’innovation thérapeutique en oncologie, Institut de Recherches Internationales Servier, Cell Death Research and Therapy (CDRT) Laboratory, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Group of Immune receptors of the Innate and Adaptive System, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Cancer Vaccines and Immune Regulation, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Translational Immunology Division, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), 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), Dept. of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità (ISS), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unit of Immunotherapy of Human Tumors, Dept. of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Molecular Biotechnology Center, Dept. of Molecular Biotechnology and Health Sciences, Università degli studi di Torino = University of Turin (UNITO), Cancer Immunology, Inflammation and Tolerance Program, Augusta University, University System of Georgia (USG)-University System of Georgia (USG), MRC Human Immunology Unit, The Weatherall Institute of Molecular Medicine, University of Oxford-University of Oxford, Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Institute of Cancer & Genetics, Cardiff University, Velindre Cancer Centre, Knight Cancer Institute, Oregon Health and Science University [Portland] (OHSU), Sect. of Hematology and Immunobiology,Yale Cancer Center, Yale University [New Haven], Institut Gustave Roussy (IGR), Cold Spring Harbor Laboratory, NY, Cold Spring Harbor, Centre de Recherche des Cordeliers (CRC), Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University [Prague] (CU), Dept. of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Lombardi Comprehensive Cancer Center, Georgetown University [Washington] (GU), Dept. of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami [Coral Gables], Glaxo Smith Kline, Cancer Immunotherapy Consortium, 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), National Center for Tumor Diseases, University Medical Center Heidelberg, Hillman Cancer Center, University of Pittsburg, Department of Surgery, Cancer Institute-University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Dept. of Immunology and Infectious Diseases and Microbiology, University of Pittsburgh (PITT), Dept. of Microbiology, Tumor and Cell Biology, Karolinska Institutet [Stockholm], Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Dept. of Oncology, Karolinska Institute Hospital, Cancer Institute Laboratory, Academic Unit of Inflammation and Tumour Targeting, Dept. of Oncology, University of Sheffield Medical School, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Institute, Institut de Biochimie, Université de Lausanne = University of Lausanne (UNIL), Dept. of Medical Biotechnologies and Translational Medicine, Università degli Studi di Milano = University of Milan (UNIMI), Dept. of Immunology, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Clínica Universidad de Navarra [Pamplona], ISA Therapeutics, Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Research Dept. of Surgical Oncology, The University of Texas, Istituto Giannina Gaslini, Center for Immunotherapy [Buffalo], Roswell Park Cancer Institute [Buffalo] (RPCI), Dept. of Neurological Surgery, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), The Jackson Laboratory [Bar Harbor] (JAX), Div. of Hematology/Oncology, Northwestern University, The James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev (BGU)-Faculty of Health Sciences and Cancer Research Center, Cell Biology and Signaling Program, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental [Buenos Aires] (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Memorial Sloane Kettering Cancer Center [New York], Dept. of Pathology, The Cancer Research Center, University of Chicago, Institute of Medical Immunology, Martin-Luther-Universität Halle Wittenberg (MLU), Department of Immuno-gene Therapy, Mie University, Instituto de Medicina Molecular, Universidade de Lisboa = University of Lisbon (ULISBOA), Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, School of Medicine, University of Queensland [Brisbane], Ludwig Cancer Research Center, Dept. of Immunology, University of Connecticut (UCONN), Carole and Ray Neag Comprehensive Cancer Center, Laboratory of Transplantation Immunology, Dept. of Pathology and Microbiology, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie biologique, 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), Dept. of Clinical Oncology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Ludwig Institute for Cancer Research, de Duve Institute, Dept. of Molecular Medicine and Immunology, Mayo Clinic College of Medicine, Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Donald A. Adam Comprehensive Melanoma Research Center, H. Lee Moffitt Cancer Center & Research Institute, University of Pittsburgh School of Medicine, Dept. of Medicine and Ludwig Center, Weill Medical College of Cornell University [New York], Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Pôle de biologie, GK is supported by the Ligue contre le Cancer(équipe labelisée), Agence Nationale de la Recherche(ANR), Association pour la recherche sur le cancer (ARC), Cancéropôle Ile-de-France, Institut National du Cancer(INCa), Fondation Bettencourt-Schueller, Fondation deFrance, Fondation pour la Recherche Médicale (FRM), theEuropean Commission (ArtForce), the European ResearchCouncil (ERC), the LabEx Immuno-Oncology, the SIRICStratified Oncology Cell DNA Repair and Tumor ImmuneElimination (SOCRATE), the SIRIC Cancer Researchand Personalized Medicine (CARPEM), and the ParisAlliance of Cancer Research Institutes (PACRI). MPC issupported by Association for Cancer Research (AIRC). SGis supported by Cancer Vaccine Collaborative and CancerResearch Institute. MJS is supported by the NationalHealth and Medical Research Council of Australia, the QIMR Berghofer Medical Research Institute, andthe Susan G Komen Breast Cancer Foundation. FM issupported by a grant from the Italian Ministry of Health., Repositório da Universidade de Lisboa, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto Superiore di Sanità, Università degli studi di Torino (UNITO), University of Oxford [Oxford]-University of Oxford [Oxford], University of Pennsylvania [Philadelphia], Georgetown University, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne (UNIL), University of Milan, Roswell Park Cancer Institute [Buffalo], University of California [San Francisco] (UCSF), University of California-University of California, Universidade de Lisboa (ULISBOA), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Bos, Mireille, Apoptose, cancer et immunité ( Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 ), Institut Gustave Roussy ( IGR ) -Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris-Sud - Paris 11 ( UP11 ), Catholic University of Leuven ( KU Leuven ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), German Cancer Research Center, Centre de Recherche en Cancérologie de Lyon ( 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 ), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Università degli studi di Torino ( UNITO ), Georgia Regents University Cancer Center, Cancer Center Karolinska [Karolinska Institutet] ( CCK ), Oregon Health & Science University [Portland] ( OHSU ), Institut Gustave Roussy ( IGR ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Charles University, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), University of Miami, Institut Cochin ( 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 ), Cancer Institute-University of Pittsburgh, University of Pittsburgh, Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lausanne ( UNIL ), Center for Immunotherapy, University of California [San Francisco] ( UCSF ), The Jackson Laboratory for Genomics Medicine, Ben-Gurion University of the Negev ( BGU ) -Faculty of Health Sciences and Cancer Research Center, Instituto de Biología y Medicina Experimental (IBYME), National Cancer Institute (NCI), Memorial Sloan Kettering Cancer Center ( MSKCC ), Martin Luther University Halle-Wittenberg, Mie University Graduate School of Medicine, Universidade de Lisboa ( ULISBOA ), University of Lausanne, University of Connecticut School of Medicine, Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Catholique de Louvain ( UCL ), Technical University of Munich ( TUM ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: immunostimulatory cytokines, medicine.medical_treatment, Review, Bioinformatics, DNA-based vaccines, Efficacy, 0302 clinical medicine, Cancer immunotherapy, Neoplasms, peptide-based vaccines, 0303 health sciences, Patología, purl.org/becyt/ford/3.1 [https], CANCER, 3. Good health, Medicina Básica, Oncology, checkpoint blockers, 030220 oncology & carcinogenesis, QR180, purl.org/becyt/ford/3 [https], Immunotherapy, CIENCIAS MÉDICAS Y DE LA SALUD, medicine.drug_class, Inmunología, adoptive cell transfer, dendritic cell-based interventions, oncolytic viruses, Toll-like receptor agonists, Monoclonal antibody, RC0254, 03 medical and health sciences, Immune system, Antigen, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, IMMUNOTHERAPIES, business.industry, Cancer, medicine.disease, R1, Oncolytic virus, Immunology, business
Abstract: © 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.
Published: 2014

32. Mouse Stress Reduction Alters Splenic Immune Cell Composition and Enhances Influenza Vaccine Responses

Author: FromentinGilles, GurfeinBlake, HechtFrederick, NixonDouglas, AcreeMichael, Premenko-LanierMary, PalmeRupert, YorkVanessa, DallmanMary, MilushJeffrey, DarcelNicolas, DavidenkoOlga, ToumaChadi, Division of Experimental Medicine - Osher Center for Integrative Medicine, University of California [San Francisco] (UCSF), University of California-University of California, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Division of Experimental Medicine, Osher Center for Integrative Medicine, Department of Physiology, Research Group of Psychoneuroendocrinology, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, University of Veterinary Medicine Vienna, University of Veterinary Medicine [Vienna] (Vetmeduni), Department of Microbiology, Immunology & Tropical Medicine [Washington, USA], The George Washington University Medical Center, Department of Medicine [San Francisco, CA, USA], Division of Experimental Medicine [San Francisco, CA, USA], University of California-University of California-University of California [San Francisco] (UCSF), Department of Medicine [San Francisco, CA, USA] (HIV/AIDS Program), and Institut National de la Recherche Agronomique (INRA)-AgroParisTech
Subjects: Stress reduction, Immune system, Molecular composition, Complementary and alternative medicine, business.industry, Influenza vaccine, [SDV]Life Sciences [q-bio], Immunology, Medicine, business, Virology, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: International audience
Published: 2014
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33. Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma

Author: Ahmad S. Halwani, Carlos Panizo, Iris Isufi, Alex F. Herrera, Craig Y. Okada, Elizabeth H. Cull, Bela Kis, Jorge M. Chaves, Nancy L. Bartlett, Weiyun Ai, Luis de la Cruz-Merino, Locke J. Bryan, Roch Houot, Kim Linton, Javier Briones, Ian Chau, Gottfried R. von Keudell, Hailing Lu, Adam Yakovich, Michael Chen, ter Meulen JH, Sergey Yurasov, Frank J. Hsu, Christopher R. Flowers, University of Utah, Clínica Universidad de Navarra [Pamplona], Universidad de Navarra [Pamplona] (UNAV), Yale University School of Medicine, H. Lee Moffitt Cancer Center and Research Institute, North-West University [Potchefstroom] (NWU), University of California [San Francisco] (UCSF), University of California, University of Sevilla, Augusta University, University System of Georgia (USG), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Manchester University NHS Foundation Trust (MFT), Memorial Sloan Kettering Cancer Center (MSKCC), The University of Texas M.D. Anderson Cancer Center [Houston], Emory University [Atlanta, GA], Immune Design Corp., Yale School of Medicine [New Haven, Connecticut] (YSM), University of California [San Francisco] (UC San Francisco), University of California (UC), Universidad de Sevilla / University of Sevilla, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0303 health sciences, Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Antibodies, Monoclonal, Humanized, 3. Good health, Toll-Like Receptor 4, 03 medical and health sciences, 0302 clinical medicine, follicular lymphoma, Oncology, glucopyranosyl lipid A, 030220 oncology & carcinogenesis, Antineoplastic Combined Chemotherapy Protocols, Humans, TLR4, immunotherapy, pembrolizumab, Lymphoma, Follicular, 030304 developmental biology
Abstract: International audience; Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 mu g/dose, or 20 mu g/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 mu g/dose expansion. Adverse events grade >= 3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 mu g (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.
Published: 2021
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34. Magnetic Resonance Spectroscopy Markers of Disease Progression in Multiple Sclerosis

