Descriptor: "Settore BIO/06 - Anatomia Comparata E Citologia" - Searchworks@Jio Institute Digital Library Search Results

599 results on '"Settore BIO/06 - Anatomia Comparata E Citologia"'

51. CHARACTERIZATION OF TRANSFORMED CELL LINES OBTAINED FROM PRIMARY RAT CORTICAL ASTROCYTES

Author: Gabriella Schiera, Fabio Caradonna, Carlo Maria Di Liegro, Ilenia Cruciata, Ambra Giurintano, Vincenzo Vitale, Italia Di Liegro, and Gabriella Schiera, Fabio Caradonna, Carlo Maria Di Liegro, Ilenia Cruciata, Ambra Giurintano, Vincenzo Vitale, Italia Di Liegro
Subjects: Settore BIO/18 - Genetica, astrocyte, epigenetic and chromosomal alterations, Settore BIO/10 - Biochimica, extracellular vesicle, Settore BIO/06 - Anatomia Comparata E Citologia, Brain cancer
Abstract: Brain cancers are complex and heterogeneous; most of them derive from glial cells[1], and are called gliomas, further subdivided into astrocytomas, oligodendrogliomas, ependymomas and glioastrocytomas[2]. The malignant cells undergo modifications of their metabolism and behaviour, and acquire the ability to migrate along the blood vessels in small groups (model of the guerrilla war)[3], thus invading the surrounding brain parenchyma. Most important, they have the capacity to affect the surrounding microenvironment, by altering both the extracellular matrix and the properties of the normal cells present in the brain, including glial-, endothelial-, and immune-cells, further promoting cancer cell growth and migration. Most of these effects are probably due to molecules (nucleic acids, proteins, lipids etc.) released from cancer cells into their environment via extracellular vesicles (EVs)[1]. Although a lot of efforts have been done, over the years, in order to acquire a better understanding of gliomas at the molecular level, and to set combined therapeutic approaches, brain cancers are mostly incurable. In order to gain a better knowledge of the cellular and molecular events that accompany their transformation, we started from primary cultures of rat cortical astrocytes, and selected three clones that showed increasingly high cell division rates. Then we analyzed both normal cells and their clones at the cytogenetic, cytogenomic and epigenetic level, and found that the most modified astrocytes (A-FC6 clone) have epigenetic and chromosomal alterations typical of cancer, such as an isochromosome (i8q) and that the other two clones (A-GS1 and A-VV5) have intermediate properties. We also analyzed the expression of the linker histone H1.0, normally expressed in differentiated cells[4]. Surprisingly, we found that the somatic histone H1.0 steadily increases from normal astrocytes to the A-FC6 clone. These results suggested that the normal cell cultures together with their three clones may constitute a potential model for studying glioma development. We are now analyzing the expression of other proteins normally expressed in higher amount in cancer cells (e.g. PDI and FABP7), and we are studying how much different is the ability of transformed cells to release EVs respect to normal astrocytes. One of the aim of this study is also to identify proteins and RNAs specifically sorted to EVs from both normal and transformed astrocytes.
Published: 2021

