Author: "Goran Petrovski" - Searchworks@Jio Institute Digital Library Search Results

319 results on '"Goran Petrovski"'

201. Clinical and molecular markers in retinal detachment—From hyperreflective points to stem cells and inflammation

Author: Miriam Kolko, Richárd Nagymihály, Natasha Josifovska, Greg Russell, Domagoj Ivastinovic, Xhevat Lumi, Endre Kristóf, Boris Malyugin, Goran Petrovski, Mária Szatmári-Tóth, and Natalia S. Anisimova
Subjects: Male, Pathology, Physiology, medicine.medical_treatment, CD34, Apoptosis, Retinal Pigment Epithelium, Pathology and Laboratory Medicine, Stem cell marker, White Blood Cells, Animal Cells, Immune Physiology, Medicine and Health Sciences, Immune Response, Innate Immune System, Multidisciplinary, Microglia, Stem Cells, Middle Aged, medicine.anatomical_structure, Cytokine, Cell Processes, Medicine, Cytokines, Retinal Disorders, Female, Cellular Types, Anatomy, medicine.symptom, Stem cell, Research Article, Adult, medicine.medical_specialty, Science, Immune Cells, Ocular Anatomy, Immunology, Surgical and Invasive Medical Procedures, Glial Cells, Inflammation, Retina, Signs and Symptoms, Phagocytosis, Diagnostic Medicine, Ocular System, medicine, Humans, Eye Proteins, Microglial Cells, Aged, Blood Cells, business.industry, Macrophages, Retinal Detachment, Biology and Life Sciences, Epithelial Cells, Cell Biology, Molecular Development, Nestin, Antigens, Differentiation, eye diseases, Ophthalmology, Immune System, sense organs, business, Developmental Biology
Abstract: PurposeRetinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment.Methods12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin).ResultsOCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs.ConclusionsFresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.
Published: 2019

202. Macular Hole Surgery Using Gas Tamponade—An Outcome from the Oslo Retrospective Cross-Sectional Study

Author: Goran Petrovski, Ragnheiður Bragadóttir, Ingar Stene-Johansen, and Beáta Éva Petrovski
Subjects: Pars plana, Intraocular pressure, medicine.medical_specialty, Visual acuity, visual acuity, genetic structures, Cross-sectional study, medicine.medical_treatment, lcsh:Medicine, Vitrectomy, ILM peeling, duration of symptoms, Article, macular hole size, 03 medical and health sciences, 0302 clinical medicine, medicine, gas tamponade, 030212 general & internal medicine, face-down positioning, Macular hole, business.industry, lcsh:R, General Medicine, Phacoemulsification, medicine.disease, eye diseases, Surgery, macular hole, medicine.anatomical_structure, 030221 ophthalmology & optometry, sense organs, Tamponade, medicine.symptom, business
Abstract: Purpose: The study aims to determine the anatomical success and functional outcome of pars plana vitrectomy (PPV) for macular holes (MH) performed at a single study center using a consistent procedure of internal limiting membrane (ILM) peeling, SF6 tamponade and 3 days face-down positioning. Methods: A retrospective cross-sectional study involving eyes with MHs which underwent 23- or 25-gauge PPV with or without phacoemulsification and all undergoing a 20% SF6 gas tamponade, follow-up to 6 months postoperatively were included at the Department of Ophthalmology, Oslo University Hospital and University of Oslo, Oslo, Norway (12-month study period between 1 January and 31 December 2015) Pre- and post-operative Best-Corrected Visual Acuity (BCVA) assessment, comprehensive eye examination and intraocular pressure (IOP) measurement. as well as Optical Coherence Tomography to determine the diameter of the MH and its closure were all carried out. Results: 198 consecutive eyes operated for MH (age: 69.4 &plusmn, 7.6 years, 1.6:1 female:male ratio) were included, 35.7%/48.6% had symptoms from 3&ndash, 6/6&ndash, 48 months, 5.1% had high-grade myopia, 21.5% focal VMT &lt, 1500 &micro, m with or without epiretinal membrane (ERM), and 74.0%/26.0% had phakic/pseudophakic status. Primary closure of the MH occurred in 93.3% of the patients. Lens status and length of symptoms showed no significant correlation with closure of the MH. The pre-operative logMAR visual acuity: 0.8 &plusmn, 0.3 (median: 0.7, interquartile range (IQR): 0.5&ndash, 0.8, range: 0.3&ndash, 1.7), improved significantly post-operatively: 0.4 &plusmn, 0.3 (median: 0.3, interquartile range (IQR): 0.1&ndash, 0.5, range: &minus, 0.02&ndash, 1.2). BCVA improvement of &lt, 0.2, 0.2&ndash, 0.4 and &gt, 0.4 was present in 28.3%, 27.3% and 44.4% of the treated patients. No significant median differences could be detected between the duration of the pre-operative symptoms and the pre-/post-operative visual acuity. Increased IOP was measured in 2.6% of the cases day after surgery. Conclusions: Our study found visual outcome not to be dependent upon the length of symptoms in MH patients treated by PPV all undergoing ILM peeling, SF6 tamponade and face-down positioning. The large diameter MH was not a limiting factor to achieve improved post-operative BCVA.
Published: 2019

203. Association between Mediators in the Tear Fluid and the Severity of Keratoconus

Author: Éva Rajnavölgyi, Péter Gogolák, Mariann Fodor, Goran Petrovski, Flóra Tóth, András Berta, and Bence Lajos Kolozsvári
Subjects: Adult, Male, medicine.medical_specialty, Keratoconus, genetic structures, macromolecular substances, Klinikai orvostudományok, Severity of Illness Index, Young Adult, Cellular and Molecular Neuroscience, Ophthalmology, Humans, Medicine, Eye Proteins, Tissue Inhibitor of Metalloproteinase-1, business.industry, Corneal Topography, Orvostudományok, General Medicine, Middle Aged, medicine.disease, Matrix Metalloproteinases, eye diseases, Sensory Systems, Tears, Cytokines, Intercellular Signaling Peptides and Proteins, Regression Analysis, Female, sense organs, business
Abstract: Purpose: To study the association between different types of mediators in the tear fluid and topographic indices characterizing the severity of keratoconus (KC). Methods: In this study, nonstimulated tear fluid samples were collected from 14 eyes of 11 patients with KC. The following indices were measured by corneal topography: maximum K value, average K value, Klyce/Maeda keratoconus index (KCI), Smolek/Klyce keratoconus severity index, opposite sector index, center/surround index, keratoconus prediction index and standard deviation of corneal power. The concentrations of interleukin (IL)-6, IL-13, CXCL8 (IL-8), chemokine (C-C motif) ligand 5 (CCL5, regulated and normal T cell expressed and secreted), matrix metalloproteinase-9 (MMP-9), MMP-13, tissue inhibitor of metalloproteinase-1, nerve growth factor (NGF) and epidermal growth factor were measured by cytometric bead array technology. Release of mediators was calculated from their concentrations and the volume of tears collected over 2 min. Results: Significant positive associations were found between CCL5, MMP-13 and NGF and several topographic indices. Significant negative correlations were found between IL-6 and KCI. Age-dependent associations were observed between IL-13, CXCL8, CCL5 and MMP-13 and the topographic data. Conclusion: Several correlations were observed between the mediators and the topographic indices, suggesting possible roles in the pathophysiology of KC. Our data indicate that some mediators have different effects on the severity of disease in an age-dependent manner.
Published: 2013

204. Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy

Author: Ketil Eriksen, Dóra Júlia Szabó, Andrea Facskó, Richárd Nagymihály, Zoltán Veréb, Goran Petrovski, Natasha Josifovska, and Morten C. Moe
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Alkylating Agents, Mitomycin, CD34, Vimentin, Enzyme-Linked Immunosorbent Assay, Pterygium, CXCR4, Models, Biological, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Organ Culture Techniques, SOX2, Cell Movement, medicine, Humans, CD90, Fluorescent Antibody Technique, Indirect, Cell Proliferation, biology, CD47, Mesenchymal stem cell, Mesenchymal Stem Cells, General Medicine, Hematopoietic Stem Cells, Ophthalmology, 030104 developmental biology, 030221 ophthalmology & optometry, biology.protein, Cancer research, Ex vivo, Biomarkers, Optometry
Abstract: Purpose Development of ex vivo model to study pathogenesis, inflammation and treatment modalities for pterygium. Methods Pterygium obtained from surgery was cultivated (3 months). Gravitational attachment method using viscoelastic facilitated adherence of graft and outgrowing cells. Medium contained serum as the only growth supplement with no use of scaffolds. Surface profiling of the multi-layered cells for hematopoietic- and mesenchymal stem cell markers was performed. Examination of cells by immunohistochemistry using pluripotency, oxidative stress, stemness, migration and proliferation, epithelial and secretory markers was performed. The effect of anti-proliferative agent Mitomycin C upon secretion of pro-inflammatory cytokines IL-6 and IL-8 was assessed. Results Cells showed high expression of migration- (CXCR4), secretory- (MUC1, MUC4) and oxidative damage- (8-OHdG) markers, and low expression of hypoxia- (HIF-1α) and proliferation- (Ki-67) markers. Moderate and low expression of the pluripotency markers (Vimentin and ΔNp63) was present, respectively, while the putative markers of stemness (Sox2, Oct4, ABCG-2) and epithelial cell markers- (CK19, CK8-18) were weak. The surface marker profile of the outgrowing cells revealed high expression of the hematopoietic marker CD47, mesenchymal markers CD90 and CD73, minor or less positivity for the hematopoietic marker CD34, mesenchymal marker CD105, progenitor marker CD117 and attachment protein markers while low levels of IL-6 and IL-8 secretion ex vivo , were inhibited upon Mitomycin C treatment. Conclusion Ex vivo tissue engineered pterygium consists of a mixture of cells of different lineage origin, suitable for use as a disease model for studying pathogenesis ex vivo , while opening possibilities for new treatment and prevention modalities.
Published: 2016

205. Hypoxia and inflammation in human retinal cells

Author: Kai Kaarniranta, Olli Arjamaa, Anu Kauppinen, Tamás Csont, Goran Petrovski, Niina Piippo, and Vesa Aaltonen
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, business.industry, Inflammation, Retinal, General Medicine, Hypoxia (medical), 03 medical and health sciences, Ophthalmology, chemistry.chemical_compound, 030104 developmental biology, chemistry, medicine, medicine.symptom, business
Published: 2016

206. Resvega induces autophagy and prevents ARPE-19 cell damage during proteasome inhibition

Author: Mika Reinisalo, Debasish Sinha, Ali Koskela, Goran Petrovski, Kai Kaarniranta, C. Olmiere, and Reijo Karjalainen
Subjects: Ophthalmology, Proteasome Inhibition, Chemistry, Autophagy, medicine, General Medicine, medicine.disease, Cell damage, Cell biology
Published: 2016

207. HuR/ELAVL1 expression in the human cataractous lens

Author: Goran Petrovski, Stefano Govoni, Marialaura Amadio, Nicoletta Marchesi, and Alessia Pascale
Subjects: Ophthalmology, Expression (architecture), Chemistry, Cataractous lens, General Medicine, Cell biology
Published: 2016

208. The future of stem cell and cell therapy in ophthalmology

Author: S. Ferrari, Goran Petrovski, Aboulghassem Shahdadfar, and Tara Moore
Subjects: Corneal endothelium, medicine.medical_specialty, business.industry, Genetic enhancement, General Medicine, eye diseases, Transplantation, Cell therapy, Ophthalmology, medicine.anatomical_structure, Biological property, Cornea, medicine, Eye disorder, sense organs, Stem cell, business
Abstract: ummary The anatomical and biological properties of stem cells in the eye have been the topic of indepth research over the last few decades. Enormous advances in the cell and tissue isolation and cultivation techniques, as well as molecular characterization of the different cell populations have been achieved, next to the major advances made in the bioscaffolds’ engineering for cell delivery and treatment of eye diseases. Advances in the cell and gene therapy have reached culmination with the human cornea being at the top and holding great promise in treating eye disorders. The eye is indeed a golden mine for stem cells. This session will include lectures from European experts in the field with high international recognition and large collaborative networks. Challenges in the clinical applications of cornea limbal stem cells will be described, along with advances in corneal endothelium engineering for future transplantation applications. In addition, examples of regulating the gene expression towards solving ocular surface diseases will be shown, as well as future directions hallmarking stem cell and cell therapy in ophthalmology.
Published: 2016

209. Comparative proteomic analysis of human embryonic stem cell-derived and primary human retinal pigment epithelium

Author: Zoltán Veréb, Heli Skottman, Hannu Uusitalo, Antti Jylhä, Goran Petrovski, Tanja Ilmarinen, Ulla Aapola, Roger W. Beuerman, Janika Nättinen, Jochen Rieck, Heidi Hongisto, Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, and University of Tampere
Subjects: 0301 basic medicine, Retinal degeneration, Proteomics, Proteome, Science, Cell, Human Embryonic Stem Cells, Retinal Pigment Epithelium, Biology, Mass Spectrometry, Article, Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, reproductive and urinary physiology, Multidisciplinary, Retinal pigment epithelium, Computational Biology, Retinal, Cell Differentiation, medicine.disease, Embryonic stem cell, eye diseases, Transport protein, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Gene Ontology, chemistry, Lääketieteen tekniikka - Medical engineering, embryonic structures, 030221 ophthalmology & optometry, Medicine, sense organs, biological phenomena, cell phenomena, and immunity, Visual phototransduction
Abstract: Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) provide an unlimited cell source for retinal cell replacement therapies. Clinical trials using hESC-RPE to treat diseases such as age-related macular degeneration (AMD) are currently underway. Human ESC-RPE cells have been thoroughly characterized at the gene level but their protein expression profile has not been studied at larger scale. In this study, proteomic analysis was used to compare hESC-RPE cells differentiated from two independent hESC lines, to primary human RPE (hRPE) using Isobaric tags for relative quantitation (iTRAQ). 1041 common proteins were present in both hESC-RPE cells and native hRPE with majority of the proteins similarly regulated. The hESC-RPE proteome reflected that of normal hRPE with a large number of metabolic, mitochondrial, cytoskeletal, and transport proteins expressed. No signs of increased stress, apoptosis, immune response, proliferation, or retinal degeneration related changes were noted in hESC-RPE, while important RPE specific proteins involved in key RPE functions such as visual cycle and phagocytosis, could be detected in the hESC-RPE. Overall, the results indicated that the proteome of the hESC-RPE cells closely resembled that of their native counterparts.
Published: 2016

210. Cultivation and characterisation of the surface markers and carbohydrate profile of human corneal endothelial cells

Author: Richárd, Nagymihály, Zoltán, Veréb, Réka, Albert, Laura, Sidney, Harminder, Dua, Andrew, Hopkinson, and Goran, Petrovski
Subjects: Gene Expression Regulation, Cell Survival, Reverse Transcriptase Polymerase Chain Reaction, Endothelium, Corneal, Carbohydrates, Humans, DNA, Eye Proteins, Flow Cytometry, Biomarkers, Cells, Cultured
Abstract: The study aims to characterise human corneal endothelial cell (HCEnC) cultures generated by the peel-and-digest method based on their surface protein/carbohydrate expression pattern.Quantitative polymerase chain reaction was used to compare expression of vimentin, CD90, Cytokeratin-19, ZO-1 and Claudin 14 in cultured HCEnC and cell line B4G12 versus stromal cells. Fluorescence-activated cell sorting was used to assess surface protein distribution of cultured and uncultured HCEnC. Distribution of surface proteins/carbohydrates was visualised by immunofluorescent and lectin staining.Human corneal endothelial cell and B4G12 showed lower expression level for vimentin, CD90, Cytokeratin-19 compared with stromal cells; while ZO-1 was expressed in endothelial cells, Claudin 14 was detected in B4G12 only. Fluorescence-activated cell sorting analyses revealed CD166, CD47, CD44, CD54, CD73, CD90, CD105, CD106, CD112, CD146 and CD325 to be present, with CD34 to be absent from cultured HCEnC. Freshly isolated, non-cultivated HCEnCs were CD90, CD73, CD146 and CD325 positive. Carbohydrates were detected by lectins LCA, PHA E, PHA L, PSA, sWGA, Con A, RCA 120 and WGA, but cultured HCEnC showed negative for GSL I, SBA, DBA, PNA and UEA I.Cultures established by the peel-and-digest method are probably not prone to stromal contamination, but the cells are likely to undergo endothelial-to mesenchymal transition as suggested by apparent morphological changes.
Published: 2016

211. Two dietary polyphenols, fisetin and luteolin, reduce inflammation but augment DNA damage-induced toxicity in human RPE cells

Author: Maria Hytti, Eveliina Korhonen, Paavo Honkakoski, Anu Kauppinen, Dóra Júlia Szabó, Niina Piippo, Kai Kaarniranta, and Goran Petrovski
Subjects: 0301 basic medicine, Programmed cell death, Antioxidant, Flavonols, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Inflammation, Retinal Pigment Epithelium, Pharmacology, Biology, medicine.disease_cause, Biochemistry, Proinflammatory cytokine, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sirtuin 1, medicine, Humans, 03.02. Klinikai orvostan, Luteolin, Molecular Biology, Etoposide, Flavonoids, Nutrition and Dietetics, Cell Death, Anti-Inflammatory Agents, Non-Steroidal, Retinitis, Acetylation, 030104 developmental biology, chemistry, Apoptosis, Dietary Supplements, 030221 ophthalmology & optometry, Cytokines, medicine.symptom, Tumor Suppressor Protein p53, Fisetin, Oxidative stress, DNA Damage
Abstract: Plant-derived polyphenols are known to possess anti-inflammatory and antioxidant effects. In recent years, several studies have investigated their potential benefits for treating chronic diseases associated with prolonged inflammation and excessive oxidative stress, such as age-related macular degeneration (AMD). Previously, two polyphenols, fisetin and luteolin, have been reported to increase the survival of retinal pigment epithelial (RPE) cells suffering from oxidative stress as well as decreasing inflammation but the benefits of polyphenol therapy seem to depend on the model system used. Our aim was to analyze the effects of fisetin and luteolin on inflammation and cellular viability in a model of nonoxidative DNA damage-induced cell death in human RPE (hRPE) cells. Pretreatment of ARPE-19 or primary hRPE cells with the polyphenols augmented etoposide-induced cell death as measured by the lactate dehydrogenase and 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. However, the treatment was able to reduce the release of two proinflammatory cytokines, IL-6 and IL-8, which were determined by enzyme-linked Immunosorbent assay. Analyses of caspase 3 activity, p53 acetylation and SIRT1 protein levels revealed the apoptotic nature of etoposide-evoked cell death and that fisetin and luteolin augmented the etoposide-induced acetylation of p53 and decreased SIRT1 levels. Taken together, our findings suggest that the cytoprotective effects of fisetin and luteolin depend on the stressor they need to combat, whereas their anti-inflammatory potential is sustained over a variety of model systems. Careful consideration of disease pathways will be necessary before fisetin or luteolin can be recommended as therapeutic agents for inflammatory diseases in general and specifically AMD.
Published: 2016

