42 results on '"Crafoord Foundation"'
Search Results
2. Combining Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in CRT Treatment (CRT clinic)
- Author
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Crafoord Foundation
- Published
- 2019
3. Brassica oleracea L. var. italica Aquaporin Reconstituted Proteoliposomes as Nanosystems for Resveratrol Encapsulation
- Author
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Ministerio de Ciencia e Innovación (España), European Commission, Fundación Séneca, Gobierno de la Región de Murcia, Crafoord Foundation, Yepes-Molina, Lucía, Teruel, José A., Johanson, Urban, Carvajal, Micaela, Ministerio de Ciencia e Innovación (España), European Commission, Fundación Séneca, Gobierno de la Región de Murcia, Crafoord Foundation, Yepes-Molina, Lucía, Teruel, José A., Johanson, Urban, and Carvajal, Micaela
- Abstract
Aquaporins (AQPs), membrane proteins responsible for facilitating water transport, found in plant membrane vesicles (MV), have been related to the functionality and stability of MV. We focused on AQPs obtained from broccoli, as they show potential for biotechnological applications. To gain further insight into the role of AQPs in MV, we describe the heterologous overexpression of two broccoli AQPs (BoPIP1;2 and BoPIP2;2) in Pichia pastoris, resulting in their purification with high yield (0.14 and 0.99 mg per gram cells for BoPIP1;2 and BoPIP2;2). We reconstituted AQPs in liposomes to study their functionality, and the size of proteoliposomes did not change concerning liposomes. BoPIP2;2 facilitated water transport, which was preserved for seven days at 4 °C and at room temperature but not at 37 °C. BoPIP2;2 was incorporated into liposomes to encapsulate a resveratrol extract, resulting in increased entrapment efficiency (EE) compared to conventional liposomes. Molecular docking was utilized to identify binding sites in PIP2s for resveratrol, highlighting the role of aquaporins in the improved EE. Moreover, interactions between plant AQP and human integrin were shown, which may increase internalization by the human target cells. Our results suggest AQP-based alternative encapsulation systems can be used in specifically targeted biotechnological applications
- Published
- 2024
4. Galectin-3 is upregulated in frontotemporal dementia patients with subtype specificity
- Author
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Instituto de Salud Carlos III, European Commission, Generalitat de Catalunya, Fundación BBVA, Ministerio de Ciencia e Innovación (España), Lund University, Swedish Brain Foundation, Crafoord Foundation, Swedish Dementia Association, Greta and Johan Kocks Foundation, Olle Engkvist Foundation, Gamla Tjänarinnor Foundation, Swedish Medical Research Council, Swedish Parkinson Foundation, Anna och Edwin Bergers Stiftelse, Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72], Borrego-Écija, Sergi, Pérez-Millan, Agnès, Antonell, Anna, Fort-Aznar, Laura, Kaya-Tilki, Elif, León-Halcón, Alberto, Lladó, Albert, Molina-Porcel, Laura, Balasa, Mircea, Juncà-Parella, Jordi, Vitorica, Javier, Venero, Jose Luis, Deierborg, Tomas, Boza-Serrano, Antonio, Sánchez-Valle, Raquel, Instituto de Salud Carlos III, European Commission, Generalitat de Catalunya, Fundación BBVA, Ministerio de Ciencia e Innovación (España), Lund University, Swedish Brain Foundation, Crafoord Foundation, Swedish Dementia Association, Greta and Johan Kocks Foundation, Olle Engkvist Foundation, Gamla Tjänarinnor Foundation, Swedish Medical Research Council, Swedish Parkinson Foundation, Anna och Edwin Bergers Stiftelse, Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72], Borrego-Écija, Sergi, Pérez-Millan, Agnès, Antonell, Anna, Fort-Aznar, Laura, Kaya-Tilki, Elif, León-Halcón, Alberto, Lladó, Albert, Molina-Porcel, Laura, Balasa, Mircea, Juncà-Parella, Jordi, Vitorica, Javier, Venero, Jose Luis, Deierborg, Tomas, Boza-Serrano, Antonio, and Sánchez-Valle, Raquel
- Abstract
Neuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin-3 (Gal-3), a microglial activation regulator, holds promise as a therapeutic target and potential biomarker. Our study aimed to investigate Gal-3 levels in patients with FTD and assess its diagnostic potential.
- Published
- 2024
5. ProLOVE - Prospective Randomized Study of Midline Incisional Hernia Treatment (ProLOVE)
- Author
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Region Skåne FoUU, Lund University, Ethicon, Inc., The Einar & Inga Nilsson Foundation, The Anna-Lisa & Sven-Eric Lundgren Foundation, Malmö Sweden, Crafoord Foundation, and Peder Rogmark, M.D.
- Published
- 2013
6. The Effect of Adalimumab (Humira) on Vascular Abnormalities in Rheumatoid Arthritis. A Pilot Study.
- Author
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Abbott, The Swedish Research Council, The Swedish Rheumatism Ass, Crafoord Foundation, and Carl Turesson, Associate Professor
- Published
- 2011
7. Galectin-3, a rising star in modulating microglia activation under conditions of neurodegeneration
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Agencia Estatal de Investigación (España), Junta de Andalucía, Universidad de Sevilla, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Crafoord Foundation, Dementia Association (Sweden), Greta and Johan Kocks Foundation, Olle Engkvist Foundation, Swedish Research Council, Anna och Edwin Bergers Stiftelse, Swedish Parkinson Foundation, García-Revilla, Juan, Boza-Serrano, Antonio, Espinosa-Oliva, Ana M., Sarmiento, Manuel, Deierborg, Tomas, Ruiz, Rocío, de Pablos, Rocío M., Burguillos, Miguel Ángel, Venero, José L., Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Agencia Estatal de Investigación (España), Junta de Andalucía, Universidad de Sevilla, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Crafoord Foundation, Dementia Association (Sweden), Greta and Johan Kocks Foundation, Olle Engkvist Foundation, Swedish Research Council, Anna och Edwin Bergers Stiftelse, Swedish Parkinson Foundation, García-Revilla, Juan, Boza-Serrano, Antonio, Espinosa-Oliva, Ana M., Sarmiento, Manuel, Deierborg, Tomas, Ruiz, Rocío, de Pablos, Rocío M., Burguillos, Miguel Ángel, and Venero, José L.
- Abstract
The advent of high-throughput single-cell transcriptomic analysis of microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature of some of these activated phenotypes is the upregulation of galectin-3. Representative examples of these phenotypes include disease-associated microglia (DAM) and white-associated microglia (WAM), whose role(s) in neuroprotection/neurotoxicity is a matter of high interest in the microglia community. In this review, we summarise the main findings that demonstrate the ability of galectin-3 to interact with key pattern recognition receptors, including, among others, TLR4 and TREM2 and the importance of galectin-3 in the regulation of microglia activation. Finally, we discuss increasing evidence supporting the involvement of this lectin in the main neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, and stroke.
- Published
- 2022
8. Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner
- Author
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Lund University, Olle Engkvist Foundation, Swedish Medical Center Foundation, Swedish Alzheimer Foundation, Swedish Brain Foundation, Crafoord Foundation, Dementia Association (Sweden), Charles Koch Foundation, Royal Physiographic Society of Lund, Fredrik O Ingrid Thurings Foundation, Anna och Edwin Bergers Stiftelse, Swedish Parkinson Foundation, Bachiller, Sara [0000-0002-9000-3787], Bachiller, Sara, Hidalgo, Isabel, García, M. G., Boza-Serrano, Antonio, Paulus, Agnes, Denis, Q., Haikal, C., Manouchehrian, O., Klementieva, Oxana, Li, J. Y., Pronk, C. J., Gouras, Gunnar K., Deierborg, Tomas, Lund University, Olle Engkvist Foundation, Swedish Medical Center Foundation, Swedish Alzheimer Foundation, Swedish Brain Foundation, Crafoord Foundation, Dementia Association (Sweden), Charles Koch Foundation, Royal Physiographic Society of Lund, Fredrik O Ingrid Thurings Foundation, Anna och Edwin Bergers Stiftelse, Swedish Parkinson Foundation, Bachiller, Sara [0000-0002-9000-3787], Bachiller, Sara, Hidalgo, Isabel, García, M. G., Boza-Serrano, Antonio, Paulus, Agnes, Denis, Q., Haikal, C., Manouchehrian, O., Klementieva, Oxana, Li, J. Y., Pronk, C. J., Gouras, Gunnar K., and Deierborg, Tomas
- Abstract
[Background] The risk of developing Alzheimer's disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD., [Methods] Here, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS., [Results] We detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found altered Bdnf and Arc expression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure., [Conclusion] Overall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms.
- Published
- 2022
9. Structure matters: Asymmetric CO oxidation at Rh steps with different atomic packing
- Author
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Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Eusko Jaurlaritza, Knut and Alice Wallenberg Foundation, Universidad del País Vasco, Swedish Research Council, Swedish Foundation for Strategic Research, Crafoord Foundation, Department of Energy (US), Brookhaven National Laboratory (US), Garcia-Martinez, Fernando, Rämisch, Lisa, Ali, Khadiza, Waluyo, Iradwikanari, Castrillo-Bodero, Rodrigo, Pfaff, Sebastian, Villar-García, Ignacio J., Walter, Andrew Leigh, Hunt, Adrian, Pérez-Dieste, Virginia, Zetterberg, Johan, Lundgren, Edvin, Schiller, Frederik, Ortega, J. Enrique, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Eusko Jaurlaritza, Knut and Alice Wallenberg Foundation, Universidad del País Vasco, Swedish Research Council, Swedish Foundation for Strategic Research, Crafoord Foundation, Department of Energy (US), Brookhaven National Laboratory (US), Garcia-Martinez, Fernando, Rämisch, Lisa, Ali, Khadiza, Waluyo, Iradwikanari, Castrillo-Bodero, Rodrigo, Pfaff, Sebastian, Villar-García, Ignacio J., Walter, Andrew Leigh, Hunt, Adrian, Pérez-Dieste, Virginia, Zetterberg, Johan, Lundgren, Edvin, Schiller, Frederik, and Ortega, J. Enrique
- Abstract
Curved crystals are a simple but powerful approach to bridge the gap between single crystal surfaces and nanoparticle catalysts, by allowing a rational assessment of the role of active step sites in gas-surface reactions. Using a curved Rh(111) crystal, here, we investigate the effect of A-type (square geometry) and B-type (triangular geometry) atomic packing of steps on the catalytic CO oxidation on Rh at millibar pressures. Imaging the crystal during reaction ignition with laser-induced CO2 fluorescence demonstrates a two-step process, where B-steps ignite at lower temperature than A-steps. Such fundamental dissimilarity is explained in ambient pressure X-ray photoemission (AP-XPS) experiments, which reveal partial CO desorption and oxygen buildup only at B-steps. AP-XPS also proves that A-B step asymmetries extend to the active stage: at A-steps, low-active O–Rh–O trilayers buildup immediately after ignition, while highly active chemisorbed O is the dominant species on B-type steps. We conclude that B-steps are more efficient than A-steps for the CO oxidation.
- Published
- 2022
10. The human bone marrow harbors a CD45− CD11B+ cell progenitor permitting rapid microglia-like cell derivative approaches
- Author
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Royal Physiographic Society of Lund, Crafoord Foundation, Per-Eric and Ulla Schyberg's Foundation, Bruzelius, Andreas, Hidalgo, Isabel, Boza-Serrano, Antonio, Hjelmér, Anna-Giorgia, Tison, Amelie, Deierborg, Tomas, Bengzon, Johan, Ramos-Moreno, Tania, Royal Physiographic Society of Lund, Crafoord Foundation, Per-Eric and Ulla Schyberg's Foundation, Bruzelius, Andreas, Hidalgo, Isabel, Boza-Serrano, Antonio, Hjelmér, Anna-Giorgia, Tison, Amelie, Deierborg, Tomas, Bengzon, Johan, and Ramos-Moreno, Tania
- Abstract
Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow-derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in an attempt to identify novel cell sources for generating microglia-like cells to use in cell-based therapies and in vitro modeling. We demonstrate that hBM stroma harbors a progenitor cell that we name stromal microglial progenitor (STR-MP). STR-MP single-cell gene analysis revealed the expression of the consensus genetic microglial signature and microglial-specific genes present in development and CNS pathologies. STR-MPs can be expanded and generate microglia-like cells in vitro, which we name stromal microglia (STR-M). STR-M cells show phagocytic ability, classically activate, and survive and phagocyte in human brain tissue. Thus, our results reveal that hBM harbors a source of microglia-like precursors that can be used in patient-centered fast derivative approaches.
- Published
- 2021
11. miR-126 contributes to the epigenetic signature of diabetic vascular smooth muscle and enhances antirestenosis effects of Kv1.3 blockers
- Author
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Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Novo Nordisk Foundation, Swedish Research Council, Swedish Heart-Lung Foundation, Crafoord Foundation, Magnus Bergvall Foundation, Universidad de Valladolid, Banco Santander, Arévalo-Martínez, Marycarmen, Cidad, Pilar, Moreno-Estar, Sara, Fernández, Mirella, Albinsson, Sebastian, Cózar-Castellano, Irene, López-López, José R., Pérez-García, M. Teresa, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Novo Nordisk Foundation, Swedish Research Council, Swedish Heart-Lung Foundation, Crafoord Foundation, Magnus Bergvall Foundation, Universidad de Valladolid, Banco Santander, Arévalo-Martínez, Marycarmen, Cidad, Pilar, Moreno-Estar, Sara, Fernández, Mirella, Albinsson, Sebastian, Cózar-Castellano, Irene, López-López, José R., and Pérez-García, M. Teresa
- Abstract
[Objectives]: Restenosis after vessel angioplasty due to dedifferentiation of the vascular smooth muscle cells (VSMCs) limits the success of surgical treatment of vascular occlusions. Type 2 diabetes (T2DM) has a major impact on restenosis, with patients exhibiting more aggressive forms of vascular disease and poorer outcomes after surgery. Kv1.3 channels are critical players in VSMC proliferation. Kv1.3 blockers inhibit VSMCs MEK/ERK signalling and prevent vessel restenosis. We hypothesize that dysregulation of microRNAs (miR) play critical roles in adverse remodelling, contributing to Kv1.3 blockers efficacy in T2DM VSMCs. [Methods and results]: We used clinically relevant in vivo models of vascular risk factors (VRF) and vessels and VSMCs from T2DM patients. [Resukts]: Human T2DM vessels showed increased remodelling, and changes persisted in culture, with augmented VSMCs migration and proliferation. Moreover, there were downregulation of PI3K/AKT/mTOR and upregulation of MEK/ERK pathways, with increased miR-126 expression. The inhibitory effects of Kv1.3 blockers on remodelling were significantly enhanced in T2DM VSMCs and in VRF model. Finally, miR-126 overexpression confered “diabetic” phenotype to non-T2DM VSMCs by downregulating PI3K/AKT axis. [Conclusions]: miR-126 plays crucial roles in T2DM VSMC metabolic memory through activation of MEK/ERK pathway, enhancing the efficacy of Kv1.3 blockers in the prevention of restenosis in T2DM patients.