52. Quercetin and MicroRNA Interplay in Apoptosis Regulation in Ovarian Cancer

Author: Haleema Sadia, Khushbukhat Khan, Zeeshan Javed, William C. Cho, Javad Sharifi-Rad, Claudio Luparello, Khan, Khushbukhat, Javed, Zeeshan, Sadia, Haleema, Sharifi-Rad, Javad, Cho, William C, and Luparello, Claudio
Subjects: Phytochemicals, Apoptosis, Carcinoma, Ovarian Epithelial, Biology, Therapeutic approach, chemistry.chemical_compound, Ovarian cancer, Drug Discovery, Oncogenic signaling, microRNA, medicine, Humans, Settore BIO/06 - Anatomia Comparata E Citologia, Cytotoxicity, Ovarian Neoplasms, Pharmacology, Chemo-preventive agent, Cancer, medicine.disease, MicroRNAs, chemistry, miRNAs, Cancer research, Female, Quercetin
Abstract: The multifaceted nature of ovarian cancer has severely hampered the development of effective therapeutics over the years. The complicate nature of ovarian cancer makes it therapeutically challenging, therefore, there has been a renewed interest in phytochemistry. Phytochemicals have emerged as a potential therapeutic option due to less side effects. Moreover, the signaling inhibition properties have also been studied extensively in recent times. A growing number of data obtained via high-throughput technologies has started to delineate the complex oncogenic signaling networks, thus broadening the therapeutic opportunities. Within the network, microRNAs (miRNAs) have been shown to play a versatile role in the regulation of cancer. Quercetin has been in the spotlight over the years because of its high pharmacological values and substantial evidence has demonstrated its anti-proliferative effect against various types of cancers. Despite the versatility of quercetin, little is known about its anti-proliferative potential towards ovarian cancer. This review sheds some light on quercetin as an alternative therapeutic approach to cancer. Furthermore, we also addresss the interplay between miRNAs and quercetin in the regulation of apoptosis in ovarian cancer.
Published: 2021

53. COTAN: scRNA-seq data analysis based on gene co-expression

Author: Francesco Morandin, Manuela Helmer-Citterich, Silvia Giulia Galfrè, Marco Pietrosanto, Federico Cremisi, Galfre, S. G., Morandin, F., Pietrosanto, M., Cremisi, F., and Helmer-Citterich, M.
Subjects: AcademicSubjects/SCI01140, nervous system development, AcademicSubjects/SCI01060, Computer science, Population, AcademicSubjects/SCI00030, Computational biology, AcademicSubjects/SCI01180, Interactome, Plot (graphics), Correlation, Settore BIO/06 - Anatomia Comparata e Citologia, Methods Article, network analysi, education, Gene, Rna-seq, cell population, Contingency table, education.field_of_study, Settore BIO/11, contingency table, gene interaction, genetic transcription, Expression (mathematics), cell level, gene expression, genetic marker, AcademicSubjects/SCI00980, Network analysis, single cell RNA seq
Abstract: Estimating the co-expression of cell identity factors in single-cell is crucial. Due to the low efficiency of scRNA-seq methodologies, sensitive computational approaches are critical to accurately infer transcription profiles in a cell population. We introduce COTAN, a statistical and computational method, to analyze the co-expression of gene pairs at single cell level, providing the foundation for single-cell gene interactome analysis. The basic idea is studying the zero UMI counts’ distribution instead of focusing on positive counts; this is done with a generalized contingency tables framework. COTAN can assess the correlated or anti-correlated expression of gene pairs, providing a new correlation index with an approximate p-value for the associated test of independence. COTAN can evaluate whether single genes are differentially expressed, scoring them with a newly defined global differentiation index. Similarly to correlation network analysis, it provides ways to plot and cluster genes according to their co-expression pattern with other genes, effectively helping the study of gene interactions, becoming a new tool to identify cell-identity markers. We assayed COTAN on two neural development datasets with very promising results. COTAN is an R package that complements the traditional single cell RNA-seq analysis and it is available at https://github.com/seriph78/COTAN.
Published: 2021

54. miR-182-5p is an evolutionarily conserved Tbx5 effector that impacts cardiac development and electrical activity in zebrafish