212. Role of Human Corneal Stroma-Derived Mesenchymal-Like Stem Cells in Corneal Immunity and Wound Healing

Author: Goran Petrovski, Anita Boratkó, Réka Albert, Andrea Facskó, Zoltán Veréb, Morten C. Moe, Csilla Csortos, Ole Kristoffer Olstad, and Szilárd Póliska
Subjects: Male, 0301 basic medicine, Chemokine, Corneal Stroma, Cellular differentiation, Models, Biological, Article, Cornea, 03 medical and health sciences, 0302 clinical medicine, Humans, Regeneration, CD90, Cells, Cultured, Aged, Aged, 80 and over, Wound Healing, Multidisciplinary, biology, Gene Expression Profiling, Corneal Diseases, Regeneration (biology), Mesenchymal stem cell, Cell Differentiation, Mesenchymal Stem Cells, Orvostudományok, Middle Aged, Flow Cytometry, High-Throughput Screening Assays, Cell biology, 030104 developmental biology, Antigens, Surface, Immunology, 030221 ophthalmology & optometry, biology.protein, Cytokines, Female, Egészségtudományok, Stem cell, Wound healing
Abstract: Corneal tissue regeneration is of crucial importance for maintaining normal vision. We aimed to isolate and cultivate human corneal stroma-derived mesenchymal stem-like cells (CSMSCs) from the central part of cadaver corneas and study their phenotype, multipotency, role in immunity and wound healing. The isolated cells grew as monolayers in vitro, expressed mesenchymal- and stemness-related surface markers (CD73, CD90, CD105, CD140b) and were negative for hematopoietic markers as determined by flow cytometry. CSMSCs were able to differentiate in vitro into fat, bone and cartilage. Their gene expression profile was closer to bone marrow-derived MSCs (BMMSCs) than to limbal epithelial stem cells (LESC) as determined by high-throughput screening. The immunosuppressive properties of CSMSCs were confirmed by a mixed lymphocyte reaction (MLR), while they could inhibit proliferation of activated immune cells. Treatment of CSMSCs by pro-inflammatory cytokines and toll-like receptor ligands significantly increased the secreted interleukin-6 (IL-6), interleukin-8 (IL-8) and C-X-C motif chemokine 10 (CXCL-10) levels, as well as the cell surface adhesion molecules. CSMSCs were capable of closing a wound in vitro under different stimuli. These cells thus contribute to corneal tissue homeostasis and play an immunomodulatory and regenerative role with possible implications in future cell therapies for treating sight-threatening corneal diseases.
Published: 2016
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213. Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE-19 Cells

Author: Céline Olmiere, Kai Kaarniranta, Mika Reinisalo, Goran Petrovski, Debasish Sinha, Reijo Karjalainen, Ali Koskela, and School of Pharmacy, Activities,Biologian laitos / Biologian laitoksen toiminta
Subjects: 0301 basic medicine, autophagy, Cell Survival, Leupeptins, p62/SQSTM1, lcsh:TX341-641, Biology, Resveratrol, resveratrol, Article, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fatty Acids, Omega-3, Stilbenes, medicine, LC3, Humans, Enzyme Inhibitors, Cell damage, Nutrition and Dietetics, Autophagy, RNA-Binding Proteins, Bafilomycin, medicine.disease, Cytoprotection, proteasome, omega-3, Cell biology, 030104 developmental biology, Gene Expression Regulation, Biochemistry, chemistry, Proteasome, Cell culture, Dietary Supplements, Proteasome inhibitor, Macrolides, Microtubule-Associated Proteins, lcsh:Nutrition. Foods and food supply, 030217 neurology & neurosurgery, Food Science, medicine.drug
Abstract: Article, Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62) and LC3 (microtubule-associated protein 1A/1B-light chain 3) were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage., published version, peerReviewed
Published: 2016