- Published
- 2021
12. Boreal forest soil carbon fluxes one year after a wildfire: Effects of burn severity and management
- Author
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Swedish Research Council, Crafoord Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Kelly, Julia, Ibáñez, Theresa S., Santín, Cristina, Doerr, Stefan H., NIlsson, Marie-Charlotte, Holst, Thomas, Lindroth, Anders, Kljun, Natascha, Swedish Research Council, Crafoord Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Kelly, Julia, Ibáñez, Theresa S., Santín, Cristina, Doerr, Stefan H., NIlsson, Marie-Charlotte, Holst, Thomas, Lindroth, Anders, and Kljun, Natascha
- Abstract
The extreme 2018 hot drought that affected central and northern Europe led to the worst wildfire season in Sweden in over a century. The Ljusdal fire complex, the largest area burnt that year (8995 ha), offered a rare opportunity to quantify the combined impacts of wildfire and post-fire management on Scandinavian boreal forests. We present chamber measurements of soil CO2 and CH4 fluxes, soil microclimate and nutrient content from five Pinus sylvestris sites for the first growing season after the fire. We analysed the effects of three factors on forest soils: burn severity, salvage-logging and stand age. None of these caused significant differences in soil CH4 uptake. Soil respiration, however, declined significantly after a high-severity fire (complete tree mortality) but not after a low-severity fire (no tree mortality), despite substantial losses of the organic layer. Tree root respiration is thus key in determining post-fire soil CO2 emissions and may benefit, along with heterotrophic respiration, from the nutrient pulse after a low-severity fire. Salvage-logging after a high-severity fire had no significant effects on soil carbon fluxes, microclimate or nutrient content compared with leaving the dead trees standing, although differences are expected to emerge in the long term. In contrast, the impact of stand age was substantial: a young burnt stand experienced more extreme microclimate, lower soil nutrient supply and significantly lower soil respiration than a mature burnt stand, due to a thinner organic layer and the decade-long effects of a previous clear-cut and soil scarification. Disturbance history and burn severity are, therefore, important factors for predicting changes in the boreal forest carbon sink after wildfires. The presented short-term effects and ongoing monitoring will provide essential information for sustainable management strategies in response to the increasing risk of wildfire.
- Published
- 2021
13. The Open Cluster Chemical Abundances and Mapping Survey. IV. Abundances for 128 Open Clusters Using SDSS/APOGEE DR16
- Author
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National Science Foundation (US), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Centro de Excelencia en Astrofísica y Tecnologías Afines (Chile), Universidad de La Serena (Chile), Crafoord Foundation, Olle Engkvist Foundation, Ruth and Nils-Erik Stenbäcks Foundation, Comisión Nacional de Investigación Científica y Tecnológica (Chile), Alfred P. Sloan Foundation, Department of Energy (US), University of Arizona, Brookhaven National Laboratory (US), Carnegie Mellon University, University of Florida, Harvard University, Instituto de Astrofísica de Canarias, Michigan State University, University of Notre Dame, Johns Hopkins University, Lawrence Berkeley National Laboratory, Max Planck Institute for Astrophysics, Max Planck Institute for extraterrestrial Physics, New Mexico State University, New York University, The Ohio State University, Pennsylvania State University, University of Portsmouth, Princeton University, University of Tokyo, University of Utah, Vanderbilt University, University of Virginia, University of Washington, Yale University, Donor, John, Anders, Friedrich, Zasowski, Gail, Gaia Collaboration, National Science Foundation (US), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Centro de Excelencia en Astrofísica y Tecnologías Afines (Chile), Universidad de La Serena (Chile), Crafoord Foundation, Olle Engkvist Foundation, Ruth and Nils-Erik Stenbäcks Foundation, Comisión Nacional de Investigación Científica y Tecnológica (Chile), Alfred P. Sloan Foundation, Department of Energy (US), University of Arizona, Brookhaven National Laboratory (US), Carnegie Mellon University, University of Florida, Harvard University, Instituto de Astrofísica de Canarias, Michigan State University, University of Notre Dame, Johns Hopkins University, Lawrence Berkeley National Laboratory, Max Planck Institute for Astrophysics, Max Planck Institute for extraterrestrial Physics, New Mexico State University, New York University, The Ohio State University, Pennsylvania State University, University of Portsmouth, Princeton University, University of Tokyo, University of Utah, Vanderbilt University, University of Virginia, University of Washington, Yale University, Donor, John, Anders, Friedrich, Zasowski, Gail, and Gaia Collaboration
- Abstract
The Open Cluster Chemical Abundances and Mapping (OCCAM) survey aims to constrain key Galactic dynamical and chemical evolution parameters by the construction of a large, comprehensive, uniform, infrared-based spectroscopic data set of hundreds of open clusters. This fourth contribution from the OCCAM survey presents analysis using Sloan Digital Sky Survey/APOGEE DR16 of a sample of 128 open clusters, 71 of which we designate to be "high quality" based on the appearance of their color-magnitude diagram. We find the APOGEE DR16 derived [Fe/H] abundances to be in good agreement with previous high-resolution spectroscopic open cluster abundance studies. Using the high-quality sample, we measure Galactic abundance gradients in 16 elements, and find evolution of some of the [X/Fe] gradients as a function of age. We find an overall Galactic [Fe/H] versus R gradient of -0.068 ± 0.001 dex kpc over the range of 6 < R < 13.9 kpc; however, we note that this result is sensitive to the distance catalog used, varying as much as 15%. We formally derive the location of a break in the [Fe/H] abundance gradient as a free parameter in the gradient fit for the first time. We also measure significant Galactic gradients in O, Mg, S, Ca, Mn, Cr, Cu, Na, Al, and K, some of which are measured for the first time. Our large sample allows us to examine four well-populated age bins in order to explore the time evolution of gradients for a large number of elements and comment on possible implications for Galactic chemical evolution and radial migration.
- Published
- 2020
14. Hyperinflammation and Fibrosis in Severe COVID-19 Patients: Galectin-3, a Target Molecule to Consider
- Author
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Swedish Research Council, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Royal Physiographic Society of Lund, Crafoord Foundation, Olle Engkvist Foundation, Ake Wiberg Foundation, Gun and Bertil Stohnes Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Ministerio de Economía y Competitividad (España), García-Revilla, Juan, Deierborg, Tomas, Venero, José L., Boza-Serrano, Antonio, Swedish Research Council, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Royal Physiographic Society of Lund, Crafoord Foundation, Olle Engkvist Foundation, Ake Wiberg Foundation, Gun and Bertil Stohnes Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Ministerio de Economía y Competitividad (España), García-Revilla, Juan, Deierborg, Tomas, Venero, José L., and Boza-Serrano, Antonio
- Abstract
COVID-19 disease have become so far the most important sanitary crisis in the XXI century. In light of the events, any clinical resource should be considered to alleviate this crisis. Severe COVID-19 cases present a so-called cytokine storm as the most life-threatening symptom accompanied by lung fibrosis. Galectin-3 has been widely described as regulator of both processes. Hereby, we present compelling evidences on the potential role of galectin-3 in COVID-19 in the regulation of the inflammatory response, fibrosis and infection progression. Moreover, we provide a strong rationale of the utility of measuring plasma galectin-3 as a prognosis biomarker for COVID-19 patients and propose that inhibition of galectin-3 represents a feasible and promising new therapeutical approach.
- Published
- 2020
15. Strain dependent light-off temperature in catalysis revealed by planar laser-induced fluorescence
- Author
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Crafoord Foundation, Swedish Foundation for Strategic Research, Swedish Research Council, Knut and Alice Wallenberg Foundation, Eusko Jaurlaritza, Ministerio de Economía y Competitividad (España), Blomberg, Sara, Zetterberg, Johan, Zhou, Jianfeng, Merte, Lindsay R., Gustafson, Johan, Shipilin, Mikhail, Trinchero, Adriana, Miccio, Luis A., Magaña, Ana, Ilyn, Max, Schiller, Frederik, Ortega, J. Enrique, Bertram, Florian, Grönbeck, Henrik, Lundgren, Edvin, Crafoord Foundation, Swedish Foundation for Strategic Research, Swedish Research Council, Knut and Alice Wallenberg Foundation, Eusko Jaurlaritza, Ministerio de Economía y Competitividad (España), Blomberg, Sara, Zetterberg, Johan, Zhou, Jianfeng, Merte, Lindsay R., Gustafson, Johan, Shipilin, Mikhail, Trinchero, Adriana, Miccio, Luis A., Magaña, Ana, Ilyn, Max, Schiller, Frederik, Ortega, J. Enrique, Bertram, Florian, Grönbeck, Henrik, and Lundgren, Edvin
- Abstract
Understanding how specific atom sites on metal surfaces lower the energy barrier for chemical reactions is vital in catalysis. Studies on simplified model systems have shown that atoms arranged as steps on the surface play an important role in catalytic reactions, but a direct comparison of how the light-off temperature is affected by the atom orientation on the step has not yet been possible due to methodological constraints. Here we report in situ spatially resolved measurements of the CO production over a cylindrical-shaped Pd catalyst and show that the light-off temperature at different parts of the crystal depends on the step orientation of the two types of steps (named A and B). Our finding is supported by density functional theory calculations, revealing that the steps, in contrast to what has been previously reported in the literature, are not directly involved in the reaction onset but have the role of releasing stress.
- Published
- 2017
16. Regulation of microRNA expression in vascular smooth muscle by MRTF-A and actin polymerization
- Author
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Crafoord Foundation, Swedish Research Council, Royal Physiographic Society of Lund, Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Swedish Heart-Lung Foundation, Magnus Bergvall Foundation, Alajbegovic, Azra, Turczyńska, Karolina M., Cidad, Pilar, Albinsson, Sebastian, Crafoord Foundation, Swedish Research Council, Royal Physiographic Society of Lund, Instituto de Salud Carlos III, European Commission, Ministerio de Economía y Competitividad (España), Swedish Heart-Lung Foundation, Magnus Bergvall Foundation, Alajbegovic, Azra, Turczyńska, Karolina M., Cidad, Pilar, and Albinsson, Sebastian
- Abstract
The dynamic properties of the actin cytoskeleton in smooth muscle cells play an important role in a number of cardiovascular disease states. The state of actin does not only mediate mechanical stability and contractile function but can also regulate gene expression via myocardin related transcription factors (MRTFs). These transcriptional co-activators regulate genes encoding contractile and cytoskeletal proteins in smooth muscle. Regulation of small non-coding microRNAs (miRNAs) by actin polymerization may mediate some of these effects. MiRNAs are short non-coding RNAs that modulate gene expression by post-transcriptional regulation of target messenger RNA. In this study we aimed to determine a profile of miRNAs that were 1) regulated by actin/MRTF-A, 2) associated with the contractile smooth muscle phenotype and 3) enriched in muscle cells. This analysis was performed using cardiovascular disease-focused miRNA arrays in both mouse and human cells. The potential clinical importance of actin polymerization in aortic aneurysm was evaluated using biopsies from mildly dilated human thoracic aorta in patients with stenotic tricuspid or bicuspid aortic valve. By integrating information from multiple qPCR based miRNA arrays we identified a group of five miRNAs (miR-1, miR-22, miR-143, miR-145 and miR-378a) that were sensitive to actin polymerization and MRTF-A overexpression in both mouse and human vascular smooth muscle. With the exception of miR-22, these miRNAs were also relatively enriched in striated and/or smooth muscle containing tissues. Actin polymerization was found to be dramatically reduced in the aorta from patients with mild aortic dilations. This was associated with a decrease in actin/MRTF-regulated miRNAs. In conclusion, the transcriptional co-activator MRTF-A and actin polymerization regulated a subset of miRNAs in vascular smooth muscle. Identification of novel miRNAs regulated by actin/MRTF-A may provide further insight into the mechanisms underlying v
- Published
- 2017
17. Regulation of smooth muscle dystrophin and synaptopodin 2 expression by actin polymerization and vascular injury
- Author
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Crafoord Foundation, Swedish Research Council, Swedish Heart-Lung Foundation, Royal Physiographic Society of Lund, Lars Hierta Memorial Foundation, European Commission, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Turczyńska, Karolina M., Cidad, Pilar, Pérez-García, M. Teresa, Albinsson, Sebastian, Crafoord Foundation, Swedish Research Council, Swedish Heart-Lung Foundation, Royal Physiographic Society of Lund, Lars Hierta Memorial Foundation, European Commission, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Turczyńska, Karolina M., Cidad, Pilar, Pérez-García, M. Teresa, and Albinsson, Sebastian
- Abstract
[Objective]: Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype. [Approach and Results]: Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknown actin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypic modulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscle and their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A. Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured human arteries. Finally, using a dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that these genes are involved in the regulation of smooth muscle differentiation and function. [Conclusions]: This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth muscle function, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlled in this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation of smooth muscle cells.