Author: Marco Pellegrini, Elena Guzzolino, Neha Ahuja, Elisabetta Tognoni, Monica Evangelista, Marco Groth, Vincenzo Lionetti, Chiara Ippolito, Alberto Mercatanti, Cathy J. Hatcher, Deborah M. Garrity, Ryuichi Fukuda, Mario Pellegrino, Romina D'Aurizio, Federico Cremisi, Mario Baumgart, Letizia Pitto, Guzzolino, E., Pellegrino, M., Ahuja, N., Garrity, D., D'Aurizio, R., Groth, M., Baumgart, M., Hatcher, C. J., Mercatanti, A., Evangelista, M., Ippolito, C., Tognoni, E., Fukuda, R., Lionetti, V., Pellegrini, M., Cremisi, F., and Pitto, L.
Subjects: Regulator, Down-Regulation, Biology, Cell Line, Animals, Genetically Modified, Kruppel-Like Factor 4, Mice, Settore BIO/06 - Anatomia Comparata e Citologia, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cardiac development, Downregulation and upregulation, Pregnancy, microRNA, Animals, Myocytes, Cardiac, Molecular Biology, Transcription factor, Zebrafish, Pharmacology, 0303 health sciences, Heart development, Effector, Calcium channel, 030302 biochemistry & molecular biology, Arrhythmias, Cardiac, Heart, Cell Biology, Holt-Oram syndrome, biology.organism_classification, Up-Regulation, microRNAs, Cell biology, Mice, Inbred C57BL, Gene Expression Regulation, Holt–Oram syndrome, Molecular Medicine, Calcium, Female, T-Box Domain Proteins, Transcription Factors
Abstract: To dissect the TBX5 regulatory circuit, we focused on microRNAs (miRNAs) that collectively contribute to make TBX5 a pivotal cardiac regulator. We profiled miRNAs in hearts isolated from wild-type, CRE, Tbx5lox/+and Tbx5del/+ mice using a Next Generation Sequencing (NGS) approach. TBX5 deficiency in cardiomyocytes increased the expression of the miR-183 cluster family that is controlled by Kruppel-like factor 4, a transcription factor repressed by TBX5. MiR-182-5p, the most highly expressed miRNA of this family, was functionally analyzed in zebrafish. Transient overexpression of miR-182-5p affected heart morphology, calcium handling and the onset of arrhythmias as detected by ECG tracings. Accordingly, several calcium channel proteins identified as putative miR-182-5p targets were downregulated in miR-182-5p overexpressing hearts. In stable zebrafish transgenic lines, we demonstrated that selective miRNA-182-5p upregulation contributes to arrhythmias. Moreover, cardiac-specific down-regulation of miR-182-5p rescued cardiac defects in a zebrafish model of Holt–Oram syndrome. In conclusion, miR-182-5p exerts an evolutionarily conserved role as a TBX5 effector in the onset of cardiac propensity for arrhythmia, and constitutes a relevant target for mediating the relationship between TBX5, arrhythmia and heart development. To dissect the TBX5 regulatory circuit, we focused on microRNAs (miRNAs) that collectively contribute to make TBX5 a pivotal cardiac regulator. We profiled miRNAs in hearts isolated from wild-type, CRE, Tbx5lox/+and Tbx5del/+ mice using a Next Generation Sequencing (NGS) approach. TBX5 deficiency in cardiomyocytes increased the expression of the miR-183 cluster family that is controlled by Kruppel-like factor 4, a transcription factor repressed by TBX5. MiR-182-5p, the most highly expressed miRNA of this family, was functionally analyzed in zebrafish. Transient overexpression of miR-182-5p affected heart morphology, calcium handling and the onset of arrhythmias as detected by ECG tracings. Accordingly, several calcium channel proteins identified as putative miR-182-5p targets were downregulated in miR-182-5p overexpressing hearts. In stable zebrafish transgenic lines, we demonstrated that selective miRNA-182-5p upregulation contributes to arrhythmias. Moreover, cardiac-specific down-regulation of miR-182-5p rescued cardiac defects in a zebrafish model of Holt–Oram syndrome. In conclusion, miR-182-5p exerts an evolutionarily conserved role as a TBX5 effector in the onset of cardiac propensity for arrhythmia, and constitutes a relevant target for mediating the relationship between TBX5, arrhythmia and heart development.
Published: 2019
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55. DNA fragmentation index, pAKT and pERK1/2 in cumulus cells are related to oocyte competence in patients undergoing in vitro fertilization programme