214. Erratum

Author: Sascha Martens, Masashi Narita, Rajkumar Cheluvappa, Kevin A. Roth, Ta Yuan Chang, Kartik Venkatachalam, Chang-Shen Lin, Sharon G. Adler, Flaminia Pavone, Dianwen Ju, Michelle A. Ozbun, Michael R. Duchen, Shu Feng Zhou, Wei-Guo Zhu, Aaron Di Antonio, Defeng Wu, Taixing Cui, Xu Guang Guo, Zhiping Xie, Lorena García Nannig, Eloy Bejarano, Stéphane D. Lemaire, Petro Starokadomskyy, Hyung Ryong Kim, Mario Pinar, Rebecca T. Marquez, Zvenyslava Husak, Anthony R. White, Joanna Poulton, Antonis S. Zervos, Shweta Sharma, Jochen Walter, Nicholas T. Ktistakis, Christopher H.K. Cheng, Sunhee Lee, Yuen Li Chung, Howard O. Fearnhead, Young J. Oh, Ivano Amelio, Guillermo A. Blanco, Jan Simak, Junfang Wu, Yingying Lu, Mary Kate McBrayer, Soo Han Bae, Ichizo Nishino, Hong-Ming Hu, Benjamin R. Underwood, Tomonori Kimura, Zexian Liu, Savithrama P. Dinesh-Kumar, Qian Yang, Andreas Kern, Hsing Jien Kung, Jan B. Parys, Cam Patterson, Celine Perier, Toshiro Okazaki, Daisuke Koya, Avinash Sonawane, Cédric Cleyrat, Robert I. Richards, Kai Y. Soo, Rodrigo Mora-Rodriguez, Gigi N.C. Chiu, Moon Moo Kim, Vladimir N. Uversky, Shengfang Ge, Matthew T. V. Chan, Irene Kyrmizi, Lara Gibellini, Ángela M. Valverde, Erik Norberg, Fan Zhang, Jan C. Koch, Alec C. Kimmelman, Jingfang Ju, Jie Bai, Lei Duan, Paulina Ordonez, Shuwen Liu, Wolfdieter Springer, Eric Deutsch, Elena Ortona, Jose M. Seguí-Simarro, Vinay Choubey, Leonidas Stefanis, Robert G. Hawley, Claudia Bincoletto, Xian-Hui He, Zhifen Yang, Thomas M. Durcan, Martine Biard-Piechaczyk, Kui Lin, Hongming Pan, Konstantinos Kambas, Cristina Muñoz-Pinedo, Marta Magariños, Yoshinori Takahashi, Adrienne M. Gorman, Philippe Gailly, Takahiko Akematsu, Justine D. Mintern, Liang Xu, Tetsuo Shioi, Luis M. Botana, Yule Liu, Yong Yeon Cho, Jinzhi Lei, Eung Kweon Kim, Alakananda Basu, Vikash Kumar Dubey, Candelaria Gomez-Manzano, Avital Eisenberg-Lerner, Chuan-Ming Xie, Wenjie Dai, Pedro Gonzalez-Alegre, Maria Condello, Zheng-Hong Qin, Zhi-Min Yuan, Catherine Andreadi, Anna Rita Migliaccio, Chong Liu, Michaël Boyer-Guittaut, Melanie Denizot, Esperanza Arias, Greet Van den Berghe, Guomei Tang, Timothy P. Devarenne, Xianyong Sheng, Louis R. Lapierre, J. Wade Harper, Zuzana Storchova, Aileen R. Ariosa, Sug Hyung Lee, Qi Zeng, Godefridus J. Peters, Daniela L. Papademetrio, Alexandre Arcaro, Zhiyuan Yao, Pablo Iribarren, Mario Chiariello, Maria Rosaria Torrisi, Parimal Karmakar, Yong Huang, Sebastiano Sciarretta, Nathalie Andrieu-Abadie, László Fésüs, Patricia Boya, Ruediger Rudolf, Leonor Miller-Fleming, Vasilis J. Promponas, Juan Segura-Aguilar, Paula Daza, Shiow Ju Lee, Songshu Meng, Paul K. Herman, Ludwig Eichinger, Ye-Guang Chen, Kay F. Macleod, Thomas Simmet, Cristina Corral-Ramos, Claudio Brancolini, Jun Ren, Ying Jiang, Benoît Derrien, Xiao Fang Yu, Qing Zhong, Zong Wan Mao, Xingcong Ren, Armando A. Genazzani, Marina Pierdominici, Sanbing Shen, Sandra Moreno, Hana Algül, Maurizio Renna, Ricardo Sánchez-Prieto, Ashok K. Saluja, Yasuo Uchiyama, Pope L. Moseley, Victor E. Dosenko, Chun-Feng Liu, Bakhos A. Tannous, Efthimios Sivridis, Baharia Mograbi, Michiko Shintani, Amanda S. Bess, Rodrigo Portes Ureshino, Avnika A. Ruparelia, Paul Hofman, Eric Chevet, Martha M. Monick, Hong Gang Wang, Daping Fan, Jorge Moscat, Giuseppe Matarese, Consiglia Pacelli, Young Seok Cho, Miriam Cnop, Stefan Böckler, Nikolai V. Gorbunov, Christina J. Sigurdson, Hang T.T. Nguyen, Aurélie François, Katarina Kågedal, Sam Gandy, Silvia Campello, Alain Bruhat, Filomena Fiorito, Hua Feng, Man Tian Mi, Gian Maria Fimia, Masaki Tanaka, Guofei Zhou, José L. Crespo, Heinz Jungbluth, Anna Chiara Nascimbeni, Arianne L. Theiss, Svetlana Dokudovskaya, Mar Lorente, Sergio Lavandero, Yu Xia Zhao, Fangming Lin, Yuchen Feng, Gad Galili, Silvia Cetrullo, Paula I. Moreira, Dhyan Chandra, Dimitrios J. Stravopodis, Roberta A. Gottlieb, Gregory A. Taylor, Longping Wen, Faqiang Li, Marco Sardiello, Umesh K. Jinwal, Francesca Belleudi, Lan Tan, Livia Di Renzo, Tamas Korcsmaros, Xinbing Sui, Douglas R. Green, Guillermo Mazzolini, Hervé Le Stunff, Kelly S. Doran, Mary E. Choi, Carlos S. Subauste, Natalia Rodriguez-Muela, Nicholas J. Talbot, Marta Palmieri, Sonia Hernández-Tiedra, Ligia C. Gomes, Irving M. Shapiro, Makoto Ubukata, Mario P. Tschan, Baris Bingol, Benjamin Loos, Terry Kwok, Luca M. Neri, Sreejayan Nair, Michele Wolfe Bianchi, Ralf Erdmann, Alexander Greenhough, Neeraj Vij, Jeong Hun Kim, Satoaki Matoba, Bo Liu, George R. Beck, Michael Moore, Vrajesh V. Parekh, Kyle A. Bauckman, Li-Lin Du, Mikihiro Fujiya, Yan G. Zhao, Renaud Legouis, Jiangwei Zhang, Kailiang Jia, Nadezda Apostolova, Sehamuddin Galadari, Khosrow Adeli, Ming Yong Zhang, Carmela Fusco, Angel Ortega, Anna Pensalfini, Zsuzsanna Szatmári, Marco Tafani, Isabella Ceccherini, Anne Hamacher-Brady, Kuen Jer Tsai, Anita C. Truttmann, Franco Fortunato, Keisuke Miyazawa, Chunhai Fan, Berge A. Minassian, Jian Zhang, Frank A. Anania, Heesun Cheong, Amal O. Amer, Ing Swie Goping, Won-Ki Huh, Anita Solhaug, Joan Cl ria, Laurent Le Cam, Seungmin Hwang, Karen L. Wright, Antonella De Matteis, Troy T. Rohn, Ivana Bjedov, Subbiah Pugazhenthi, Hal E. Broxmeyer, Xue Yuan Bai, Koenraad Norga, Minnie M. Sarwal, Daniel F. Schorderet, Ioannis P. Nezis, Mei Qing Wang, Jun Hee Lee, Yong J. Lee, David A. Tumbarello, Fernando Macian, Joern Dengjel, Dmitry V. Bulavin, Andrew J. Halayko, Ben Berkhout, Aseem Pandey, Santosh Kesari, Karin Przyklenk, Elena V. Tchetina, Matthew L. Albert, Laura Segatori, Joel N. Meyer, Mustapha Rouis, Éva Margittai, Ashish Jain, David Hahn, Thomas Vaccari, Lori R. Covey, Ghanshyam Swarup, Kuo Yang Huang, Gennaro Napolitano, Sam W. Lee, Seong Who Kim, Alberto Anel, Vladimir V. Rogov, Laura A. Carleton, Amine Belaid, Byoung Kuk Jang, Sheng-Han Kuo, Patricia L. Yeyati, Jae U. Jung, Teresa Zoladek, Sabrina Di Bartolomeo, Clémence Richetta, Peixin Yang, Daniela Trisciuoglio, Hye Seung Jung, Katsumi Higaki, Eui-Bae Jeung, Ivan Topisirovic, Isabella Caniggia, Susan E. Logue, Issidora S. Papassideri, Lynda A. Morrison, Caihong Wang, Graeme Sargent, Beth Levine, Mingxiang Ye, David M. Sabatini, Consuelo Amantini, Julio A. Aguirre-Ghiso, Lawrence H. Boise, Patricia Silvia Romano, Sean T. Sweeney, Takayuki Tsukuba, Reinhard Dechant, Benoit Barbeau, Marta Martinez-Vicente, Kuo How Huang, Edésio José Tenório de Melo, Faustino Mollinedo, José M. Fuentes, Joaquín Jordán, Dong-Hyung Cho, Dexian Zheng, Jeroen J.M. Hoozemans, Zhong Chen, Waleska Kerllen Martins, Abraham Acevedo Arozena, Marcos P. Thomé, Gordon C. Shore, Fabienne C. Fiesel, Teng Jiang, Feng Han, Marc Poirot, Anne Sophie Nicot, Eileen White, Olivier Feron, Arthur I. Cederbaum, Wen Bin Qian, Yingjie Sun, Rejko Krüger, Shingo Kajimura, Jianzhen Xu, Shang Der Chen, Maximiliano G. Gutierrez, Zhengping Yu, Jiaren Sun, Utpal Sen, Giovanna Galliciotti, Hilde Nilsen, Benjamin T. Kopp, Benedikt Westermann, Inmaculada Galindo, Eeva-Liisa Eskelinen, Rubem F. S. Menna-Barreto, Guillermo Mariño, Andrea Ballabio, Izabela Poprawa, Yanjin Zhang, Clay F. Semenkovich, Martin E. Fernandez-Zapico, Helin Vakifahmetoglu-Norberg, Hongchi Jiang, Eugenia Morselli, Angelo A. Manfredi, Marianne Boes, Han-Jung Chae, Covadonga Alonso, Min Chen, Safia Costes, David Kessel, Rakesh Kumar, Yang Zhang, Reinhild Prange, Vassiliki E. Mpakou, Laura Santambrogio, Javier E. Irazoqui, Anna Skwarska, Junichi Sadoshima, Rika Umemiya-Shirafuji, Michael I. Koukourakis, Norma Maugeri, Yuqing Wang, Pedro R. Cutillas, Jiqin Lian, Jiri Stulik, Takashi Ueno, Craig Montell, Rena Balzan, Meiyan Jin, Mara C. Duncan, Cathleen R. Carlin, Yasuo Yanagi, Maite G. Fernandez-Barrena, Yuyan Xiong, Martin Graef, Wei Yuan Yang, Renato V. Iozzo, Mark Screen, Patrick Brest, Haichao Wang, Ming Tan, Werner J. Kovacs, Weili Shen, Alessandro Fraldi, Paul Saftig, Alberto Faggioni, Krisna Prak, Christos E. Zois, Timothy E. Weaver, Marc Lecuit, Yu-Ying He, Michele Caraglia, Walter Balduini, M. Isabel G. Roncero, B. Schneider, Monika Cahova, Mathias Faure, Chihiro Sasakawa, Simon Michaeli, Sandy Giuliano, Dario C. Altieri, Eun-Kyeong Jo, Myung-Shik Lee, Carol Imbriano, John H. Brumell, Gustavo H. Goldman, Yan Wang, Junyan Shi, Quan Chen, Jayanta Debnath, Yonggeun Hong, Mohamed Amessou, Richard W. Wong, Robert E. Burke, Mauro De Santi, Trevor G. Shepherd, Anna Maria Joseph, Wouter G. van Doorn, Erkang Fei, Huey Lan Huang, F. Gisou van der Goot, Xinfeng Liu, Alexandru Almasan, Akiko Maeda, Yu Qiu, Yaohua Wu, Annie Sittler, Wen-Xing Ding, Wenhua Zhu, Hung-Jen Liu, Moisés Martínez-Velázquez, Jeffery S. Cox, Seung Yong Yoon, Concepcio Marin, Wilian A. Silveira, Fulvio Chiacchiera, W. Douglas Fairlie, Jian Xin Gao, Shuilong Leng, Nathan R. Brady, Josef M. Penninger, Puran Singh Sijwali, Florian Gruber, Tibor Vellai, Jiunn-Liang Ko, Laura Korhonen, Slimane Ait-Si-Ali, Hirokazu Arimoto, Alberto M. Martelli, Teresa L. M. Thurston, Chuanshan Xu, Kathrin Pallauf, Eduardo Couve, Shweta Saran, Lionel Blanc, Maylin Almonte-Beceril, Yong-Keun Jung, Lena Lavie, Junsoo Park, Camilla Palumbo, Claire H. Mitchell, Sophie Pattingre, Guillermo Velasco, Steve S.-L. Chen, Xiu-Fen Ming, Xin Qi, Vania Gelmetti, Nicolas Dupont, Soraya S. Smaili, Chinnaswamy Jagannath, Uta Dahmen, Daolin Tang, Rodrigo Franco, John H. Kehrl, Xiaonan Dong, Carsten Sachse, Jeff Kuret, Genzou Takemura, Supawadee Sukseree, Joëlle Botti, W. Haung Yu, Aurelia Lugea, Scott J. Bultman, Divaker Choubey, Frank A. Sinicrope, You-Wen He, Jian Wu, Yoshitaka Isaka, Geert Bultynck, Giuseppe Merla, Luigi Maiuri, Sonia Melino, Hannelore Maes, Daniele Lettieri Barbato, Ian G. Ganley, Zhihong Yang, Daniel Hofius, Kimberly McCall, Peiwen Chen, Istvan Lekli, Alicia Rosello, Eric Ghigo, Atsushi Kuno, Iman Tavassoly, Chris Albanese, Agustín Aranda, Salvatore Pepe, Hong Jiang, Henri Batoko, Giovanna Elvira Granato, Vincent Zecchini, Stephen E. Girardin, Maria T. Diaz-Meco, Philippe Marambaud, G. Amadoro, Sangeeta Khare, Christelle Koechlin-Ramonatxo, Emery H. Bresnick, Christian Behl, Mikio Nishimura, Julien Puyal, Wenjie Guo, Hsinyu Lee, Carolyn M. Sue, Derrick Gibbings, Alina Maloyan, Philippe Pierre, Serge N. Manié, Gerry Melino, Elizabeth A. Woodcock, Roberto Ciarcia, Liwen Jiang, Michael C. Kruer, Vladimir Trajkovic, Yunjiao Zhang, Nina Raben, Beata Pajak, Michael J. 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Sylvester, Daniel E. Voth, Canhua Huang, Andrea Boman, Gérard Lizard, Rut Valdor, Marc Flajolet, Graham S. Taylor, Nicola Di Daniele, Leonardo H. Travassos, Ying Yang, Anumantha G. Kanthasamy, Hasan Mukhtar, Yuhua Zhu, Noor Gammoh, Ignacio Vega-Naredo, Victoria Ryabovol, Sara W. Bird, Gang Min Hur, Qun-Ying Lei, Fan Yi, Laura Caberlotto, Maria F. Galindo, Bilal Piperdi, Leonidas C. Platanias, P. Hande Özdinler, Régis Delage-Mourroux, Julio Madrigal-Matute, Xu Liu, Nagio Takigawa, Aurora Pujol, Marta Margeta, Hee Jeong Kong, Christian Behrends, Michael Thumm, Shirley Luckhart, Emilio Clementi, John W. Steele, Liliana Schaefer, Philip L. Lorenzi, Chao-Yu Miao, She Min Lu, Jane E. Ishmael, Jin Hyoung Kim, V. Izzo, Yanming Wang, Balindiwe J.N. Sishi, Vincent Galy, Andras Perl, Shouqing Luo, Giovanni Vitale, Yongsheng Che, Rodrigo Troncoso, Liu Yang, Thomas J. Begley, Sebastien G. Bouret, Elizete Rizzo, James M. Piret, Junjun Wang, Herman P. Spaink, Thomas S. Jacques, Robin F. B. 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Tait, Aimee L. Edinger, Jeffrey P. MacKeigan, Paul A. Ney, Mireia Niso-Santano, Valeria Crippa, Andreas S. Reichert, Isabelle Dugail, Jon D. Lane, Farida V. Minibayeva, Gianluca Tettamanti, Scott Pattison, Péter Lõrincz, Kamal Chowdhury, Ulrich E. Schaible, Maria Agnello, Paolo Pinton, Niels Jessen, Lei Guo, Kwang-Huei Lin, David N. Zacks, Ying Jan Wang, Simone Fulda, John J. Lemasters, Andrea Viale, Anna Maria Marconi, Valerie Askanas, Yoshitaka Nagai, François M. Vallette, Joan K. Heath, Srinivasan Dasarathy, Soo-Youl Kim, Günter U. Höglinger, Tamara Kravic-Stevovic, Iraide Alloza, Tiago F. Outeiro, Ana Serrano-Puebla, Elena A. Minina, Terrence M. Donohue, Ming Guo, Alexandra Giatromanolaki, Abdel Halim Harrath, Ken Sato, Anne Elisabeth Theron, Usha P. Andley, Claudio Cardinali, Maija Pesonen, Penny E. Lovat, Chanhee Kang, Sabah N. A. Hussain, Lisa A. Brennan, Jose A. Tapia, Christoph Becker, Huixin Yu, Pei-Yu Wang, Bertrand Joseph, Zhen Yan, Georgia Minakaki, Ricardo Escalante, Ralph A. Nixon, Katsuhiko Asanuma, M. Helena Vasconcelos, David J. Reiner, Shengkan Jin, David Dávila, Theo Rein, Balakrishna L. Lokeshwar, Antonio Miranda-Vizuete, Carl Ward, Vito Turk, Frederick D. Quinn, Katja Köhler, Masaru Harada, Kathleen Boesze-Battaglia, Fraser P. Coxon, Paulo R. Jannig, Miguel A. Peñalva, Manjula Kalia, Marco Corazzari, Chunjuan Song, Xianghua Yan, Lilach Toker, Benjamin Pineda, Vanessa Ginet, Ye Xu, Chun Jung Chen, Roberto Towns, Amy A. Kiger, Rajagopal Ramesh, Maria Rita Rippo, Joseph A. Hill, Boris Zhivotovsky, Peter Speck, Ya Hua, Peter J. Roach, Fabio Penna, Kasper M.A. Rouschop, Jeng-Jer Shieh, Maria Angeles Mena, Mei Zhao, Sonia Rocha, Xin Wen, Sylvain Lefort, Michael Scharl, Ramnik J. Xavier, Alan Cheng, Marion Bouchecareilh, Stella Y. Lee, Maria Xilouri, Qi Chen, Claudia Spies, Pengfei Ge, Natascia Ventura, Luca Galluzzi, Yau Hung Chen, Jing Pu Zhang, Diego Albani, Dingzhong Tang, Nikolai Engedal, Stefania Meschini, Maria Lyngaas Torgersen, Shibu M. Poulose, Jean-Paul Decuypere, Ziheng Xu, Jocelyn Laporte, Thierry Arnould, Albert Haas, Ida J. van der Klei, Agustín Hernández, Dong Wook Shin, Per E. Stromhaug, Valentín Ceña, Ugo Pagnini, Karolina Pakos-Zebrucka, Blagovesta Popova, Lisa M Lindqvist, Sangita C. Sinha, Yuguang Shi, Zvonimir Marelja, Robin Candau, Xin Wang, Evelina Gatti, Olatz Pampliega, Michael P. Lisanti, Elena Tamagno, Mei Lan Tan, Gary Warnes, Zdena Palková, Shigeomi Shimizu, Ingo Schmitz, Tino Kurz, Soledad Matus, Gopal Chakrabarti, Joseph J.Y. Sung, Beáta G. Vértessy, Giuliana Cassinelli, Giovanni Benard, Yin Chen, Emma Colucci-Guyon, Craig Blackstone, Lizhi Cao, Sebastian Schuck, Qingqiu Gong, Theocharis Panaretakis, Jayoung Choi, Sven R. Carlsson, Libuše Váchová, Raymond Chuen-Chung Chang, Yang Liu, Zheng Dong, Qinghua Shi, Hélène Duez, Tiziana Bachetti, Axel H. Schönthal, Sumit Sahni, Bo Wang, Naomichi Matsumoto, Markus Rehm, Liliana Torosantucci, Toren Finkel, Yi Hsin Tseng, Hsiang Cheng Chi, Fang Lin, Tony George Jacob, Ju-Xian Song, Alessandro Fanzani, Marc Tatar, Paola Costelli, Rubén Gómez-Sánchez, Yunfei Wen, Juha J. Hulmi, Francesca V. Mariani, Min Zeng, Chiung Chyi Shen, Carine Michiels, Yan Burelle, Andreas L. Serra, Goran Petrovski, Kwang Woon Kim, Paula Ludovico, Darius Ebrahimi-Fakhari, Yee Joo Tan, Luisa De Martino, Alvaro Glavic, Pierre Lapaquette, Edmund B. Rucker, Andreas Mayer, Shigeko Yamashiro, Scott K. Powers, Robert M. Gogal, Ebru Goncu, Yuichiro J. Suzuki, Anna Maria Giammarioli, Claudio Hetz, Eric H. Baehrecke, Cheryl L. Walker, Cinzia Lanzi, Deepti S. 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St. Clair, Darren J. Moore, Michael Lee, Katia Aquilano, Norbert Frey, Tibor Kovács, Ru Jeng Teng, Federico Pietrocola, Alfredo Criollo, Nadia Jaber, Walter T. Klimecki, Xiaohong Zhuang, Beata Sikorska, Inmaculada Tasset-Cuevas, Iwona A. Ciechomska, Robert C. Dickson, Haruo Kanno, Hua She, Xiaolei Xu, Maria Laura Avantaggiati, Isei Tanida, Jun Li, Diego Pérez-Rodríguez, Agnieszka Bagniewska-Zadworna, Viktor I. Korolchuk, Thirumala-Devi Kanneganti, Simone Nardin Weis, Thorsten Nürnberger, Guanghui Wang, Luigi Puglielli, Valina L. Dawson, Santosh Chauhan, Carole Kretz-Remy, Po-Yuan Ke, Haijun Bao, Patrícia Sampaio Tavares Veras, Sharad Kumar, Guo-Qiang Chen, Congfeng Xu, Annie M. Joubert, Diego L. Medina, Andrea Hamann, Christian Münz, Hongchuan Jin, Zhen Chen, Cristina López-Vicario, Seung Il Choi, Ivanka Markovic, Ronit Pinkas-Kramarski, Lei Jin, Yonghyun Kim, Michael J. Clague, James D. 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Span, Megumi Inomata, Ivica Arsov, Zhi-Xiang Xu, Saeid Ghavami, Tania C. Felizardo, Konstanze F. Winklhofer, Weidong Han, Jianhua Zhang, Eva Maria Mandelkow, Lydia Alvarez-Erviti, Wanderley de Souza, Pawel P. Liberski, Yang Sun, Cornelia M. Weyand, William D. Hill, Eric J. Brown, Christopher M. Adams, Felix Randow, Jose Luis Rosa, Ivan R. Nabi, Patricia V. Aguilar, Laure Aurelian, Jae-sung Bae, Gábor Juhász, Hing Y. Leung, Karla Kirkegaard, Peter J. O'Dwyer, Daniele Bergamaschi, Thomas Farkas, Tsunenori Saito, Laura Knuppertz, Leyuan Liu, Dongxu Fu, Liesu Meng, Alon Kahana, Viktor Billes, Shohreh Issazadeh-Navikas, Ljubica Harhaji-Trajkovic, Xiangguo Liu, Takahiro Yamada, Ciro Isidoro, Huiping Zhou, William A. Dunn, Takeshi Into, Giampietro Viola, Eumorphia G. Konstantakou, G. William Wong, Peter W. Szlosarek, Jeffrey S. Isenberg, Mikkel H. Vendelbo, Zuzana Papackova, Carlos B. 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Heinzen, Xiangmei Chen, Nihal Altan-Bonnet, Sung Sik Lee, Hai Jie Wang, Catherine Dargemont, Jie Du, Sofie Claerhout, Edmond Chan, Yi Sun, Xiangbo Wan, Paul Lingor, Shilpa Buch, Gerald M. McInerney, Zhenlong Wu, Guo Chang Zhang, Iain A. McNeish, Suresh Awale, Mark P. Mattson, Srinivasa Subramaniam, Wuhan Xiao, Katsuhiko Mikoshiba, Giancarlo Parenti, Bruno Miguel Neves, Benjamin Dehay, Fatima Teixeira-Clerc, Patricia Huebbe, Calvin K. Yip, Ryan J. Schulze, Pallabi Sarkar, Vladimir I. Titorenko, Johanna Laukkarinen, Martin E. Gleave, Veronika Stoka, Pascal Genschik, Karen Brown, Zhaoliang Su, Walter Malorni, Arlette Darfeuille-Michaud, Vincent C. O. Njar, Jeffrey E. Pessin, Thomas Wileman, Alexander J. Whitworth, Stefano Santaguida, Gustavo A. Nader, Gláucia Maria Machado-Santelli, Marie-Josée Hébert, Skye C. McIver, Scott A. Soleimanpour, Jia-Hong Lu, Fei Liu, Yu Wang, Elisa Motori, Chad A. 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Edelstein, Julie Gavard, Miklós Sass, Maria Chiara Maiuri, Zhendong Zhao, Pu Duann, Julián Pardo, Atsuhiro Ichihara, Lester M. Davids, Swamynathan Ganesan, Shengyun Fang, Hernando Gomez, Yun Chau Long, Mark J. Czaja, Arnaud Echard, Pilar Gonzalez-Cabo, Chuanyong Guo, Katherine L. Cook, Isabel Varela-Nieto, Li Yu, Yi Ran Huang, Binfeng Lu, Athanassios D. Velentzas, Koji Yamanaka, Giuseppe Russo, Ester M. Hammond, Kelsey B. Law, Sheng Li, Samisubbu R. Naidu, Michael E. Boulton, Anna-Mart Engelbrecht, Ba-Bie Teng, Zixu Mao, Vania M.M. Braga, Núria S. Coll, Eliana M. Coccia, Akihisa Abe, V. Ashutosh Rao, Nava Segev, Regina Menezes, Zufeng Ding, Hyman M. Schipper, Álvaro F. Fernández, Peter K. Kim, Lucia Micale, Biplab Dasgupta, Nazzy Pakpour, Janna L. Morrison, Yue Qin Chen, Rolf J. Craven, Zvulun Elazar, Anders Aune Tveita, Lian Li, Hsueh Fen Juan, Ulrich Koenig, Qiang Shi, Harald W. Platta, Michele S. Swanson, Olga V. Voitsekhovskaja, Bruce H. 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Kumar, Deok Ryong Kim, Jianjie Ma, Sang Won Suh, Guido Kroemer, Klára Megyeri, Michael N. Sack, Heinrich Taegtmeyer, Gilles Pagès, Gabriella Marfe, Gregg L. Semenza, Karine G. Le Roch, Marisa Brini, Marina Bouché, Oliver Kepp, Vinay V. Eapen, J. David Beckham, Stephan T. Stern, Xudong Zhang, Marcello Pinti, Xiangnan Zhang, Jae Keun Lee, Ana Coto-Montes, Assaf Rudich, Laura D. Attardi, Debabrata Ghosh, Philip Rosenstiel, Sébastien Besteiro, Maria Rosa Sarrias, R. Andres Floto, Xiao Ming Yin, Nicholas W. Lukacs, Hermann Pavenstädt, Matias Simons, Hitoshi Nakatogawa, Sandro Alves, Krisztina Takács-Vellai, Masato Koike, Debasish Sinha, Shoji Notomi, Faraj Terro, Maria Carmela Roccheri, Santiago Ambrosio, K. Ulrich Bayer, Yumin Li, Terje Johansen, Christian Kuhn, Yee Shin Lin, David C. Rubinsztein, Ziwei Qu, Ronit Shiri-Sverdlov, Emmanuel T. Akporiaye, Galila Agam, Hui Ling Chiang, Seung-Jae Lee, Yu Xue, Francesca Giampieri, Markus Damme, Tassula Proikas-Cezanne, Tianwei Lin, Marc Kantorow, Guang-Chao Chen, Qiangrong Liang, Claudia Manzoni, Joan S. Steffan, Emilio Boada-Romero, Damien Freyssenet, Sepp D. Kohlwein, Maria D. Barrachina, Yulin Liao, Jiankang Chen, Erika Isono, Hugo Seca, Mei Wang, Taras Y. Nazarko, Yannick Bailly, Nadya V. Koshkina, Tapas K. Maiti, Bärbel Rohrer, Karin Nowikovsky, James H. Hurley, Gerald W. Dorn, Nils C. Gassen, Kazuhiro Nagata, Eiki Kominami, A. Ivana Scovassi, Ana Maria Cuervo, Adi Kimchi, Minghua Yang, Sylviane Muller, Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Defense in Plant-Pathogen Interactions [Nagoya, Japan], Nagoya University-Graduate School of Bioagricultural Sciences [Nagoya, Japan], Facultad de Quimica [Santiago], Pontificia Universidad Católica de Chile (UC), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain, Harvard University Statistics Department, Harvard University [Cambridge], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Conway Institute of Biomolecular and Biomedical Research and School of Chemical and Bioprocess Engineering, University College Dublin [Dublin] (UCD), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry and Molecular Biology, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Centro de Estudios Farmacológicos y Botánicos [Buenos Aires] (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Thérapie génique, Génomique et Epigénomique (U 1169), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Department of Experimental Medicine and Public Health, University of Camerino, MRC Toxicology Unit, University of Leicester, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Departamento de Bioquímica y Biología Molecular y Celular, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pharmaco-Biology, Università della Calabria [Arcavacata di Rende] (Unical), Department of Molecular Genetics [Rehovot, Israël], Weizmann Institute of Science, Fondation Universitaire Notre Dame de la Paix (FUNDP), Facultés Universitaires Notre-Dame de la Paix, Département Advanced Research And Techniques For Multidimensional Imaging Systems (ARTEMIS), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), USC Neuromuscular Center, Department of Neurology, University of Southern California (USC), Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Giannina Gaslini Institute, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Department of Cancer Biology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Inner Mongolia Agricultural University (IMAU), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Indian Institute of Science [Bangalore] (IISc Bangalore), Politecnico di Milano [Milan] (POLIMI), Département des Sciences Biologiques [Montréal], Université du Québec à Montréal (UQAM), Laboratory of Molecular Biology, Scientific Institute E. Medea, Université Catholique de Louvain (UCL), Univ Ancona, Politecn Marche, University of Toronto, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Department of Clinical and Molecular Medicine, Università degli Studi di Roma 'La Sapienza' [Rome]-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hémato-Cancérologie Expérimentale, CRP-Santé, Dpt of Neuroscience and Brain Technologies [Genova], NeuroEngineering & bio-arTificial Synergic SystemS Laboratory [Genova] (NetS3 Lab), Istituto Italiano di Tecnologia (IIT)-Istituto Italiano di Tecnologia (IIT), Center for Infection and Immunity Amsterdam (CINIMA), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Régulation de l'expression génétique (REG), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology and Immunology, Stanford University School of Medicine [CA, USA], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Dermatology, Brigham and Women's Hospital [Boston], San Raffaele Scientific Institute, Milan, Italy, Laboratory of Molecular Neuroembryology, University of Rome 'Tor Vergeta'-Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma]-Dulbecco Telethon Institute, Department of Pharmacology, Universidade de Santiago de Compostela, Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Complexo Hospitalario Universitario A Coruña, Mécanismes moléculaires de l'angiogénèse, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Florida [Gainesville], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U1172 Inserm), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infection bactérienne, inflammation, et carcinogenèse digestive, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Universita degli Studi di Padova, University of British Columbia (UBC), University of Edinburgh, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Australian Regenerative Medicine Institute, Monash University, Clayton, 3800, VIC, Australia, Faculty of Engineering and Natural Sciences, Sabanci University [Istanbul], Department of Biological Sciences [Stanford], Stanford University [Stanford], Université de Montréal (UdeM), Department of Human Genetics, Department of Psychiatry, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Centre for Computational and Systems Biology (COSBI), Department of Computer Science [Tsukuba], Graduate School of Systems and Information Engineering [Tsukuba], University of Tsukuba-University of Tsukuba, Institut de biochimie et génétique cellulaires (IBGC), University of Western Ontario (UWO), Genetics, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Department of Biochemistry and Biophysics, University of Naples Federico II, Lund University [Lund], Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB), Karl-Franzens-Universität Graz, Polytechnic University of Marche, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Cell Biology, Physiology and Immunology, Research Unit on BioActive Molecules, Departamento de Química Orgánica Biológica, Instituto de Investigaciones Quimicas y Ambientales de Barcelona, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), The Buck Institute for Age Research, University of Pisa - Università di Pisa, Laboratorio di Genetica Molecolare, Istituto Gaslini, Universidad de Castilla-La Mancha (UCLM), Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, University of Crete [Heraklion] (UOC), Division of Molecular and Cellular Pathology [Birmingham], Department of Medical Research, Taichung Veterans General Hospital, Modélisation et Simulation Numérique en Mécanique et Génie des Procédés (MSNMGP), Université de la Méditerranée - Aix-Marseille 2-Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), University of Queensland [Brisbane], Dept of Mathematics, Purdue University, Purdue University [West Lafayette], Virologie et Pathologie Humaine (VirPath), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Zhejiang University, Équipe Micro et nanosystèmes HyperFréquences Fluidiques (LAAS-MH2F), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), King Abdullah University of Science and Technology (KAUST), Southern University of Science and Technology of China (SUSTech), OASE, National University of Tainan, Taiwan (OASE), National Taiwan University [Taiwan] (NTU), Weifang Bureau of Land Resources [Weifang], Department of cardiology [Guy's and St. Thomas ' hospitals] [London], Guy's and St Thomas' Hospital [London]-Guy's Hospital [London], University of Pennsylvania [Philadelphia], CRLCC Eugène Marquis (CRLCC), Emory University School of Medicine, Emory University [Atlanta, GA], Korea University, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology [Tartu, Estonie], Institute of Biomedicine and Translational Medicine [Tartu, Estonie], University of Tartu-University of Tartu, Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Max-Planck-Gesellschaft, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Cincinnati (UC), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Experimental Medicine, Oxford University, University of Oxford [Oxford], Division of regenerative Medicine, San Raffaele Scientific Institute, The University of New Mexico [Albuquerque], Université Libre de Bruxelles [Bruxelles] (ULB), Macrophages et Développement de l'Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Department of Experimental Medicine