Author: Hélène Ratiney, Don Brenneman, Daniel Pelletier, Stephen L. Hauser, Sara Llufriu, Mehul Sampat, Joonmi Oh, Sarah J. Nelson, Bruce A.C. Cree, John Kornak, Department of Neurology, University of California [San Francisco] (UCSF), University of California-University of California, Center for Neuroimmunology, Service of Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Epidemiology and Biostatistics, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Radiology [San Francisco], Yale University [New Haven], Department of Diagnostic Radiology [YALE], Yale University [New Haven]-Yale University School of Medicine, University of California [San Francisco] ( UCSF ), 5 - RMN et optique : De la mesure aux biomarqueurs, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of California, Université Yale - New Haven, and Yale School of Medicine-Université Yale - New Haven
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Pathology, Magnetic Resonance Spectroscopy, Multiple Sclerosis, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, Severity of Illness Index, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, Cerebral atrophy, Aspartic Acid, Expanded Disability Status Scale, Multiple sclerosis, Odds ratio, Middle Aged, medicine.disease, 3. Good health, medicine.anatomical_structure, Multiple sclerosis functional composite, Predictive value of tests, Case-Control Studies, Cohort, Disease Progression, Female, Neurology (clinical), Atrophy, Psychology, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, Biomarkers, Inositol, Follow-Up Studies
Abstract: International audience; Importance Predicting disease evolution is becoming essential for optimizing treatment decision making in multiple sclerosis (MS). Multiple sclerosis pathologic damage typically includes demyelination, neuro-axonal loss, and astrogliosis. Objective To evaluate the potential of magnetic resonance markers of central nervous system injury to predict brain-volume loss and clinical disability in multiple sclerosis. Design, Setting, and Participants Participants were selected from the Multiple Sclerosis Center at the University of California-San Francisco. The preliminary data set included 59 patients with MS and 43 healthy control individuals. The confirmatory data set included 220 patients from an independent, large genotype-phenotype research project. Main Outcomes and Measures Baseline N-acetylaspartate (NAA) level, myo-inositol (mI) in normal-appearing white and gray matter, myelin water fraction in normal-appearing white matter, markers of axonal damage, astrogliosis, and demyelination were evaluated as predictors in a preliminary data set. Potential predictors were subsequently tested for replication in a confirmatory data set. Clinical scores and percentage of brain-volume change were obtained annually over 4 years as outcomes. Predictors of outcomes were assessed using linear models, linear mixed-effects models, and logistic regression. Results N-acetylaspartate and mI both had statistically significant effects on brain volume, prompting the use of the mI:NAA ratio in normal-appearing white matter as a predictor. The ratio was a predictor of brain-volume change in both cohorts (annual slope in the percentage of brain-volume change/unit of increase in the ratio: −1.68; 95% CI, −3.05 to −0.30; P = .02 in the preliminary study cohort and −1.08; 95% CI, −1.95 to −0.20; P = .02 in the confirmatory study cohort). Furthermore, the mI:NAA ratio predicted clinical disability (Multiple Sclerosis Functional Composite evolution: −0.52 points annually, P
Published: 2014
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35. Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren's syndrome

Author: Gaetane Nocturne, Saida Boudaoud, Corinne Miceli-Richard, Say Viengchareun, Thierry Lazure, Joanne Nititham, Taylor, E., Averil Ma, Florence Busato, Judith Melki, Lessard, J., Sivils, Kathy L., Jean-Jacques Dubost, Eric Hachulla, Jacques Eric Gottenberg, Lombes, M., Jorg Tost, Criswell, Lindsey A., Xavier Mariette, Taylor, Kimberly E., Lessard, Christopher J., Marc Lombès, Alain Saraux, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Rosalind Russell Medical Research Center for Arthritis, University of California [San Francisco] (UCSF), University of California-University of California-Howard Hugues Medical Institute, Department of Medicine (Dep Med - San Francisco), University of California-University of California, Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Neuroprotection et neurogénération (UMR788), Neuroprotection et Neurodégénération (UMR788), University of Oklahoma Health Sciences Center (OUHSC), Service de Rhumatologie [CHU Gabriel-Montpied], CHU Gabriel Montpied [Clermont-Ferrand], Département de Rhumatologie (LILLE - Rhumatologie), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique INSERM 1412 (CIC 1412 - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), 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), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Howard Hughes Medical Institute (HHMI)-University of California [San Francisco] (UCSF), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), University of California-University of California-Howard Hughes Medical Institute (HHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Howard Hughes Medical Institute (HHMI)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), and Calvez, Ghislaine
Subjects: Male, MESH: Neoplasm Proteins, Somatic cell, [SDV]Life Sciences [q-bio], MESH: NF-kappa B, medicine.disease_cause, Biochemistry, Germline, Autoimmunity, BCL9, immune system diseases, hemic and lymphatic diseases, MESH: Germ-Line Mutation, Prospective Studies, MESH: Lymphoma, B-Cell, Marginal Zone, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Lymphoid Neoplasia, MESH: Polymorphism, Single Nucleotide, Intracellular Signaling Peptides and Proteins, NF-kappa B, Nuclear Proteins, Exons, Hematology, MESH: Follow-Up Studies, BCL10, Neoplasm Proteins, [SDV] Life Sciences [q-bio], DNA-Binding Proteins, Sjogren's Syndrome, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Female, Immunology, Biology, Polymorphism, Single Nucleotide, Germline mutation, MESH: Intracellular Signaling Peptides and Proteins, medicine, Humans, Germ-Line Mutation, Tumor Necrosis Factor alpha-Induced Protein 3, B cell, MESH: Humans, Lymphoma, B-Cell, Marginal Zone, Cell Biology, medicine.disease, MESH: Prospective Studies, MESH: Male, Lymphoma, stomatognathic diseases, MESH: Sjogren's Syndrome, MESH: Tumor Necrosis Factor alpha-Induced Protein 3, MESH: Exons, MESH: Nuclear Proteins, MESH: Female, MESH: DNA-Binding Proteins, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; Several autoimmune diseases, including primary Sjögren's syndrome (pSS), are associated with an increased risk for lymphoma. Polymorphisms of TNFAIP3, which encodes the A20 protein that plays a key role in controlling nuclear factor κB activation, have been associated with several autoimmune diseases. Somatic mutations of TNFAIP3 have been observed in the mucosa-associated lymphoid tissue lymphoma subtype frequently associated with pSS. We studied germline and somatic abnormalities of TNFAIP3 in 574 patients with pSS, including 25 with lymphoma. Nineteen additional patients with pSS and lymphoma were available for exome sequence analysis. Functional abnormalities of A20 were assessed by gene reporter assays. The rs2230926 exonic variant was associated with an increased risk for pSS complicated by lymphoma (odds ratio, 3.36 [95% confidence interval, 1.34-8.42], and odds ratio, 3.26 [95% confidence interval, 1.31-8.12], vs controls and pSS patients without lymphoma, respectively; P = .011). Twelve (60%) of the 20 patients with paired germline and lymphoma TNFAIP3 sequence data had functional abnormalities of A20: 6 in germline DNA, 5 in lymphoma DNA, and 1 in both. The frequency was even higher (77%) among pSS patients with mucosa-associated lymphoid tissue lymphoma. Some of these variants showed impaired control of nuclear factor κB activation. These results support a key role for germline and somatic variations of A20 in the transformation between autoimmunity and lymphoma.
Published: 2013

36. Maternal effects in quail and zebra finches: behavior and hormones

Author: Sunayana B. Banerjee, Stephanie M. Correa, Cécile Schweitzer, Elizabeth Adkins-Regan, Department of Psychology, Cornell University [New York], Department of Neurobiology and Behavior, Department of Biology, Emory University [Atlanta, GA], Department of Cellular and Molecular Pharmacology, University of California [San Francisco] (UCSF), University of California-University of California, Biogéosciences [UMR 6282] [Dijon] (BGS), 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), Research supported by the U. S. National Science Foundation., Cornell University, University of California [San Francisco] ( UCSF ), Biogéosciences [Dijon] ( BGS ), and 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 )
Subjects: 0106 biological sciences, Hypothalamo-Hypophyseal System, medicine.medical_specialty, food.ingredient, Offspring, Maternal effects, Pituitary-Adrenal System, Stress, Quail, 010603 evolutionary biology, 01 natural sciences, Birds, 03 medical and health sciences, Receptors, Glucocorticoid, Endocrinology, food, biology.animal, Yolk, Internal medicine, medicine, [ SDV.EE.IEO ] Life Sciences [q-bio]/Ecology, environment/Symbiosis, Animals, Gonadal Steroid Hormones, Glucocorticoid receptors, Testosterone, 030304 developmental biology, Steroid hormones, 0303 health sciences, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, Sexual differentiation, biology, Environmental stressor, Maternal effect, Sex determination, Animal Science and Zoology, Finches, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Hormone, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: 8 pages; International audience; Maternal effects are influences of parents on offspring phenotype occurring through pathways other than inherited DNA. In birds, two important routes for such transmission are parental behavior and non-DNA egg constituents such as yolk hormones. Offspring traits subject to parental effects include behavior and endocrine function. Research from the Adkins-Regan lab has used three avian species to investigate maternal effects related to hormones and behavior. Experiments with chickens and Japanese quail have shown that maternal sex steroids can influence sex determination to produce biased offspring sex ratios. Because all birds have a ZZ/ZW chromosomal sex determining system in which the female parent determines the sex of the offspring, these results raise the possibility that maternal steroids can influence the outcome of sex chromosome meiosis. Learning has been shown to influence egg investment by female quail in ways that are likely to alter offspring phenotype. In quail, embryonic and exogenous sex steroids have well established and long-lasting effects on sexual differentiation of behavior during a critical period in ovo, but elevated yolk testosterone has long-term effects on behavior that do not seem to be occurring through an alteration in sexual differentiation. In biparental zebra finches, removal of mothers alters not only later behavior, but also the adult response of the hypothalamic-pituitary-adrenal (HPA) axis to an environmental stressor, as indicated by plasma corticosterone. Birds raised only by fathers have lower levels of mRNA for both glucocorticoid receptors in several brain regions as adults. These studies add to the evidence that one generation influences the behavioral or endocrine phenotype of the next through routes other than transmission of DNA. Additional research will be required to understand the adaptive significance of these effects.
Published: 2013
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37. Urea transporter UT-B deletion induces DNA damage and apoptosis in mouse bladder urothelium