Author: Domenica Matranga, Maria Carmela Roccheri, Giovanni Ruvolo, Alberto Ferrigno, Claudio Luparello, Liana Bosco, Ruvolo Giovanni, Roccheri Maria Carmela, Luparello Claudio, Matranga Domenica, Ferrigni Alberto, and Bosco Liana
Subjects: medicine.medical_treatment, Molecular marker, Biology, Cell survival, Intracytoplasmic sperm injection, Settore MED/01 - Statistica Medica, Andrology, 03 medical and health sciences, 0302 clinical medicine, Oocyte quality, medicine, Blastocyst, Viability assay, Settore BIO/06 - Anatomia Comparata E Citologia, 030304 developmental biology, 0303 health sciences, 030219 obstetrics & reproductive medicine, In vitro fertilisation, Apoptosi, Cell Biology, Oocyte, medicine.anatomical_structure, Apoptosis, DNA fragmentation, DFI, Intracellular, Developmental Biology
Abstract: SummaryActivated pERK1/2 and pAKT are key players in supporting cell survival and proliferation pathways. Translocation of pERK1/2 into the nucleus, where it interacts with transcription factors and DNA itself, is instrumental in exerting an anti-apoptotic effect. In this study, pAKT levels, pERK1/2 nuclear localization and DNA fragmentation index (DFI) in cumulus cells of single cumulus–oocyte complexes of patients undergoing in vitro fertilization programmes were evaluated and correlated with the clinical outcome of the related embryos. For a positive clinical outcome of blastocyst development, pERK1/2 nuclear localization and DFI value had a significant inverse relationship, whereas the former and the intracellular accumulation of pAKT had a significant direct relationship. This relationship was not observed for the negative clinical outcome of the arrested embryos. Moreover, intracellular accumulation of pAKT and DFI value had a significant inverse relationship in all samples examined. The obtained data suggest that the intranuclear relocation of pERK1/2, along with an enhanced intracellular accumulation of pAKT, may exert a survival effect and increase cell viability, therefore providing a novel marker tool to choose the best oocyte to be fertilized and submitted to an intracytoplasmic sperm injection cycle.
Published: 2019
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56. Effects of dietary dehydrated lemon peel on some biochemical markers related to general metabolism, welfare and stress in gilthead seabream (Sparus aurataL.)

Author: María Ángeles Esteban, José María García Beltrán, Francisco A. Guardiola, Andrea Santulli, Cristóbal Espinosa, Concetta Maria Messina, Simona Manuguerra, Garcia Beltran J.M., Espinosa C., Guardiola F.A., Manuguerra S., Santulli A., Messina C.M., and Esteban M.A.
Subjects: medicine.medical_specialty, Gilthead Seabream, antioxidant, dehydrated lemon peel, Aquatic Science, Biology, medicine.disease_cause, gilthead seabream (Sparus aurata), antioxidants, dehydrated lemon peel, gilthead seabream (Sparus aurata), metabolism, welfare, 03 medical and health sciences, Settore AGR/20 - Zoocolture, Internal medicine, medicine, Settore BIO/06 - Anatomia Comparata E Citologia, Alanine aminotransferase, Biochemical markers, 030304 developmental biology, 0303 health sciences, Lemon peel, 04 agricultural and veterinary sciences, Metabolism, Mucus, welfare, Endocrinology, Apoptosis, 040102 fisheries, 0401 agriculture, forestry, and fisheries, metabolism, Oxidative stress
Abstract: Dehydrated lemon peel (DLP) at two levels (1.5% and 3%) was included for 30days in the diet of gilthead seabream (Sparus aurata L.) and after 15 and 30days the serum and skin mucus of fish were analysed. In serum, both experimental diets led to an initial decrease in glucose and lactate after which the levels became comparable to the control. Dietary DLP modulated the activity of transaminases, alanine aminotransferase and aspartate aminotransferase. The total antioxidant status showed a progressive increase in relation to levels of inclusion of DLP and time of administration (p'.05). In skin mucus, some biomolecular markers related to general stress, oxidative stress and apoptosis exhibited variations that suggest an adaptive response of fish to the new metabolic situation, resulting from the experimental diet. The inclusion of DLP in the diet seems to positively modulate the central metabolism and welfare of gilthead seabream.
Published: 2019
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57. Biotechnological Applications for the Sustainable Use of Marine By-products: In Vitro Antioxidant and Pro-apoptotic Effects of Astaxanthin Extracted with Supercritical CO2 from Parapeneus longirostris