and Oncology, University of Turin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CNV, University of Valparaiso, Institut Gustave Roussy (IGR), Universidad Autonoma de Madrid (UAM), Cell Signalling & Proteomics Group [Londres, Royayme-Uni], Barts Cancer Institute [Londres, Royayme-Uni], Queen Mary University of London (QMUL)-Queen Mary University of London (QMUL), Department of General, Visceral and Vascular Surgery [Jena], Friedrich-Schiller-Universität Jena, Department of Biomedical Engineering, The University of Texas at Austin, University of Texas at Austin, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Fondazione Santa Lucia (IRCCS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Biology, Johns Hopkins University (JHU), Neurogenetics Group, Instituto de Investigación en Recursos Cinegéticos (IREC), Laboratório de Ultraestrutura Celular Hertha Meyer (IBCCF), Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Molecular and Cellular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National University of Ireland [Galway] (NUI Galway), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Freiburg Institute for Advanced Studies-LifeNet, Albert-Ludwigs-Universität Freiburg, Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Brunel University London [Uxbridge], Unité Propre de Recherche 2357, Institution de Biologie Moléculaire des Plantes, Radiothérapie moléculaire (UMR 1030), Department of Chemistry, University of Kentucky, Universidad de Córdoba [Cordoba], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Facultad de Ciencias Químicas y Farmacéuticas, Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology, Goethe-University Frankfurt am Main, Department of Biological and Environmental Sciences and Technologies (DiSTeBA), Università del Salento, Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Institut National Polytechnique de Lorraine (INPL), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Trafic membranaire et Division cellulaire, Landesbetrieb Hessisches Landeslabor, Hematology-Oncology Division, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Pavia, Instituto de Investigaciones Biotecnológicas [San Martín] (IIB-INTECH), Universidad Nacional de San Martin (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), University of Helsinki, School of Physics and Astronomy [Exeter], University of Exeter, Department of Biomedicinal Chemistry (CSIC), Institut de Química Avançada de Catalunya, Laboratory of Vascular Pathology (IDI-IRCCS), Istituto Dermopatico dell'Immacolata, Peking University [Beijing], MRC Centre for Developmental Neurobiology, University of Brescia, Immunobiologie fondamentale et clinique, Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), University of Rome 'Tor Vergeta', Universidad de Oviedo [Oviedo], Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Dulbecco Telethon Institute/Department of Biology, Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Rockefeller University [New York], The Babraham Institute, Kansas State University, McGill University, Service d'Anatomie et Cytologie Pathologique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), ATOS Origin, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences-Tohoku University [Sendai], Goethe-University, Goethe-Universität Frankfurt am Main, Institute of physiological chemistry, Hannover Medical School [Hannover] (MHH), Department of Physiology, Department of Plant and Environmental Sciences, Apoptose, cancer et immunité (U848), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Departments of Neurology and Psychiatry, Alzheimer's Disease Research Center, Institute of Experimental Immunology - IEI [Zürich, Switzerland], Université de Zurich [Switzerland], Digital Enterprise Research Institute (DERI-NUIG), Spanish National Research Council (CSIC), Cell Death Research and Therapy Unit [Leuven, Belgium] ( Department of Cellular and Molecular Medicine), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCINA - Département ONCO - Equipe 15), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Medicine [San Francisco], University of California [San Francisco] (UCSF), University of California-University of California, Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy, Histology, Forensic Medicine and Orthopedic, N.A., Division of Pharmacology and Chemotherapy, Department of Internal Medicine, Pathogénie Microbienne Moléculaire, University of Chile [Santiago], Université de Montpellier (UM), Faculdade de Ciências Farmacêuticas de Ribeirão Preto [São Paulo], Universidade de São Paulo (USP), Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Catalan Institute of Oncology, Department of Cell Biology, National Institute for Basic Biology [Okazaki], Instituto de Bioquímica Vegetal y Fotosíntesis (IBVF), Universidad de Sevilla-Centro de Investigaciones Científicas Isla de la Cartuja, The Adams Super Center for Brain Studies, Tel Aviv University [Tel Aviv], Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology and biochemistry, Virginia Commonwealth University (VCU), Department of Immunology, St Jude Children's Research Hospital, Department of Biology and Biotechnologies 'Charles Darwin', Lettres, Idées, Savoir (LIS), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institute of Biological Chemistry and Nutrition, University of Hohenheim, China Seismological Bureau, Massachusetts Institute of Technology (MIT), Rosenstiel Basic Medical Sciences Research Center [Waltham], Brandeis University, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Meakins-Christie Laboratories, Sanford Burnham Medical Research Institute, La Jolla, National Institute of Advanced Industrial Science and Technology (AIST), ORIENT ET MÉDITERRANÉE : Textes, Archéologie, Histoire (OM), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Biochemistry and Molecular Biology I, Department of Immunology and Infectious Diseases, Harvard School of Public Health, aDepartment of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences (SLU), Philipps University of Marburg, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Renal Division, University Medical Center Freiburg, Freiburg, Germany, Rural Health Academic Centre, University of Melbourne-Rural Clinical School, Department of Pathology, University of Veterinary and Animal Sciences, Dipartimento di Scienze della Vita [Modena, Italy], Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Anatomy & Cell Biology [Philadelphia, Pennsylvania, USA], Thomas Jefferson University, Department of Molecular Neuroscience, Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Centro de Investigación en Bioquímica Clínica e Inmunología (CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina, Neuroinflammation Unit, Biotech Research and Innovation Centre-University of Copenhagen = Københavns Universitet (KU), Mathematics and Computing in Automatic Control and Optimization for the User (MIAOU), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Danish Cancer Society, Institute of Cancer Biology, UCL-Institute of Child Health (ICH), Institute of Child Health-Great Ormond Street Hospital for Children [London] (GOSH), Division of Renal Diseases and Hypertension, University of Colorado [Boulder], Institut de biologie et chimie des protéines [Lyon] (IBCP), Joslin Diabetes Center, Universität Ulm - Ulm University [Ulm, Allemagne], Qingdao Institute of Marine Geology, China Geological Survey, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Institute of Software, Chinese Academy of Sciences [Beijing] (CAS), Metabolic Engineering Group, Departamento de Microbiologia y Genetica, Edificio Departamental, Campus Miguel de Unamuno, Universidad de Salamanca, University of Minnesota [Twin Cities], University of Minnesota System, Department of Cellular and Molecular Physiology, Yale University School of Medicine, The Arctic University of Norway, Department of Biological Sciences, The Open University [Milton Keynes] (OU), Summit Analytical, CALRG, Institute of Educational Technology, Institute for Neurologic Disabilities Research, Faculty of Health Sciences-University of Pretoria [South Africa], Department of Paediatric Neurology, Guy's and St Thomas' Hospital [London]-Evelina Children's Hospital, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Dana-Farber Cancer Institute and the Department of Cell Biology, Harward Medical School, Translational Health Science and Technology Institute [Faridabad] (THSTI), Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, School of Reliability and Systems Engineering [Beijing], Beihang University, Oxford Centre for Integrative Systems Biology, Center for Membrane and Cell Physiology [Charlottesville, VA, USA] (School of Medicine), University of Virginia [Charlottesville], Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Karlsruher Institut für Technologie (KIT), Faculty of Pharmaceutical Sciences, Hokkaido University, École normale supérieure - Paris (ENS Paris), School of Electrical Engineering [Seoul] (Korea University), Department of Mathematics and Statistics [Guelph], University of Guelph, Department of Molecular Genetics, Department of Genetics [Stanford, CA, États-Unis], Institute of Immunology, University Hospital Schleswig-Holstein, Arizona Respiratory Center, Okazaki Institute for Integrative Bioscience, ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Newcastle University [Newcastle], JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Department of Neuroscience, University of Texas Southwestern Medical Center [Dallas], Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Laboratory of Functional Neurogenomics [Tuebingen, Germany], University of Tuebingen-Center of Neurology and Hertie-Institute for Clinical Brain Research [Tuebingen, Germany], Indian Institute of Technology Bombay (IIT Bombay), European Organization for Nuclear Research (CERN), Harvard Medical School [Boston] (HMS), Indian School of Mines, Department of Computer Science [UIUC] (UIUC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, Centre for Cancer Biology, Hanson Institute, Adelaide, University of California [San Diego] (UC San Diego), University of California, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry, University of Bristol, Organisation Nucléaire et Oncogenèse, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FONDAP Center CEMC Estudios Moleculares de la Célula, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Chungnam National Univesity School of Medicine, Taejon, Korea, Chungnam National Univesity School of Medicine, Micro & Nanobiotechnologies, Institut des Sciences Analytiques (ISA), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Center for Applied Mathematics, Tsinghua University [Beijing], University of Connecticut School of Medicine, University of Connecticut (UCONN), Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes (LBMCE), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et Physiopathologie de la Differenciation, Division of Nephrology and Hypertension, Mayo Clinic, Beatson Institute for Cancer Research, Beatson institute for cancer research, Howard Hughes Medical Institute, Howard Hugues Medical Institute, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Computing Technology [Beijing] (ICT), Chinese Academy of Sciences [Changchun Branch] (CAS), School of Electronics and Computer Science (ECS), University of Southampton, Third Hospital, Department of Anesthesiology, Cognitive Interaction Technology [Bielefeld] (CITEC), Universität Bielefeld = Bielefeld University, Procédés, Matériaux et Energie Solaire (PROMES), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Faculty of Pharmacy- University of Coimbra, National Neuroscience Institute, Key Laboratory of Molecular Virology & Immunology (LMVI), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Coll Life Sci, Beijing Normal University, Delft University of Technology (TU Delft), Christian-Albrechts-Universität zu Kiel (CAU), Department of Molecular Pathology and Microbiology, Center for Applied Proteomics and Molecular Medicine-George Mason University [Fairfax], Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University), Institut des Sciences Chimiques de Rennes (ISCR), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Department of Chemistry, University of Pittsburgh, University of Pittsburg, Tianjin University of Science and Technology (TUST), Hunan University of Science and Technology [Xiangtan], Laboratoire de Génie Civil et Génie Mécanique (LGCGM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), China Agricultural University (CAU), Acad Disaster Reduct and Emergency Management, Minist Civil Affairs, Minist Educ, Beijing, Peoples R China, affiliation inconnue, Département Technologie des Polymères et Composites & Ingénierie Mécanique (TPCIM), École des Mines de Douai (Mines Douai EMD), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Ministère de l'Economie, des Finances et de l'Industrie, MOE Key Laboratory of Bioinformatics, Centre for Plant Biology, School of Life Sciences, Laboratoire d'Informatique Gaspard-Monge (ligm), Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Center for International Blood and Marrow Transplant Research (CIBMTR), Emory University [Atlanta, GA]-Medical College of Wisconsin, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Illman Cancer Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Ingénierie des Matériaux Polymères (IMP), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Department of Medical Microbiology and Immunology, University of California [Davis] (UC Davis), School of Health Sciences, University of Minho [Braga], Équipe Calcul Distribué et Asynchronisme (LAAS-CDA), University of California [Riverside] (UCR), Ohio State University [Columbus] (OSU), Laboratory of Systems Biology, Van Andel Institute [Grand Rapids], Division of Genetics and Cell Biology, National Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Oregon Health and Science University [Portland] (OHSU), Dendrite Differenciation Group [DZNE - Bonn], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Equipe 12, Génétique moléculaire, signalisation et cancer (GMSC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Medical Center [Utrecht], Institut d'Investigacions Biomèdiques August Pi I Sunyer [Barcelona, Spain] (Hospital Clinic ), Department of Genetics, Trinity College Dublin, Fisiopatologia de los procesos inflamatorios, Vall d'Hebron Research Institute, Institució Catalana de Recerca i Estudis Avançats (ICREA), Department of Human Genetics, Nagasaki University, Transduction du signal et oncogénèse, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie, Center for Experimental and Molecular Medicine, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of medical Biochemistry, University of Amsterdam [Amsterdam] (UvA), IDI-IRCCS Biochemistry Laboratory, Università degli Studi di Roma Tor Vergata [Roma], Program Against Cancer Therapeutic Resistance/Metabolism & Cancer Group [Catalonia, Spain] (ProCURE), Catalan Institute of Oncology-Girona (ICO-Girona), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa (NOVA), Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, CNR, Consiglio Nazionale delle Ricerche (CNR), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, The Hospital for sick children [Toronto] (SickKids), Universidad de Sevilla, Immunité muqueuse et vaccination, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), DIMS, University of Trento [Trento], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Department of Cellular and Molecular Medicine [Madrid, Spain], Laboratory of Cell Death and Cancer Therapy [Madrid, Spain], Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC) -Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3HD, UK, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dpt. of Cancer & Cell Biology, Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Max planck Institute for Biology of Ageing [Cologne], Euromov (EuroMov), Wellcome Trust Centre for Molecular Parasitology [Glasgow, UK], University of Glasgow- Institute of Infection, Immunity and Inflammation [Glasgow, UK], Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), UMR 1599, Centre National de la Recherche Scientifique (CNRS), EA 4100, Histoire culturelle et sociale de l'art (HiCSA), Université Panthéon-Sorbonne (UP1)-Université Panthéon-Sorbonne (UP1), Centre for Astrophysics and Supercomputing (Centre for Astrophysics and Supercomputing), Swinburne University of Technology [Melbourne], Department of Cellular and Physiological Sciences [Vancouver, BC, Canada] (Life Sciences Institute), University of British Columbia (UBC)-Life Sciences Institute [Vancouver, BC, Canada], School of Pharmacy, Department of Experimental Medicine, Dept. Neurosciences, Department of Internal Medicine, Radboud University Medical Center [Nijmegen], Institute of Medical Genetics and Applied Genomics, Radiation Physics, School of Life Science, Department of Basic Biology, The Graduate University for Advanced Studies, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Doshisha University, National Cancer Research Center [Tokyo, Japan], University of Washington [Seattle], Department of Experimental Neurodegeneration [Göttingen, Germany], University Medical Center Göttingen (UMG), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), BioCeV-Institute of Microbiology, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto di chimica biologica, Università degli Studi di Verona, Département Image et Traitement Information (ITI), Institut Mines-Télécom [Paris] (IMT)-Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne, Department of Cell Biology and Biophysics, Università degli Studi di Firenze [Firenze], Cell Immunity in Cancer, Inflammation and infection Group [Zaragoza, Spain] (Biomedical Research Center), Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain]-University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pediatrics, Università degli studi di Napoli Federico II, Transfert de Genes a Visee Therapeutique Dans les Cellules Souches, Developpement Normal et Pathologique du Système Immunitaire, Signalisation et physiopathologie des cellules épithéliales, Facultad de Medicina, Universidad de Santiago de Chile [Santiago] (USACH), Departamento de Farmacobiología, Cinvestav-Sede Sur, Centre de recherche Croissance et signalisation (UMR_S 845), College of Life Sciences, Central China Normal University, Institute of Molecular Biotechnology, Austrian Academy of Sciences (OeAW), Laboratory of Cardiac Surgical Research, Monash University [Clayton], Universidade do Minho, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neurodegenerative Diseases Research Group (CIBERNED), Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases, Barcelona, Department of medicine, Syracuse, NY, USA, State University of New York (SUNY), National University of Singapore (NUS)-Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, McGill University Health Center [Montreal] (MUHC), National Institute for Infectious Diseases, Transporteurs en Imagerie et Radiothérapie en Oncologie (TIRO - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biomedical Sciences, Department of Genetics of Eukaryotic Microorganisms, Georg-August-University [Göttingen]-Institute of Microbiology and Genetics, Sterol metabolism and therapeutic innovations in oncology, Institut Claudius Regaud, CRLCC Institut Claudius Regaud-CRLCC Institut Claudius Regaud-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Molecular, Cellular and Developmental Biology, Señalización Celular 4, Institute of integrative biology (Liverpool), University of Liverpool, Department of Human Biology, University of Cape Town, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Department of Molecular Biology, Eberhard Karls Universität Tübingen, Technical University of Munich (TUM), Biophysics and Bioinformatics Laboratory, Department of Cell Biology and Morphology, Université de Lausanne (UNIL), Shenyang Institute of Automation, the Chinese Academy of Sciences (SIA), Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, Xi'an Jiaotong University (Xjtu), Dipartimento di Biologia, Mechanics laboratory , UniversityAmar Telidji, 3000 Laghouat, Algéria., Mechanics laboratory , University Amar Telidji, sans affiliation, Service d'hépatologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University of Waterloo, Waterloo, ON, Canada, Institute of Cell Biology and Immunology, University of Stuttgart, Chaperones Research Group, Institute of Biosciences and Technology [Houston, TX, États-Unis] (IBT), Texas A&M Health Science Center [Houston, TX, États-Unis] (TAMHSC), Texas A&M University Health Science Center-Texas A&M University Health Science Center, Aquatic and Crop Resource Development, National Research Council of Canada (NRC), Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche [Ancona] (UNIVPM), Department of Biochemistry and Molecular Biology [Indianapolis, IN, USA], Indiana University School of Medicine, Indiana University System-Indiana University System, Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, iMed.UL, Faculty of Pharmacy, University of Lisbon, CESAM & Biology Department, Universidade de Aveiro, Celullar and Molecular Medicine, Università degli Studi di Perugia (UNIPG), Institute of Clinical Molecular Biology, Kiel University, Apoptose et Système Immunitaire (ASI), Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematical Sciences [Aalborg], Aalborg University [Denmark] (AAU), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Biozentrum, University of Basel (Unibas), Structural and Computational Biology Unit, European Molecular Biology Laboratory [Grenoble] (EMBL), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Université de Perpignan Via Domitia (UPVD), Universidad Pablo de Olavide [Sevilla] (UPO), Department of Neurosciences, Agronomes et Vétérinaires Sans Frontières (AVSF), AVSF, Department of Mathematics [Gakushuin], Gakushuin University, Department of Internal Medicine [Münster, Germany], University of Münster, Neurogenetics laboratory, University Medicine Goettingen, Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université d'Uruguay, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Institute for Conservation & Improvement of Valentian Agrodiversity (COMAV), Universitat Politecnica de Valencia (UPV), ICBM, University of Chile [Santiago]-Faculty of Medicine, Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Department of Cell Biology, Baltimore, Johns Hopkins University School of Medicine, Baylor College of Medicine (BCM), Baylor University, University of Minnesota Medical School, Beijing Candid soft Technology Co. Ltd, Nanjing University of Information Science and Technology, Department of Hepatobiliary and Pancreatic Surgery [Maebashi, Japan], Gunma University Graduate Schoolof Medicine [Maebashi, Japan], Department of Molecular Genetics [Maastricht, The Netherlands], Maastricht University [The Netherlands], Institute of Cell Biology and Genetic Engineering, National Academy of Sciences of Ukraine (NASU), Institute of Pharmacology of Natural Products and Clinical Pharmacology, Institute of Pharmacology, University of Bern, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Wilmer Eye Institute, Mayo Clinic and Mayo College of Medicine, Rochester, Institute of Biochemistry and Biophysics, Polska Akademia Nauk (PAN)-Sciences, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Chemistry and Toxicology, Norwegian Veterinary Institute, Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], University of Minho, Friedrich Miescher Laboratory (FML), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Biomedical Sciences and Biotechnologies, Brescia University, Department of Physiological Chemistry [Bochum], Ruhr-Universität Bochum [Bochum], University of Oslo (UiO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Facultés Universitaires Notre Dame de la Paix (FUNDP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226, Université du Québec à Montréal = University of Québec in Montréal (UQAM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Université Lille 2 - Faculté de Médecine -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées, Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal do Rio de Janeiro (UFRJ), Institut Bergonié [Bordeaux], UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), McGill University = Université McGill [Montréal, Canada], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Universidad de Chile = University of Chile [Santiago] (UCHILE), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISC), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Collège de France (CdF (institution)), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, Hokkaido University [Sapporo, Japan], Université Paris sciences et lettres (PSL), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Lyon-Université de Lyon, Centre d’Infection et d’Immunité de Lille (CIIL) - INSERM U1019 - UMR 9017 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), The Beatson Institute for Cancer Research, Beijing Normal University (BNU), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Bézout-ESIEE Paris-École des Ponts ParisTech (ENPC)-Université Paris-Est Marne-la-Vallée (UPEM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon], Vall d’Hebron Research Institute (VHIR), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Doshisha University [Kyoto], Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Università degli Studi di Firenze = University of Florence [Firenze], University of Zaragoza - Universidad de Zaragoza [Zaragoza]-Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain], Central China Normal University [Wuhan, China], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie structurale [1992-2019] (IBS - UMR 5075 [1992-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nanjing University of Information Science and Technology (NUIST), Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Clermont Auvergne (UCA)-Institut National de la Recherche Agronomique (INRA), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de San Martin (UNSAM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, George Mason University [Fairfax]-Center for Applied Proteomics and Molecular Medicine, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institute of Infection, Immunity and Inflammation [Glasgow, UK]-University of Glasgow, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Settore BIO/06, biology, Cell Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, biology.organism_classification, Cell biology, Interpretation (model theory), 03 medical and health sciences, Arama, 030104 developmental biology, Molecular Biology, Humanities, ComputingMilieux_MISCELLANEOUS
Abstract: Author(s): Klionsky, DJ; Abdelmohsen, K; Abe, A; Abedin, MJ; Abeliovich, H; Arozena, AA; Adachi, H; Adams, CM; Adams, PD; Adeli, K; Adhihetty, PJ; Adler, SG; Agam, G; Agarwal, R; Aghi, MK; Agnello, M; Agostinis, P; Aguilar, PV; Aguirre-Ghiso, J; Airoldi, EM; Ait-Si-Ali, S; Akematsu, T; Akporiaye, ET; Al-Rubeai, M; Albaiceta, GM; Albanese, C; Albani, D; Albert, ML; Aldudo, J; Algul, H; Alirezaei, M; Alloza, I; Almasan, A; Almonte-Beceril, M; Alnemri, ES; Alonso, C; Altan-Bonnet, N; Altieri, DC; Alvarez, S; Alvarez-Erviti, L; Alves, S; Amadoro, G; Amano, A; Amantini, C; Ambrosio, S; Amelio, I; Amer, AO; Amessou, M; Amon, A; An, Z; Anania, FA; Andersen, SU; Andley, UP; Andreadi, CK; Andrieu-Abadie, N; Anel, A; Ann, DK; Anoopkumar-Dukie, S; Antonioli, M; Aoki, H; Apostolova, N; Aquila, S; Aquilano, K; Araki, K; Arama, E; Aranda, A; Araya, J; Arcaro, A; Arias, E; Arimoto, H; Ariosa, AR; Armstrong, JL; Arnould, T; Arsov, I; Asanuma, K; Askanas, V; Asselin, E; Atarashi, R; Atherton, SS; Atkin, JD; Attardi, LD; Auberger, P; Auburger, G; Aurelian, L; Autelli, R
Published: 2016

215. Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration

Author: Kai Kaarniranta, László Fésüs, Goran Petrovski, Endre Kristóf, Saeed Akhtar, Anu Kauppinen, Mária Szatmári-Tóth, Andrea Facskó, and Zoltán Veréb
Subjects: 0301 basic medicine, Cancer Research, Cell, Gene Expression, Retinal Pigment Epithelium, Triamcinolone, Culture Media, Serum-Free, chemistry.chemical_compound, Macular Degeneration, 0302 clinical medicine, Genes, Reporter, Elméleti orvostudományok, education.field_of_study, Chloroquine, Orvostudományok, Cell biology, medicine.anatomical_structure, Original Article, medicine.symptom, Microtubule-Associated Proteins, Programmed cell death, Immunology, Population, Green Fluorescent Proteins, Primary Cell Culture, Inflammation, Biology, Models, Biological, Cell Line, 03 medical and health sciences, Cellular and Molecular Neuroscience, Phagocytosis, medicine, Autophagy, Humans, education, Retina, Interleukin-6, Adenine, Macrophages, Interleukin-8, Retinal, Cell Biology, Hydrogen Peroxide, eye diseases, Coculture Techniques, Oxidative Stress, 030104 developmental biology, chemistry, Cell culture, 030221 ophthalmology & optometry, sense organs, Biomarkers
Abstract: Retinal pigment epithelial (RPE) cells can undergo different forms of cell death, including autophagy-associated cell death during age-related macular degeneration (AMD). Failure of macrophages or dendritic cells (DCs) to engulf the different dying cells in the retina may result in the accumulation of debris and progression of AMD. ARPE-19 and primary human RPE cells undergo autophagy-associated cell death upon serum depletion and oxidative stress induced by hydrogen peroxide (H2O2). Autophagy was revealed by elevated light-chain-3 II (LC3-II) expression and electron microscopy, while autophagic flux was confirmed by blocking the autophago-lysosomal fusion using chloroquine (CQ) in these cells. The autophagy-associated dying RPE cells were engulfed by human macrophages, DCs and living RPE cells in an increasing and time-dependent manner. Inhibition of autophagy by 3-methyladenine (3-MA) decreased the engulfment of the autophagy-associated dying cells by macrophages, whereas sorting out the GFP-LC3-positive/autophagic cell population or treatment by the glucocorticoid triamcinolone (TC) enhanced it. Increased amounts of IL-6 and IL-8 were released when autophagy-associated dying RPEs were engulfed by macrophages. Our data suggest that cells undergoing autophagy-associated cell death engage in clearance mechanisms guided by professional and non-professional phagocytes, which is accompanied by inflammation as part of an in vitro modeling of AMD pathogenesis.
Published: 2016

216. A link between diabetes mellitus and glaucoma:Danish nationwide study

Author: Beáta Éva Petrovski, Goran Petrovski, Anna Horwitz, Miriam Kolko, and Christian Torp-Pedersen
Subjects: medicine.medical_specialty, Glaucoma medication, business.industry, medicine.medical_treatment, Glaucoma, General Medicine, Diabetic retinopathy, medicine.disease, Lower risk, Surgery, Diabetic nephropathy, Ophthalmology, Internal medicine, Diabetes mellitus, Relative risk, medicine, business, Cohort study
Abstract: Purpose To determine the effect of anti-diabetic medication on glaucoma. Furthermore, to investigate if diabetic comorbidities and concomitant medications are associated with glaucoma in patients treated with anti-diabetic medication. Methods Retrospective nationwide cohort study, spanning a 16-year follow-up period. The National Danish Registry of Medicinal Products Statistics was used to identify all claimed prescriptions for glaucoma medication and anti-diabetic drugs. Comorbidities with diabetic retinopathy and diabetic nephropathy were identified using the ICD-10 classification and the Danish National Patient Register. Results A total of 6,343,747 individuals in the period 1996–2012 were included. The overall incidence rates of new-onset glaucoma were 0.07 and 0.36 per 1,000 person-years for the reference population and for diabetes mellitus, respectively. Patients treated with anti-diabetic drugs at any time during the study period had a significantly higher overall relative risk of glaucoma (RR = 5.11, p
Published: 2016

217. Endophthalmitis Prevention, Diagnostic Procedures and Treatment

Author: Angela Thaler, Xhevat Lumi, Goran Petrovski, and Biljana Vasileva
Subjects: medicine.medical_specialty, genetic structures, medicine.drug_class, business.industry, medicine.medical_treatment, Antibiotics, Vitrectomy, Pathogenic bacteria, Disease, medicine.disease, medicine.disease_cause, Surgery, Therapeutic approach, Endophthalmitis, Immunity, Internal medicine, medicine, Endogenous Infection, business
Abstract: Endophthalmitis is a severe inflammation of the inner eye's structures, caused by an exogenous or endogenous infection with microorganisms which can multiply rapidly. It occurs most frequently after intraocular surgery. Moreover, it can also be a consequence of a penetrant eye injury or a hematogenous dissemination of microorganisms. The most common pathogens of this inflammation are bacteria, next to fungi and less frequently parasites. The occurrence, severity and clinical presentation of endophthalmitis depend on the way of infection, the number and virulence of pathogenic bacteria, as well as the patient's immunity state. The type of endophthalmitis can suggest the possible causative agent. Furthermore, it can help determine therapeutic approach or antibiotics to choose. The more virulent are the causative agents, the early the symptoms and signs of endophthalmitis appear. Such types of endophthalmitis have a bad course and poor prognosis concerning visual function. In these cases the red fundus reflex is lost quite at the beginning of the disease. Patients treated with prompt vitrectomy and intravitreal injections of antibiotics have statistically better visual outcomes and less likelihood of severe visual loss.
Published: 2016

218. Activation of neural progenitor cells in human eyes with proliferative vitreoretinopathy

Author: Réka Albert, Zsolt Sarang, Bjørn Nicolaissen, Rebecca C. Frøen, Bente K. Omdal, Erik O. Johnsen, András Berta, Goran Petrovski, and Morten C. Moe
Subjects: Male, Proliferative vitreoretinopathy, Pathology, PAX6 Transcription Factor, genetic structures, Nestin, Mice, Intermediate Filament Proteins, Paired Box Transcription Factors, Fluorescent Antibody Technique, Indirect, Pigment Epithelium of Eye, Aged, 80 and over, education.field_of_study, Stem Cells, Middle Aged, Cadherins, Sensory Systems, Neural stem cell, Neuroepithelial cell, medicine.anatomical_structure, Female, Stem cell, Muller glia, Retinal Neurons, Adult, Rhodopsin, medicine.medical_specialty, Adolescent, Population, Nerve Tissue Proteins, Biology, Real-Time Polymerase Chain Reaction, Cellular and Molecular Neuroscience, Glial Fibrillary Acidic Protein, medicine, Animals, Humans, Progenitor cell, Eye Proteins, education, Homeodomain Proteins, Retina, SOXB1 Transcription Factors, Ciliary Body, Vitreoretinopathy, Proliferative, Retinal Detachment, medicine.disease, eye diseases, Mice, Inbred C57BL, Repressor Proteins, Vitreous Body, Disease Models, Animal, Ophthalmology, nervous system, sense organs, Biomarkers
Abstract: In addition to the ability for self-renewal and functional differentiation, neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted migration. In lower vertebrates, retinal injury is known to activate NSCs in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Müller glia in the peripheral retina (PR) of the adult human eye. However, these cells seem to be quiescent in the adult human eye and recent reports have shown that CE cells have limited properties of NSCs. In order to further clarify whether NSCs exist in the adult human eye, we tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse model of PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured in a stem cell-promoting medium and compared to cells cultured from the post-mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the proximal pars plana region and the PR, the latter population also staining for the glial marker GFAP. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect NSC-associated markers in the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin activation was also found in the CE. In human PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR, and expressed glial - and NSC-associated markers both after direct fixation and repetitive passages. In conclusion, the adult human eye may harbor two different populations of neuroepithelial stem/progenitor cells; a non-glial population located in the proximal pars plana around peripheral cysts in addition to a population with Müller glia characteristics. Yet, we only found that the glial population was able to respond to retinal injury by targeted migration into the vitreous.
Published: 2012

219. Microplasma Induced Cell Morphological Changes and Apoptosis of Ex Vivo Cultured Human Anterior Lens Epithelial Cells - Relevance to Capsular Opacification

Author: Nina Recek, Gregor Filipič, Gregor Primc, Nataša Hojnik, Goran Petrovski, Sofija Andjelic, Miran Mozetič, Marko Hawlina, Alenka Vesel, Uroš Cvelbar, and Saša Lazović
Subjects: Plasma Gases, Physiology, Cell, Cell Membranes, lcsh:Medicine, Apoptosis, 01 natural sciences, CXCR4, 010305 fluids & plasmas, Micromanipulation, White Blood Cells, Animal Cells, Medicine and Health Sciences, lcsh:Science, Cells, Cultured, 010302 applied physics, Fluids, Multidisciplinary, Cell Death, Chemistry, Physics, Ophthalmic Procedures, Classical Mechanics, Cataract Surgery, Anatomy, Equipment Design, Hematology, Cell biology, Body Fluids, medicine.anatomical_structure, Blood, Cell Processes, Lens (anatomy), Physical Sciences, Vapors, DNA fragmentation, Cellular Structures and Organelles, Cellular Types, Research Article, Capsule Opacification, States of Matter, Immune Cells, Plasma Cells, Immunology, Lens Capsule, Crystalline, Surgical and Invasive Medical Procedures, Fluid Mechanics, Caspase 8, Continuum Mechanics, 0103 physical sciences, medicine, Humans, Plasma Volume, Electrodes, Fluid Flow, Nitrites, Blood Cells, lcsh:R, Chemical Compounds, Biology and Life Sciences, Epithelial Cells, Fluid Dynamics, Cell Biology, lcsh:Q, Ex vivo
Abstract: Inducing selective or targeted cell apoptosis without affecting large number of neighbouring cells remains a challenge. A plausible method for treatment of posterior capsular opacification (PCO) due to remaining lens epithelial cells (LECs) by reactive chemistry induced by localized single electrode microplasma discharge at top of a needle-like glass electrode with spot size ~3 μm is hereby presented. The focused and highly-localized atmospheric pressure microplasma jet with electrode discharge could induce a dose-dependent apoptosis in selected and targeted individual LECs, which could be confirmed by real-time monitoring of the morphological and structural changes at cellular level. Direct cell treatment with microplasma inside the medium appeared more effective in inducing apoptosis (caspase 8 positivity and DNA fragmentation) at a highly targeted cell level compared to treatment on top of the medium (indirect treatment). Our results show that single cell specific micropipette plasma can be used to selectively induce demise in LECs which remain in the capsular bag after cataract surgery and thus prevent their migration (CXCR4 positivity) to the posterior lens capsule and PCO formation.
Published: 2015

220. The Nobel Prized cellular target autophagy in eye diseases

Author: Goran Petrovski, Anu Kauppinen, and Kai Kaarniranta
Subjects: 0301 basic medicine, Biomedical Research, Eye Diseases, Autophagy, Cell Biology, General Medicine, Computational biology, Biology, History, 21st Century, Nobel Prize, 03 medical and health sciences, Ophthalmology, 030104 developmental biology, 0302 clinical medicine, 030221 ophthalmology & optometry, Humans
Published: 2017

221. Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells

Author: Narasimman Gurusamy, Nikolai V. Gorbunov, Dipak K. Das, Goran Petrovski, Do Han Kim, and Diptarka Ray
Subjects: Male, Cardiac function curve, medicine.medical_specialty, Cardiac output, Pathology, Stromal cell, medicine.medical_treatment, Cell- and Tissue-Based Therapy, Myocardial Infarction, SDF, heart, resveratrol, Resveratrol, Biology, Nrf2, Antioxidants, Ref-1, Rats, Sprague-Dawley, chemistry.chemical_compound, Stilbenes, medicine, Animals, Regeneration, Cell Proliferation, Ejection fraction, Myocardium, Stem Cells, cardiac stem cells, Original Articles, Cell Biology, Stem-cell therapy, Rats, Surgery, Transplantation, chemistry, Echocardiography, redox, cardiovascular system, Molecular Medicine, ischaemia, Stem cell, Biomarkers, NFκB, Stem Cell Transplantation
Abstract: The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells after transplantation. Indeed, the vast majority of host-transfused cells do not survive beyond 24–72 hrs. To increase the survival and engraftment of implanted cardiac stem cells in the host, we developed a technique of treating these cells with resveratrol, and tested it in a rat model of left anterior descending (LAD) occlusion. Multi-potent clonogenic cardiac stem cells isolated from rat heart and stably transfected with EGFP were pre-treated with 2.5 μM resveratrol for 60 min. Rats were anaesthetized, hearts opened and the LAD occluded to induce heart attack. One week later, the cardiac reduced environment was confirmed in resveratrol treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). M-mode echocardiography after stem cell therapy, showed improvement in cardiac function (left ventricular ejection fraction, fractional shortening and cardiac output) in both, the treated and control group after 7 days, but only resveratrol-modified stem cell group revealed improvement in cardiac function at the end of 1, 2 and 4 months time. The improvement of cardiac function was accompanied by enhanced stem cell survival and engraftment as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the expression of EGFP up to 4 months after LAD occlusion in the resveratrol-treated stem cell group. Expression of stromal cell-derived factor and myosin conclusively demonstrated homing of stem cells in the infarcted myocardium, its regeneration leading to improvement of cardiac function.
Published: 2011

222. Molecular mechanisms of retinal pigment epithelium damage and development of age-related macular degeneration

Author: Kati Kinnunen, András Berta, Morten C. Moe, Kai Kaarniranta, and Goran Petrovski
Subjects: Pathology, medicine.medical_specialty, genetic structures, Inflammation, Retinal Pigment Epithelium, Degeneration (medical), Biology, Drusen, medicine.disease_cause, Lipofuscin, Pathogenesis, Macular Degeneration, medicine, Humans, Retinal pigment epithelium, General Medicine, Macular degeneration, medicine.disease, eye diseases, Oxidative Stress, Ophthalmology, Phenotype, medicine.anatomical_structure, sense organs, medicine.symptom, Lysosomes, Oxidative stress
Abstract: Age-related macular degeneration (AMD) is attributed to a complex interaction of genetic and environmental factors. It is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium (RPE) and Bruch's membrane, as well as alterations in choroidal capillaries. AMD pathogenesis is strongly associated with chronic oxidative stress and inflammation that ultimately lead to protein damage, aggregation and degeneration of RPE. Specific degenerative findings for AMD are accumulation of intracellular lysosomal lipofuscin and extracellular drusens. In this review, we discuss thoroughly RPE-derived mechanisms in AMD pathology.
Published: 2011