- Published
- 2015
18. Developments in biobanking workflow standardization providing sample integrity and stability
- Author
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Swedish Research Council, VINNOVA (Sweden), Swedish Foundation for Strategic Research, Crafoord Foundation, Swedish Academy of Pharmaceutical Sciences, Fuentes, Manuel, Marko-Varga, György, Swedish Research Council, VINNOVA (Sweden), Swedish Foundation for Strategic Research, Crafoord Foundation, Swedish Academy of Pharmaceutical Sciences, Fuentes, Manuel, and Marko-Varga, György
- Abstract
Recommendations and outlines for standardization in biobanking processes are presented by a research team with long-term experience in clinical studies. These processes have important bearing on the use of samples in developing assays. These measurements are useful to document states of health and disease that are beneficial for academic research, commercial healthcare, drug development industry and government regulating agencies. There is a need for increasing awareness within proteomic and genomic communities regarding the basic concepts of collecting, storing and utilizing clinical samples. Quality control and sample suitability for analysis need to be documented and validated to ensure data integrity and establish contexts for interpretation of results. Standardized methods in proteomics and genomics are required to be practiced throughout the community allowing datasets to be comparable and shared for analysis. For example, sample processing of thousands of clinical samples, performed in 384 high-density sample tube systems in a fully automated workflow, preserves sample content and is presented showing validation criteria. Large studies will be accompanied by biological and molecular information with corresponding clinical records from patients and healthy donors. These developments position biobanks of human patient samples as an increasingly recognized major asset in disease research, future drug development and within patient care. Biological significance: The current manuscript is of major relevance to the proteomic and genomic fields, as it outlines the standardization aspects of biobanking and the requirements that are needed to run future clinical studies that will benefit the patients where OMICS science will play a major role. A global view of the field is given where best practice and conventional acceptances are presented along with ongoing large-scale biobanking projects. The authors represent broadly stakeholders that cover the academic, pharma, b
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- 2013
19. Chromosome 19 annotations with disease speciation: A first report from the global research consortium
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VINNOVA (Sweden), Thermo Fisher Scientific, European Commission, Instituto de Salud Carlos III, University of Texas, Swedish Cancer Society, National Cancer Institute (US), Prostate Cancer Foundation of Australia, Memorial Sloan Kettering Cancer Center, Crafoord Foundation, Swedish Research Council, Swedish Foundation for Strategic Research, González González, María, Dasilva, Noelia, Díez, Paula, Fuentes, Manuel, Marko-Varga, György, VINNOVA (Sweden), Thermo Fisher Scientific, European Commission, Instituto de Salud Carlos III, University of Texas, Swedish Cancer Society, National Cancer Institute (US), Prostate Cancer Foundation of Australia, Memorial Sloan Kettering Cancer Center, Crafoord Foundation, Swedish Research Council, Swedish Foundation for Strategic Research, González González, María, Dasilva, Noelia, Díez, Paula, Fuentes, Manuel, and Marko-Varga, György
- Abstract
A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC-MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks. © 2012 American Chemical Society.
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- 2013
20. Proteorhodopsin phototrophy promotes survival of marine bacteria during starvation
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Swedish Research Council, Crafoord Foundation, Ministerio de Educación y Ciencia (España), Gómez-Consarnau, Laura, Akram, Neelam, Lindell, Kristoffer, Pedersen, Anders, Neutze, Richard, Milton, Debra L., Reyes-González, José M., Pinhassi, Jarone, Swedish Research Council, Crafoord Foundation, Ministerio de Educación y Ciencia (España), Gómez-Consarnau, Laura, Akram, Neelam, Lindell, Kristoffer, Pedersen, Anders, Neutze, Richard, Milton, Debra L., Reyes-González, José M., and Pinhassi, Jarone
- Abstract
Proteorhodopsins are globally abundant photoproteins found in bacteria in the photic zone of the ocean. Although their function as proton pumps with energy-yielding potential has been demonstrated, the ecological role of proteorhodopsins remains largely unexplored. Here, we report the presence and function of proteorhodopsin in a member of the widespread genus Vibrio, uncovered through whole-genome analysis. Phylogenetic analysis suggests that the Vibrio strain AND4 obtained proteorhodopsin through lateral gene transfer, which could have modified the ecology of this marine bacterium. We demonstrate an increased long-term survival of AND4 when starved in seawater exposed to light rather than held in darkness. Furthermore, mutational analysis provides the first direct evidence, to our knowledge, linking the proteorhodopsin gene and its biological function in marine bacteria. Thus, proteorhodopsin phototrophy confers a fitness advantage to marine bacteria, representing a novel mechanism for bacterioplankton to endure frequent periods of resource deprivation at the ocean's surface.
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- 2010
21. Hyperinflammation and Fibrosis in Severe COVID-19 Patients: Galectin-3, a Target Molecule to Consider
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Garcia-Revilla, Juan, Deierborg, Tomas, Venero, Jose Luis, Boza-Serrano, Antonio, [Garcia-Revilla,J, Venero,JL, Boza-Serrano,A] Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. [Deierborg,T] Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, BMC, Lund University, Lund, Sweden. [Boza-Serrano,A] Department of Experimental Medical Sciences, Experimental Dementia Research Laboratory, BMC, Lund University, Lund, Sweden., This work was supported by grants from the Swedish Research Council (2019-06333, AB-S), and the Strong Research Environment MultiPark (Multidisciplinary Research in Parkinson’s and Alzheimer’s Disease at Lund University), Bagadilico (Linné consortium sponsored by the Swedish Research Council), the Swedish Alzheimer’s Foundation, Swedish Brain Foundation, A.E. Berger Foundation, Gyllenstiern-ska Krapperup Foundation, the Royal Physiographic Society, Crafoord Foundation, Olle Engkvist Byggmästare Foundation, Wiberg Foundation, G&J Kock Foundation, Stohnes Foundation, and Swedish Dementia Association and the Medical Faculty at Lund University. This perspective was also funded by the Spanish Ministerio de Ciencia, Innovación y Universidades/FEDER/UE RTI2018-098645-B-100, FEDER I+D+i-USE US-1265062, and US-1264806. JG-R has been funded by a grant from the Spanish Ministerio de Economia y Competitividad SAF2015-64171-R (MINECO/FEDER, EU)., Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Swedish Research Council, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Royal Physiographic Society of Lund, Crafoord Foundation, Olle Engkvist Foundation, Ake Wiberg Foundation, Gun and Bertil Stohnes Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, and Ministerio de Economía y Competitividad (España)
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Galectina 3 ,Galectin 3 ,Galectins ,Pulmonary Fibrosis ,Infecciones por coronavirus ,Immunology ,Pneumonia, Viral ,Peptidyl-Dipeptidase A ,Cytokine storm ,Severity of Illness Index ,Betacoronavirus ,Animals ,Humans ,Galectin-3 ,Molecular Targeted Therapy ,Diseases::Respiratory Tract Diseases::Lung Diseases::Pulmonary Fibrosis [Medical Subject Headings] ,Pandemics ,Inflammation ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines [Medical Subject Headings] ,Inflamación ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Lectins::Galectins::Galectin 3 [Medical Subject Headings] ,SARS-CoV-2 ,COVID-19 ,Citocinas ,Blood Proteins ,Biomarker ,Prognosis ,Fibrosis ,Diseases::Respiratory Tract Diseases::Lung Diseases::Pneumonia [Medical Subject Headings] ,Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings] ,Perspective ,Host-Pathogen Interactions ,Spike Glycoprotein, Coronavirus ,Disease Progression ,biomarker ,Cytokines ,Angiotensin-Converting Enzyme 2 ,Biomarcadores ambientales ,Coronavirus Infections ,Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings] ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings] ,Biomarkers - Abstract
COVID-19 disease have become so far the most important sanitary crisis in the XXI century. In light of the events, any clinical resource should be considered to alleviate this crisis. Severe COVID-19 cases present a so-called cytokine storm as the most life-threatening symptom accompanied by lung fibrosis. Galectin-3 has been widely described as regulator of both processes. Hereby, we present compelling evidences on the potential role of galectin-3 in COVID-19 in the regulation of the inflammatory response, fibrosis and infection progression. Moreover, we provide a strong rationale of the utility of measuring plasma galectin-3 as a prognosis biomarker for COVID-19 patients and propose that inhibition of galectin-3 represents a feasible and promising new therapeutical approach., This work was supported by grants from the Swedish Research Council (2019-06333, AB-S), and the Strong Research Environment MultiPark (Multidisciplinary Research in Parkinson’s and Alzheimer’s Disease at Lund University), Bagadilico (Linné consortium sponsored by the Swedish Research Council), the Swedish Alzheimer’s Foundation, Swedish Brain Foundation, A.E. Berger Foundation, Gyllenstiern-ska Krapperup Foundation, the Royal Physiographic Society, Crafoord Foundation, Olle Engkvist Byggmästare Foundation, Wiberg Foundation, G&J Kock Foundation, Stohnes Foundation, and Swedish Dementia Association and the Medical Faculty at Lund University. This perspective was also funded by the Spanish Ministerio de Ciencia, Innovación y Universidades/FEDER/UE RTI2018-098645-B-100, FEDER ICDCi-USE US-1265062, and US-1264806. JG-R has been funded by a grant from the Spanish Ministerio de Economia y Competitividad SAF2015-64171-R (MINECO/FEDER, EU).
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- 2020
22. Structure Matters: Asymmetric CO Oxidation at Rh Steps with Different Atomic Packing
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Fernando García-Martínez, Lisa Rämisch, Khadiza Ali, Iradwikanari Waluyo, Rodrigo Castrillo Bodero, Sebastian Pfaff, Ignacio J. Villar-García, Andrew Leigh Walter, Adrian Hunt, Virginia Pérez-Dieste, Johan Zetterberg, Edvin Lundgren, Frederik Schiller, J. Enrique Ortega, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Eusko Jaurlaritza, Knut and Alice Wallenberg Foundation, Universidad del País Vasco, Swedish Research Council, Swedish Foundation for Strategic Research, Crafoord Foundation, Department of Energy (US), and Brookhaven National Laboratory (US)
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surface oxide ,General Chemistry ,Biochemistry ,Catalysis ,carbon monoxide ,Colloid and Surface Chemistry ,adsorption sites ,in-situ ,RH(111) ,nanoparticles ,phases ,oxygen ,catalytic oxidation - Abstract
Curved crystals are a simple but powerful approach to bridge the gap between single crystal surfaces and nanoparticle catalysts, by allowing a rational assessment of the role of active step sites in gas-surface reactions. Using a curved Rh(111) crystal, here, we investigate the effect of A-type (square geometry) and B-type (triangular geometry) atomic packing of steps on the catalytic CO oxidation on Rh at millibar pressures. Imaging the crystal during reaction ignition with laser-induced CO2 fluorescence demonstrates a two-step process, where B-steps ignite at lower temperature than A-steps. Such fundamental dissimilarity is explained in ambient pressure X-ray photoemission (AP-XPS) experiments, which reveal partial CO desorption and oxygen buildup only at B-steps. AP-XPS also proves that A-B step asymmetries extend to the active stage: at A-steps, low-active O–Rh–O trilayers buildup immediately after ignition, while highly active chemisorbed O is the dominant species on B-type steps. We conclude that B-steps are more efficient than A-steps for the CO oxidation., We acknowledge financial support from Grant Nos. PID2020-116093RB-C44 and PID2019-107338RB-C6-3, funded by the Spanish MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, the Basque Government (Grant No. IT-1591-22), Knut and Alice Wallenberg (KAW) project “Atomistic design of new catalysts” (Project No. KAW2015.0058), the Swedish Research Council (Project No. 2018-03434), the Swedish Foundation for Strategic Research (Project No. ITM17-0045), the Å Forsk Foundation, and the Crafoord Foundation. This research used resources of the 23-ID-2 (IOS) beamline of the National Synchrotron Light Source II, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Brookhaven National Laboratory, under Contract No. DE-SC0012704. Part of these experiments were performed at Circe beamline at ALBA Synchrotron with the collaboration of ALBA staff., Open Access funding is provided by the University of the Basque Country.
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- 2022
23. Galectin-3, a rising star in modulating microglia activation under conditions of neurodegeneration
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Juan García-Revilla, Antonio Boza-Serrano, Ana M. Espinosa-Oliva, Manuel Sarmiento Soto, Tomas Deierborg, Rocío Ruiz, Rocío M. de Pablos, Miguel Angel Burguillos, Jose L. Venero, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Agencia Estatal de Investigación (España), Junta de Andalucía, Universidad de Sevilla, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Crafoord Foundation, Dementia Association (Sweden), Greta and Johan Kocks Foundation, Olle Engkvist Foundation, Swedish Research Council, Anna och Edwin Bergers Stiftelse, and Swedish Parkinson Foundation
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Cancer Research ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,Galectin 3 ,Immunology ,Humans ,Parkinson Disease ,Microglia ,Cell Biology - Abstract
The advent of high-throughput single-cell transcriptomic analysis of microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature of some of these activated phenotypes is the upregulation of galectin-3. Representative examples of these phenotypes include disease-associated microglia (DAM) and white-associated microglia (WAM), whose role(s) in neuroprotection/neurotoxicity is a matter of high interest in the microglia community. In this review, we summarise the main findings that demonstrate the ability of galectin-3 to interact with key pattern recognition receptors, including, among others, TLR4 and TREM2 and the importance of galectin-3 in the regulation of microglia activation. Finally, we discuss increasing evidence supporting the involvement of this lectin in the main neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, and stroke., We thank the Spanish Ministerio de Ciencia, Innovación y Universidades/FEDER/UE RTI2018-098645-B-100, PID2019-107948RA-I00 and RYC-2017-21804; the Agencia Española de Investigación PID2021-124096OB-I00 and PID2021-126090OA-I00; the Spanish Junta de Andalucia /FEDER/EU P18-RT-1372 and the Spanish FEDER I + D + i-USE US-1264806, US-1264152 and US-1265062 from University of Seville. This work has also been supported by the Strategic Research Area MultiPark (Multidisciplinary Research focused on neurodegenerative diseases) at Lund University, the Swedish Alzheimer foundation, the Swedish Brain Foundation, the Crafoord Foundation, the Swedish Dementia Association, the G&J Kock Foundation, the Olle Engkvist Foundation, the Swedish Research Council (Project 2019-06333), the Royal Physiographic Society (42222 and 40594), the A.E. Berger Foundation, the Swedish Parkinson Foundation and the Medical Faculty at Lund University. Open access funding provided by Lund University.