Author: Giuseppe Renda, Simona Manuguerra, Andrea Santulli, Concetta Maria Messina, Messina Concetta Maria, Manuguerra Simona, Renda Giuseppe, and Santulli Andrea
Subjects: 0106 biological sciences, 0301 basic medicine, Marine bioactive compound, Antioxidant, medicine.medical_treatment, Biology, medicine.disease_cause, Supercritical fluid extraction, 01 natural sciences, Applied Microbiology and Biotechnology, 03 medical and health sciences, chemistry.chemical_compound, Nutraceutical, Settore AGR/20 - Zoocolture, Astaxanthin, 010608 biotechnology, medicine, Food science, Settore BIO/06 - Anatomia Comparata E Citologia, Carotenoid, chemistry.chemical_classification, Anti-proliferative, Apoptosi, Marine bioactive compounds, Astaxanthin, Supercritical fluid extraction, Antioxidants, Anti-proliferative, Apoptosis, 030104 developmental biology, chemistry, Cell culture, Apoptosis, Toxicity, Oxidative stress
Abstract: In this study, the carotenoid astaxanthin was obtained by supercritical fluid extraction (SFE) from shrimp by-products (SBP). Its bioactive properties were evaluated in vitro in human normal and cancerous cells lines. The antioxidant activity of the extracted astaxanthin of the SFE fraction (ASTA) was tested in fibroblast cells (HS-68), by inducing oxidative stress and by evaluating the protective effect of the pre-treatment with different levels of ASTA against toxicity. The anti-proliferative activity was evaluated in hepatoma cells (HEP-G2), treated with increased concentrations of ASTA and measuring the effects on vitality and on some biomolecular markers related to oxidative stress, cell cycle, and apoptosis. It was found that pre-treating normal fibroblast cells with ASTA resulted in a marked increase in cell viability in a dose-dependent manner (P < 0.05) attesting its antioxidant power; in cancer cell line, increased concentrations of ASTA caused a time-dose-dependent decrease in the vitality, attesting its anti-proliferative activity (P < 0.05). The increased levels of the protein p-53 and the reduced levels of the proteins c-Jun and c-Fos at higher concentrations of ASTA, as well as, suggest the pro-apoptotic and anti-cancerous effects that this extract has on hepatocellular carcinomas, confirmed also by caspase-3 activation. These findings suggest biotechnological utilisation of marine by-products for nutraceutical and pharmaceutical applications avoiding the employment of organic solvents for extraction.
Published: 2019
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58. Effects of magnesium deprivation on development and biomineralization in the sea urchin Arbacia lixula