223. Pigment epithelial cells isolated from human peripheral iridectomies have limited properties of retinal stem cells

Author: Bjørn Nicolaissen, Goran Petrovski, Rebecca C. Frøen, Erik O. Johnsen, Erika Berényi, Morten C. Moe, András Berta, and Andrea Facskó
Subjects: Adult, Iridectomy, Pathology, medicine.medical_specialty, Adolescent, Cellular differentiation, Iris, Cell Separation, Retinal Pigment Epithelium, Biology, Ciliary body, Microscopy, Electron, Transmission, SOX2, medicine, Humans, Iris pigment epithelium, Progenitor cell, Fluorescent Antibody Technique, Indirect, Pigment Epithelium of Eye, Cells, Cultured, Aged, Cell Proliferation, DNA Primers, Aged, 80 and over, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Ciliary Body, Glaucoma, General Medicine, Middle Aged, Nestin, Cell biology, Ophthalmology, medicine.anatomical_structure, sense organs, Stem cell, Biomarkers, Adult stem cell
Abstract: Purpose: The identification of cells with properties of retinal progenitor cells (RPCs) in the adult human ciliary margin (CM) prompted a number of studies of their proliferative and differentiation potential. One of the remaining challenges is to find a feasible method of isolating RPCs from the patient’s eye. In the human CM, only the iris pigment epithelium (IPE) is easily obtained by a minimally invasive procedure. In the light of recent studies questioning the existence of RPCs in the adult mammalian CM, we wanted to assess the potential of the adult human IPE as source of RPCs. Methods: The IPE were isolated from peripheral iridectomies during glaucoma surgery, and IPE and ciliary body (CB) epithelium were also isolated from post-mortem tissue. Cells were cultivated in sphere-promoting conditions or as monolayers. Whole-tissue samples, undifferentiated and differentiated cells were studied by immunocytochemistry, RT-PCR and transmission electron microscopy. Results: The adult human IPE, like the CB, expressed markers of RPCs such as Pax6, Sox2 and Nestin in vivo. Both sphere-promoting and monolayer cultures preserved this phenotype. However, both IPE ⁄ CB cultures expressed markers of differentiated epithelial cells such as Claudin, microphtalmia-associated transcription factor (MITF) and Cytokeratin-19. Ultrastructurally, IPE spheres displayed epithelial-like junctions and contained mature melanosomes. After induced differentiation, IPE-derived cells showed only partial neuronal differentiation expressing b-III-tubulin, Map-2 and Rhodopsin, whereas no mature glial markers were found. Conclusion: Proliferative cells with some properties of RPCs can be isolated from the adult human IPE by peripheral iridectomies. Yet, many cells retain properties of differentiated epithelial cells and lack central properties of somatic stem cells.
Published: 2011

224. Autophagy Shapes Inflammation

Author: Goran Petrovski, Máté Á. Demény, and László Fésüs
Subjects: Programmed cell death, Cell type, Necrosis, Physiology, Clinical Biochemistry, Apoptosis, Inflammation, Adaptive Immunity, Biology, Biochemistry, Crohn Disease, Neoplasms, Autophagy, medicine, Animals, Humans, Elméleti orvostudományok, Molecular Biology, General Environmental Science, Effector, Neurodegenerative Diseases, Inflammasome, Orvostudományok, Cell Biology, Acquired immune system, Immunity, Innate, Cell biology, Lysosomal Storage Diseases, General Earth and Planetary Sciences, medicine.symptom, medicine.drug
Abstract: Autophagy is a basic cell biological process ongoing under physiologic circumstances in almost all cell types of the human organism and upregulated by various stress conditions including those leading to inflammation. Since autophagy affects the effector cells of innate and adaptive immunity mediating the inflammatory response, its activity in these cells influences the antimicrobial response, the development of an effective cognate immune defense, and the course of the normal sterile inflammatory reactions. The level of autophagic activity may determine whether tissue cells die by apoptosis, necrosis, or through autophagy, and, as a consequence, whether the clearance of these dying cells is a silent process or results in an inflammatory response. Loss or decreased autophagy may lead to necrotic death that can initiate an inflammatory reaction in phagocytes through their surface and cytosolic receptors. Engulfment of certain cells dying through autophagy can activate the inflammasome. The intertwining regulatory connections between inflammation and immunity extend to pathologic conditions including chronic inflammatory diseases, autoimmunity and cancer.
Published: 2011

225. Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1β release in human macrophages

Author: Goran Petrovski, Gizem Ayna, András Mádi, Gyöngyike Majai, Szilvia Benko, Judit Hodrea, and László Fésüs
Subjects: Lipopolysaccharides, Inflammasomes, Phagocytosis, Interleukin-1beta, NALP3, Biológiai tudományok, Adenosine Triphosphate, Természettudományok, Cell Line, Tumor, Autophagy, medicine, Humans, Macrophage, Secretion, Molecular Biology, biology, Macrophages, Inflammasome, Cell Biology, Cell biology, Apoptosis, Myeloid Differentiation Factor 88, biology.protein, Tumor necrosis factor alpha, Receptors, Purinergic P2X7, Inflammation Mediators, medicine.drug
Abstract: Phagocytosis of naturally dying cells usually blocks inflammatory reactions in host cells. We have recently observed that clearance of cells dying through autophagy leads to a pro-inflammatory response in human macrophages. Investigating this response further, we found that during engulfment of MCF-7 or 293T cells undergoing autophagic death, but not apoptotic or anoikic ones, caspase-1 was activated and IL-1β was processed, then secreted in a MyD88-independent manner. Autophagic dying cells were capable of preventing some LPS-induced pro-inflammatory responses, such as TNFα, IL-6 and IL-8 induction, but synergized with LPS for IL-1β production. Caspase-1 inhibition prevented macrophage IL-1β release triggered by the dying cells and also other pro-inflammatory cytokines which were not formed in the presence of IL-1 receptor antagonist anakinra either. IL-1β secretion was also observed using calreticulin knock down or necrostatin treated autophagic MCF-7 cells and it required phagocytosis of the dying cells which led to ATP secretion from macrophages. Blocking K (+) efflux during phagocytosis, the presence of apyrase, adding an antagonist of the P2X7 receptor or silencing the NOD-like receptor protein NALP3 inhibited IL-1β secretion. These data suggest that during phagocytosis of autophagic dying cells ATP, acting through its receptor, initiates K (+) efflux, inflammasome activation and secretion of IL-1β, which initiates further pro-inflammatory events. Thus, autophagic death of malignant cells and their clearance may lead to immunogenic response.
Published: 2011

226. Successful desensitization in patient with type 2 diabetes with an insulin allergy using insulin pump and glargine

Author: Goran Petrovski, Marija Zivkovic, Iskra Bitovska, Irfan Ahmeti, and Tatjana Milenkovic
Subjects: Male, Insulin pump, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin Glargine, Type 2 diabetes, Drug Hypersensitivity, Insulin Infusion Systems, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, Humans, Insulin, Medicine, In patient, Desensitization (medicine), business.industry, Insulin glargine, Insulin allergy, General Medicine, Middle Aged, medicine.disease, Insulin, Long-Acting, Treatment Outcome, Diabetes Mellitus, Type 2, Desensitization, Immunologic, business, medicine.drug
Abstract: Insulin allergy is rare, but they can occur in patients starting insulin therapy. There are different insulin desensitization protocols where insulin is diluted and given to the patient in small doses for a period of couple of days. We report the case of patient with type 2 diabetes with insulin allergy, where desensitization was performed using insulin pump (Medtronic Minimed Veo) with glargine.
Published: 2014

227. Clearance of dying ARPE-19 cells by professional and nonprofessional phagocytesin vitro- implications for age-related macular degeneration (AMD)

Author: Attila Vajas, Andrea Facskó, Goran Petrovski, Morten C. Moe, András Berta, Erika Berényi, and László Fésüs
Subjects: Retina, Pathology, medicine.medical_specialty, medicine.diagnostic_test, Phagocytosis, General Medicine, Phosphatidylserine, Biology, Molecular biology, In vitro, Flow cytometry, Ophthalmology, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Annexin, Apoptosis, medicine, Anoikis
Abstract: Acta Ophthalmol. 2011: 89: e30–e34 Abstract. Purpose: Failure of retinal pigment epithelial (RPE) cells and macrophages to engulf different dying cells in the retina may result in accumulation of debris and development of age-related macular degeneration (AMD). The dynamics and influence of different treatments on this clearance process can be studied in vitro using human ARPE-19 cells and macrophages as phagocytes modelling dry and wet type of AMD, respectively. Methods: Death through extracellular matrix detachment using polyHEMA-coated surfaces (anoikis) and UV irradiation (apoptosis) was induced in ARPE-19 cells. Two-coloured phagocytic assays were performed to quantify the amount of dying cells phagocytes engulfed (flow cytometry) and for visualization (fluorescent and scanning electron microscopy). The effect of phosphatidylserine inhibition with recombinant annexin-V and glucocorticoid (triamcinolone) treatment on the phagocytic process was tested. Results: The clearance of anoikic and apoptotic cells by nondying ARPE-19 cells over 8 hr of co-incubation increased over time (at 8 hr, over 53% and 35% of the phagocytes contained engulfed dying cells, respectively). The human macrophages engulfed the anoikic and apoptotic ARPE-19 cells with seven and four times lower capacity, respectively. Phosphatidylserine appearance on the dying cells did not affect, but triamcinolone treatment enhanced the phagocytosis of the dying cells by macrophages. Conclusions: ARPE-19 cells are more efficient in clearing anoikic than UV-induced apoptotic cells. Macrophages are less efficient in the clearance process than ARPE-19 cells. The present model can be used for studying both dry and wet type of AMD in vitro and for testing different pharmacological aspects affecting this disease.
Published: 2010

228. Does autophagy take a front seat in lifespan extension?

Author: Dipak K. Das and Goran Petrovski
Subjects: AMPK, autophagy, aging, Calorie restriction, Autophagy, Reviews, Cell Biology, resveratrol, Resveratrol, Biology, Cell biology, Lipofuscin, Spermidine, chemistry.chemical_compound, longevity, chemistry, Ageing, SirT, Animals, Humans, Molecular Medicine, FoxO, PI3K/AKT/mTOR pathway
Abstract: This review focuses on the interrelationship between ageing and autophagy. There is a striking similarity between the signalling aspects of these two processes. Both ageing and autophagy involve several of the signalling components such as insulin/IGF-1, AMPK, Ras-cAMP-PKA, Sch9 and mTOR. Ageing and ageing-mediated defective autophagy involve accumulation of lipofuscin. Components of anti-ageing and autophagy include SirTs and FoxOs. Nutritional deprivation or calorie restriction as well as several nutriceuticals including resveratrol, spermidine, curcumin and piperine can enhance autophagy and increase lifespan. Such striking similarities indicate that lifespan is strongly dependent on autophagy.
Published: 2010

229. Cell death and autophagy: Cytokines, drugs, and nutritional factors

Author: Julia Dornetshuber, Anneliese Karwan, Wilfried Bursch, Miriam Mayer, Goran Petrovski, Barbara Fazi, Rolf Schulte-Hermann, László Fésüs, Mauro Piacentini, Christopher Gerner, Federica Di Sano, Ulrike Fröhwein, and Lucia Piredda
Subjects: Proteomics, Human breast cancer cell line (MCF-7), Programmed cell death, Settore BIO/06, Cell, Nutritional Status, Apoptosis, Vacuole, Biology, Toxicology, Human hepatoma cell line (HCC-1.2).Phagocytosis, Phagocytosis, Cell Line, Tumor, Hexokinase, Autophagy, Caspase-3, Cell injury, Defense, Glucose deprivation, medicine, Animals, Homeostasis, Humans, Cell damage, Caspase 3, medicine.disease, Cell biology, medicine.anatomical_structure, Aggresome, Cytoplasm, Cytokines
Abstract: Cells may use multiple pathways to commit suicide. In certain contexts, dying cells generate large amounts of autophagic vacuoles and clear large proportions of their cytoplasm, before they finally die, as exemplified by the treatment of human mammary carcinoma cells with the anti-estrogen tamoxifen (TAM,or = 1 microM). Protein analysis during autophagic cell death revealed distinct proteins of the nuclear fraction including GST-pi and some proteasomal subunit constituents to be affected during autophagic cell death. Depending on the functional status of caspase-3, MCF-7 cells may switch between autophagic and apoptotic features of cell death [Fazi, B., Bursch, W., Fimia, G.M., Nardacci R., Piacentini, M., Di Sano, F., Piredda, L., 2008. Fenretinide induces autophagic cell death in caspase-defective breast cancer cells. Autophagy 4(4), 435-441]. Furthermore, the self-destruction of MCF-7 cells was found to be completed by phagocytosis of cell residues [Petrovski, G., Zahuczky, G., Katona, K., Vereb, G., Martinet, W., Nemes, Z., Bursch, W., Fésüs, L., 2007. Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes. Cell Death Diff. 14 (6), 1117-1128]. Autophagy also constitutes a cell's strategy of defense upon cell damage by eliminating damaged bulk proteins/organelles. This biological condition may be exemplified by the treatment of MCF-7 cells with a necrogenic TAM-dose (10 microM), resulting in the lysis of almost all cells within 24h. However, a transient (1h) challenge of MCF-7 cells with the same dose allowed the recovery of cells involving autophagy. Enrichment of chaperones in the insoluble cytoplasmic protein fraction indicated the formation of aggresomes, a potential trigger for autophagy. In a further experimental model HL60 cells were treated with TAM, causing dose-dependent distinct responses: 1-5 microM TAM, autophagy predominant; 7-9 microM, apoptosis predominant; 15 microM, necrosis. These phenomena might be attributed to the degree of cell damage caused by tamoxifen, either by generating ROS, increasing membrane fluidity or forming DNA-adducts. Finally, autophagy constitutes a cell's major adaptive (survival) strategy in response to metabolic challenges such as glucose or amino acid deprivation, or starvation in general. Notably, the role of autophagy appears not to be restricted to nutrient recycling in order to maintain energy supply of cells and to adapt cell(organ) size to given physiological needs. For instance, using a newly established hepatoma cell line HCC-1.2, amino acid and glucose deprivation revealed a pro-apoptotic activity, additive to TGF-beta1. The pro-apoptotic action of glucose deprivation was antagonized by 2-deoxyglucose, possibly by stabilizing the mitochondrial membrane involving the action of hexokinase II. These observations suggest that signaling cascades steering autophagy appear to provide links to those regulating cell number. Taken together, our data exemplify that a given cell may flexibly respond to type and degree of (micro)environmental changes or cell death stimuli; a cell's response may shift gradually from the elimination of damaged proteins by autophagy and the recovery to autophagic or apoptotic pathways of cell death, the failure of which eventually may result in necrosis.
Published: 2008

230. Comparative proteomics reveals human pluripotent stem cell-derived limbal epithelial stem cells are similar to native ocular surface epithelial cells

Author: Alexandra Mikhailova, Antti Jylhä, Zoltán Veréb, Tanja Ilmarinen, Ulla Aapola, Roger W. Beuerman, Heli Skottman, Jochen Rieck, Janika Nättinen, Goran Petrovski, Hannu Uusitalo, BioMediTech - BioMediTech, Lääketieteen yksikkö - School of Medicine, and University of Tampere
Subjects: Male, Pluripotent Stem Cells, Proteomics, Pathology, medicine.medical_specialty, Proteome, Cellular differentiation, Human Embryonic Stem Cells, Cell, Biology, Article, Cell Line, medicine, Humans, Stem Cell Niche, Induced pluripotent stem cell, Aged, Cell Proliferation, Corneal epithelium, Multidisciplinary, Biolääketieteet – Biomedicine, Cell growth, Epithelium, Corneal, Cell Differentiation, Epithelial Cells, Korva-, nenä- ja kurkkutaudit, silmätaudit - Otorhinolaryngology, ophthalmology, Embryonic stem cell, eye diseases, 3. Good health, Cell biology, medicine.anatomical_structure, Cell culture, sense organs, Stem cell, Apoptosis Regulatory Proteins, Biomarkers
Abstract: Limbal epithelial stem cells (LESCs) are tissue-specific stem cells responsible for renewing the corneal epithelium. Acute trauma or chronic disease affecting LESCs may disrupt corneal epithelial renewal, causing vision threatening and painful ocular surface disorders, collectively referred to as LESC deficiency (LESCD). These disorders cannot be treated with traditional corneal transplantation and therefore alternative cell sources for successful cell-based therapy are needed. LESCs derived from human pluripotent stem cells (hPSCs) are a prospective source for ocular surface reconstruction, yet critical evaluation of these cells is crucial before considering clinical applications. In order to quantitatively evaluate hPSC-derived LESCs, we compared protein expression in native human corneal cells to that in hPSC-derived LESCs using isobaric tag for relative and absolute quantitation (iTRAQ) technology. We identified 860 unique proteins present in all samples, including proteins involved in cell cycling, proliferation, differentiation and apoptosis, various LESC niche components and limbal and corneal epithelial markers. Protein expression profiles were nearly identical in LESCs derived from two different hPSC lines, indicating that the differentiation protocol is reproducible, yielding homogeneous cell populations. Their protein expression profile suggests that hPSC-derived LESCs are similar to the human ocular surface epithelial cells and possess LESC-like characteristics.
Published: 2015

231. The study of needle tip aspirates and entry sites after intravitreal injections with different needle types

Author: I. Savytska, Goran Petrovski, Lyubomyr Lytvynchuk, A. Sergiienko, and Susanne Binder
Subjects: Pathology, medicine.medical_specialty, business.industry, Enucleation, Balanced salt solution, General Medicine, Entry site, Ophthalmology, Ciliary body, medicine.anatomical_structure, Tissue damage, medicine, sense organs, business
Abstract: Purpose To compare the entry site and study the cellular content of different needle tip aspirates after transscleral intravitreal injection (IVI) on rat eyes. Methods The intravitreal injections (IVI) were performed on 20 white outbred rat eyes (10 IVI with 30-gauge subcutaneous needles (SCN), 10 with 27-gauge Pencan needle (PCN) (B. Braun)). The 1.0 cc syringes were preloaded with 0.02 cc of balanced salt solution (BSS) and connected to the needles. The penetration was performed 1 mm posterior to the limbus, followed by aspiration of 0.01 cc vitreous body. Aspirated material was evacuated onto glass slides and stained by Azure-2-Eosin. Enucleation and histological analysis of the IVI entry site was performed at magnification 100 and 400 times. Results Cellular content of the aspirated material was revealed in all cases. The aspirated cells represented conjunctival epithelial-, ciliary body non-pigmented epithelial-, sclerocyte-like cells and vitreous crystallised specimens. The amount of conjunctival epithelial cells prevailed in 27-gauge PCN IVI cases. The stained granular proteins were less significant in the case of 27-gauge PCN tips. The entry sites after 30-gauge SCN injection showed concrete cut of all tissues, while partial reassembling of the sclerocyte bindings was seen after 27-gauge PCN injections. Conclusions The use of 30-gauge SCN and 27-gauge PCN needles for transscleral IVI has resulted in trauma of all layers of the rats’ eye wall. Histological analysis of the needle tip aspirates showed less tissue damage by 27-gauge PCN; moreover, the SCN tips created complete cuts due to their sharp edges, in contrast to the PCN tips.
Published: 2015