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- 2022
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24. APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases
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Rosalía Fernández-Calle, Sabine C. Konings, Javier Frontiñán-Rubio, Juan García-Revilla, Lluís Camprubí-Ferrer, Martina Svensson, Isak Martinson, Antonio Boza-Serrano, José Luís Venero, Henrietta M. Nielsen, Gunnar K. Gouras, Tomas Deierborg, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, European Union (UE). Marie Curie, Ministerio de Ciencia e Innovación (MICIN). España, Junta de Andalucía, Universidad de Sevilla, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Crafoord Foundation, Dementia Association (Sweden), G&J Kock Foundation, Olle Engkvist Foundation, Swedish Medical Research Council SMRC, Swedish Parkinson Foundation, Anna och Edwin Bergers Stiftelse, Fredrik O Ingrid Thurings Foundation, Swedish National Association for Social and Mental Health RSMH, Royal Physiographic Society of Lund, European Commission, Ministerio de Ciencia e Innovación (España), and Fernández-Calle, Rosalía
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Amyloid beta-Peptides ,Genotype ,Apolipoprotein E2 ,Apolipoprotein E4 ,Apolipoprotein E3 ,Neurodegenerative Diseases ,Plaque, Amyloid ,tau Proteins ,Cellular and Molecular Neuroscience ,Apolipoproteins E ,Neuroinflammation ,Alzheimer Disease ,Humans ,Neurology (clinical) ,Apolipoprotein E ,Neurodegeneration ,Molecular Biology ,Alzheimer’s disease - Abstract
ApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell-cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field., Open access funding provided by Lund University. This work was supported by The Strategic Research Area MultiPark (Multidisciplinary Research in neurodegenerative diseases) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, Crafoord Foundation, Swedish Dementia Association, G&J Kock Foundation, Olle Engkvist Foundation, the Swedish Medical Research Council, the Swedish Parkinson Foundation, the A.E. Berger Foundation, the Thurings Foundation, and the Swedish mental health foundation to T.D., M.S, A.B-S. The Royal Physiographic Society of Lund grant to R.F–C. SYNDEGEN, Marie Curie grant n°721802 to G.K.G and S.K. We also thank the Spanish Ministerio de Ciencia e Innovación/FEDER/UE/PID2021-124096OB-I00; the Spanish Junta de Andalucia/FEDER/EU P18-RT-1372 and the Spanish FEDER I + D + i-USE US-1264806 to J.L.V.
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- 2022
25. Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner
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S. Bachiller, I. Hidalgo, M. G. Garcia, A. Boza-Serrano, A. Paulus, Q. Denis, C. Haikal, O. Manouchehrian, O. Klementieva, J. Y. Li, C. J. Pronk, G. K. Gouras, T. Deierborg, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Lund University, Olle Engkvist Foundation, Swedish Medical Center Foundation, Swedish Alzheimer Foundation, Swedish Brain Foundation, Crafoord Foundation, Dementia Association (Sweden), Charles Koch Foundation, Royal Physiographic Society of Lund, Fredrik O Ingrid Thurings Foundation, Anna och Edwin Bergers Stiftelse, Swedish Parkinson Foundation, and Bachiller, Sara
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Male ,Amyloid beta-Peptides ,General Neuroscience ,Maternal Deprivation ,Immunology ,Immunity ,Brain ,Mice, Transgenic ,Cellular and Molecular Neuroscience ,Mice ,Disease Models, Animal ,Sex Factors ,Neurology ,Neuroinflammation ,Alzheimer Disease ,Sex differences ,Animals ,Female ,Early-life stress ,Maternal separation ,Alzheimer’s disease ,Stress, Psychological - Abstract
[Background] The risk of developing Alzheimer's disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD., [Methods] Here, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS., [Results] We detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found altered Bdnf and Arc expression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure., [Conclusion] Overall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms., Open access funding provided by Lund University. This study was funded by the Olle Engkvist Foundation, the Swedish Medical Research Council, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Crafoord Foundation, the Swedish Dementia Association, the G&J Kock Foundation, the Royal Physiographic Society, the Fredrik O Ingrid Thurings Stiftelse, the A.E. Berger Foundation, the Swedish Parkinson Foundation and the Strategic Research Area MultiPark at Lund University.
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- 2021
26. miR-126 contributes to the epigenetic signature of diabetic vascular smooth muscle and enhances antirestenosis effects of Kv1.3 blockers
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José R. López-López, Pilar Cidad, Mirella Fernández, Sebastian Albinsson, Sara Moreno-Estar, M. Teresa Pérez-García, Irene Cózar-Castellano, Marycarmen Arévalo-Martínez, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Novo Nordisk Foundation, Swedish Research Council, Swedish Heart-Lung Foundation, Crafoord Foundation, Magnus Bergvall Foundation, Universidad de Valladolid, and Banco Santander
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Male ,MAPK/ERK pathway ,Vascular smooth muscle ,endocrine system diseases ,Remodelación muscular ,Muscle, Smooth, Vascular ,Epigenesis, Genetic ,Vascular remodelling in the embryo ,Coronary Restenosis ,Mice ,Diabetes mellitus ,Downregulation and upregulation ,Restenosis ,Type 2 diabetes mellitus ,Potassium Channel Blockers ,Animals ,Humans ,Medicine ,Vascular remodeling ,Molecular Biology ,Protein kinase B ,Internal medicine ,PI3K/AKT/mTOR pathway ,Cell proliferation ,Aged ,Kv1.3 Potassium Channel ,business.industry ,Vascular disease ,Cell Biology ,medicine.disease ,musculoskeletal system ,RC31-1245 ,MicroRNAs ,Kv1.3 channel blockers ,Diabetes Mellitus, Type 2 ,miRNAs ,Cancer research ,cardiovascular system ,Original Article ,Female ,business ,Músculo liso vascular - Abstract
Producción Científica, Objectives: Restenosis after vessel angioplasty due to dedifferentiation of the vascular smooth muscle cells (VSMCs) limits the success of surgical treatment of vascular occlusions. Type 2 diabetes (T2DM) has a major impact on restenosis, with patients exhibiting more aggressive forms of vascular disease and poorer outcomes after surgery. Kv1.3 channels are critical players in VSMC proliferation. Kv1.3 blockers inhibit VSMCs MEK/ERK signalling and prevent vessel restenosis. We hypothesize that dysregulation of microRNAs (miR) play critical roles in adverse remodelling, contributing to Kv1.3 blockers efficacy in T2DM VSMCs. Methods and results: We used clinically relevant in vivo models of vascular risk factors (VRF) and vessels and VSMCs from T2DM patients. Results: Human T2DM vessels showed increased remodelling, and changes persisted in culture, with augmented VSMCs migration and proliferation. Moreover, there were downregulation of PI3K/AKT/mTOR and upregulation of MEK/ERK pathways, with increased miR-126 expression. The inhibitory effects of Kv1.3 blockers on remodelling were significantly enhanced in T2DM VSMCs and in VRF model. Finally, miR-126 overexpression confered “diabetic” phenotype to non-T2DM VSMCs by downregulating PI3K/AKT axis. Conclusions: miR-126 plays crucial roles in T2DM VSMC metabolic memory through activation of MEK/ERK pathway, enhancing the efficacy of Kv1.3 blockers in the prevention of restenosis in T2DM patients., Ministerio de Economía, Industria y Competitividad (grant BFU2016-75360-R and SAF2016-77871-C2-1-R), Junta de Castilla y León (grants VA114P17; VA172P20 and CLU-2019-02), Novo Nordisk Foundation (grant 34366), Swedish Research Council (grants 2017–00860 and 2020-01145), Swedish Heart and Lung Foundation (grant 20200322)
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- 2021
27. The human bone marrow harbors a CD45− CD11B+ cell progenitor permitting rapid microglia-like cell derivative approaches
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Tomas Deierborg, Amelie Tison, Johan Bengzon, Tania Ramos-Moreno, Anna Giorgia Hjelmér, Antonio Boza-Serrano, Andreas Bruzelius, Isabel Hidalgo, Royal Physiographic Society of Lund, Crafoord Foundation, Per-Eric and Ulla Schyberg's Foundation, and Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
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0301 basic medicine ,Central Nervous System ,Stromal cell ,Pluripotent stem cell ,microglia‐like cell in vitro model ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Human bone marrow ,medicine ,Humans ,Bone marrow ,Yolk sac ,Progenitor cell ,lcsh:QH573-671 ,Induced pluripotent stem cell ,Progenitor ,lcsh:R5-920 ,CD11b Antigen ,Microglia ,lcsh:Cytology ,Microglia-like cell in vitro model ,Monocyte ,Stem Cells ,Microglial precursor ,Cell Biology ,General Medicine ,Common myeloid progenitor ,Cell biology ,Standards, Protocols, Policies, and Regulations for Cell‐based Therapies ,030104 developmental biology ,medicine.anatomical_structure ,Primitive myeloid progenitor ,Leukocyte Common Antigens ,lcsh:Medicine (General) ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Microglia, the immune sentinel of the central nervous system (CNS), are generated from yolk sac erythromyeloid progenitors that populate the developing CNS. Interestingly, a specific type of bone marrow-derived monocyte is able to express a yolk sac microglial signature and populate CNS in disease. Here we have examined human bone marrow (hBM) in an attempt to identify novel cell sources for generating microglia-like cells to use in cell-based therapies and in vitro modeling. We demonstrate that hBM stroma harbors a progenitor cell that we name stromal microglial progenitor (STR-MP). STR-MP single-cell gene analysis revealed the expression of the consensus genetic microglial signature and microglial-specific genes present in development and CNS pathologies. STR-MPs can be expanded and generate microglia-like cells in vitro, which we name stromal microglia (STR-M). STR-M cells show phagocytic ability, classically activate, and survive and phagocyte in human brain tissue. Thus, our results reveal that hBM harbors a source of microglia-like precursors that can be used in patient-centered fast derivative approaches., This work was supported by Craafordska Stiftelsen, the Royal Physiographic Society of Lund, Per Eric and Ulla Shyberg's Foundation, and Viveca Jeppsson.
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- 2021
28. Boreal forest soil carbon fluxes one year after a wildfire: Effects of burn severity and management
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Julia Kelly, Marie-Charlotte Nilsson, Natascha Kljun, Thomas Holst, Cristina Santín, Stefan H. Doerr, Theresa S. Ibáñez, Anders Lindroth, Swedish Research Council, Crafoord Foundation, and Ministerio de Ciencia, Innovación y Universidades (España)
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0106 biological sciences ,010504 meteorology & atmospheric sciences ,Microclimate ,Growing season ,Forests ,010603 evolutionary biology ,01 natural sciences ,Fires ,Wildfires ,Soil respiration ,Soil ,Taiga ,Humans ,Environmental Chemistry ,0105 earth and related environmental sciences ,General Environmental Science ,Forest floor ,Global and Planetary Change ,Ecology ,Forest Science ,Carbon sink ,Soil carbon ,Carbon ,Agronomy ,Soil water ,Environmental science ,Burns ,Salvage logging - Abstract
The extreme 2018 hot drought that affected central and northern Europe led to the worst wildfire season in Sweden in over a century. The Ljusdal fire complex, the largest area burnt that year (8995 ha), offered a rare opportunity to quantify the combined impacts of wildfire and post-fire management on Scandinavian boreal forests. We present chamber measurements of soil CO2 and CH4 fluxes, soil microclimate and nutrient content from five Pinus sylvestris sites for the first growing season after the fire. We analysed the effects of three factors on forest soils: burn severity, salvage-logging and stand age. None of these caused significant differences in soil CH4 uptake. Soil respiration, however, declined significantly after a high-severity fire (complete tree mortality) but not after a low-severity fire (no tree mortality), despite substantial losses of the organic layer. Tree root respiration is thus key in determining post-fire soil CO2 emissions and may benefit, along with heterotrophic respiration, from the nutrient pulse after a low-severity fire. Salvage-logging after a high-severity fire had no significant effects on soil carbon fluxes, microclimate or nutrient content compared with leaving the dead trees standing, although differences are expected to emerge in the long term. In contrast, the impact of stand age was substantial: a young burnt stand experienced more extreme microclimate, lower soil nutrient supply and significantly lower soil respiration than a mature burnt stand, due to a thinner organic layer and the decade-long effects of a previous clear-cut and soil scarification. Disturbance history and burn severity are, therefore, important factors for predicting changes in the boreal forest carbon sink after wildfires. The presented short-term effects and ongoing monitoring will provide essential information for sustainable management strategies in response to the increasing risk of wildfire., This project has been funded by Swedish Research Council Formas grants 2018-02700, 2019-00836, the strategic research program of the Crafoord Foundation grant 20190763, and the Swedish Strategic Research Area BECC (Biodiversity and Ecosystem Services in a Changing Climate). C.S. also received funding from the Spanish ‘Ramon y Cajal’ programme, Ref. N. RYC2018-025797-I.