Author: Baoxue Yang, Lise Bankir, Yi Sun, Zixun Dong, Jihui Chen, Weiling Wang, Guiting Lin, Tianluo Lei, Jianhua Ran, Hong Zhou, Peking University [Beijing], Chongqing University [Chongqing], University of California [San Francisco] (UC San Francisco), University of California (UC), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), University of California [San Francisco] (UCSF), University of California, University of California [San Francisco] ( UCSF ), Centre de Recherche des Cordeliers ( CRC ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Urea transporter, Apoptosis, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Mice, 0302 clinical medicine, Urea, Oligonucleotide Array Sequence Analysis, Mice, Knockout, 0303 health sciences, Multidisciplinary, Urinary bladder, biology, female genital diseases and pregnancy complications, 3. Good health, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Knockout mouse, Medicine, Research Article, DNA damage, MAP Kinase Signaling System, Science, Blotting, Western, Urinary Bladder, Arginine, Nitric Oxide, Bladder Urothelium, 03 medical and health sciences, Microscopy, Electron, Transmission, Cell Line, Tumor, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Autophagy, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Urothelium, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Cell Proliferation, Dose-Response Relationship, Drug, Cell growth, Gene Expression Profiling, Membrane Transport Proteins, Cell Cycle Checkpoints, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Mice, Inbred C57BL, Microscopy, Fluorescence, biology.protein, DNA Damage
Abstract: International audience; Background: Previous studies found that urea transporter UT-B is abundantly expressed in bladder urothelium. However, the dynamic role of UT-B in bladder urothelial cells remains unclear. The objective of this study is to evaluate the physiological roles of UT-B in bladder urothelium using UT-B knockout mouse model and T24 cell line.Methodology/Principal Findings: Urea and NO measurement, mRNA expression micro-array analysis, light and transmission electron microscopy, apoptosis assays, DNA damage and repair determination, and intracellular signaling examination were performed in UT-B null bladders vs wild-type bladders and in vitro T24 epithelial cells. UT-B was highly expressed in mouse bladder urothelium. The genes, Dcaf11, MCM2-4, Uch-L1, Bnip3 and 45 S pre rRNA, related to DNA damage and apoptosis were significantly regulated in UT-B null urothelium. DNA damage and apoptosis highly occurred in UT-B null urothelium. Urea and NO levels were significantly higher in UT-B null urothelium than that in wild-type, which may affect L-arginine metabolism and the intracellular signals related to DNA damage and apoptosis. These findings were consistent with the in vitro study in T24 cells that, after urea loading, exhibited cell cycle delay and apoptosis.Conclusions/Significance: UT-B may play an important role in protecting bladder urothelium by balancing intracellular urea concentration. Disruption of UT-B function induces DNA damage and apoptosis in bladder, which can result in bladder disorders.
Published: 2013
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38. Clinical Benefit of Extubation in Patients on Venoarterial Extracorporeal Membrane Oxygenation

Author: Nicolas Massart, James T. Ross, Erwan Flecher, Alexandre Mansour, Yoann Launey, Vincent Auffret, Claude Ecoffey, Jean-Philippe Verhoye, Nicolas Nesseler, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of California [San Francisco] (UCSF), University of California, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_treatment, Shock, Cardiogenic, Critical Care and Intensive Care Medicine, Lower risk, Extracorporeal, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Extracorporeal membrane oxygenation, medicine, Humans, Cardiac Surgical Procedures, Retrospective Studies, Mechanical ventilation, business.industry, Hazard ratio, 030208 emergency & critical care medicine, Retrospective cohort study, Odds ratio, Oxygenation, 3. Good health, 030228 respiratory system, Anesthesia, Airway Extubation, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract: International audience; OBJECTIVES: Although patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock are usually supported with mechanical ventilation, it is not clear whether sedation cessation and extubation might improve outcomes. DESIGN: Retrospective cohort study with propensity score overlap weighting analysis. SETTING: Three ICUs in a 1,500-bed tertiary university hospital. PATIENTS: From an overall cohort of 641 patients with venoarterial-extracorporeal membrane oxygenation support, the primary analysis was performed in 344 patients who had been successfully decannulated in order to reduce immortal time bias. MEASUREMENTS AND MAIN RESULTS: Seventy-five patients (22%) were extubated during extracorporeal membrane oxygenation support and were subsequently decannulated alive. Forty-nine percent received noninvasive ventilation, and 25% had emergency reintubation for respiratory, neurologic, or hemodynamic reasons. Higher Simplified Acute Physiology Score II at admission (odds ratio, 0.97; 95% CI [0.95-0.99]; p = 0.008) was associated with a lower probability of extubation, whereas cannulation in cardiac surgery ICU (odds ratio, 3.14; 95% CI [1.21-8.14]; p = 0.018) was associated with an increased probability. Baseline characteristics were well balanced after propensity score overlap weighting. The number of ICU-free days within 30 days of extracorporeal membrane oxygenation decannulation was significantly higher among extubated patients compared with nonextubated patients (22 d [11-26 d] vs 18 d [7-25 d], respectively; p = 0.036). There were no differences in other outcomes including ventilator-associated pneumonia (odds ratio, 0.96; 95% CI [0.51-1.82]; p = 0.90) and all-cause mortality within 30 days of extracorporeal membrane oxygenation decannulation (5% vs 17%; hazard ratio, 0.54; 95% CI [0.19-1.59]; p = 0.27).As a secondary analysis, outcomes were compared in the overall cohort of 641 venoarterial extracorporeal membrane oxygenation-supported patients. Results were consistent with the primary analysis as extubated patients had a higher number of ICU-free days (18 d [0-24 d] vs 0 d [0-18 d], respectively; < 0.001) and a lower risk of death within 30 days of extracorporeal membrane oxygenation cannulation (hazard ratio, 0.45; 95% CI [0.29-0.71]; p = 0.001). CONCLUSIONS: Extubation during venoarterial-extracorporeal membrane oxygenation support is safe, feasible, and associated with greater ICU-free days.
Published: 2021
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39. The benefit of early surgery on overall survival in incidental low-grade glioma patients: A multicenter study

Author: John Kelly, David Ben-Israel, Miran Skrap, Hugues Duffau, Jacob S. Young, Barbara Tomasino, Mitchel S. Berger, Tamara Ius, Maurizio Polano, Sam Ng, Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Università degli Studi di Udine - University of Udine [Italie], Neurochirurgie [Hôpital Gui de Chauliac], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UCSF), University of California, IRCCS Eugenio Medea, IRCCS, University of Calgary, Service de Neurochirurgie [Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier]
Subjects: Cancer Research, medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], Population, Clinical Investigations, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluid-attenuated inversion recovery, Neurosurgical Procedures, 03 medical and health sciences, Early surgery, 0302 clinical medicine, Overall survival, Humans, Medicine, Extension of Resection, education, Retrospective Studies, High-Grade Glioma, Brain Mapping, education.field_of_study, Brain Neoplasms, business.industry, Glioma, Molecular pattern, Incidental findings, Treatment Outcome, Low Grade Gliomas, Oncology, Multicenter study, 030220 oncology & carcinogenesis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Low-Grade Glioma, Neurology (clinical), Radiology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background The role of surgery for incidentally discovered diffuse incidental low-grade gliomas (iLGGs) is debatable and poorly documented in current literature. Objective The aim was to identify factors that influence survival for patients that underwent surgical resection of iLGGs in a large multicenter population. Methods Clinical, radiological, and surgical data were retrospectively analyzed in 267 patients operated for iLGG from 4 neurosurgical Centers. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and tumor recurrence (TR). Results The OS rate was 92.41%. The 5- and 10-year estimated OS rates were 98.09% and 93.2%, respectively. OS was significantly longer for patients with a lower preoperative tumor volume (P = .001) and higher extent of resection (EOR) (P = .037), regardless the WHO-defined molecular class (P = .2). In the final model, OS was influenced only by the preoperative tumor volume (P = .006), while TR by early surgery (P = .028). A negative association was found between preoperative tumor volumes and EOR (rs = −0.44, P < .001). The median preoperative tumor volume was 15 cm3. The median EOR was 95%. Total or supratotal resection of T2-FLAIR abnormality was achieved in 61.62% of cases. Second surgery was performed in 26.22%. The median time between surgeries was 5.5 years. Histological evolution to high-grade glioma was detected in 22.85% of cases (16/70). Permanent mild deficits were observed in 3.08% of cases. Conclusions This multicenter study confirms the results of previous studies investigating surgical management of iLGGs and thereby strengthens the evidence in favor of early surgery for these lesions.
Published: 2021
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40. The small G protein H-Ras in the mesolimbic system is a molecular gateway to alcohol-seeking and excessive drinking behaviors

Author: Ben Hamida, Sami, Neasta, Jeremie, Lasek, Amy, Kharazia, Viktor, Zou, Mimi, Carnicella, Sebastien, Janak, Patricia, Ron, Dorit, Cell Biology of Addiction in Neurology, Ernest Gallo Clinic and Research Center, INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Department of neurology, University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California-Cell Biology of Addiction in Neurology, Ernest Gallo Clinic and Research Center-Ernest Gallo Clinic and Research Center, Department of neurology, University of California-University of California, NIH-NIAAA P50 AA017072, and State of California for medical research on alcohol and substance abuse.
Subjects: MESH: Ethanol, MESH: Phosphorylation, MESH: Rats, MESH: Mice, Transgenic, MESH: Sucrose, MESH: ras-GRF1, MESH: Choice Behavior, MESH: Male, MESH: Binge Drinking, MESH: Proto-Oncogene Proteins p21(ras), MESH: Rats, Long-Evans, MESH: Methionine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Nucleus Accumbens, MESH: Farnesyltranstransferase, MESH: Mice, MESH: Alcohol Drinking
Abstract: International audience; Uncontrolled consumption of alcohol is a hallmark of alcohol abuse disorders; however, the central molecular mechanisms underlying excessive alcohol consumption are still unclear. Here, we report that the GTP binding protein, H-Ras in the nucleus accumbens (NAc) plays a key role in neuroadaptations that underlie excessive alcohol-drinking behaviors. Specifically, acute (15 min) systemic administration of alcohol (2.5 g/kg) leads to the activation of H-Ras in the NAc of mice, which is observed even 24 h later. Similarly, rat operant self-administration of alcohol (20%) also results in the activation of H-Ras in the NAc. Using the same procedures, we provide evidence suggesting that the exchange factor GRF1 is upstream of H-Ras activation by alcohol. Importantly, we show that infection of mice NAc with lentivirus expressing a short hairpin RNA that targets the H-Ras gene produces a significant reduction of voluntary consumption of 20% alcohol. In contrast, knockdown of H-Ras in the NAc of mice did not alter water, quinine, and saccharin intake. Furthermore, using two-bottle choice and operant self-administration procedures, we show that inhibiting H-Ras activity by intra-NAc infusion of the farnesyltransferase inhibitor, FTI-276, produced a robust decrease of rats' alcohol drinking; however, sucrose consumption was unaltered. Finally, intra-NAc infusion of FTI-276 also resulted in an attenuation of seeking for alcohol. Together, these results position H-Ras as a central molecular mediator of alcohol's actions within the mesolimbic system and put forward the potential value of the enzyme as a novel target to treat alcohol use disorders.
Published: 2012
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41. Ethanol-mediated facilitation of AMPA receptor function in the dorsomedial striatum: implications for alcohol drinking behavior