Author: Maria Byrne, Maria Carmela Roccheri, Chiara Martino, Valeria Matranga, Roberto Chiarelli, Martino C., Chiarelli R., Roccheri M.C., Matranga V., and Byrne M.
Subjects: 0106 biological sciences, animal structures, chemistry.chemical_element, Calcium, 010603 evolutionary biology, 01 natural sciences, chemistry.chemical_compound, Endoskeleton, biology.animal, Skeletogenesis, Settore BIO/06 - Anatomia Comparata E Citologia, Sea urchin, Arbacia lixula, primary mesenchyme cell, Calcite, biology, Magnesium, magnesium calcite, 010604 marine biology & hydrobiology, fungi, Pigment cells, echinopluteu, biology.organism_classification, pigment cell, chemistry, embryonic structures, Biophysics, Animal Science and Zoology, Developmental Biology, Biomineralization
Abstract: Echinoderms have an extensive endoskeleton composed of magnesian calcite and occluded matrix proteins. As biomineralization in sea urchin larvae is sensitive to the Magnesium:Calcium ratio of seawater, we investigated the effects of magnesium deprivation on development and skeletogenesis in the sea urchin Arbacia lixula. We focused on the localization of the skeletogenic cells (primary mesenchyme cells) and the spatial expression of associated genes. Embryos reared in Mg-free seawater exhibited developmental delay from 6-h post-fertilization and at 24 h embryos showed complete lack of biomineral formation. Larvae (48–72 h) exhibited severe skeleton malformations. Fluorescent labelling revealed that the primary mesenchyme cells and the developing skeleton of treated embryos were in an abnormal ectopic location. Expression of the skeleton matrix protein gene (msp130) in the primary mesenchyme cells as seen using in situ hybridization was normal at 24 h. At 48 h this gene was down-regulated in control larvae, but not in treated larvae. Development of the pigment cells, immune cells that, like the skeleton, are mesodermal derivatives, was also impaired. Our results highlight the essential role of Mg in skeleton formation in sea urchin embryos with an indication that this element is also generally important for the development of mesoderm. Abbreviations: hpf: hours post fertilization; PMCs: primary mesenchyme cells; ACC: amorphous calcium carbonate; MgFSW: magnesium-free seawater; FSW: filtered seawater Impact statement Echinoderms have an extensive endoskeleton composed of magnesian calcite We investigated the effects of magnesium deprivation on development and skeletogenesis in the sea urchin Arbacia lixula Magnesium deprivation caused developmental delay and skeleton malformations Primary mesenchyme cells of treated embryos were in an abnormal ectopic location The spatial and temporal expression profile of the skeleton matrix protein gene (msp130) was found to be different from controls Our results highlight the essential role of Mg across developmental processes in sea urchin embryos.
Published: 2019
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59. Biological and Proteomic Characterization of the Anti-Cancer Potency of Aqueous Extracts from Cell-Free Coelomic Fluid of Arbacia lixula Sea Urchin in an In Vitro Model of Human Hepatocellular Carcinoma

Author: Claudio Luparello, Rossella Branni, Giulia Abruscato, Valentina Lazzara, Simon Sugár, Vincenzo Arizza, Manuela Mauro, Vita Di Stefano, Mirella Vazzana, Luparello, Claudio, Branni, Rossella, Abruscato, Giulia, Lazzara, Valentina, Sugár, Simon, Arizza, Vincenzo, Mauro, Manuela, Di Stefano, Vita, and Vazzana, Mirella
Subjects: reactive oxygen specie, Settore CHIM/10 - Chimica Degli Alimenti, Settore BIO/05 - Zoologia, HepG2 cell, Ocean Engineering, apoptosi, sea urchin, echinoderm, mitochondrial transmembrane potential, cell cycle, acidic vesicular organelle, Settore BIO/06 - Anatomia Comparata E Citologia, coelomic fluid, HepG2 cells, apoptosis, acidic vesicular organelles, reactive oxygen species, wound healing assay, Water Science and Technology, Civil and Structural Engineering
Abstract: Echinoderms are an acknowledged source of bioactive compounds exerting various beneficial effects on human health. Here, we examined the potential in vitro anti-hepatocarcinoma effects of aqueous extracts of the cell-free coelomic fluid obtained from the sea urchin Arbacia lixula using the HepG2 cell line as a model system. This was accomplished by employing a combination of colorimetric, microscopic and flow cytometric assays to determine cell viability, cell cycle distribution, the possible onset of apoptosis, the accumulation rate of acidic vesicular organelles, mitochondrial polarization, cell redox state and cell locomotory ability. The obtained data show that exposed HepG2 cells underwent inhibition of cell viability with impairment of cell cycle progress coupled to the onset of apoptotic death, the induction of mitochondrial depolarization, the inhibition of reactive oxygen species production and acidic vesicular organelle accumulation, and the block of cell motile attitude. We also performed a proteomic analysis of the coelomic fluid extract identifying a number of proteins that are plausibly responsible for anti-cancer effects. Therefore, the anti-hepatocarcinoma potentiality of A. lixula’s preparation can be taken into consideration for further studies aimed at the characterization of the molecular mechanism of cytotoxicity and the development of novel prevention and/or treatment agents.
Published: 2022
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60. Chromatin Maturity Index (CMI) in unfixed and live spermatozoa and Aniline Blue (AB) stained as an additional evaluation parameter in idiopathic male infertility