- Published
- 2021
29. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- Author
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Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjornsson, Gardar, Fatemifar, Ghazaleh, Hedman, Asa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Arnlov, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Doerr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engstrom, Gunnar, Esko, Tonu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Gudbjartsson, Daniel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Kober, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, Maerz, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, Stott, David J, Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G, Veluchamy, Abirami, Voelker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Waterworth, Dawn, Weeke, Peter E, Weiss, Raul, Wiggins, Kerri L, Xing, Heming, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J, McMurray, John JV, Yang, Jian, Visscher, Peter M, Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A, Sattar, Naveed, Holmes, Michael V, Cappola, Thomas P, Asselbergs, Folkert W, Hingorani, Aroon D, Kuchenbaecker, Karoline, Ellinor, Patrick T, Lang, Chim C, Stefansson, Kari, Smith, J Gustav, Vasan, Ramachandran S, Swerdlow, Daniel I, Lumbers, R Thomas, Abecasis, Goncalo, Backman, Joshua, Bai, Xiaodong, Balasubramanian, Suganthi, Banerjee, Nilanjana, Baras, Aris, Barnard, Leland, Beechert, Christina, Blumenfeld, Andrew, Cantor, Michael, Chai, Yating, Coppola, Giovanni, Damask, Amy, Dewey, Frederick, Economides, Aris, Eom, Gisu, Forsythe, Caitlin, Fuller, Erin D, Gu, Zhenhua, Gurski, Lauren, Guzzardo, Paloma M, Habegger, Lukas, Hahn, Young, Hawes, Alicia, van Hout, Cristopher, Jones, Marcus B, Khalid, Shareef, Lattari, Michael, Li, Alexander, Lin, Nan, Liu, Daren, Lopez, Alexander, Manoochehri, Kia, Marchini, Jonathan, Marcketta, Anthony, Maxwell, Evan K, McCarthy, Shane, Mitnaul, Lyndon J, O'Dushlaine, Colm, Overton, John D, Padilla, Maria Sotiropoulos, Paulding, Charles, Penn, John, Pradhan, Manasi, Reid, Jeffrey G, Schleicher, Thomas D, Schurmann, Claudia, Shuldiner, Alan, Staples, Jeffrey C, Sun, Dylan, Toledo, Karina, Ulloa, Ricardo H, Widom, Louis, Wolf, Sarah E, Yadav, Ashish, Ye, Bin, Ctr, Regeneron Genetics, Shah, Sonia [0000-0001-5860-4526], Henry, Albert [0000-0001-7422-2288], Roselli, Carolina [0000-0001-5267-6756], Lin, Honghuang [0000-0003-3043-3942], Chaffin, Mark D. [0000-0002-1234-5562], Helgadottir, Anna [0000-0002-1806-2467], Verweij, Niek [0000-0002-4303-7685], Almgren, Peter [0000-0002-0473-0241], Chen, Xu [0000-0002-7299-3238], Ghanbari, Mohsen [0000-0002-9476-7143], Giedraitis, Vilmantas [0000-0003-3423-2021], Gross, Stefan [0000-0003-4121-7161], Guðbjartsson, Daníel F. [0000-0002-5222-9857], Hyde, Craig L. [0000-0002-6939-287X], Ingelsson, Erik [0000-0003-2256-6972], Jukema, J. Wouter [0000-0002-3246-8359], Kleber, Marcus E. [0000-0003-0663-7275], Koekemoer, Andrea [0000-0001-8222-3547], Langenberg, Claudia [0000-0002-5017-7344], Lindgren, Cecilia M. [0000-0002-4903-9374], Lovering, Ruth C. [0000-0002-9791-0064], Luan, Jian’an [0000-0003-3137-6337], Magnusson, Patrik [0000-0002-7315-7899], Mahajan, Anubha [0000-0001-5585-3420], Mordi, Ify R. [0000-0002-2686-729X], Morris, Andrew D. [0000-0002-1766-0473], Nagle, Michael W. [0000-0002-4677-7582], Nelson, Christopher P. [0000-0001-8025-2897], Palmer, Colin N. A. [0000-0002-6415-6560], Rice, Kenneth M. [0000-0002-3071-7278], Rotter, Jerome I. [0000-0001-7191-1723], Salomaa, Veikko [0000-0001-7563-5324], van Setten, Jessica [0000-0002-4934-7510], Svensson, Per [0000-0003-0372-6272], Taylor, Kent D. [0000-0002-2756-4370], Teder-Laving, Maris [0000-0002-5872-1850], Teumer, Alexander [0000-0002-8309-094X], Tyl, Benoit [0000-0001-5297-8412], Uitterlinden, Andre G. [0000-0002-7276-3387], Völker, Uwe [0000-0002-5689-3448], Wiggins, Kerri L. [0000-0003-2749-1279], Hemingway, Harry [0000-0003-2279-0624], Yang, Jian [0000-0003-2001-2474], Visscher, Peter M. [0000-0002-2143-8760], Lubitz, Steven A. [0000-0002-9599-4866], Sattar, Naveed [0000-0002-1604-2593], Cappola, Thomas P. [0000-0002-9630-7204], Asselbergs, Folkert W. [0000-0002-1692-8669], Kuchenbaecker, Karoline [0000-0001-9726-603X], Ellinor, Patrick T. [0000-0002-2067-0533], Vasan, Ramachandran S. [0000-0001-7357-5970], Lumbers, R. Thomas [0000-0002-9077-4741], Apollo - University of Cambridge Repository, Chaffin, Mark D [0000-0002-1234-5562], Guðbjartsson, Daníel F [0000-0002-5222-9857], Hyde, Craig L [0000-0002-6939-287X], Jukema, J Wouter [0000-0002-3246-8359], Kleber, Marcus E [0000-0003-0663-7275], Lindgren, Cecilia M [0000-0002-4903-9374], Lovering, Ruth C [0000-0002-9791-0064], Luan, Jian'an [0000-0003-3137-6337], Mordi, Ify R [0000-0002-2686-729X], Morris, Andrew D [0000-0002-1766-0473], Nagle, Michael W [0000-0002-4677-7582], Nelson, Christopher P [0000-0001-8025-2897], Palmer, Colin NA [0000-0002-6415-6560], Rice, Kenneth M [0000-0002-3071-7278], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Uitterlinden, Andre G [0000-0002-7276-3387], Wiggins, Kerri L [0000-0003-2749-1279], Visscher, Peter M [0000-0002-2143-8760], Lubitz, Steven A [0000-0002-9599-4866], Cappola, Thomas P [0000-0002-9630-7204], Asselbergs, Folkert W [0000-0002-1692-8669], Ellinor, Patrick T [0000-0002-2067-0533], Vasan, Ramachandran S [0000-0001-7357-5970], Lumbers, R Thomas [0000-0002-9077-4741], Palmer, Colin N A [0000-0002-6415-6560], Cardiovascular Centre (CVC), University of Queensland [Brisbane], University College of London [London] (UCL), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University Medical Center Groningen [Groningen] (UMCG), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), deCODE genetics [Reykjavik], Karolinska Institutet [Stockholm], Pfizer, University of Pennsylvania [Philadelphia], University of Groningen [Groningen], Imperial College London, Lund University [Lund], Herlev and Gentofte Hospital, Massachusetts General Hospital [Boston], Department of Neurobiology, Care Sciences and Society [Stockholm, Sweden] (Division of Family Medicine), Dalarna University, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, Department of Biostatistics, University of Washington [Seattle], Emory University School of Medicine, Emory University [Atlanta, GA], The University of Texas Medical School at Houston, Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, Novartis Institutes for BioMedical Research (NIBR), University of Liverpool, Universität Heidelberg [Heidelberg], Medizinische Fakultät Mannheim, The Alan Turing Institute, Ninewells Hospital and Medical School [Dundee], Universität Greifswald - University of Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Minnesota System, Regeneron Pharmaceuticals [Tarrytown], Department of Clinical Sciences, Cardiovascular Epidemiology, Skane University Hospital [Lund], Institute of Genomics [Tartu, Estonia], University of Tartu, Robertson Centre for Biostatistics, University of Glasgow, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Uppsala University, Brigham & Women’s Hospital [Boston] (BWH), University of Maryland School of Medicine, University of Maryland System, School of Science and Engineering (Reykjavik University), Carver College of Medicine, University of Iowa, Geisinger Health System [Danville, PA, USA], Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford Cardiovascular Institute, Uppsala Universitet [Uppsala], Leiden University Medical Center (LUMC), Einthoven Laboratory for Experimental Vascular Medicine (ELEVM - LEIDEN), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Glenfield Hospital, University Hospitals Leicester, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Big Data Institute, University of Oxford [Oxford], University of Iowa [Iowa City], The Wellcome Trust Centre for Human Genetics [Oxford], Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Medical University Graz, Skane University Hospital [Malmo], Vanderbilt University School of Medicine [Nashville], University of Edinburgh, Université médicale de Vienne, Autriche, National Institute for Health and Welfare [Helsinki], University of Turku, Birmingham Women's and Children's NHS Foundation Trust, Kaiser Permanente, Harbor UCLA Medical Center [Torrance, Ca.], Los Angeles Biomedical Research Institute (LA BioMed), University Medical Center [Utrecht], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Seattle Epidemiologic Research and Information Center [Seattle], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Department of Cardiology, Södersjukhuset, Stockholm, Estonian Genome and Medicine, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Aalborg University [Denmark] (AAU), Institut de Recherches SERVIER (IRS), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, GlaxoSmithKline, Glaxo Smith Kline, Northeastern Ohio Medical University (NEOMED), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Department of Cardiovascular Sciences [Leicester], University of Leicester, Queensland Brain Institute, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, University of Dundee, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Atherosclerosis Risk in Communities Study (ARIC)The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC- 55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694 and RC2 HL102419, National Human Genome Research Institute contract U01HG004402, and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT- CHF)This project was funded by a grant from the European Commission (FP7‐242209‐ BIOSTAT‐CHF, EudraCT 2010–020808–29). Cardiovascular Health Study (CHS) This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Heart Failure Study (deCODE) We at deCODE thank the women and men of Iceland that have participated in our studies and our colleagues that contributed to data collection and processing. DiscovEHR We acknowledge and thank all participants in Geisinger’s MyCode Community Health Initiative for their support and permission to use their health and genomic information in the DiscovEHR collaboration. This work was supported by the Regeneron Genetics Center and Geisinger. Estonian Genome Center at the University of Tartu (EGCUT) This study was supported by Estonian Research Council Grant IUT20-60, EU, H2020 grant 692145, European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012) GENTRANSMED. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) The EPHESUS was supported by Pfizer, Inc. The European Prospective Investigation of Cancer, Norfolk study (EPIC-Norfolk) The EPIC-Norfolk Study is supported by programme grants from the Medical Research Council UK (G1000143) and Cancer Research UK (C864/A14136) and with additional support from the European Union, Stroke Association, British Heart Foundation, Research into Ageing, Department of Health, The Wellcome Trust and the Food Standards Agency. NJW and CL also acknowledge support from the Medical Research Council, UK (MC_UU_12015/1, MC_PC_13048). We thank all EPIC participants and staff for their contribution to the study, and thank staff from the Technical, Field Epidemiology and Data Functional Group Teams of the Medical Research Council Epidemiology Unit in Cambridge, UK, for carrying out sample preparation, DNA provision and quality control, genotyping and data handling work. Framingham Heart Study (FHS) This work was conducted using data and resources from the Framingham Heart Study (FHS) of the National Heart Lung and Blood Institute and Boston University School of Medicine. The study was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC-25195 and HHSN268201500001I) and its contract with Affymetrix, Inc for genotyping services (Contract No.N02-HL-6-4278). The work was also supported by R01 HL093328, R01 HL105993, and R01 HL71039 (PI: Ramachandran). FINRISK V.S. has been supported by the Finnish Foundation for Cardiovascular Research. Genetics of Diabetes Audit and Research Tayside Scotland GoDARTS) The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (supporting GoDARTS) was funded by the Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT programme. We acknowledge the support of the Health Informatics Centre, University of Dundee, for managing and supplying the anonymized data and NHS Tayside, the original data owner. The Genetic Risk Assessment of Defibrillator Events (GRADE) NIH-NHLBI R01 HL77398 (Genetic Modulators of Sudden Death). S.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study We extend our appreciation to the participants of the LURIC study, without their collaboration, this article would not have been written. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg and Ulm, Germany. LURIC has received funding from the 7th Framework Program (RiskyCAD, grant agreement number 305739 and Atheroremo, grant agreement number 201668) of the European Union. Malmö Diet and Cancer Study (MDCS) J. Gustav Smith was supported by grants from the Swedish Heart-Lung Foundation (2016- 0134 and 2016-0315), the Swedish Research Council (2017-02554), the European Research Council (ERC-STG-2015-679242), the Crafoord Foundation, Skåne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349-2006-237, Strategic Research Area Exodiab Dnr 2009-1039) and Swedish Foundation for Strategic Research (Dnr IRC15- 0067) to the Lund University Diabetes Center. The Malmo Diet and Cancer Study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, and the Malmo city council. Penn Heart Failure Study (PHFS) The study was supported by NIH grants (NIH R01L088577 and NIH R01H105993). Prevention of REnal and Vascular ENd-stage Disease (PREVEND) The Prevention of Renal and Vascular Endstage Disease Study (PREVEND) genetics is supported by the Dutch Kidney Foundation (Grant E033), the EU project grant GENECURE (FP-6 LSHM CT 2006 037697), the National Institutes of Health (grant LM010098), the Netherlands organisation for health research and development (NWO VENI grant 916.761.70), and the Dutch Inter University Cardiology Institute Netherlands (ICIN). Niek Verweij was supported by NWO VENI grant 016.186.125. PROspective Study of Pravastatin in the Elderly at Risk for vascular disease (PROSPER)The PROSPER study was supported by an investigator-initiated grant obtained from Bristol- Myers Squibb. Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Study of Health in Pomerania (SHIP) SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID)SOLID-TIMI 52 was funded by GlaxoSmithKline. TwinGene (TwinGene) TwinGene received funding from the Swedish Research Council (M-2005-1112), GenomEUtwin (EU/QLRT-2001-01254, QLG2-CT-2002-01254), NIH DK U01-066134, The Swedish Foundation for Strategic Research (SSF) and the Heart and Lung foundation no. 20070481. TwinGene is part of the Swedish Twin Registry which is managed by Karolinska Institutet and receives funding through the Swedish Research Council (2017–00641). UK Biobank (UKBiobank) This research has been conducted using the UK Biobank Resource under Application Number 15422. This work was supported in part by grants to R.T.L. from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074, MRC Proximity to Discovery Award Scheme, the American Heart Association Institute for Precision Mecidine, Pfizer Ltd, the University College London British Heart Foundation Research Accelerator (AA/18/6/34223), and was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A. H. is supported by the British Heart Foundation Cardiovascular Biomedicine PhD studentship. R.T.L is supported by a UK Research and Innovation Rutherford Fellowship and was previously supported by a National Institutes of Health Research Clinical Lectureship. Uppsala Longitudinal Study of Adult Men (ULSAM) J.Ä. is supported by the Swedish Research Council and the Swedish Heart Lung foundation. C.M.L is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138- 27). Women’s Genome Health Study (WGHS) The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467, HL099355) and the National Cancer Institute (CA047988 and UM1CA182913), with collaborative scientific support and funding for genotyping provided by Amgen., Epidemiology, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
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0301 basic medicine ,Dánartíðni ,Epidemiology ,LOCI ,45/43 ,General Physics and Astronomy ,Muscle Proteins ,Genome-wide association study ,Disease ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Bioinformatics ,Genome-wide association studies ,DISEASE ,Ventricular Function, Left ,Coronary artery disease ,0302 clinical medicine ,Risk Factors ,Atrial Fibrillation ,IMPUTATION ,Medicine ,Blóðrásarsjúkdómar ,692/308/174 ,lcsh:Science ,2. Zero hunger ,RISK ,Multidisciplinary ,Microfilament Proteins ,article ,Atrial fibrillation ,Mendelian Randomization Analysis ,CATALOG ,3. Good health ,OBESITY ,Erfðarannsóknir ,Cardiomyopathies ,Medical Genetics ,Cyclin-Dependent Kinase Inhibitor p21 ,Science ,631/208/205/2138 ,Heart failure ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,631/443/592/2727 ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,RESOURCE ,Humans ,Mortality ,METAANALYSIS ,Genetic association ,Medicinsk genetik ,Adaptor Proteins, Signal Transducing ,Heart Failure ,HYPERTENSION ,business.industry ,Case-control study ,Klinisk medicin ,692/699/75/230 ,General Chemistry ,Cardiovascular genetics ,medicine.disease ,R1 ,030104 developmental biology ,Case-Control Studies ,lcsh:Q ,Morbidity ,Clinical Medicine ,business ,Apoptosis Regulatory Proteins ,Carrier Proteins ,Genome-Wide Association Study - Abstract
Publisher's version (útgefin grein), Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies., We acknowledge the contribution from the EchoGen Consortium.