232. In-vitro anti angiogenic effects of cryo-preserved amniotic membrane

Author: Réka Albert, Elizabeth A. Stewart, Harminder S Dua, Lana A Faraj, Claire Allen, W. Amoaku, and Goran Petrovski
Subjects: Ophthalmology, Membrane, Chemistry, Anti angiogenic, General Medicine, In vitro, Cell biology
Published: 2015

233. The Impact of Insulin Pump Therapy on Glycemic Profiles in Patients with Type 2 Diabetes: Data from the OpT2mise Study

Author: Ignacio, Conget, Javier, Castaneda, Goran, Petrovski, Bruno, Guerci, Anne-Sophie, Racault, Yves, Reznik, Ohad, Cohen, Sarah, Runzis, Simona, de Portu, Ronnie, Aronson, and H, Hanaire
Subjects: Insulin pump, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Injections, Subcutaneous, 030209 endocrinology & metabolism, Type 2 diabetes, Hypoglycemia, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Insulin Infusion Systems, Internal medicine, Blood Glucose Self-Monitoring, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, 030212 general & internal medicine, Meals, Glycemic, Aged, Breakfast, Glycated Hemoglobin, business.industry, Original Articles, Middle Aged, medicine.disease, Postprandial Period, Medical Laboratory Technology, chemistry, Diabetes Mellitus, Type 2, Female, Glycated hemoglobin, business
Abstract: Background: The OpT2mise randomized trial was designed to compare the effects of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) on glucose profiles in patients with type 2 diabetes. Research Design and Methods: Patients with glycated hemoglobin (HbA1c) levels of ≥8% (64 mmol/mol) and ≤12% (108 mmol/mol) despite insulin doses of 0.7–1.8 U/kg/day via MDI were randomized to CSII (n=168) or continued MDI (n=163). Changes in glucose profiles were evaluated using continuous glucose monitoring data collected over 6-day periods before and 6 months after randomization. Results: After 6 months, reductions in HbA1c levels were significantly greater with CSII (−1.1±1.2% [−12.0±13.1 mmol/mol]) than with MDI (−0.4±1.1% [−4.4±12.0 mmol/mol]) (P180 mg/dL (−12.4%; P=0.0004) and SG >250 mg/dL (−5.5%; P=0.0153), and more time in the SG range of 70–180 mg/dL (12.3%; P=0.0002), with no differences in exposure to SG180 mg/dL were significantly greater with CSII than with MDI after breakfast (−775.9±1,441.2 mg/dL/min vs. −160.7±1,074.1 mg/dL/min; P=0.0015) and after dinner (−731.4±1,580.7 mg/dL/min vs. −71.1±1,083.5 mg/dL/min; P=0.0014). Conclusions: In patients with suboptimally controlled type 2 diabetes, CSII significantly improves selected glucometrics, compared with MDI, without increasing the risk of hypoglycemia.
Published: 2015

234. The configuration of the vitreomacular interface determines the pattern of pseudophakic cystoid macular oedema

Author: Christoph Schwab, Martin Weger, Goran Petrovski, Andreas Wedrich, Domagoj Ivastinovic, Simone Laura Pössl, M Velikay-Parel, and Georg Mossböck
Subjects: Male, medicine.medical_specialty, Pseudophakia, Interface (Java), Visual Acuity, Cataract Extraction, Macular Edema, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Ophthalmology, medicine, Humans, Macula Lutea, Prospective Studies, Aged, business.industry, General Medicine, Vitreous Body, Cystoid macular oedema, 030221 ophthalmology & optometry, Female, business, 030217 neurology & neurosurgery, Tomography, Optical Coherence
Published: 2015

235. Triamcinolone regulated apopto-phagocytic gene expression patterns in the clearance of dying retinal pigment epithelial cells. A key role of Mertk in the enhanced phagocytosis

Author: Endre Kristóf, László Fésüs, Gábor Zahuczky, Réka Albert, Brigitta Oláh, Goran Petrovski, Mária Szatmári-Tóth, Andrea Facskó, Zoltán Veréb, and Morten C. Moe
Subjects: Male, Phagocytosis, Biophysics, Anti-Inflammatory Agents, Retinal Pigment Epithelium, Triamcinolone, Biochemistry, Receptor tyrosine kinase, Gene Expression Regulation, Enzymologic, Cell Line, Macular Degeneration, Proto-Oncogene Proteins, medicine, Humans, Anoikis, Gene Silencing, Elméleti orvostudományok, Eye Proteins, Molecular Biology, Retinal pigment epithelium, AXL receptor tyrosine kinase, biology, c-Mer Tyrosine Kinase, GAS6, Chemistry, Macrophages, Receptor Protein-Tyrosine Kinases, Epithelial Cells, Orvostudományok, MERTK, Antibodies, Neutralizing, Cell biology, medicine.anatomical_structure, Immunology, biology.protein, Female, Tyrosine kinase
Abstract: Background The apopto-phagocytic gene expression patterns during clearance of dying cells in the retina and the effect of triamcinolone (TC) upon these processes have relevance to development of age-related macular degeneration (AMD). Methods ARPE-19 cells and primary human retinal pigment epithelium (hRPE) were induced to undergo cell death by anoikis and the clearance of these cells by living hRPE/ARPE-19 or human monocyte-derived macrophages (HMDMs) in the presence or absence of TC was quantified by flow cytometry. TaqMan low-density gene expression array determining known markers of phagocytosis and loss-of-function studies on selected apopto-phagocytic genes was carried out in HMDM engulfing anoikic cells. Results The glucocorticoid TC had a profound phagocytosis-enhancing effect on HMDM engulfing anoikic ARPE-19 or hRPE cells, causing a selective upregulation of the Mer tyrosine kinase (MERTK) receptor, while decreasing the expression of the AXL receptor tyrosine kinase and thrombospondin-1 (THSB-1). The key role of the MERTK could be demonstrated in HMDM engulfing dying cells using gene silencing as well as blocking antibodies. Similar pathways were found upregulated in living ARPE-19 engulfing anoikic ARPE-19 cells. Gas6 treatment enhanced phagocytosis in TC-treated HMDMs. Conclusions Specific agonists of the Mertk receptor may have a potential role as phagocytosis enhancers in the retina and serve as future targets for AMD therapy. General significance The use of Gas6 as enhancer of retinal phagocytosis via the MerTK receptor, alone or in combination with other specific ligands of the tyrosine kinase receptors' family may have a potential role in AMD therapy.
Published: 2015

236. Enhanced Regeneration of Corneal Tissue Via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique

Author: Mehrdad Rafat, Saeed Akhtar, Neil Lagali, Per Fagerholm, Zoltán Veréb, Marina Koulikovska, and Goran Petrovski
Subjects: Male, Stromal cell, Optical Phenomena, medicine.medical_treatment, Corneal Stroma, Sus scrofa, Biomedical Engineering, Bioengineering, Ophthalmologic Surgical Procedures, Biochemistry, Biomaterials, Collagen fibril organization, Cornea, Corneal Transplantation, Implants, Experimental, Cell Movement, Materials Testing, medicine, Animals, Humans, Regeneration, Myofibroblasts, Corneal transplantation, Inflammation, Wound Healing, Tissue Scaffolds, business.industry, Regeneration (biology), Lasers, Mesenchymal stem cell, Biochemistry and Molecular Biology, Epithelial Cells, Mesenchymal Stem Cells, Transplantation, medicine.anatomical_structure, Proteoglycans, Collagen, Rabbits, business, Type I collagen, Biokemi och molekylärbiologi, Biomedical engineering
Abstract: Severe shortage of donor corneas for transplantation, particularly in developing countries, has prompted the advancement of bioengineered tissue alternatives. Bioengineered corneas that can withstand transplantation while maintaining transparency and compatibility with host cells, and that are additionally amenable to standardized low-cost mass production are sought. In this study, a bioengineered porcine construct (BPC) was developed to function as a biodegradable scaffold to promote corneal stromal regeneration by host cells. Using high-purity medical-grade type I collagen, high 18% collagen content and optimized EDC-NHS cross-linker ratio, BPCs were fabricated into hydrogel corneal implants with over 90% transparency and four-fold increase in strength and stiffness compared with previous versions. Remarkably, optical transparency was achieved despite the absence of collagen fibril organization at the nanoscale. In vitro testing indicated that BPC supported confluent human epithelial and stromal-derived mesenchymal stem cell populations. With a novel femtosecond laser-assisted corneal surgical model in rabbits, cell-free BPCs were implanted in vivo in the corneal stroma of 10 rabbits over an 8-week period. In vivo, transparency of implanted corneas was maintained throughout the postoperative period, while healing occurred rapidly without inflammation and without the use of postoperative steroids. BPC implants had a 100% retention rate at 8 weeks, when host stromal cells began to migrate into implants. Direct histochemical evidence of stromal tissue regeneration was observed by means of migrated host cells producing new collagen from within the implants. This study indicates that a cost-effective BPC extracellular matrix equivalent can incorporate cells passively to initiate regenerative healing of the corneal stroma, and is compatible with human stem or organ-specific cells for future therapeutic applications as a stromal replacement for treating blinding disorders of the cornea.
Published: 2015

237. Long-Term Cultures of Human Cornea Limbal Explants Form 3D Structures Ex Vivo - Implications for Tissue Engineering and Clinical Applications

Author: Agate Noer, Natasha Josifovska, Sofija Andjelic, Goran Petrovski, Richárd Nagymihály, Dóra Júlia Szabó, Andrea Facskó, Zoltán Veréb, and Morten C. Moe
Subjects: Pathology, medicine.medical_specialty, Primary Cell Culture, Gene Expression, lcsh:Medicine, Biology, Limbus Corneae, Extracellular matrix, Tissue engineering, Antigens, CD, Cornea, medicine, ATP Binding Cassette Transporter, Subfamily G, Member 2, Humans, Vimentin, lcsh:Science, ALCAM, Cell Proliferation, Multidisciplinary, Tissue Engineering, Stem Cells, Tumor Suppressor Proteins, lcsh:R, Epithelium, Corneal, Cell Differentiation, Epithelial Cells, Epithelium, Culture Media, Neoplasm Proteins, Transplantation, medicine.anatomical_structure, Ki-67 Antigen, Cell culture, Keratins, ATP-Binding Cassette Transporters, lcsh:Q, Autopsy, Collagen, sense organs, Stem cell, Biomarkers, Research Article, Transcription Factors
Abstract: Long-term cultures of cornea limbal epithelial stem cells (LESCs) were developed and characterized for future tissue engineering and clinical applications. The limbal tissue explants were cultivated and expanded for more than 3 months in medium containing serum as the only growth supplement and without use of scaffolds. Viable 3D cell outgrowth from the explants was observed within 4 weeks of cultivation. The outgrowing cells were examined by immunofluorescent staining for putative markers of stemness (ABCG2, CK15, CK19 and Vimentin), proliferation (p63α, Ki-67), limbal basal epithelial cells (CK8/18) and differentiated cornea epithelial cells (CK3 and CK12). Morphological and immunostaining analyses revealed that long-term culturing can form stratified 3D tissue layers with a clear extracellular matrix deposition and organization (collagen I, IV and V). The LESCs showed robust expression of p63α, ABCG2, and their surface marker fingerprint (CD117/c-kit, CXCR4, CD146/MCAM, CD166/ALCAM) changed over time compared to short-term LESC cultures. Overall, we provide a model for generating stem cell-rich, long-standing 3D cultures from LESCs which can be used for further research purposes and clinical transplantation.
Published: 2015

238. Inflammation and the apopto-phagocytic system

Author: Goran Petrovski, Gyöngyike Majai, and László Fésüs
Subjects: Inflammation, Phagocytes, Innate immune system, Immunology, Innate lymphoid cell, Apoptosis, Orvostudományok, Biology, medicine.disease_cause, Immunity, Innate, Autoimmunity, Proinflammatory cytokine, Cell biology, Mice, Phagocytosis, Immunity, medicine, Animals, Humans, Immunology and Allergy, Elméleti orvostudományok, medicine.symptom, Opsonin
Abstract: Although under normal conditions many cells die daily mainly by apoptosis in human tissues, inflammation does not occur. The redundant function of a relatively large number of molecules are available to recognize changes occurring on the surface of apoptotic cells, to opsonize the dead cells and to engulf the apoptotic cells previously opsonized or not. Several components of the innate immune system are utilized in this process, mainly soluble factors which bind to the distinct molecular pattern of apoptotic cells. These cells, unlike necrotic ones, do not induce the expression of inflammatory cytokines in phagocytic cells, they can even inhibit such a response and engage an active signaling process to elicit a direct anti-inflammatory effect. The molecular details of these signaling processes have not been clarified yet. Both professional and "amateur" cells can engulf apoptotic cells and mediate an anti-inflammatory action. Disturbance of these processes have significant roles in development of autoimmune diseases and highly malignant tumors.
Published: 2006

239. Characterization of ex vivo cultured neuronal- and glial- like cells from human idiopathic epiretinal membranes

Author: Sofija Andjelic, Goran Petrovski, Andrea Facsk ó, Xiaohe Yan, Marko Hawlina, Jochen Graw, Morten C. Moe, and Xhevat Lumi
Subjects: Male, Pathology, Sox2, Mechanostimulation, Calcium dynamics, Pathogenesis, Nestin, Vitrectomy, Fluorescent Antibody Technique, Indirect, Cells, Cultured, Microscopy, Confocal, Glial fibrillary acidic protein, biology, GFAP, Epiretinal Membrane, General Medicine, Middle Aged, Membrane, medicine.anatomical_structure, Idiopathic epiretinal membrane, Glial- and neuronal cell growth, Neuroglia, Female, Epiretinal membrane, Fura-2, Retinal Neurons, Research Article, Pluripotency, medicine.medical_specialty, Idiopathic Epiretinal Membrane, Glial- And Neuronal Cell Growth, Calcium Dynamics, Acetylcholine, Gfap, Nestin-1, Pax2, Immunophenotyping, SOX2, Glial Fibrillary Acidic Protein, medicine, Humans, Aged, Cell Proliferation, Fluorescent Dyes, business.industry, medicine.disease, Ophthalmology, nervous system, biology.protein, Calcium, business, Ex vivo
Abstract: Background Characterization of the neuro-glial profile of cells growing out of human idiopathic epiretinal membranes (iERMs) and testing their proliferative and pluripotent properties ex vivo is needed to better understand the pathogenesis of their formation. Methods iERMs obtained during uneventful vitrectomies were cultivated ex vivo under adherent conditions and assessed by standard morphological and immunocytochemical methods. The intracellular calcium dynamics of the outgrowing cells was assessed by fluorescent dye Fura-2 in response to acetylcholine (ACh)- or mechano- stimulation. Results The cells from the iERMs formed sphere-like structures when cultured ex vivo. The diameter of the spheres increased by 5% at day 6 and kept an increasing tendency over a month time. The outgrowing cells from the iERM spheres had mainly glial- and some neuronal- like morphology. ACh- or mechano- stimulation of these cells induced intracellular calcium propagation in both cell types; in the neuronal-like cells resembling action potential from the soma to the dendrites. Immunocytochemistry confirmed presence of glial- and neuronal cell phenotype (GFAP and Nestin-1 positivity, respectively) in the iERMs, as well as presence of pluripotency marker (Sox2). Conclusion iERMs contain cells of neuronal- and glial- like origin which have proliferative and pluripotent potential, show functionality reflected through calcium dynamics upon ACh and mechano- stimulation, and a corresponding molecular phenotype.
Published: 2014

240. A Simple Method for Establishing Adherent Ex Vivo Explant Cultures from Human Eye Pathologies for Use in Subsequent Calcium Imaging and Inflammatory Studies

Author: Natasha Josifovska, Xhevat Lumi, Sofija Andjelic, Goran Petrovski, Marko Hawlina, Andrea Facskó, and Zoltán Veréb
Subjects: lcsh:Immunologic diseases. Allergy, Pathology, medicine.medical_specialty, Article Subject, Immunology, chemistry.chemical_element, Inflammation, Stimulation, Cataract Extraction, Viscoelastic Substances, Biology, Calcium, Cataract, Tissue Culture Techniques, Calcium imaging, Lens, Crystalline, medicine, Cell Adhesion, Immunology and Allergy, Humans, Calcium Signaling, Cells, Cultured, Acetylcholine receptor, Calcium signaling, Cell Proliferation, Diabetic Retinopathy, Vitreoretinopathy, Proliferative, Epiretinal Membrane, Epithelial Cells, General Medicine, Anatomy, eye diseases, Acetylcholine, chemistry, Microscopy, Fluorescence, Anterior Capsule of the Lens, Cytokines, sense organs, medicine.symptom, Inflammation Mediators, lcsh:RC581-607, Ex vivo, medicine.drug, Research Article
Abstract: A novel, simple, and reproducible method for cultivating pathological tissues obtained from human eyes during surgery was developed using viscoelastic material as a tissue adherent to facilitate cell attachment and expansion and calcium imaging of cultured cells challenged by mechanical and acetylcholine (ACh) stimulation as well as inflammatory studies. Anterior lens capsule-lens epithelial cells (aLC-LECs) from cataract surgery and proliferative diabetic retinopathy (PDR) fibrovascular epiretinal membranes (fvERMs) from human eyes were used in the study. We hereby show calcium signaling in aLC-LECs by mechanical and acetylcholine (ACh) stimulation and indicate presence of ACh receptors in these cells. Furthermore, anex vivostudy model was established for measuring the inflammatory response in fvERMs and aLC-LECs upon TNFα treatment.
Published: 2014

241. Human retinal pigment epithelial cells dying through autophagy are engulfed by professional and non-professional phagocytes

Author: Goran Petrovski, Réka Albert, Zoltán Veréb, Z Doró, Márta Tóth, Endre Kristóf, and László Fésüs
Subjects: Programmed cell death, medicine.diagnostic_test, Phagocytosis, Autophagy, Retinal, General Medicine, Biology, eye diseases, In vitro, Cell biology, Flow cytometry, Ophthalmology, chemistry.chemical_compound, chemistry, Western blot, Annexin, medicine, sense organs
Abstract: Purpose Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional and non-professional phagocytes can result in debris formation and development of age-related macular degeneration (AMD). We aimed to study the clearance of autophagic dying RPE cells serving as a model for dry and wet type of AMD, respectively. Methods Autophagic cell death was induced by serum deprivation and H2O2 co-treatment in ARPE-19 and primary human RPE (hRPE) cells. Annexin-V FITC/PI labelling was used to determine the cell death rate, while autophagy detection was achieved by Western blot quantification of LC3 II/LC3 I ratio. The clearance of autophagic dying cells by non-professional and professional phagocytes was quantified using flow cytometry. Results An increasing percentage of dying RPE cells was observed in a time- and concentration dependent manner upon H2O2 treatment. Paralelly, an induction of autophagy could be detected within 2hrs of H2O2 treatment. Phagocytosis studies found autophagic dying cells to be efficiently and increasingly engulfed by both professional and non-professional phagocytes over time. Conclusion The clearance of autophagic dying RPE cells can be used as a model for studying both dry and wet type of AMD in vitro, as well as for testing future pharmacological agents for treating this disease.
Published: 2014

242. Functional and molecular characterization of ex vivo cultured neuronal- and glial- like cells from idiopathic epiretinal membranes