Author: Wang, Jun, Ben Hamida, Sami, Darcq, Emmanuel, Zhu, Wenheng, Gibb, Stuart, Lanfranco, Maria Fe, Carnicella, Sebastien, Ron, Dorit, Cell Biology of Addiction in Neurology, Ernest Gallo Clinic and Research Center, Department of Neurology, University of California [San Francisco] (UCSF), University of California-University of California, ANTE-INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Ernest Gallo Clinic and Research Center-Ernest Gallo Clinic and Research Center-Department of Neurology, University of California-University of California-University of California [San Francisco] (UCSF), and This research was supported by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (D.R.), by NIAAA (R01AA/MH13438) (D.R.) and (P50AA017072) (D.R. and J.W.), and by ABMRF/The Foundation for Alcohol Research (J.W.).
Subjects: MESH: Sulpiride, MESH: Ethanol, MESH: Rats, MESH: Picrotoxin, MESH: Neurons, MESH: Conditioning, Operant, MESH: Rats, Sprague-Dawley, MESH: GABA Antagonists, MESH: Choice Behavior, MESH: Animals, Newborn, MESH: Corpus Striatum, MESH: Long-Term Potentiation, MESH: Quinoxalines, MESH: Rats, Long-Evans, MESH: Analysis of Variance, MESH: Patch-Clamp Techniques, MESH: Up-Regulation, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Animals, MESH: Excitatory Postsynaptic Potentials, MESH: Food Preferences, MESH: Sweetening Agents, MESH: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, musculoskeletal, neural, and ocular physiology, fungi, MESH: Sucrose, MESH: Electric Stimulation, MESH: Excitatory Amino Acid Antagonists, MESH: Male, MESH: N-Methylaspartate, MESH: Evoked Potentials, nervous system, MESH: Receptors, AMPA, MESH: Synaptosomes, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Central Nervous System Depressants, MESH: Excitatory Amino Acid Agonists, MESH: Self Administration, MESH: Dopamine Antagonists
Abstract: International audience; We found previously that acute ex vivo as well as repeated cycles of in vivo ethanol exposure and withdrawal, including excessive voluntary consumption of ethanol, produces a long-lasting increase in the activity of NR2B-containing NMDA receptors (NR2B-NMDARs) in the dorsomedial striatum (DMS) of rats (Wang et al., 2010a). Activation of NMDARs is required for the induction of long-term potentiation (LTP) of AMPA receptor (AMPAR)-mediated synaptic response. We therefore examined whether the ethanol-mediated upregulation of NMDAR activity alters the induction of LTP in the DMS. We found that ex vivo acute exposure of striatal slices to, and withdrawal from, ethanol facilitates the induction of LTP in DMS neurons, which is abolished by the inhibition of NR2B-NMDARs. We also report that repeated systemic administration of ethanol causes an NR2B-NMDAR-dependent facilitation of LTP in the DMS. LTP is mediated by the insertion of AMPAR subunits into the synaptic membrane, and we found that repeated systemic administration of ethanol, as well as cycles of excessive ethanol consumption and withdrawal, produced a long-lasting increase in synaptic localization of the GluR1 and GluR2 subunits of AMPARs in the DMS. Importantly, we report that inhibition of AMPARs in the DMS attenuates operant self-administration of ethanol, but not of sucrose. Together, our data suggest that aberrant synaptic plasticity in the DMS induced by repeated cycles of ethanol exposure and withdrawal contributes to the molecular mechanisms underlying the development and/or maintenance of excessive ethanol consumption.
Published: 2012
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42. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Author: Mulligan, Anna Marie, Couch, Fergus J, Barrowdale, Daniel, Domchek, Susan M, Eccles, Diana, Nevanlinna, Heli, Ramus, Susan J, Robson, Mark, Sherman, Mark, Spurdle, Amanda B, Wappenschmidt, Barbara, Lee, Andrew, McGuffog, Lesley, Healey, Sue, Sinilnikova, Olga M, Janavicius, Ramunas, Hansen, Thomas vO, Nielsen, Finn C, Ejlertsen, Bent, Osorio, Ana, Muñoz-Repeto, Iván, Durán, Mercedes, Godino, Javier, Pertesi, Maroulio, Benítez, Javier, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Cattaneo, Elisa, Bonanni, Bernardo, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Ottini, Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Hamann, Ute, Verheus, Martijn, Meijers-Heijboer, Hanne EJ, Wijnen, Juul, Gómez García, Encarna B, Nelen, Marcel R, Kets, C Marleen, Seynaeve, Caroline, Tilanus-Linthorst, Madeleine MA, van der Luijt, Rob B, van Os, Theo, Rookus, Matti, Frost, Debra, Jones, J Louise, Evans, D Gareth, Lalloo, Fiona, Eeles, Ros, Izatt, Louise, Adlard, Julian, Davidson, Rosemarie, Cook, Jackie, Donaldson, Alan, Dorkins, Huw, Gregory, Helen, Eason, Jacqueline, Houghton, Catherine, Barwell, Julian, Side, Lucy E, McCann, Emma, Murray, Alex, Peock, Susan, Godwin, Andrew K, Schmutzler, Rita K, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ruehl, Ina, Arnold, Norbert, Niederacher, Dieter, Sutter, Christian, Deissler, Helmut, Gadzicki, Dorothea, Kast, Karin, Preisler-Adams, Sabine, Varon-Mateeva, Raymonda, Schoenbuchner, Ines, Fiebig, Britta, Heinritz, Wolfram, Schäfer, Dieter, Gevensleben, Heidrun, Caux-Moncoutier, Virginie, Fassy-Colcombet, Marion, Cornelis, François, Mazoyer, Sylvie, Léoné, Mélanie, Boutry-Kryza, Nadia, Hardouin, Agnès, Berthet, Pascaline, Muller, Danièle, Fricker, Jean-Pierre, Mortemousque, Isabelle, Pujol, Pascal, Coupier, Isabelle, Lebrun, Marine, Kientz, Caroline, Longy, Michel, Sevenet, Nicolas, Stoppa-Lyonnet, Dominique, Isaacs, Claudine, Caldes, Trinidad, de la Hoya, Miguel, Heikkinen, Tuomas, Aittomäki, Kristiina, Blanco, Ignacio, Lazaro, Conxi, Barkardottir, Rosa B, Soucy, Penny, Dumont, Martine, Simard, Jacques, Montagna, Marco, Tognazzo, Silvia, D'Andrea, Emma, Fox, Stephen, Yan, Max, Rebbeck, Tim, Olopade, Olufunmilayo, Weitzel, Jeffrey N, Lynch, Henry T, Ganz, Patricia A, Tomlinson, Gail E, Wang, Xianshu, Fredericksen, Zachary, Pankratz, Vernon S, Lindor, Noralane M, Szabo, Csilla, Offit, Kenneth, Sakr, Rita, Gaudet, Mia, Bhatia, Jasmine, Kauff, Noah, Singer, Christian F, Tea, Muy-Kheng, Gschwantler-Kaulich, Daphne, Fink-Retter, Anneliese, Mai, Phuong L, Greene, Mark H, Imyanitov, Evgeny, O'Malley, Frances P, Ozcelik, Hilmi, Glendon, Gordon, Toland, Amanda E, Gerdes, Anne-Marie, Thomassen, Mads, Kruse, Torben A, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A, Soller, Maria, Henriksson, Karin, Wachenfeldt, von Anna, Arver, Brita, Stenmark-Askmalm, Marie, Karlsson, Per, Ding, Yuan Chun, Neuhausen, Susan L, Beattie, Mary, Pharoah, Paul DP, Moysich, Kirsten B, Nathanson, Katherine L, Karlan, Beth Y, Gross, Jenny, John, Esther M, Daly, Mary B, Buys, Saundra M, Southey, Melissa C, Hopper, John L, Terry, Mary Beth, Chung, Wendy, Miron, Alexander F, Goldgar, David, Chenevix-Trench, Georgia, Easton, Douglas F, Andrulis, Irene L, Antoniou, Antonis C, Breast Cancer Family Registry, EMBRACE, GEMO Study Collaborators, HEBON, kConFab Investigators, Ontario Cancer Genetics Network, SWE-BRCA, CIMBA, Pediatric Surgery, Neurology, Medical Oncology, Surgery, Clinical Genetics, Department of Laboratory Medicine, St Michael's Hospital-Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Laboratory Medicine and Pathology, Mayo Clinic, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Department of Medicine, University of Pennsylvania [Philadelphia]-Abramson Cancer Center, Faculty of Medicine, University of Southampton-University Hospital Southampton, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), Memorial Sloane Kettering Cancer Center [New York]-Weill Medical College of Cornell University [New York], Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Queensland Institute of Medical Research, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), 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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, State Research Institute Innovative Medicine Center, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Oncology, Human Genetics Group, Spanish National Cancer Research Centre-Spain and the Spanish Network on Rare Diseases, Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Instituto de investigación sanitaria de Aragón (IIS), Hospital clinico Universitario 'Lozano Blesa', Molecular Diagnostics Laboratory, National Center for Scientific Research 'Demokritos' (NCSR)-IRRP, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Fondazione Istituto FIRC di Oncologia Molecolare, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Unit of Medical Genetics, Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Unit of Experimental Oncology 1, Centro di Riferimento Oncologico, Department of Genetics, Biology and Biochemistry, University of Turin, Medical Genetics Unit, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Division of Medical Oncology, Regina Elena Cancer Institute, Department of Experimental Oncology, Consortium for Genomics Technology (Cogentech)-Istituto Europeo di Oncologia. Milan, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, Netherlands Cancer Institute, Department of Clinical Genetics, VU Medical Center, Department of Human Genetics and Department of Clinical Genetics, Leiden University Medical Center (LUMC), Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Medical Oncology, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Surgical Oncology, Department of Clinical Molecular Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Barts Cancer Institute, Queen Mary University of London (QMUL), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Clinical Genetics Department, St Michael's Hospital, North West Thames Regional Genetics Service, Kennedy-Galton Centre, North of Scotland Regional Genetics Service, University of Aberdeen-NHS Grampian, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Cheshire and Merseyside Clinical Genetics Service, Liverpool Women's NHS Foundation Trust, Leicestershire Clinical Genetics Service, University Hospitals Leicester, North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children [London] (GOSH), All Wales Medical Genetics Services, Singleton Hospital, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Lawrence], Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Klinikum Rechts der Isar, Ludwig-Maximillians University, University Hospital of Schleswig-Holstein (UKSH), University Hospital Düsseldorf, Institute of Human Genetics, Heidelberg University Hospital [Heidelberg], Universitätsklinikum Ulm - University Hospital of Ulm, Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), University Hospital Carl Gustav Carus, Westfälische Wilhelms-Universität Münster (WWU), Campus Virchov Klinikum, Department of Medical Genetic, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, Universität Regensburg (UR), University Hospital, Frankfurt, Breakthrough Breast Cancer Research Centre, Institute of cancer research, Service de Génétique Oncologique, Institut Curie [Paris], Service de génétique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, CHU Clermont-Ferrand, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Unité d'oncogénétique, CRLCC Paul Strauss, Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lombardi Comprehensive Cancer Center, Georgetown University, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Hereditary Cancer Program, Institut Català d'Oncologia-Hospital Duran i Reynals, Department of Pathology, Landspitali University Hospital, University of Iceland [Reykjavik], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Research Chair in Oncogenetics, Université Laval [Québec] (ULaval), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Oncology and Surgical Sciences, Universita degli Studi di Padova, Peter MacCallum Cancer Centre, Peter MacCallum Cancer Center, Department of Anatomical Pathology, Prince of Wales Hospital, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Chicago, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Departments of Medicine, and Preventive Medicine and Public Health, Creighton University, Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California-University of California, Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth)-Harold C. Simmons Comprehensive Cancer Center, Department of Pediatrics, The University of Texas Health Science Center at Houston (UTHealth), Department of Medical Genetics, University of Delaware [Newark], Epidemiology Research Program, American Cancer Society, Department of Obstetrics/Gynaecology and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Prevention & Cancer Control, Cancer Care Ontario, Departments of Molecular VirologyImmunology and Medical Genetics and Internal Medicine, Ohio State University [Columbus] (OSU), University of Copenhagen = Københavns Universitet (KU)-Rigshospital, Odense University Hospital, Aarhus University Hospital, Vejle Hospital, Section of Genetic Oncology, University of Pisa - Università di Pisa, Lund University Hospital, Oncological Centre, Karolinska University Hospital [Stockholm], Department of Clinical and Experimental Medicine, Linköping University (LIU), Sahlgrenska University Hospital [Gothenburg], Department of Population Sciences, Beckman Research Institute of the City of Hope, UCSF Cancer Risk Program and Departments of Medicine and Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), Department of Cancer Prevention and Control, Roswell Park Cancer Institute [Buffalo], Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention Institute of California, Fox Chase Cancer Center, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Genetic Epidemiology Laboratory, University of Melbourne, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Columbia University [New York], Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Dermatology, University of Utah School of Medicine [Salt Lake City], This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175). ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow., for Breast Cancer Family Registry, for EMBRACE, for Ontario Cancer Genetics Network, for SWE-BRCA, for CIMBA, European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), BMC, Ed., Collaborative Oncological Gene-environment Study - COGS - - EC:FP7:HEALTH2009-05-01 - 2014-01-31 - 223175 - VALID, University of Pennsylvania-Abramson Cancer Center, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Consortium for Genomics Technology (Cogentech)-Istituto Europeo di Oncologia [Milano] (IEO), University of Kansas Medical Center [Kansas City, KS, USA], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Julius-Maximilians-Universität Würzburg (JMU)-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Georgetown University [Washington] (GU), Università degli Studi di Padova = University of Padua (Unipd), University of Pennsylvania-University of Pennsylvania, University of California (UC)-University of California (UC), Rigshospital-University of Copenhagen = Københavns Universitet (UCPH), Vejle Hospital [Danemark], University of California [San Francisco] (UC San Francisco), Lee, Andrew [0000-0003-0677-0252], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, University of Cambridge [UK] ( CAM ), University of Southampton [Southampton]-University Hospital Southampton, University of Southern California ( USC ) -Keck School of Medicine [Los Angeles], Memorial Sloan-Kettering Cancer Center-Weill Medical College of Cornell University [New York], National Cancer Institute ( NIH ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de investigación sanitaria de Aragón ( IIS ), National Center for Scientific Research 'Demokritos' ( NCSR ) -IRRP, IFOM, University of Florence, Università degli Studi di Roma 'La Sapienza' [Rome], Deutsches Krebsforschungszentrum ( DKFZ ), Erasmus University Medical Center-Family Cancer Clinic, University Medical Center Utrecht, Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Queen Mary University of London ( QMUL ), Sheffield Children's Hospital, University Hospitals of Leicester, Great Ormond Street Hospital for Children [London] ( GOSH ), University of Kansas Medical Center, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, University Hospital Ulm, Hannover Medical School [Hannover] ( MHH ), Westfälische Wilhelms-Universität Münster ( WWU ), University Wurzburg-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, University Regensburg, INSTITUT CURIE, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre Hospitalier Universitaire Clermont-Ferrand, Centre François Baclesse, Hôpital Bretonneau-CHRU Tours, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Validation et identification de nouvelles cibles en oncologie ( VINCO ), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laval University [Québec], University of Padua and Istituto Oncologico Veneto IOV - IRCCS, University of Pennsylvania Perelman School of Medicine, University of California at Los Angeles [Los Angeles] ( UCLA ), University of Texas at Houston [Houston] ( UTHealth ) -Harold C. Simmons Comprehensive Cancer Center, University of Texas Health Science, Medical University of Vienna, Mount Sinai Hospital, The Ohio State University Comprehensive Cancer Center, University of Copenhagen ( KU ) -Rigshospital, University of Pisa [Pisa], Linköping University ( LIU ), Sahlgrenska University Hospital, the Beckman Research Institute of the City of Hope, University of California [San Francisco] ( UCSF ), European Project : 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS ( 2009 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Human Genetics, Universiteit Leiden-Universiteit Leiden, Nottingham University Hospitals NHS Trust (NUH), Universität Leipzig, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Roswell Park Cancer Institute [Buffalo] (RPCI)
Subjects: Risk, Heterozygote, endocrine system diseases, Population, Genes, BRCA2, Genes, BRCA1, Social Sciences, Estrogen receptor, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 610 Medical sciences Medicine, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Genotype, medicine, Humans, Genetic Predisposition to Disease, education, skin and connective tissue diseases, Estrogen Receptor Status, Alleles, 030304 developmental biology, Medicine(all), 0303 health sciences, education.field_of_study, Samhällsvetenskap, medicine.disease, 3. Good health, TOX3, Receptors, Estrogen, Cancer and Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, Ovarian cancer, Receptors, Progesterone, Research Article
Abstract: [Introduction]: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. [Methods]: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. [Results]: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. [Conclusions]: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.
Published: 2011
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43. No paradox, no progress: inverse cancer comorbidity in people with other complex diseases