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- 2020
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30. Geosmin Attracts Aedes aegypti Mosquitoes to Oviposition Sites
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Jeffrey A. Riffell, Muriel Gugger, Marcus C. Stensmyr, Gabriella H. Wolff, Matthew DeGennaro, André Luis Costa-da-Silva, Merybeth Fernandez Triana, Robert Arribas, Nadia Melo, Lund University [Lund], University of Washington [Seattle], Florida International University [Miami] (FIU), Universidade Federal de Alagoas = Federal University of Alagoas (UFAL), Collection des Cyanobactéries, Institut Pasteur [Paris] (IP), N.M. and M.C.S. were supported by the Crafoord Foundation, Carl Tryggers Foundation, and the Swedish Research Council. A.L.C., R.A., and M.D. were supported by The Florida Department of Agriculture and Consumer Services ('Highly attractive biological insecticide trap (HABIT) to reduce mosquito populations') and The Centers for Disease Control and Prevention (CDC), Southeastern Center of Excellence in Vector-borne Disease. We would like to thank the entire DeGennaro laboratory for their help in obtaining the field collections of mosquito eggs. G.H.W. and J.A.R. were supported by awards from the National Science Foundation (IOS-1354159), Air Force Office of Scientific Research (FA9550-16-1-0167), and University of Washington Innovation Award. M.G. and the Pasteur Collection of Cyanobacteria is funded by the Pasteur Institute. The Centers for Disease Control andPrevention (CDC), Southeastern Center of Excellence in Vector-borne Disease, and Institut Pasteur [Paris]
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0301 basic medicine ,Oviposition ,[SDV]Life Sciences [q-bio] ,Zoology ,Naphthols ,Aedes aegypti ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Aedes ,parasitic diseases ,Animals ,Larva ,biology ,Extramural ,Chemotaxis ,fungi ,Hate ,food and beverages ,biology.organism_classification ,Geosmin ,3. Good health ,Smell ,Mosquito control ,030104 developmental biology ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,chemistry ,Female ,Drosophila melanogaster ,General Agricultural and Biological Sciences ,030217 neurology & neurosurgery ,Field conditions - Abstract
In Brief Melo et al. show that geosmin mediates egg laying in the yellow fever mosquito Aedes aegypti, which associates geosmin with microbes present in the larval aquatic habitat. The authors further show that geosmin can be used as bait in oviposition traps and that geosmin can be substituted by beetroot peel for mosquito trapping in developing countries., Graphical Abstract
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- 2020
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31. Anti‐tumor effects of <scp>PIM</scp> / <scp>PI</scp> 3K/ <scp>mTOR</scp> triple kinase inhibitor <scp>IBL</scp> ‐302 in neuroblastoma
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Carmen Blanco-Apiricio, Daniel Bexell, Katarzyna Radke, Javanshir Esfandyari, Charlotte Welinder, Sofie Mohlin, Kristoffer von Stedingk, Cristian Garcia-Ruiz, Karin Hansson, Sonia Sánchez Martínez, Joaquín Pastor, Michael O'Neill, Swedish Research Council, Swedish Cancer Society, Region Skane, Magnus Bergvalls stiftelse, Skane University Hospital, Mary Beve Foundation, Thelma Zoega Foundation, Hans von Kantzow Foundation, Crafoord Foundation, Ollie och Elof Ericssons stiftelser, Ake Wiberg Foundation, Berth von Kantzows stiftelse, Royal Physiographic Society of Lund, Ministerio de Ciencia e Innovación (España), RFI/VR, Jeanssons Stiftelser, and Science for Life Laboratory, Sweden
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0301 basic medicine ,Medicine (General) ,Pyridines ,cisplatin ,Apoptosis ,QH426-470 ,PI3K ,IBL-302 ,Neuroblastoma ,0302 clinical medicine ,Cell Movement ,Antineoplastic Combined Chemotherapy Protocols ,Etoposide ,Cancer ,Phosphoinositide-3 Kinase Inhibitors ,N-Myc Proto-Oncogene Protein ,Chemistry ,Kinase ,TOR Serine-Threonine Kinases ,Cell Differentiation ,Articles ,Tumor Burden ,Molecular Medicine ,Female ,Corrigendum ,Signal Transduction ,medicine.drug ,Mice, Nude ,Thiophenes ,Protein Serine-Threonine Kinases ,Article ,neuroblastoma ,03 medical and health sciences ,R5-920 ,IBL‐302 ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Chemical Biology ,Genetics ,medicine ,Animals ,Humans ,Doxorubicin ,multikinase inhibition ,PI3K/AKT/mTOR pathway ,Cisplatin ,medicine.disease ,Xenograft Model Antitumor Assays ,Pyrimidines ,030104 developmental biology ,Cancer research ,Phosphatidylinositol 3-Kinase ,030217 neurology & neurosurgery ,Neuroscience - Abstract
The PI3K pathway is a major driver of cancer progression. However, clinical resistance to PI3K inhibition is common. IBL-302 is a novel highly specific triple PIM, PI3K, and mTOR inhibitor. Screening IBL-302 in over 700 cell lines representing 47 tumor types identified neuroblastoma as a strong candidate for PIM/PI3K/mTOR inhibition. IBL-302 was more effective than single PI3K inhibition in vitro, and IBL-302 treatment of neuroblastoma patient-derived xenograft (PDX) cells induced apoptosis, differentiated tumor cells, and decreased N-Myc protein levels. IBL-302 further enhanced the effect of the common cytotoxic chemotherapies cisplatin, doxorubicin, and etoposide. Global genome, proteome, and phospho-proteome analyses identified crucial biological processes, including cell motility and apoptosis, targeted by IBL-302 treatment. While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma. This work was supported by funding from the Swedish Cancer Society (to SM, DB), the Swedish Research Council (to DB), the Swedish Childhood Cancer Fund (to SM, KvS, DB), Region Skåne and the research funds of Skåne University Hospital (to DB), the Mary Bevé Foundation (to SM, KvS, DB), Magnus Bergvalls stiftelse (to SM, DB), the Thelma Zoéga Foundation (to SM), Hans von Kantzow Foundation (to SM), Crafoord Foundation (to DB), Åke Wiberg Foundation (to DB), Jeanssons Stiftelser (to DB), Ollie och Elof Ericssons stiftelser (to DB), Berth von Kantzows stiftelse (to DB), the Royal Physiographic Society of Lund (to SM, DB), and the Spanish Ministry of Health and Social Policy (ADE 08 / 90038 ) and the Spanish Ministry of Science and Innovation (CIT- 090000 - 2008 - 14 ) (to JP, SMa, CBA). We would like to thank the Local MS Support at Medical Faculty, Lund University. The authors would like to acknowledge support of the National Genomics Infrastructure (NGI)/Uppsala Genome Center and UPPMAX for providing assistance in massive parallel sequencing and computational infrastructure. Work performed at NGI/Uppsala Genome Center has been funded by RFI/VR and Science for Life Laboratory, Sweden Sí
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- 2019
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32. Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
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Agnes Paulus, José L. Venero, Yiyi Yang, Raquel Sanchez-Varo, Javier Vitorica, Maria Swanberg, Tomas Deierborg, Sebastian Jimenez, Sara Linse, María Angustias Roca-Ceballos, Guy C. Brown, David H. Allendorf, John Stegmayr, Jose Carlos Davila, Itzia Jimenez-Ferrer, Juan García-Revilla, Malin Wennström, Christine L. Hsieh, Antonia Gutierrez, Luis Miguel Real, Victoria Navarro-Garrido, Hakon Leffler, Ulf J. Nilsson, Elisabet Englund, Anna Vilalta, Antonio Boza-Serrano, Rocío Ruiz, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Ministerio de Economía y Competitividad (MINECO). España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Centro de Investigaciones Biomédicas en Red (CIBERNED). España, Junta de Andalucía, Universidad de Málaga, Swedish Research Council, Lund University, Swedish Alzheimer Foundation, Swedish Brain Foundation, Anna och Edwin Bergers Stiftelse, Gyllenstiernska Krapperupsstiftelsen, Royal Physiographic Society of Lund, Crafoord Foundation, Olle Engkvist Foundation, Ake Wiberg Foundation, Charles Koch Foundation, Gun and Bertil Stohnes Foundation, Ministerio de Economía y Competitividad (España), European Commission, Agencia Estatal de Investigación (España), Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Innovative Medicines Initiative, Alzheimer's Association, Ahlen Foundation, and Knut and Alice Wallenberg Foundation
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0301 basic medicine ,Male ,Galectin 3 ,Alzheimer’s disease (AD) ,Hippocampus ,Mice ,0302 clinical medicine ,TREM2 ,Galectin-3 ,Molecular Targeted Therapy ,Receptors, Immunologic ,Cells, Cultured ,Amyloid aggregation ,Mice, Knockout ,Membrane Glycoproteins ,biology ,Microglia ,Chemistry ,Alzheimer's disease ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Female ,medicine.symptom ,Alzheimer’s disease ,Amyloid ,Amyloid beta ,Inflammation ,Mice, Transgenic ,Infammation ,Polymorphism, Single Nucleotide ,Protein Aggregation, Pathological ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Downregulation and upregulation ,Alzheimer Disease ,medicine ,Extracellular ,Animals ,Humans ,Genetic Predisposition to Disease ,Maze Learning ,Original Paper ,Amyloid beta-Peptides ,Colocalization ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,biology.protein ,Neurology (clinical) ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD., This work was supported by Grants from the Swedish Research Council, and the Strong Research Environment MultiPark (Multidisciplinary Research in Parkinson’s and Alzheimer’s Disease at Lund University), Bagadilico (Linné consortium sponsored by the Swedish Research Council), the Swedish Alzheimer’s Foundation, Swedish Brain Foundation, A.E. Berger Foundation, Gyllenstiernska Krapperup Foundation, the Royal Physiographic Society, Crafoord Foundation, Olle Engkvist Byggmästare Foundation, Wiberg Foundation, G&J Kock Foundation, Stohnes Foundation, Swedish Dementia Association and the Medical Faculty at Lund University. This work was supported by Grant SAF2015-64171R (Spanish MINECO/FEDER, UE), by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union through grants PI15/00796 and PI18/01557 (to AG), PI15/00957 and PI18/01556 (to JV), and CIBERNED (to AG and JV), by Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucia Proyecto de Excelencia (CTS-2035) (to JV and AG), and by Malaga University grant PPIT.UMA.B1.2017/26 (to RSV). AV and GCB received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant agreement no. 115976 (PHAGO). CIBERNED “Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid (Spain)”. HL and AF were supported by the Swedish Research Council, the Swedish Brain Foundation, the Alzheimer Foundation and the Åhlén Foundation. UJN was supported by Grants from the Knut and Alice Wallenberg Foundation (KAW 2013.0022) and the Swedish Research Council (Grant no. 621-2012-2978).
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- 2019
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33. Strain Dependent Light-off Temperature in Catalysis Revealed by Planar Laser-Induced Fluorescence
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Ana Magaña, Johan Zetterberg, Jianfeng Zhou, Mikhail Shipilin, M. Ilyn, Frederik Schiller, Adriana Trinchero, Johan Gustafson, J. Enrique Ortega, Henrik Grönbeck, Sara Blomberg, Edvin Lundgren, Lindsay R. Merte, Florian Bertram, Luis A. Miccio, Crafoord Foundation, Swedish Foundation for Strategic Research, Swedish Research Council, Knut and Alice Wallenberg Foundation, Eusko Jaurlaritza, and Ministerio de Economía y Competitividad (España)
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02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Chemical reaction ,Catalysis ,Metal ,Crystal ,Atom ,Reactivity (chemistry) ,Chemistry ,Steps ,General Chemistry ,021001 nanoscience & nanotechnology ,CO oxidation ,0104 chemical sciences ,Crystallography ,Planar laser-induced fluorescence ,Chemical physics ,visual_art ,Density functional theory ,visual_art.visual_art_medium ,Cylindrical crystal ,0210 nano-technology - Abstract
Understanding how specific atom sites on metal surfaces lower the energy barrier for chemical reactions is vital in catalysis. Studies on simplified model systems have shown that atoms arranged as steps on the surface play an important role in catalytic reactions, but a direct comparison of how the light-off temperature is affected by the atom orientation on the step has not yet been possible due to methodological constraints. Here we report in situ spatially resolved measurements of the CO production over a cylindrical-shaped Pd catalyst and show that the light-off temperature at different parts of the crystal depends on the step orientation of the two types of steps (named A and B). Our finding is supported by density functional theory calculations, revealing that the steps, in contrast to what has been previously reported in the literature, are not directly involved in the reaction onset but have the role of releasing stress., The authors thank the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Crafoord Foundation. Support by the MAX IV staff is gratefully acknowledged. The calculations were performed at C3SE through a SNIC grant. J.E.O. acknowledges support from the Spanish Ministry of Economy (MAT2013-46593-C6-4-P) and the Basque Government (IT621-13).