Author: Jochen Graw, Xhevat Lumi, Xiaohe Yan, Marko Hawlina, Goran Petrovski, Andrea Facskó, and Sofija Andjelic
Subjects: Cell, Immunocytochemistry, Stimulation, General Medicine, Biology, Phenotype, Calcium in biology, Cell biology, Ophthalmology, Membrane, medicine.anatomical_structure, medicine, Ex vivo, Acetylcholine, medicine.drug
Abstract: Purpose To test the proliferating potential and characterize the functional and molecular profile of cells growing out of human idopathic epiretinal membranes (iERMs) ex vivo. Methods iERMs were obtained from uneventful vitrectomies from cases with iERM. Preoperative and postoperative BCVA, CFT and TMV were compared. Ex vivo cultivation under adherent conditions was carried out and followed up to 6 days. Morphological and immunocytochemical characterization of the cells was carried out. The dynamics of the intracellular calcium was measured using fluorescent dye Fura-2 and imaged in response to pharmacological stimulation by acetylcholine (ACh) or mechanostimulation. Results Visual acuity improved in 9/10 patients. CFT and TMV dereased significantly 3 months after surgery. The cells from the iERMs formed sphere-like structures when cultured ex vivo. The diameter of the spheres increased by 5% at day 6 and kept an increasing tendency over a month. The cells growing out of the iERM spheres had mainly a glial- and some neuronal- like morphology. Stimulation of these cells with ACh or mechanostimulation induced intracellular calcium propagation in both cell phenotypes – in the neuronal-like cells resembling action potential from the soma to the dendrites. Immunocytochemistry confirmed presence of glial- and neuronal cell phenotype in the iERMs, as well as presence of pluripotency marker. Conclusion iERMs contain cells of neuronal- and glial- like origin which have proliferative and pluripotent potential, show functionality reflected through calcium dynamics upon ACh and mechano- stimulation, and a corresponding molecular phenotype.
Published: 2014

243. Effect of hydration on the ultra-structural distribution of collagen fibrils and proteoglycans in human corneal stroma

Author: Goran Petrovski, Saeed Akhtar, Arif O. Khan, Réka Albert, Omar Kirat, and T Almubrad
Subjects: Cuprolinic blue, Chemistry, General Medicine, Anatomy, eye diseases, Collagen fibril, law.invention, Structural distribution, Ophthalmology, chemistry.chemical_compound, medicine.anatomical_structure, Stroma, Osmium tetroxide, law, Cornea, Biophysics, medicine, sense organs, Glutaraldehyde, Electron microscope
Abstract: Purpose We investigated the ultra-structural changes in the distribution of collagen fibrils (CF) and proteoglycans (PGs) due to hydration in the human corneal stroma. Methods Six fresh human scleral corneal rings were hydrated separately in deionized water for 2hrs and 48hrs. Corneas were divided into two parts. The first part of each cornea was fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer and processed for electron microscopy to assess proteoglycans. A second part of each cornea was fixed in 2.5% glutaraldehyde in 0.1M phosphate buffer and post fixed in 1% osmium tetroxide to assess collagen fibril diameter. Results In the hydrated corneas the mean diameter of CF in the anterior stroma (23.40±2.61nm), middle stroma (22.48±3.28nm) and posterior stroma (23.58±2.46nm) was less than the CF diameter in the anterior (28.27±4.05nm), middle (28.22±3.09nm) and posterior stroma (29.73±3.72nm) of the normal cornea. Micro-fibrils within the CF in the hydrated cornea were degenerated. In the hydrated cornea, the mean area of the PGs in the anterior stroma was reduced whereas it increased in the middle stroma compared to those in the normal cornea. The density of the PGs in the hydrated cornea was reduced in the anterior, middle and posterior stroma compared to those in the normal cornea. Conclusion The effect of hydration on the uniform organisation of CF and PGs was higher in the middle and posterior stroma than in the anterior stroma. This could be due to less penetration of water in the interlacing lamellae of the anterior stroma. The reduction in the collagen fibrils diameter could be due to degeneration of microfibrils within the collagen fibrils.
Published: 2014

244. Estrogen signalling in the pathogenesis of age-related macular degeneration

Author: Kai Kaarniranta, Anna Machalińska, Goran Petrovski, Anu Kauppinen, A Salminen, and Zoltán Veréb
Subjects: Male, medicine.medical_specialty, genetic structures, Inflammation, Biology, Drusen, medicine.disease_cause, Retina, Lipofuscin, Pathogenesis, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Macular Degeneration, Internal medicine, medicine, Humans, Retinal, Estrogens, Macular degeneration, medicine.disease, eye diseases, Sensory Systems, Ophthalmology, Oxidative Stress, Endocrinology, medicine.anatomical_structure, chemistry, Female, sense organs, medicine.symptom, Oxidative stress, Signal Transduction
Abstract: Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch’s membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.
Published: 2014

245. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration

Author: Goran Petrovski, Andrea Facskó, Janusz Blasiak, Kai Kaarniranta, and Zoltán Veréb
Subjects: genetic structures, lcsh:Medicine, Review Article, Retinal Pigment Epithelium, Drusen, Biology, medicine.disease_cause, Antioxidants, General Biochemistry, Genetics and Molecular Biology, Lipofuscin, Macular Degeneration, Autophagy, medicine, Humans, Elméleti orvostudományok, Hypoxia, chemistry.chemical_classification, Reactive oxygen species, Retinal pigment epithelium, Neovascularization, Pathologic, General Immunology and Microbiology, lcsh:R, General Medicine, Anatomy, Orvostudományok, Macular degeneration, Hypoxia (medical), medicine.disease, eye diseases, Cell biology, Oxidative Stress, medicine.anatomical_structure, chemistry, sense organs, medicine.symptom, Reactive Oxygen Species, Oxidative stress
Abstract: Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.
Published: 2014

246. Immunogenicity of Dying Cancer Cells–The Inflammasome Connection

Author: Gizem Ayna, László Fésüs, and Goran Petrovski
Subjects: Innate immune system, Autophagy, chemical and pharmacologic phenomena, Inflammasome, Inflammation, Biology, Cell biology, Immune system, Apoptosis, Cancer cell, medicine, Immunogenic cell death, medicine.symptom, medicine.drug
Abstract: One of the natural functions of the immune system is to find and eradicate neoplastic and dysplastic cells in tissues. This immune surveillance can be impaired due to the unpredictable immune escape strategies of cancer cells. Induction of apoptotic cell death by chemotherapy is applied to kill malignant cells in patients with cancer even though it has many weak points, such as the fact that apoptotic cells are usually ignored by the immune system since they are immunologically silent and even suppress inflammation. Inducing immunogenic cell death can promote efficient clearance of cancerous cells before they become aggressive and lethal. Unlike the generally anti-inflammatory apoptotic cells, clearance of immunogenic apoptotic, necrotic, and autophagic dying cells often triggers an innate immune response through inflammasome activation with subsequent release of IL-1β and IL-18 from immune-competent cells. These immunogenic dying cells can expose or release danger-associated molecular pattern molecules (DAMPs), which are the inducers of inflammasome components’ expression and/or assembly of the inflammasome to activate caspase-1 for the formation of active cytokines. In this chapter, we discuss which inflammasome-stimulant DAMPs have been recognized so far, and how immunogenic apoptotic, necrotic, and particularly autophagic dying cells may provoke inflammasome induction and/or activation.
Published: 2014

247. Contributors

Author: Patrizia Agostinis, Macarena Alanís Sánchez, Gizem Ayna, Mario D. Cordero, David Cotán, Ana Delgado Pavón, Mario de la Mata, Luisa De Martino, Guido R.Y. De Meyer, Karin Eberhart, Alejandro Fernández-Vega, László Fésüs, Filomena Fiorito, Yuuki Fujiwara, Padmaja Gade, Juan Garrido Maraver, David A. Gewirtz, Madan M. Godbole, Devrim Gozuacik, Rafael Guerrero-Preston, M.A. Hayat, Eun-Kyeong Jo, José A. Sánchez Alcázar, Tomohiro Kabuta, Dhan V. Kalvakolanu, Jin-A. Lee, Jiankang Liu, Jiangang Long, Wim Martinet, Cédéric F. Michiels, Tsunehiro Mizushima, Kris Nys, Ozlem Oral, Manuel Oropesa-Ávila, Marina Villanueva Paz, Carmen Pérez Calero, Goran Petrovski, Edward A. Ratovitski, Ángeles Rodríguez Hernández, Noemí Rubio Romero, Emil Rudolf, Dorien M. Schrijvers, Lokendra K. Sharma, Dong-Min Shin, Rajesh Singh, Kenji Takagi, Ying Tang, S. Tariq Ahmad, Meenakshi Tiwari, Dhanendra Tomar, Séverine Vermeire, Keiji Wada, Yuran Xie, Zhonglin Xie, Jae-Min Yuk, Ke Zen, and Qipeng Zhang
Published: 2014

248. Omics Technologies and Neovascular Ocular Disorders

Author: Daniel Petrovič, Goran Petrovski, Quan Dong Nguyen, and Borut Peterlin
Subjects: Epigenomics, Pathology, medicine.medical_specialty, Article Subject, Population, lcsh:Medicine, Biology, General Biochemistry, Genetics and Molecular Biology, chemistry.chemical_compound, PEDF, medicine, Humans, education, education.field_of_study, Diabetic Retinopathy, Retinal pigment epithelium, Neovascularization, Pathologic, General Immunology and Microbiology, lcsh:R, Genomics, General Medicine, Diabetic retinopathy, Macular degeneration, medicine.disease, Vascular endothelial growth factor, Editorial, medicine.anatomical_structure, chemistry, Cancer research, Eye disorder, Stem cell
Abstract: Neovascular ocular disorders such as diabetic retinopathy and neovascular age-related macular degeneration (neovascular AMD) are an important cause of blindness in the world [1]. In these disorders, neoangiogenesis plays an important role [2], while various environmental and genetics factors are involved in their pathogenesis [2]. In the last decade of research, the importance of gene-environmental interactions and epigenetic mechanisms has been increasingly emphasized. Inflammation has an important role in the development of proliferative diabetic retinopathy (PDR) as described in the paper by M. Urbancic et al., 2013, “A flow cytometric analysis of vitreous inflammatory cells in patients with proliferative diabetic retinopathy.” Histological and flow cytometric analyses have recently demonstrated the importance of histiocytes/macrophages and T lymphocytes in the development and activation of this disease, but no prediction on the visual prognosis was made. Moreover, higher CD4/CD8 ratio in the vitreous of patients with PDR compared to that in their blood was consistent with local inflammatory response in the disease. Characterization of the cell surface marker phenotype of ex vivo cultured cells growing out of human fibrovascular epiretinal membranes (fvERMs) from PDR can give insight into their function in immunity, angiogenesis, and retinal detachment, as described in the paper by Z. Vereb et al., 2013, “Functional and molecular characterization of ex vivo cultured epiretinal membrane cells from human proliferative diabetic retinopathy.” Several surface markers such as hematopoietic (CD34, CD47) and mesenchymal stem cell markers (CD73, CD90/Thy-1, and PDGFR β) have recently been reported in fvERMs from patients with PDR. Additionally, secretion of different angiogenesis-related factors (DPPIV/CD26, EG-VEGF/PK1, ET-1, IGFBP-2 and 3, IL-8/CXCL8, MCP-1/CCL2, MMP-9, PTX3/TSG-14, serpin E1/PAI-1, serpin F1/PEDF, TIMP-1, and TSP-1) was demonstrated in cells growing out of the fvERMs. The importance of different genes in the pathogenesis of PDR has been reviewed by D. Petrovic, 2013, in the paper “Candidate genes for proliferative diabetic retinopathy.” Several pathogenetic mechanisms have been implicated in the development of PDR such as alteration in retinal blood flow, hemostatic abnormalities, metabolic changes, increased oxidative stress, increased polyol and hexosamine pathway flux, activation of protein kinase C isoforms, and increased advanced glycation end-product formation, growth factors, and so forth (D. Petrovic, 2013, “Candidate genes for proliferative diabetic retinopathy” [1]). One of the regulatory genes that has been implicated in the development of diabetic retinopathy is osteoprotegerin acting as an important regulatory molecule in the vasculature, as shown in the paper by S. M. Ramus et al., 2013, “SNP rs2073618 of the osteoprotegerin gene is associated with diabetic retinopathy in Slovenian patients with type 2 diabetes.” Epigenetic mechanisms are expected to be involved in the pathogenesis of PDR as well. Gene polymorphisms and epigenetic mechanisms responsible for PDR are reviewed in this paper (D. Petrovic, 2013, “Candidate genes for proliferative diabetic retinopathy”; R. A. Kowluru et al., 2013, “Epigenetic modifications and diabetic retinopathy”). The role of epigenetics in diabetic retinopathy is now an emerging area as described in “Epigenetic modifications and diabetic retinopathy” by R. A. Kowluru et al., 2013. It is well known that diabetic environment facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. It has been shown recently that genes encoding mitochondrial superoxide dismutase and matrix metalloproteinase-9 are epigenetically modified, and, by activation of epigenetically modified enzymes, DNA methyltransferases are increased and micro-RNAs responsible for regulating nuclear transcriptional factor and growth factors are upregulated. Additionally, omics analysis provides important information that enables the development of new treatment modalities in vascular eye disorders as described in the paper by A. Maver et al., 2013, “Integration of data from omic studies with the literature-based discovery towards identification of novel treatments for neovascularization in diabetic retinopathy.” Discovery of novel treatments for diabetic retinopathy by complementing the interpretation of omics results using the vast body of information existing in the published literature is a promising approach. With collection of data from transcriptomic studies performed on retinal tissue from animal models of diabetic retinopathy, identification of altered genes and pathways can be enabled, and this approach may help determine new therapies in diabetic retinopathy. In the development of AMD, one of the leading causes of blindness in the elderly, many environmental, lifestyle, and genetic factors are involved. Among them, oxidative stress seems to play a pivotal role. The response to oxidative stress involves several cellular defense reactions leading to the accumulation of detrimental products such as intracellular lipofuscin and extracellular drusen. Moreover, there are many anatomical changes in the retinal pigment epithelium, Bruch's membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD, as shown in the paper by J. Blasiak et al., 2013, “Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration.” The disease has remained at the epicenter of clinical research in ophthalmology. During the past decade, the focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept have become increasingly well-established therapies as shown in the paper by M. Hanout et al., 2013, “Therapies for neovascular age-related macular degeneration: current approaches and pharmacologic agents in development.” Additionally, many other new therapeutic agents, which are in the early phase of clinical trials, have shown promising results. Stem cell therapy is a promising approach in different diseases, including those causing blindness. Recent reports of retinal stem cells being present in several locations of the adult eye have sparked great hopes that they may be used to treat the millions of people worldwide who suffer from blindness as a result of retinal disease or injury [3]. A population of proliferative cells derived from the ciliary body epithelium has been considered one of the prime stem cell candidates, and as such they have received much attention in recent years ([3] “R. Froen et al., 2013, “Does the adult human ciliary body epithelium contain “true” retinal stem cells?”). However, until fully accepted as an important treatment modality in different eye disorders, their usefulness must be confirmed in well-designed clinical trials. Daniel Petrovic Quan Dong Nguyen Borut Peterlin Goran Petrovski
Published: 2014

249. Comparative gene expression analysis of corneal stroma mesenchymal stem cell-like cells, limbal epithelial stem cells and bone marrow-derived mesenchymal stem cells

Author: Zoltán Veréb, Goran Petrovski, Réka Albert, Mc Moe, Sz. Póliska, László Fésüs, and Ok Olstad
Subjects: Cluster of differentiation, Microarray analysis techniques, Mesenchymal stem cell, Notch signaling pathway, General Medicine, Biology, Bioinformatics, Helsinki declaration, Cell biology, Ophthalmology, medicine.anatomical_structure, Stroma, medicine, Bone marrow, Stem cell
Abstract: Purpose Purpose Stem cells in the central part of the cornea serve an important regenerative and homeostatic function. We aimed to describe the genetic fingerprint of these cells and compare that to limbal epithelial stem cells (LESC) and bone marrow-derived MSCs (bmMSCs). Methods Corneal tissue and bmMSCs were harvested from cadavers and healthy donors, respectively (according to the Guidelines of the Helsinki Declaration) and cultured ex vivo. MSC-specific cell surface markers- and genome-wide microarray analysis were performed using FACS and Affymetrix GeneChip Human Gene 1.0 ST Array (~23,000 gene transcripts). Results Genes related to stemness (228), differentiation and lineage (220), cell cycle (108) and HOX, SOCS, Notch signaling (218) were collected into functional groups and clustered hierarchically: 45 genes were found to be specific for corneal stroma (CS)-MSCs, 62 for LESCs and 9 for bmMSCs. The hierarchical clustering clearly separated the CS-MSCs from the LESCs and bmMSCs, but formed a higher cluster with the later. The top 10 genes related to the differences were VCAM1, FNDC1, MFAP5, SFRP2, IGF2, MMP, ITGA2, COLEC12, SEMA3A and MGARP. Number of molecules functioning in cellular movement (381), cellular growth and proliferation (408), development (370) and cellular development (360) were found with top biological functions in CSMSCs compared to LESCs or bmMSCs (p
Published: 2013

250. Cultivation and characterisation of human peripheral cornea derived endothelial cells

Author: Goran Petrovski, Andrew Hopkinson, Aaron M. Yeung, Matthew J. Branch, Reka Albert, Owen D. McIntosh, Laura E. Sidney, Lana A Faraj, Samantha L. Wilson, and Harminder S Dua
Subjects: chemistry.chemical_classification, Stromal cell, General Medicine, Biology, Ascorbic acid, Cell morphology, Molecular biology, Endothelial stem cell, Ophthalmology, Tissue culture, chemistry, Transferrin, Immunology, Collagenase, medicine, sense organs, Ex vivo, medicine.drug
Abstract: To confirm that human corneal rims left over from DALK/DSEK/PK surgeries could be useful sources for ex vivo endothelial cell expansion. Human corneal rims remaining from DALK/DSEK/PK surgeries were utilized (1:1 sex ratio, age 63+20 years, endothelial cell density >2,500 cells/mm2). The time from death to use varied between 3 days and 1.5 months. Endothelial cells isolated using a two-step, peel-and-digest method, whereby the Descemet’s membrane and endothelial cells were peeled off under a dissecting microscope, followed by digestion in collagenase. The isolated cells were suspended in TrypLE prior to plating onto FNC-coated tissue culture plates. The cells were then cultured in Ham’s F12:M199 (1:1) media supplemented with, ascorbic acid, transferrin, sodium selenite and bFGF. Characterisation of the cultured cells was performed by RT-qPCR and immunofluorescence staining accordingly. The number of isolated endothelial cells was repeatedly low (< 20,000 cells). However, improved techniques allowed to reduce stromal cell contamination. It was observed that endothelial cell proliferation was improved when the culture surface area was reduced. Furthermore, typical endothelial cobble stone morphology was observed when the cell density was high. Cell morphology and growth showed notable difference related to donor age and preservation time. ZO-1, Na/K-ATPase and PITX2 were used to confirm the endothelial phenotype. Preserved human corneal rims can be utilized for ex vivo expansion of corneal endothelial cells but further optimization is needed.
Published: 2013

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