Author: Jose M Valderas, Alfonso Valencia, Rafael Tabarés-Seisdedos, Manuel Gómez-Beneyto, Joan Climent, Nancy Dumont, Eduard Vieta, Salvador Martinez, Benedicto Crespo-Facorro, John L.R. Rubenstein, Anaïs Baudot, Department of Medicine, University of Valencia-Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94158, USA., UCSF, University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Spanish National Cancer Research Center (CNIO), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad Miguel Hernández [Elche] (UMH), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), and University of Oxford
Subjects: medicine.medical_specialty, Down syndrome, Anorexia Nervosa, Neuregulin-1, Disease, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Neoplasms, Epidemiology, medicine, Humans, Genetic Predisposition to Disease, Psychiatry, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Cancer, Parkinson Disease, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Oncology, Schizophrenia, Anorexia nervosa (differential diagnoses), Alzheimer's disease, Down Syndrome, business, 030217 neurology & neurosurgery, Chromosomes, Human, Pair 8
Abstract: Salvador Martínez [et al.]. 5 p., 2 tables and references., In the past 5 years, several leading groups have attempted to explain why individuals with Down's syndrome have a reduced risk of many solid tumours and an increased risk of leukaemia and testicular cancer. Niels Bohr, the Danish physicist, noted that a paradox could initiate progress. We think that the paradox of a medical disorder protecting against cancer could be formalised in a new model of inverse cancer morbidity in people with other serious diseases. In this Personal View, we review evidence from epidemiological and clinical studies that supports a consistently lower than expected occurrence of cancer in patients with Down's syndrome, Parkinson's disease, schizophrenia, diabetes, Alzheimer's disease, multiple sclerosis, and anorexia nervosa. Intriguingly, most comorbidities are neuropsychiatric or CNS disorders. We provide a brief overview of evidence indicating genetic and molecular connections between cancer and these complex diseases. Inverse comorbidity could be a valuable model to investigate common or related pathways or processes and test new therapies, but, most importantly, to understand why certain people are protected from the malignancy., This article was supported in part by grants to RT-S from the Spanish Ministry of Science and Innovation, Institute of Health Carlos III, CIBERSAM, Generalitat Valenciana (PROMETEO11/2011/042), and Alicia Koplowitz Foundation.
Published: 2011
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44. Dependence receptors: from basic research to drug development