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- 2016
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34. Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice
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Karin Berger, Elin Sand, Frida Fåk, Merichel Plaza, Dorota Kotowska, Mikael Bjursell, Lovisa Heyman-Lindén, Cecilia Holm, Charlotta Turner, Sara Larsson and Maria Lindahl, Lund University, Anders Brinte, Imagene-IT, Lund University Antidiabetic Food Centre, Crafoord Foundation, Royal Physiographic Society in Lund, Swedish Research Council, Swedish Diabetes Association, and A. Påhlsson Foundation.
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0301 basic medicine ,medicine.medical_specialty ,obesity ,berries ,Inflammation ,lcsh:TX341-641 ,Gut flora ,digestive system ,03 medical and health sciences ,Internal medicine ,LBP ,medicine ,high-fat diet Responsible Editor: Wendy Russell, University of Aberdeen, United Kingdom ,Lingonberries ,Nutrition and Dietetics ,biology ,hepatic steatosis ,metabolic syndrome ,microbiota ,gut-diet interactions ,obesity, akkermansia, hepatic steatosis, lingonberries, inflammation ,metabolic endotoxemia, LBP, high fat diet ,Public Health, Environmental and Occupational Health ,High fat diet ,Akkermansia ,medicine.disease ,biology.organism_classification ,metabolic endotoxemia ,Obesity ,high-fat diet ,030104 developmental biology ,Endocrinology ,Nutrition ,Associations and effects of foods and nutrients on health ,Original Article ,Metabolic syndrome ,Steatosis ,medicine.symptom ,lcsh:Nutrition. Foods and food supply ,Food Science - Abstract
Background : The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. Methods : Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. Results : HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium , genera associated with healthy gut mucosa and anti-inflammation, was found to increase in response to lingonberry intake. Conclusions : Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the anti-inflammatory properties of lingonberries seem to be independent of effects on body weight gain. Keywords: obesity; Akkermansia; hepatic steatosis; berries; metabolic endotoxemia; LBP; high-fat diet (Published: 27 April 2016) Citation: Food & Nutrition Research 2016, 60: 29993 - http://dx.doi.org/10.3402/fnr.v60.29993
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- 2016
35. The Open Cluster Chemical Abundances and Mapping Survey. IV. Abundances for 128 Open Clusters Using SDSS/APOGEE DR16
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D. A. García-Hernández, Carlos Allende Prieto, Ricardo Carrera, Doug Geisler, Julia O'Connell, Roger Cohen, Steven R. Majewski, Andres Almeida, Kaike Pan, Dmitry Bizyaev, John Donor, Jennifer Sobeck, Christian Moni Bidin, Henrik Jönsson, Sten Hasselquist, Joel R. Brownstein, Peter M. Frinchaboy, Katia Cunha, Richard R. Lane, Rachael L. Beaton, Gail Zasowski, Alexandre Roman-Lopes, Friedrich Anders, Cristina Chiappini, Dante Minniti, National Science Foundation (US), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Centro de Excelencia en Astrofísica y Tecnologías Afines (Chile), Universidad de La Serena (Chile), Crafoord Foundation, Olle Engkvist Foundation, Ruth and Nils-Erik Stenbäcks Foundation, Comisión Nacional de Investigación Científica y Tecnológica (Chile), Alfred P. Sloan Foundation, Department of Energy (US), University of Arizona, Brookhaven National Laboratory (US), Carnegie Mellon University, University of Florida, Harvard University, Instituto de Astrofísica de Canarias, Michigan State University, University of Notre Dame, Johns Hopkins University, Lawrence Berkeley National Laboratory, Max Planck Institute for Astrophysics, Max Planck Institute for extraterrestrial Physics, New Mexico State University, New York University, The Ohio State University, Pennsylvania State University, University of Portsmouth, Princeton University, University of Tokyo, University of Utah, Vanderbilt University, University of Virginia, University of Washington, and Yale University
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010504 meteorology & atmospheric sciences ,Infrared ,Chemical abundances ,FOS: Physical sciences ,Astrophysics::Cosmology and Extragalactic Astrophysics ,Astrophysics ,Milky Way evolution ,01 natural sciences ,Measure (mathematics) ,Open star clusters ,Galactic abundances ,Abundance (ecology) ,0103 physical sciences ,010303 astronomy & astrophysics ,Astrophysics::Galaxy Astrophysics ,0105 earth and related environmental sciences ,Physics ,Diagram ,Time evolution ,Astronomy and Astrophysics ,Function (mathematics) ,Astrophysics - Astrophysics of Galaxies ,13. Climate action ,Space and Planetary Science ,Astrophysics of Galaxies (astro-ph.GA) ,Free parameter ,Open cluster - Abstract
The Open Cluster Chemical Abundances and Mapping (OCCAM) survey aims to constrain key Galactic dynamical and chemical evolution parameters by the construction of a large, comprehensive, uniform, infrared-based spectroscopic data set of hundreds of open clusters. This fourth contribution from the OCCAM survey presents analysis using Sloan Digital Sky Survey/APOGEE DR16 of a sample of 128 open clusters, 71 of which we designate to be "high quality" based on the appearance of their color-magnitude diagram. We find the APOGEE DR16 derived [Fe/H] abundances to be in good agreement with previous high-resolution spectroscopic open cluster abundance studies. Using the high-quality sample, we measure Galactic abundance gradients in 16 elements, and find evolution of some of the [X/Fe] gradients as a function of age. We find an overall Galactic [Fe/H] versus R gradient of -0.068 ± 0.001 dex kpc over the range of 6 < R < 13.9 kpc; however, we note that this result is sensitive to the distance catalog used, varying as much as 15%. We formally derive the location of a break in the [Fe/H] abundance gradient as a free parameter in the gradient fit for the first time. We also measure significant Galactic gradients in O, Mg, S, Ca, Mn, Cr, Cu, Na, Al, and K, some of which are measured for the first time. Our large sample allows us to examine four well-populated age bins in order to explore the time evolution of gradients for a large number of elements and comment on possible implications for Galactic chemical evolution and radial migration., comments. J.D. and P.M.F. acknowledge support for this research from the National Science Foundation (AST-1311835 & AST-1715662). K.C. acknowledges support for this research from the National Science Foundation (AST-0907873). D.A.G.H. acknowledges support from the State Research Agency (AEI) of the Spanish Ministry of Science, Innovation, and Universities (MCIU), and the European Regional Development Fund (FEDER) under grant AYA2017-88254-P. D.G. and D.M. gratefully acknowledge support from the Chilean Centro de Excelencia en Astrofísica y Tecnologías Afines (CATA) BASAL grant AFB-170002. D.G. also acknowledges financial support from the Dirección de Investigación y Desarrollo de la Universidad de La Serena through the Programa de Incentivo a la Investigación de Académicos (PIA-DIDULS). D.M. is also supported by the Programa Iniciativa Científica Milenio grant IC120009, awarded to the Millennium Institute of Astrophysics (MAS), and by Proyecto FONDECYT regular No. 1170121. H.J. acknowledges support from the Crafoord Foundation, Stiftelsen Olle Engkvist Byggmästare, and Ruth och Nils-Erik Stenbäcks stiftelse. A.R.-L. acknowledges financial support provided in Chile by Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) through the FONDECYT project 1170476 and by the QUIMAL project 130001 Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science. The SDSS-III website is http://www.sdss3.org/. SDSS-III is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS-III Collaboration including the University of Arizona, the Brazilian Participation Group, Brookhaven National Laboratory, Carnegie Mellon University, University of Florida, the French Participation Group, the German Participation Group, Harvard University, the Instituto de Astrofisica de Canarias, the Michigan State/Notre Dame/JINA Participation Group, Johns Hopkins University, Lawrence Berkeley National Laboratory, Max Planck Institute for Astrophysics, Max Planck Institute for Extraterrestrial Physics, New Mexico State University, New York University, Ohio State University, Pennsylvania State University, University of Portsmouth, Princeton University, the Spanish Participation Group, University of Tokyo, University of Utah, Vanderbilt University, University of Virginia, University of Washington, and Yale University. Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS-IV acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. The SDSS website is www.sdss.org.
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- 2020
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36. Sulforaphane improves disrupted ER-mitochondria interactions and suppresses exaggerated hepatic glucose production
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Guillaume Vial, Jennifer Rieusset, Annika S. Axelsson, Anders Rosengren, Claes B. Wollheim, Emily Tubbs, 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), 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), Crafoord foundation, Swedish Foundation for Strategic Research, Ragnar Soderberg foundation, Wallenberg Centre for Molecular and Translational Medicine in Gothenburg, 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), Lund University [Lund], 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), Faculté De Medecine Et De Maïeutique Lyon Sud [Lyon] (Charles Mérieux), University medical center and campus biotech Geneva, University of Gothenburg (GU), and Vial, Guillaume
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0301 basic medicine ,Male ,[SDV.BA] Life Sciences [q-bio]/Animal biology ,[SDV]Life Sciences [q-bio] ,Type 2 diabetes ,Mitochondrion ,CHOP ,Endoplasmic Reticulum ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Isothiocyanates ,Phosphorylation ,Endoplasmic Reticulum Chaperone BiP ,biology ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,3. Good health ,Metformin ,Mitochondria ,[SDV] Life Sciences [q-bio] ,Liver ,Sulfoxides ,medicine.drug ,medicine.medical_specialty ,Mitochondria-associated ER membranes ,03 medical and health sciences ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,ddc:612 ,Molecular Biology ,Sulphoraphane ,Intracellular Membranes ,medicine.disease ,Mice, Inbred C57BL ,Insulin receptor ,030104 developmental biology ,Glucose ,chemistry ,biology.protein ,Unfolded protein response ,Hepatocytes ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery ,Drug metabolism ,Sulforaphane - Abstract
International audience; AIMS: Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs. MATERIALS AND METHODS: We used proximity ligation assays, analysis of ER stress markers and glucose production assays in hepatoma cell lines, primary mouse hepatocytes and diabetic animal models. RESULTS: SFN counteracted the increase of glucose production in palmitate-treated mouse hepatocytes. SFN also counteracted palmitate-induced MAM disruptions. Moreover, SFN decreased the ER stress markers CHOP and Grp78. In ob/ob mice, SFN improved glucose tolerance and reduced exaggerated glucose production. In livers of these mice, SFN increased MAM protein content, restored impaired VDAC1-IP3R1 interactions and reduced ER stress markers. In mice on HFHSD, SFN improved glucose tolerance, MAM protein content and ER-mitochondria interactions to a similar extent to that of metformin. CONCLUSIONS: The present findings show that MAMs are severely reduced in animal models of glucose intolerance, which reinforces the role of MAMs as a hub for insulin signaling in the liver. We also show that SFN restores MAMs and improves glucose tolerance by a similar magnitude to that of metformin. These data highlight SFN as a new potential anti-diabetic compound.
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- 2017
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37. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia
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Martina Svensson, Kate Lykke Lambertsen, Shohreh Issazadeh-Navikas, Yawei Liu, Bettina Hjelm Clausen, Reza Khorooshi, Totte Stankovich, Tomas Deierborg, Ana R. Inácio, Krzysztof Kucharz, Yiyi Yang, Department of Clinical Sciences, Laboratory for Experimental Brain Research, Lund University [Lund]-Lund University [Lund], Neuroinflammation Unit, Biotech Research and Innovation Centre-University of Copenhagen = Københavns Universitet (UCPH), Department of Neurobiology Research, University of Southern Denmark (SDU)-Institute of Molecular Medicine, Department of Experimental Medical Sciences [Lund], Lund University [Lund], This work was supported by grants from: Fundação para a Ciência e aTecnologia (ARI), Portugal, A.E. Berger, The Crafoord Foundation, G.E. Kock’sFoundation, The Gyllenstiernska Krapperup Foundation, The Royal PhysiographicSociety in Lund, Swedish National Stroke Foundation, and the Swedish ResearchCouncil grant no. 2012–2229 (TD), Sweden, The Danish Independent ResearchCouncil, and The Lundbeck Foundation (SI-N), Denmark, Brødrene HartmannFond (BHC), Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat (KLL),and The Lundbeck Foundation (BHC and KLL), Denmark, Agency for Researchand Innovation, Council for Health Research (RK supported by a grant to TrevorOwens), Denmark, and BMC, BMC
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Male ,[SDV]Life Sciences [q-bio] ,IFN-α/β receptor ,Brain Ischemia/pathology ,Systemic inflammation ,Brain Ischemia ,Brain ischemia ,Mice ,Infarction, Middle Cerebral Artery/pathology ,Spleen/cytology ,Ischemic Attack, Transient/pathology ,Leukocytes ,Medicine ,Hand Strength/physiology ,Postural Balance ,Stroke ,Receptors, Interferon ,Mice, Knockout ,B-Lymphocytes ,Hand Strength ,General Neuroscience ,Receptors, Interferon/genetics ,Leukocytes/pathology ,Brain ,Infarction, Middle Cerebral Artery ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Neurology ,Ischemic Attack, Transient ,Knockout mouse ,Cytokines ,medicine.symptom ,Genetically modified mouse ,medicine.medical_specialty ,Stroke/pathology ,Immunology ,Central nervous system ,Ischemia ,Inflammation ,Cytokines/blood ,Cellular and Molecular Neuroscience ,Inflammatory and immune cells ,Internal medicine ,Animals ,Brain/pathology ,Lymphocyte Count ,Middle cerebral artery occlusion ,Interferon-beta/genetics ,business.industry ,Research ,Interferon-beta ,medicine.disease ,Mice, Inbred C57BL ,Endocrinology ,Interferon-β ,business ,B-Lymphocytes/pathology ,Spleen ,Inflammation/pathology ,Knockout mice - Abstract
Background Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear. Methods To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. Results Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and IFN-βKO mice further supports an important immunoregulatory function of IFN-β in stroke. Moreover, we observed a significant weight loss 2–3 days and a reduction in grip strength 2 days after stroke in the IFN-βKO group, while endogenous IFN-β signaling did not affect the infarct volume. Conclusions We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0427-0) contains supplementary material, which is available to authorized users.