Author: T. Notari, M. Piscopo, L. Bosco, S. Pecoraro, N. Serra, D. Ricciardi, G. Capra, L. Montano, and T. Notari, M. Piscopo, L. Bosco, S. Pecoraro, N. Serra, D. Ricciardi, G. Capra, L. Montano
Subjects: spermatozoa, Aniline Blue, Chromatin Maturity Index, Settore BIO/06 - Anatomia Comparata E Citologia, male infertility
Abstract: Study question: To investigate whether idiopathic male infertility may be due to the presence of histones in motile spermatozoa using a modified AB staining protocol. Summary answer: No correlation between CMI in live motile spermatozoa, DNA Fragmentation Index (DFI) and other conventional seminal parameters were found in male infertile patients. What is known already: The AB stain discriminates between lysine-rich histones and arginine/cysteine-rich protamines. Transition from histones to protamines during spermatogenesis remodels chromatin packaging and abnormalities in the substitution of those proteins maybe interfere with seminal parameters and affect male infertility. The correlation between CMI and seminal parameters is known, but little is knowledge about live and motile spermatozoa associated to CMI because literature report only spermatozoa fixation before staining. Sperm chromatin carries half of the genomic material to offspring. Spermatozoa nuclear status is crucial for balanced transmission to future generations, and histones modifications are directly involved in epigenetic mutations. Study design, size, duration: Retrospective observational study of 77 men underwent to standard semen analysis, including the evaluation of CMI and DFI, enrolled from January to December 2020. Mean age of the men was 36.63±8.26 years old, sperm concentration 46.69±37.23 mill/mL, linear progressive motility 39.35±15.31%, normal morphology 6.42±3.40%, DFI 25.91±10.29%. 200 spermatozoa for evaluation of CMI and 300 for DFI were analyzed respectively. Participants/materials, setting, methods: Semen samples of 77 patients were collected and analyzed according to 5th edition of WHO guidelines (2010) for examination of human semen. For the evaluation of CMI we performed a new modified protocol for AB stain directly in live spermatozoa. Dilution 1:1 fresh semen and Aniline Blue colorant were mixed and placed on a slide and examined in bright field microscopy x1000 magnification. DFI was evaluated using Sperm Chromatin Dispersion (SCD) test. Main results and the role of chance: Of all spermatozoa analyzed, 82.58±29.98% were white, 17.17±17.21% were pale blue, and 28.53±21.09% were dark blue. By our modified protocol, directly in live spermatozoa, we correlated AB staining with motility and , surprisingly, all motile spermatozoa observed were not stained (white), while pale or dark blue spermatozoa resulted always immotile. For this reason, we have considered pale blue spermatozoa as AB positive, in disagreement with some authors. So, maybe, we should reconsider pale blue stained spermatozoa as abnormal. We also observed AB negative spermatozoa with morphological head, neck and tail defects, underlining the independence of these two parameters: nuclear status and morphology. We have observed no statistically significant differences between conventional semen parameters, DFI and CMI, so nuclear analysis seems to be independent parameters. The statistical analysis was performed by Matlab statistical toolbox version 2008 (MathWorks, Natick, MA, USA) for Windows at 32 bit; finally all tests with p-value (p) < 0.05 were considered significant. Attention should be paid to the evaluation of CMI not only in astenozoospermic patients, where a lower CMI is known, but also in normozoospermic infertile patients. Limitations, reasons for caution: This is a preliminary observational study on a small number of normozoospermic or mild asthenozoospermic patients. The study should be considered as a pilot study. Future studies with higher number of samples are necessary in order to confirm the results obtained. Wider implications of the findings: This is the first study that reports AB staining on unfixed live spermatozoa with a modified protocol. Our study underlines the necessity of classify pale blue spermatozoa as AB positive. Further investigations are necessary. This is a starting point for future analysis to be carried out under the project EcoFoodFertility. Trial registration number: not applicable
Published: 2021