Author: Patrick Mehlen, Dale E. Bredesen, Equipe 1, Centre de Recherche en Cancérologie de Lyon ( 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]-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 ), Biological and Medical Informatics [San Francisco] ( BMI ), University of California [San Francisco] ( UCSF ), 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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological and Medical Informatics [San Francisco] (BMI), University of California [San Francisco] (UCSF), and University of California-University of California
Subjects: MESH : Drug Design, Angiogenesis, MESH: Low Back Pain, MESH : Prospective Studies, MESH : Aged, MESH : Receptors, Cell Surface, Apoptosis, MESH : Analysis of Variance, Dependence receptor, MESH: Pain Measurement, MESH : Models, Biological, Pharmacology, MESH: Drug Design, Ligands, medicine.disease_cause, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Chronic Disease, Basic research, MESH: Ligands, MESH: Double-Blind Method, MESH : Pain Measurement, MESH : Female, Receptor, MESH: Physical Therapy Modalities, MESH: Treatment Outcome, MESH: Receptors, Cell Surface, MESH: Aged, 0303 health sciences, MESH : Ligands, MESH: Middle Aged, Neurodegeneration, MESH: Disability Evaluation, MESH : Questionnaires, MESH : Adult, MESH: Patient Compliance, MESH: Interviews as Topic, Drug development, MESH : Motivation, Caspases, 030220 oncology & carcinogenesis, MESH: Cell Adhesion Molecules, Netrin Receptors, MESH : Male, MESH: Motivation, Receptors, Cell Surface, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Disability Evaluation, MESH : Treatment Outcome, Biology, Models, Biological, MESH : Patient Compliance, MESH : Cell Adhesion Molecules, 03 medical and health sciences, MESH: Analysis of Variance, MESH : Adolescent, medicine, Humans, MESH : Double-Blind Method, MESH : Middle Aged, Molecular Biology, 030304 developmental biology, MESH: Adolescent, MESH: Caspases, MESH: Humans, MESH: Questionnaires, MESH: Apoptosis, MESH: Chronic Disease, MESH : Humans, MESH: Models, Biological, MESH: Adult, Cell Biology, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH : Low Back Pain, MESH : Physical Therapy Modalities, Drug Design, MESH : Interviews as Topic, MESH : Caspases, Carcinogenesis, Cell Adhesion Molecules, Neuroscience, MESH: Female, Function (biology), MESH : Apoptosis
Abstract: International audience; The fourth meeting on dependence receptors featured descriptions of previously unknown dependence receptors. New mechanistic data were presented on the switch between the trophic, antiapoptotic response with the proapoptotic response that occurs with loss of trophic support. The possibility that the loss of trophic support may also involve the binding of an active antitrophin was also discussed. New in vivo data were presented on the roles of dependence receptors in development, angiogenesis, oncogenesis, and neurodegeneration, as well as new therapeutic approaches based on dependence receptor function. The next meeting on dependence receptors is scheduled for 2012.
Published: 2011
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45. Defining the critical hurdles in cancer immunotherapy

Author: Andrea Nicolini, Francesco M. Marincola, William E. Carson, Paolo A. Ascierto, Michele Maio, Jedd D. Wolchok, Michael T. Lotze, Jirina Bartunkova, Weihua Xiao, Hauke Winter, Barbara Seliger, Jon M. Wigginton, Cedrik M. Britten, Ignacio Melero, Guido Kroemer, Neil L. Berinstein, Jill O'Donnell-Tormey, Heinz Zwierzina, Lothar Bergmann, Lloyd J. Old, Christian H. Ottensmeier, Jérôme Galon, Per thor Straten, Koji Kawakami, Michael Papamichail, Yutaka Kawakami, Michael I. Nishimura, Mary L. Disis, Steinar Aamdal, C. J. M. Melief, Pedro Romero, Kristen Hege, Wenru Song, Pawel Kalinski, Jonathan L. Bramson, Harpreet Singh-Jasuja, Jens Peter Marschner, Bernard A. Fox, Samir N. Khleif, Brad H. Nelson, Marij J. P. Welters, Elizabeth M. Jaffee, Patrick Hwu, Rik J. Scheper, Robert C. Rees, Giuseppe Masucci, Hideaki Tahara, Cristina Bonorino, Glenn Dranoff, Ernest C. Borden, William J. Murphy, Zhigang Tian, Michael B. Atkins, Robert O. Dillman, Thomas F. Gajewski, Hiroshi Shiku, Leif Håkansson, Michael J. Mastrangelo, Lisa H. Butterfield, Shukui Qin, Laurence Zitvogel, Harry Dolstra, Michele Guida, George Coukos, Mohamed L. Salem, Xuetao Cao, Giorgio Parmiani, Enrico Proietti, Ena Wang, Sylvia Janetzki, A. Raja Choudhury, Gerd Ritter, Hyam I. Levitsky, Kunle Odunsi, Kohzoh Imai, Paul von Hoegen, Christoph Huber, Réjean Lapointe, Antoni Ribas, Dolores J. Schendel, Pamela S. Ohashi, Beatrix Kotlan, Cécile Gouttefangeas, James H. Finke, Alfred E. Chang, Howard L. Kaufman, Lindy G. Durrant, Sjoerd H. van der Burg, Jared Gollob, Dainius Characiejus, Tara Withington, Padmanee Sharma, Ronald B. Herberman, Cristina Maccalli, Ulrich Keilholtz, Axel Hoos, Graham Pawelec, Fabio Grizzi, Tanja D. de Gruijl, F. Stephen Hodi, Ruggero Ridolfi, James P. Allison, Licia Rivoltini, Carl H. June, Rolf Kiessling, Department of Molecular Microbiology and Immunology, Oregon Health and Science University [Portland] (OHSU)-Knight Cancer Institute, Earle A. Chiles Research Institute, Providence Portland Medical Center-Robert W. Franz Research Center-Providence Cancer Center, Clinical Cooperation Group 'Immune Monitoring', German Research Center for Environmental Health-Helmholtz Centre Munich-Institute of Molecular Immunology, Division of Hematology Oncology, University of Pittsburgh Cancer Institute-Departments of Medicine, Department of Surgery, Cancer Institute-University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Immunology, University of Pittsburgh Cancer Institute, Department of Clinical Cancer Research, The Norwegian Radium Hospital-Oslo University Hospital [Oslo], Memorial Sloane Kettering Cancer Center [New York], Howard Hughes Medical Institute (HHMI), Medical Oncology and Innovative Therapy, Instituto Nazionale Tumori-Fondazione 'G. Pascale', Beth Israel Deaconess Medical Center, Harvard Medical School [Boston] (HMS), Institute of Immunology, Charles University [Prague] (CU)-FOCIS Center of Excellence-2nd Medical School, Goethe-Universität Frankfurt am Main, IRX Therapeutics, Stanford University-ImmunoVaccine Inc., Instituto Nacional para o Controle do Câncer, Instituto de Pesquisas Biomédicas-PUCRS Faculdade de Biociências, Department of Solid Tumor Oncology, Cleveland Clinic, Department of Translational Hematology and Oncology Research, Department of Pathology, McMaster University [Hamilton, Ontario], University Medical Center Mainz, III. Medical Department, Ribological GmbH, Department of Medicine-University Medical Center of the Johannes Gutenberg-University-Clinical Development, BioNTech AG, Chinese Academy of Medical Sciences, Second Military Medical University-National Key Laboratory of Medical Immunology, Ohio State University [Columbus] (OSU), University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Institute of Oncology, Vilnius University [Vilnius]-Faculty of Medicine, Department of Medicine, University of Queensland [Brisbane], Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Department of Medical Oncology, VU Medical Center-Cancer Center Amsterdam, Hoag Institute for Research and Education, Hoag Cancer Institute, Department of Laboratory Medicine, Radboud university [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre [Nijmegen], Brigham and Women's Hospital [Boston], Dana-Farber Cancer Institute [Boston], Academic Department of Clinical Oncology, University of Nottingham, UK (UON), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Alnylam Pharmaceuticals, Inc., Institute for Cell Biology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Oncology Department, University of Lund, CanImGuide Therapeutics AB, University of California [San Francisco] (UCSF), University of California, Intrexon Corporation, Germantown, Bristol-Myers Squibb Company, Translational Oncology & Immunology, Centre TRON at the Mainz University Medical Center, Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], The Institute of Medical Science, The University of Tokyo (UTokyo), Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore], ZellNet Consulting, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Rush University Cancer Center, Rush University Medical Center [Chicago], School of Medicine and Public Health, Kyoto University [Kyoto], Division of Cellular Signaling, Institute for Advanced Medical Research, Dept. of Hematology and Medical Oncology, Charité Comprehensive Cancer Center, Cancer Vaccine Section, NCI, Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Department of Molecular Immunology and Toxicology, Center of Surgical and Molecular Tumor pathology, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), School of Medicine, Johns Hopkins University (JHU)-Oncology Center, Department of Molecular Oncology, Foundation San Raffaele Scientific Institute, Medical Oncology and Immunotherapy, Istituto Toscano Tumori-University Hospital of Siena-Department of Oncology, Merck KGaA, Merck & Co. Inc, Thomas Jefferson University, Department of Oncology-Pathology, karolinska institute, CIMA, CUN and Medical School University of Navarra, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Davis Medical Center, Sacramento-University of California, Deeley Research Centre, BC Cancer Agency (BCCRC), Department of Internal Medicine, University of Pisa - Università di Pisa, Oncology Institute, Loyola University Medical Center (LUMC)-Cardinal Bernardin Cancer Center, Tumor Immunology and Immunotherapy Program, Roswell Park Cancer Institute [Buffalo]-Department of Gynecologic Oncology, Ontario Cancer Institute, University Health Network, Cancer Immunotherapy Consortium (CIC), Cancer Research Institute, Cancer Research, Ludwig Institute, Experimental Cancer Medicine Centre, University of Southampton-Faculty of Medicine, Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, San Raffaele Scientific Institute, Center for Medical Research, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita', Chinese PLA Cancer Center, Department of Oncology-The Eighty-First Hospital, The John van Geest Cancer Research Centre, School of Science and Technology-Nottingham Trent University, Jonsson Comprehensive Cancer Center, Immunoterapia e Terapia Cellulare Somatica, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori-IRCCS Foundation, Division of Clinical Onco-Immunology, Université de Lausanne (UNIL)-Ludwig Center for Cancer Research, Immunology and Biotechnology Unit, Faculty of Science-Department of Zoology-Tanta University, VU University Medical Center [Amsterdam], Institute of Medical Immunology, Martin-Luther-Universität Halle Wittenberg (MLU), Departments of Immunology, Department of Cancer Vaccine, Mie University, Department of Immuno-gene Therapy, Immatics Biotechnologies GmbH, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen-Department of Immunology-Institute for Cell Biology, Millennium: The Takeda Oncology Company, Pfizer Oncology, Center for Cancer Immune Therapy (CCIT), Herlev and Gentofte Hospital-Department of Hematology, Department of Surgery and Bioengineering, The University of Tokyo (UTokyo)-Institute of Medical Science-Advanced Clinical Research Center, School of Life Sciences-University of Science & Technology of China [Suzhou], Institute of Immunopharmacology & Immunotherapy, Shandong University-School of Pharmaceutical Sciences, Experimental Cancer Immunology and Therapy, Leiden University Medical Center (LUMC)-Department of Clinical Oncology, Euraccine Consulting Group, Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine-Clinical Center-National Institute of Health NIH), Center for Human Immunology (CHI), National Institute of Health (NIH), Leiden University Medical Center (LUMC)-Department of Clinical Oncology (K1-P), Ludwig Maximilians University-Klinikum Grosshadern, Biological Therapy of Cancer, Medical and Surgical Services Organizations-International Society For Biological Therapy Of Cancer, School of Life Science-University of Science and Technology of China [Hefei] (USTC), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Department Haematology and Oncology, Innsbruck Medical University [Austria] (IMU), Medical Center, University of Chicago, Discovery Medicine-Oncology, Tumor Vaccine Group, University of Washington [Seattle]-Center for Translational Medicine in Women's Health, The work of CIMT-CIP was supported by a grant from the Wallace Coulter foundation (Florida, USA)., Helmholtz Centre Munich-Institute of Molecular Immunology-Helmholtz Zentrum München = German Research Center for Environmental Health, University of Pennsylvania-University of Pennsylvania, Radboud University [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre [Nijmegen], Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Kyoto University, Sacramento-University of California (UC), Université de Lausanne = University of Lausanne (UNIL)-Ludwig Center for Cancer Research, Klinikum Grosshadern-Ludwig-Maximilians University [Munich] (LMU), University of Science and Technology of China [Hefei] (USTC)-School of Life Science, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), BMC, Ed., Computer Systems, Medical oncology laboratory, Pathology, CCA - Immuno-pathogenesis, CCA - Innovative therapy, Oregon Health and Science University-Knight Cancer Institute, Cancer Institute-University of Pittsburgh, The Norwegian Radium Hospital-Oslo University Hospital, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, Howard Hughes Medical Institute, Ludwig Center for Cancer Immunotherapy, A Teaching Hospital of Harvard Medical School, Charles University [Prague]-FOCIS Center of Excellence-2nd Medical School, Stanford University [Stanford]-ImmunoVaccine Inc., Ohio State University [Columbus] ( OSU ), University of Michigan Medical Center, University of Pennsylvania Medical Center, Radboud university [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre, University of Nottingham, UK ( UON ), Cleveland Clinic Foundation, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Istituto Clinico Humanitas [Milan] ( IRCCS Milan ), Humanitas University [Milan] ( Hunimed ), University of California [San Francisco] ( UCSF ), Harvard Medical School [Boston] ( HMS ), MD Anderson Cancer Center, The University of Tokyo, Rush University Medical Center, Cancer Center Karolinska [Karolinska Institutet] ( CCK ), Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame Research Center ( CRCHUM ), Department of Medicine-University of Montreal, Johns Hopkins University ( JHU ) -Oncology Center, BC Cancer Agency ( BCCRC ), University of Pisa [Pisa], Loyola University Medical Center ( LUMC ) -Cardinal Bernardin Cancer Center, Cancer Immunotherapy Consortium ( CIC ), University of Southampton [Southampton]-Faculty of Medicine, Eberhard Karls Universität Tübingen, University of Lausanne-Ludwig Center for Cancer Research, Martin-Luther-University Halle-Wittenberg, Mie University Graduate School of Medicine, Eberhard Karls Universität Tübingen-Department of Immunology-Institute for Cell Biology, Center for Cancer Immune Therapy ( CCIT ), Herlev Hospital-Department of Hematology, The University of Tokyo-Institute of Medical Science-Advanced Clinical Research Center, Infectious Disease and Immunogenetics Section ( IDIS ), Center for Human Immunology ( CHI ), University of Science and Technology of China [Hefei] ( USTC ) -School of Life Science, Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Innsbruck Medical University [Austria] ( IMU ), Department of Medicine-Clinical Development, BioNTech AG-Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Universiteit Leiden-Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI)-Department of Gynecologic Oncology, Istituto Superiore di Sanità (ISS), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Universiteit Leiden-Universiteit Leiden-Department of Clinical Oncology, and Universiteit Leiden-Universiteit Leiden-Department of Clinical Oncology (K1-P)
Subjects: medicine.medical_specialty, International Cooperation, medicine.medical_treatment, Alternative medicine, lcsh:Medicine, Translational research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Immunotherapy, General Biochemistry, Genetics and Molecular Biology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Translational Research, Biomedical, 03 medical and health sciences, SDG 17 - Partnerships for the Goals, 0302 clinical medicine, Cancer immunotherapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Neoplasms, medicine, Humans, In patient, 030304 developmental biology, Medicine(all), 0303 health sciences, geography, Summit, geography.geographical_feature_category, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Biochemistry, Genetics and Molecular Biology(all), business.industry, lcsh:R, Cancer, General Medicine, Public relations, medicine.disease, 3. Good health, Clinical trial, Immunotherapy, Neoplasms/therapy, Translational Medical Research, 030220 oncology & carcinogenesis, Immunology, Commentary, Working group, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. © 2011 Fox et al; licensee BioMed Central Ltd.
Published: 2011
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46. Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration

Author: Carnicella, Sebastien, He, Dao-Yao, Yowell, Quinn V., Glick, Stanley D., Ron, Dorit, ANTE-INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Department of neurology, University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California-Department of Neurology, University of California-University of California, Center of Neuropharmacology and Neuroscience, Albany Medical College, Department of Neurology, State of California for Medical Research on Alcohol and Substance Abuse through the University of California, San Francisco (D.R.), Department of the Army, Grant # W81XWH-07-1-0079 (D.R.), Savasta, Marc, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-Department of Neurology, and University of California (UC)-University of California (UC)
Subjects: Male, MESH: Cell Line, Tumor, MESH: Gene Expression, Alcohol Drinking, MESH: Rats, MESH: Motivation, Gene Expression, MESH: Conditioning, Operant, Self Administration, MESH: Alcohol Deterrents, Article, MESH: Rats, Long-Evans, MESH: Alcoholism, Cell Line, Tumor, 18-Methoxycoronaridine, Animals, Humans, Rats, Long-Evans, MESH: Animals, RNA, Messenger, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Ibogaine, MESH: RNA, Messenger, Motivation, MESH: Humans, Ventral Tegmental Area, ibogaine, GDNF, MESH: Male, Rats, Alcoholism, nervous system, noribogaine, MESH: Ventral Tegmental Area, Conditioning, Operant, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Ethanol self-administration, MESH: Alcohol Drinking, MESH: Self Administration, Alcohol Deterrents
Abstract: Carnicella S present adress: Grenoble Institut des Neurosciences, Inserm U836; International audience; Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action.
Published: 2010
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47. Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders

Author: Sebastien Carnicella, Sami Ben Hamida, Quinn V. Yowell, Dorit Ron, Jérémie Neasta, Savasta, Marc, Cell Biology of Addiction in Neurology, Ernest Gallo Clinic and Research Center, INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Department of neurology, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-Cell Biology of Addiction in Neurology, Ernest Gallo Clinic and Research Center-Ernest Gallo Clinic and Research Center, Department of neurology, University of California (UC)-University of California (UC), NIH-NIAAA P50 AA017072, State of California for Medical Research on Alcohol and Substance Abuse through the University of California, San Francisco, University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California-Cell Biology of Addiction in Neurology, and University of California-University of California
Subjects: MESH: Signal Transduction, Sucrose, nucleus accumbens, Alcohol abuse, Self Administration, mTORC1, Pharmacology, Nervous System, Mice, 0302 clinical medicine, Homer Scaffolding Proteins, MESH: Up-Regulation, MESH: Proteins, MESH: Animals, reward, MESH: Drug-Seeking Behavior, media_common, 0303 health sciences, Multidisciplinary, TOR Serine-Threonine Kinases, MESH: Transcription Factors, Adaptation, Physiological, MESH: Motor Activity, 3. Good health, Up-Regulation, MESH: Receptors, AMPA, mTOR, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], addiction, biological phenomena, cell phenomena, and immunity, Signal transduction, MESH: Nucleus Accumbens, Alcohol-Related Disorders, MESH: Self Administration, Signal Transduction, MESH: Alcohol-Related Disorders, MESH: Rats, media_common.quotation_subject, Drug-Seeking Behavior, MESH: Carrier Proteins, Biology, Nucleus accumbens, Mechanistic Target of Rapamycin Complex 1, Motor Activity, 03 medical and health sciences, medicine, Animals, Receptors, AMPA, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Transcription factor, MESH: Mice, MESH: Alcohols, 030304 developmental biology, Sirolimus, MESH: Nervous System, Addiction, MESH: Sucrose, Proteins, medicine.disease, MESH: Adaptation, Physiological, Rats, Alcohols, Multiprotein Complexes, Synaptic plasticity, ethanol, MESH: Sirolimus, Carrier Proteins, Neuroscience, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Present adress of Sébastien Carnicella: Grenoble Institute of Neuroscience, Institut National de la Santé et de la Recherche Médicale U836, 38100 Grenoble, France. Equipe 10, Dynamique des réseaux neuronaux du mouvement; International audience; Alcohol addiction is a chronically relapsing disorder that includes certain maladaptive learning and memory. The serine and threonine kinase complex, mammalian target of rapamycin complex 1 (mTORC1), has been implicated in synaptic plasticity, learning, and memory by controlling protein translation. Here we show that administration of alcohol and excessive voluntary consumption of alcohol induce the activation of the mTORC1-mediated signaling pathway in the nucleus accumbens (NAc) of rodents. We further show that the protein expression levels of GluR1 and Homer, two synaptic proteins whose translation has been shown to be modulated by mTORC1, are up-regulated in the NAc of rodents with a history of excessive alcohol consumption. In addition, our results document that the Food and Drug Administration-approved inhibitor of mTORC1, rapamycin, decreases expression of alcohol-induced locomotor sensitization and place preference, as well as excessive alcohol intake and seeking in preclinical rodent models of alcohol abuse. Together, our results suggest that mTORC1 within the NAc is a contributor to molecular mechanisms underlying alcohol-drinking behaviors. Furthermore, despite its massive health and socioeconomic impact worldwide, pharmacotherapies for alcohol abuse and addiction remain limited. Our data therefore put forward the possibility that targeting the mTORC1 signaling cascade is an innovative and valuable strategy for the treatment of alcohol use and abuse disorders.
Published: 2010
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48. Energetic dysfunction in sepsis: a narrative review