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- 2015
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38. Genetic and phenotypic diversity characterization of natural populations of the parasitoid Parvilucifera sinerae
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Isabel Ferrera, Rosa Isabel Figueroa, Esther Garcés, Marta Turon, Elisabet Alacid, Isabel Bravo, Albert Reñé, Isabel Ramilo, Crafoord Foundation, and Ministerio de Ciencia e Innovación (España)
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biology ,Parasitoids ,Host (biology) ,Ecology ,Virulence ,Parasitism ,Zoology ,Ribosomal marker ,Aquatic Science ,Ribosomal RNA ,biology.organism_classification ,Dinoflagellates ,Parasitoid ,Intergenic region ,Centro Oceanográfico de Vigo ,Host-parasite interactions ,Medio Marino ,Gene ,Apicomplexa ,Ecology, Evolution, Behavior and Systematics ,Dinophyceae ,Perkinsozoa - Abstract
16 pages, 5 figures, 3 tables, 1 appendix, Parasites exert important top-down control of their host populations. The host-parasite system formed by Alexandrium minutum (Dinophyceae) and Parvilucifera sinerae (Perkinsozoa) offers an opportunity to advance our knowledge of parasitism in planktonic communities. In this study, DNA extracted from 73 clonal strains of P. sinerae, from 10 different locations along the Atlantic and Mediterranean coasts, was used to genetically characterize this parasitoid at the species level. All strains showed identical sequences of the small and large subunits and internal transcribed spacer of the ribosomal RNA, as well as of the β-tubulin genes. However, the phenotypical characterization showed variability in terms of host invasion, zoospore success, maturation time, half-maximal infection, and infection rate. This characterization grouped the strains within 3 phenotypic types distinguished by virulence traits. A particular virulence pattern could not be ascribed to host-cell bloom appearance or to the location or year of parasite-strain isolation; rather, some parasitoid strains from the same bloom significantly differed in their virulence traits. Identical markers such as ITS and β-tubulin genes of P. sinerae strains from different geographic areas and from different years precludes their use in assessing intra-specific diversity and could indicate a recent dispersion of this species, This study was supported by the Spanish Ministry of Science and Innovation through the project PARAL (CTM2009-08399). [...] R.I.F. was funded by the Crafoord Foundation (Sweden, contract 2011:0882)
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- 2015
39. Airway resistance and reactance are affected in systemic sclerosis
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Dirk M. Wuttge, Gracijela Bozovic, Roger Hesselstrand, Ellen Tufvesson, David Aronsson, The Swedish Heart and Lung foundation, Evy and Gunnar Sandberg’s Foundation, Apotekare Hedbergs fund, Alfred Österlund foundation, Crafoord Foundation, Donation fund at the Department of Rheumatology, Lund University Hospital, and Greta and Johan Kock Fund
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Pulmonary and Respiratory Medicine ,Spirometry ,medicine.medical_specialty ,Pathology ,systemic sclerosis ,impulse oscillometry ,fibrosis ,HRCT ,Pulmonary function testing ,resistance ,Airway resistance ,Interquartile range ,Internal medicine ,medicine ,Original Research Article ,Lung ,medicine.diagnostic_test ,business.industry ,reactance ,Interstitial lung disease ,medicine.disease ,medicine.anatomical_structure ,Impulse Oscillometry ,Cardiology ,Airway ,business - Abstract
Background : Interstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc. Methods : Seventy-eight SSc patients, of which 65 had limited cutaneous SSc (lcSSc) and 13 had diffuse cutaneous SSc (dcSSc), were subjected to high-resolution computed tomography (HRCT) and pulmonary function tests (spirometry, IOS, and single breath CO diffusion capacity test). Twenty-six healthy individuals served as controls. Results : Patients with lcSSc had higher levels of peripheral airway resistance, that is, R5–R20 (difference between resistance at 5 Hz and resistance at 20 Hz) showed a median (and interquartile range) of 0.05 (0.02–0.09) in lcSSc, 0.01 (0.00–0.04) in dcSSc and 0.04 (0.01–0.06) in healthy controls. They also had higher levels of reactance: reactance area was 0.26 (0.15–0.56) in lcSSc, 0.20 (0.11–0.29) in dcSSc and 0.18 (0.08–0.30) in healthy controls, and resonant frequency was 10.9 (8.8–14.8) in lcSSc, 9.0 (8.3–11.6) in dcSSc and 9.1 (8.0–13.1) in healthy controls. Airway reactance correlated to fibrotic findings on HRCT, such as ground glass opacities and reticulations. Discussion : This implies that IOS parameters to some extent are related to fibrosis in patients with SSc. Keywords: fibrosis; impulse oscillometry; reactance; resistance; systemic sclerosis (Published: 21 October 2015) Citation: European Clinical Respiratory Journal 2015, 2: 28667 - http://dx.doi.org/10.3402/ecrj.v2.28667
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- 2015
40. Regulation of smooth muscle dystrophin and synaptopodin 2 expression by actin polymerization and vascular injury
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Johan Sjögren, Ingrid Yao Mattisson, Tran Thi Hien, Per Hellstrand, Mari Ekman, Anna Hultgårdh-Nilsson, Johan Nilsson, Karolina M. Turczyńska, Johan Wohlfahrt, Vignesh Murugesan, M. Teresa Pérez-García, Pilar Cidad, Karl Swärd, Sebastian Albinsson, Crafoord Foundation, Swedish Research Council, Swedish Heart-Lung Foundation, Royal Physiographic Society of Lund, Lars Hierta Memorial Foundation, European Commission, Ministerio de Economía y Competitividad (España), and Instituto de Salud Carlos III
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mdx mouse ,Vascular smooth muscle ,Angioplastia ,Transcription, Genetic ,Muscle Relaxation ,macromolecular substances ,Muscle, Smooth, Vascular ,Enfermedades vasculares ,Polymerization ,Dystrophin ,32 Ciencias Médicas ,Animals ,Humans ,Cardiac and Cardiovascular Systems ,Transcription factor ,Vascular diseases ,Cells, Cultured ,Actin ,Mice, Knockout ,Gene knockdown ,biology ,Microfilament Proteins ,Angioplasty ,Arteries ,Phenotype ,Actins ,3. Good health ,Cell biology ,Myocardin ,Mice, Inbred mdx ,biology.protein ,Gene expression ,Cardiology and Cardiovascular Medicine ,Muscle Contraction ,Expresión génica - Abstract
et al., [Objective]: Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype. [Approach and Results]: Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknown actin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypic modulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscle and their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A. Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured human arteries. Finally, using a dystrophin mutant mdx mouse and synaptopodin 2 knockdown, we demonstrate that these genes are involved in the regulation of smooth muscle differentiation and function. [Conclusions]: This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth muscle function, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlled in this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation of smooth muscle cells., This work was supported by the Swedish Research Council; the Swedish Heart and Lung Foundation, the Crafoord Foundation; the Royal Physiographic Society; the Per-Eric and Ulla Schyberg Foundation; the Åke Wiberg Foundation; the Jeansson Foundation; the Tore Nilson Foundation; the Greta and Johan Kock Foundation; the Magnus Bergvall Foundation, the Zoegas foundation and the Lars Hierta Memorial Foundation. K.M. Turczyńska was in part supported by the European Union FP7 Marie Curie Initial Training Network Small Artery Remodeling (SmArt). M.T. Pérez-García was supported by grants from the Instituto de Salud Carlos III (ISCIII-FEDER RD12/0042/0006 (Heracles Program) and Spanish MINECO grant BFU2010-15898 (M.T. Pérez-García) and BFU2013-45867-R.
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- 2015
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41. Chromosome 19 annotations with disease speciation: A first report from the global research consortium
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Hans Lilja, György Marko-Varga, Henrik Lindberg, Huiling Liu, Anna Nilsson, Melinda Rezeli, Joseph R. Moskal, Noelia Dasilva, Maria Gonzales-Gonzales, Per E. Andrén, Goutham Edula, Manuel Fuentes, Frode S. Berven, Elisabet Carlsohn, Karin Sjödin, Ákos Végvári, Johan Malm, Sophia Hober, Paula Díez, Carol L. Nilsson, Frode Selheim, Erik P. Sulman, Thomas Laurell, Frederick F. Lang, Xiangdong Wang, Thomas E. Fehniger, Devipriya Subramaniyam, Charles A. Conrad, David Fenyö, Charlotte Welinder, Roger A. Kroes, VINNOVA (Sweden), Thermo Fisher Scientific, European Commission, Instituto de Salud Carlos III, University of Texas, Swedish Cancer Society, National Cancer Institute (US), Prostate Cancer Foundation of Australia, Memorial Sloan Kettering Cancer Center, Crafoord Foundation, Swedish Research Council, and Swedish Foundation for Strategic Research
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Proteome ,Protein Array Analysis ,Gene Expression ,Disease ,Biology ,Biochemistry ,Article ,Mass Spectrometry ,03 medical and health sciences ,Chromosome 19 ,Human proteome project ,Humans ,Multiplex ,RNA, Messenger ,Databases, Protein ,030304 developmental biology ,Genetics ,0303 health sciences ,Genome, Human ,030302 biochemistry & molecular biology ,General Chemistry ,Biobank ,3. Good health ,Protein microarray ,Human genome ,Transcriptome ,Chromosomes, Human, Pair 19 - Abstract
PMCID: PMC3539432; NIHMSID: NIHMS430346.-- et al., A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC-MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks. © 2012 American Chemical Society., This work was supported by grants from the Swedish Academy of Pharmaceutical Sciences who is the core founder our consortium, Swedish Research Council, the Swedish Foundation for Strategic Research, Vinnova, Ingabritt & Arne Lundbergs forskningsstiftelse, the Crafoord Foundation and by Thermo Fisher Scientific for mass spectrometry instrument support. T.E.F. is supported by the Mobilitas Program sponsored by the European Union Social Fund and administered by the Estonian Science Foundation. We gratefully acknowledge financial support to M.F. from Health Institute Carlos III of Spain (ISCIII, FIS PI02114) and M.G.-G. is supported by a PhD scholarship of ISCIII FI08/00721. C.L.N. is supported by the Cancer Prevention and Research Institute of Texas and the University of Texas Medical Branch. [11-0624]; National Cancer Institute [R33 CA 127768-03, R01CA160816, and P50-CA92629]; Sidney Kimmel Center for Prostate and Urologic Cancers; and David H. Koch through the Prostate Cancer Foundation.
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- 2013
42. Developments in biobanking workflow standardization providing sample integrity and stability
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David Erlinge, Melinda Rezeli, Thomas E. Fehniger, Manuel Fuentes, Magnus Dahlbäck, Goutham Edula, Frode S. Berven, Henrik Lindberg, Elisabet Carlsohn, David Fenyö, Johan Malm, Xiangdong Wang, Roger Appelqvist, Thomas Laurell, Karin Sjödin, Sophia Hober, Pia Danmyr, Carol L. Nilsson, Per E. Andrén, Charlotte Welinder, Elisabet Wieslander, György Marko-Varga, Ákos Végvári, Swedish Research Council, VINNOVA (Sweden), Swedish Foundation for Strategic Research, Crafoord Foundation, and Swedish Academy of Pharmaceutical Sciences
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Automation, Laboratory ,Proteomics ,Engineering ,Standardization ,business.industry ,GeneralLiterature_INTRODUCTORYANDSURVEY ,Biophysics ,InformationSystems_DATABASEMANAGEMENT ,TheoryofComputation_GENERAL ,Bioinformatics ,Biochemistry ,Biobank ,Specimen Handling ,Engineering management ,Workflow ,ComputingMethodologies_PATTERNRECOGNITION ,Humans ,Sample integrity ,business ,Biological Specimen Banks - Abstract
This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics.-- et al., Recommendations and outlines for standardization in biobanking processes are presented by a research team with long-term experience in clinical studies. These processes have important bearing on the use of samples in developing assays. These measurements are useful to document states of health and disease that are beneficial for academic research, commercial healthcare, drug development industry and government regulating agencies. There is a need for increasing awareness within proteomic and genomic communities regarding the basic concepts of collecting, storing and utilizing clinical samples. Quality control and sample suitability for analysis need to be documented and validated to ensure data integrity and establish contexts for interpretation of results. Standardized methods in proteomics and genomics are required to be practiced throughout the community allowing datasets to be comparable and shared for analysis. For example, sample processing of thousands of clinical samples, performed in 384 high-density sample tube systems in a fully automated workflow, preserves sample content and is presented showing validation criteria. Large studies will be accompanied by biological and molecular information with corresponding clinical records from patients and healthy donors. These developments position biobanks of human patient samples as an increasingly recognized major asset in disease research, future drug development and within patient care. Biological significance: The current manuscript is of major relevance to the proteomic and genomic fields, as it outlines the standardization aspects of biobanking and the requirements that are needed to run future clinical studies that will benefit the patients where OMICS science will play a major role. A global view of the field is given where best practice and conventional acceptances are presented along with ongoing large-scale biobanking projects. The authors represent broadly stakeholders that cover the academic, pharma, biotech and healthcare fields with extensive experience and deliveries. This contribution will be a milestone paper to the proteomic and genomic scientists to present data in the future that will have impact to the life science area., This work was supported by grants from the Swedish Academy of Pharmaceutical Sciences, C-HPP (HUPO), Swedish Research Council, the Swedish Foundation for Strategic Research (SSF, TOTAL AMI), Vinnova, Ingabritt & Arne Lundbergs forskningsstiftelse, and by the Crafoord Foundation.
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- 2013
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