Author: Guillaume Voiriot, Mehdi Oualha, Peter Radermacher, Sébastien Preau, Aurelien Flatres, Steve Lancel, Youenn Jouan, Stein Silva, Nicolas de Prost, Lara Zafrani, Eric Azabou, Dominique Vodovar, Jérémie Joffre, Fabrice Huel, Boris Jung, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hopital Saint-Louis [AP-HP] (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), CHU Necker - Enfants Malades [AP-HP], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UCSF), University of California, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, CHU Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitätsklinikum Ulm - University Hospital of Ulm, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Système immunitaire et neuroinflammation [CRSA], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [AP-HP], SFB 1149 and GRK 2203/Deutsche Forschungsgemeinschaft, MORNET, Dominique, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Organ dysfunction, Cardiomyopathy, Review, 030204 cardiovascular system & hematology, Mitochondrion, Critical Care and Intensive Care Medicine, Bioinformatics, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Lipid oxidation, Septic shock, medicine, Energetic dysfunction, Immunodeficiency, business.industry, RC86-88.9, Acute kidney injury, Correction, Medical emergencies. Critical care. Intensive care. First aid, medicine.disease, 3. Good health, Mitochondria, [SDV] Life Sciences [q-bio], 030104 developmental biology, Metabolism, medicine.symptom, business, Infection, Mitochondrial dysfunction
Abstract: BackgroundGrowing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.Main textSepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.ConclusionsRecent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.
Published: 2021
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49. DHPR α1S subunit controls skeletal muscle mass and morphogenesis

Author: Arnaud Ferry, Luis Garcia, Isabelle Marty, Etienne Mouisel, Dominique Baas, Laurent Schaeffer, Alban Vignaud, Christophe Hourdé, Stéphane Vassilopoulos, Thomas Voit, Christel Gentil, Thérapie des maladies du muscle strié, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] (UCSF), University of California-University of California, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), 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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Paris Descartes - Paris 5 (UPD5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), École normale supérieure de Lyon (ENS de 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), Department of bio-engineering and Therapeutic Science, University of California, This work was supported by the Association Franc¸aise contre les Myopathies (AFM), Association Institut de Myologie (AIM), Duchenne Parent Project France (DPPF) and the Association Mone´gasque contre les Myopathies (AMM)., École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), University of California (UC), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of California [San Francisco] ( UCSF ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), and Roux-Buisson, Nathalie
Subjects: MESH: Organ Size, DHPR α1S, MESH: Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type I, MESH: Base Sequence, Inbred C57BL, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Morphogenesis, Tissue Distribution, MESH: Animals, Cells, Cultured, Mice, Knockout, 0303 health sciences, MESH: Muscle, Skeletal, MESH: Calcium Channels, L-Type, Cultured, Voltage-dependent calcium channel, General Neuroscience, MESH: Muscle Strength, Skeletal, Organ Size, MESH: Protein Subunits, L-Type, Hedgehog signaling pathway, Cell biology, Muscular Atrophy, medicine.anatomical_structure, Biochemistry, MESH: Calcium Channels, Muscle, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Cells, Cultured, exon skipping, autophagy, Calcium Channels, L-Type, Protein subunit, Knockout, Cells, Molecular Sequence Data, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Atrophy, Downregulation and upregulation, MESH: Mice, Inbred C57BL, medicine, Animals, MESH: Autophagy, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Muscle Strength, MESH: Tissue Distribution, skeletal muscle, Muscle, Skeletal, Molecular Biology, MESH: Mice, 030304 developmental biology, Sarcolemma, MESH: Molecular Sequence Data, General Immunology and Microbiology, Base Sequence, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Autophagy, MESH: Muscular Atrophy, Skeletal muscle, medicine.disease, MESH: Morphogenesis, Mice, Inbred C57BL, Protein Subunits, Calcium Channels, 030217 neurology & neurosurgery
Abstract: International audience; The alpha1S subunit has a dual function in skeletal muscle: it forms the L-type Ca(2+) channel in T-tubules and is the voltage sensor of excitation-contraction coupling at the level of triads. It has been proposed that L-type Ca(2+) channels might also be voltage-gated sensors linked to transcriptional activity controlling differentiation. By using the U7-exon skipping strategy, we have achieved long-lasting downregulation of alpha1S in adult skeletal muscle. Treated muscles underwent massive atrophy while still displaying significant amounts of alpha1S in the tubular system and being not paralysed. This atrophy implicated the autophagy pathway, which was triggered by neuronal nitric oxide synthase redistribution, activation of FoxO3A, upregulation of autophagy-related genes and autophagosome formation. Subcellular investigations showed that this atrophy was correlated with the disappearance of a minor fraction of alpha1S located throughout the sarcolemma. Our results reveal for the first time that this sarcolemmal fraction could have a role in a signalling pathway determining muscle anabolic or catabolic state and might act as a molecular sensor of muscle activity.
Published: 2009
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50. CX(3)CR1(+) CD115(+) CD135(+) common macrophage/DC precursors and the role of CX(3)CR1 in their response to inflammation

Author: Cédric Auffray, Ana Cumano, Grégoire Lauvau, Laura Campisi, Frederic Geissmann, Darin K. Fogg, Thierry Jo Molina, David A. Hume, Céline Trouillet, Brigitte Senechal, Julia Leemput, Karine Bigot, Emilie Narni-Mancinelli, Marc Abitbol, Noah Saederup, Israel F. Charo, Système des phagocytes mononucléés et immunopathologie, Université Paris Descartes - Paris 5 (UPD5), Immunologie des maladies infectieuses allergiques et autoimmunes, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Cellular and Molecular Biology of Inflammation, King‘s College London, Gladstone Institute of Cardiovascular Disease, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Centre d'étude et de recherche thérapeutiques en ophtalmologie, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Développement des Lymphocytes, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by an European Young Investigator (EURYI) award to F. Geissmann, grants from Institut National de la Sant é et de la Recherche M é dicale (Avenir) and Human Frontier Science Program (CDA) to G. Lauvau, grants from the Agence Nationale de la Recherche (ANR IRAP2005) to F. Geissmann and G. Lauvau, and grants from the Fondation pour la Recherche Medicale to F. Geissmann (Equipe FRM 2006) and to G. Lauvau (FRM equipments fund)., Université Nice Sophia Antipolis (... - 2019) (UNS), University of California [San Francisco] (UCSF), University of California-University of California, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Vougny, Marie-Christine, Université Paris Descartes - Paris 5 ( UPD5 ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of California [San Francisco] ( UCSF ), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH: Inflammation, Monocytes/cytology, MESH: Spleen, MESH: Monocytes, MESH: Listeria monocytogenes, Monocytes, Mice, 0302 clinical medicine, Cell Movement, Spleen/cytology, MESH : Cell Proliferation, MESH : Cell Movement, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Macrophage, MESH: Animals, MESH: Cell Movement, MESH : Macrophages, MESH : Cell Survival, 0303 health sciences, MESH: Bone Marrow Cells, Stem Cells, hemic and immune systems, Dendritic Cells/enzymology, Receptors, Chemokine/metabolism, 3. Good health, Cell biology, MESH : Phenotype, MESH: Cell Survival, Tumor necrosis factor alpha, Receptors, Chemokine, MESH : Cell Differentiation, MESH: fms-Like Tyrosine Kinase 3, MESH: Receptor, Macrophage Colony-Stimulating Factor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, CX3C Chemokine Receptor 1, Bone Marrow Cells/cytology, Tumor Necrosis Factor-alpha/biosynthesis, Spleen, Dendritic Cells/cytology, MESH: Phenotype, Article, 03 medical and health sciences, Receptor, Macrophage Colony-Stimulating Factor/metabolism, MESH : Inflammation, fms-Like Tyrosine Kinase 3/metabolism, Tumor Necrosis Factor-alpha, MESH : Listeria Infections, Macrophages, Monocytes/immunology, Dendritic cell, Dendritic Cells, Listeria monocytogenes, fms-Like Tyrosine Kinase 3, Dendritic Cells/immunology, MESH : Dendritic Cells, MESH: Tumor Necrosis Factor-alpha, Reactive Oxygen Species, MESH : Bone Marrow Cells, Myeloid, MESH : Reactive Oxygen Species, Nitric Oxide Synthase Type II, Macrophages/immunology, Inflammation/enzymology, Immunology and Allergy, Listeriosis, MESH : Tumor Necrosis Factor-alpha, MESH: Dendritic Cells, MESH: Reactive Oxygen Species, Cell Differentiation, Inflammation/immunology, Listeriosis/immunology, medicine.anatomical_structure, Phenotype, MESH : Stem Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Nitric Oxide Synthase Type II, medicine.symptom, Stem cell, MESH: Listeria Infections, Nitric Oxide Synthase Type II/metabolism, MESH : Spleen, MESH: Cell Differentiation, MESH : Receptors, Chemokine, MESH : fms-Like Tyrosine Kinase 3, Cell Survival, Macrophages/enzymology, Inflammation, Bone Marrow Cells, Receptor, Macrophage Colony-Stimulating Factor, MESH: Stem Cells, Biology, MESH : Receptor, Macrophage Colony-Stimulating Factor, Reactive Oxygen Species/metabolism, MESH: Cell Proliferation, MESH : Mice, medicine, Animals, MESH: Mice, 030304 developmental biology, Cell Proliferation, MESH: Macrophages, Macrophages/cytology, MESH : Nitric Oxide Synthase Type II, Receptors, Chemokine/deficiency, MESH : Monocytes, Fms-Like Tyrosine Kinase 3, MESH : Animals, MESH : Listeria monocytogenes, MESH: Receptors, Chemokine, Bone Marrow Cells/immunology, 030215 immunology
Abstract: International audience; CX(3)CR1 expression is associated with the commitment of CSF-1R(+) myeloid precursors to the macrophage/dendritic cell (DC) lineage. However, the relationship of the CSF-1R(+) CX(3)CR1(+) macrophage/DC precursor (MDP) with other DC precursors and the role of CX(3)CR1 in macrophage and DC development remain unclear. We show that MDPs give rise to conventional DCs (cDCs), plasmacytoid DCs (PDCs), and monocytes, including Gr1(+) inflammatory monocytes that differentiate into TipDCs during infection. CX(3)CR1 deficiency selectively impairs the recruitment of blood Gr1(+) monocytes in the spleen after transfer and during acute Listeria monocytogenes infection but does not affect the development of monocytes, cDCs, and PDCs.
Published: 2009
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