61. Functional investigations of matrix metalloproteinases in breast cancer: focus on MMP9 and MMP2

Author: Miriam Buttacavoli, Gianluca Di Cara, E. Roz, I. Pucci-Minafra, P. Cancemi, and Miriam Buttacavoli, Gianluca Di Cara, E. Roz, I. Pucci-Minafra, P. Cancemi
Subjects: Settore BIO/06 - Anatomia Comparata E Citologia, matrix metalloproteinases, biomarkers, breast cancer
Published: 2021

62. Cadmium-Associated Molecular Signatures in Cancer Cell Models

Author: Claudio Luparello and Luparello, Claudio
Subjects: 0301 basic medicine, Cancer Research, cadmium, nasopharyngeal cancer, Review, Biology, gene signature, differential expression, liver cancer, 03 medical and health sciences, 0302 clinical medicine, breast cancer, Gene silencing, Settore BIO/06 - Anatomia Comparata E Citologia, RC254-282, Regulation of gene expression, gastric cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gene signature, in vitro cell models, Phenotype, in vitro cell model, Gene expression profiling, lung cancer, 030104 developmental biology, Oncology, colon cancer, Tumor progression, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Reprogramming
Abstract: Simple Summary The exposure of cancer cells to cadmium compounds may be associated with the acceleration of tumor progression. It is known that cadmium is a transcriptional regulator, and the study of differentially expressed genes has enabled the identification and classification of cadmium-associated molecular signatures as useful biomarkers that are potentially transferable to clinical research. This review recapitulates the studies that report the detection of such signatures in breast, gastric, colon, liver, lung, and nasopharyngeal tumor cell models, as specifically demonstrated by individual gene or whole genome expression profiling. Abstract The exposure of cancer cells to cadmium and its compounds is often associated with the development of more malignant phenotypes, thereby contributing to the acceleration of tumor progression. It is known that cadmium is a transcriptional regulator that induces molecular reprogramming, and therefore the study of differentially expressed genes has enabled the identification and classification of molecular signatures inherent in human neoplastic cells upon cadmium exposure as useful biomarkers that are potentially transferable to clinical research. This review recapitulates selected studies that report the detection of cadmium-associated signatures in breast, gastric, colon, liver, lung, and nasopharyngeal tumor cell models, as specifically demonstrated by individual gene or whole genome expression profiling. Where available, the molecular, biochemical, and/or physiological aspects associated with the targeted gene activation or silencing in the discussed cell models are also outlined.
Published: 2021

63. Glial cells of the developing amphioxus: a molecular study

Author: BOZZO, MATTEO
Subjects: Settore BIO/06 - Anatomia Comparata e Citologia, nervous system, astroglia, invertebrate glia, radial glia, glial and neural progenitors, neuroglia, invertebrate glia, cephalochordates, astroglia, nervous system evolution, glial and neural progenitors, radial glia, cephalochordates, nervous system evolution, neuroglia
Abstract: Glial cells play important roles in the development and homeostasis of metazoan nervous systems. However, while their involvement in the development and function in the central nervous system (CNS) of vertebrates is increasingly well understood, much less is known about invertebrate glia and the evolutionary history of glial cells more generally. An investigation into amphioxus glia is therefore timely, as this organism is the best living proxy for the last common ancestor of all chordates, and hence provides a window on the role of glial cells development and function at the transition between invertebrates and vertebrates. We report here our findings on amphioxus glia as characterized by molecular probes correlated with anatomical data at the TEM level. The results show amphioxus glial lineages express genes typical of vertebrate astroglia and radial glia and segregate early in development, forming what appears to be a spatially separated cell proliferation zone positioned laterally, between the dorsal and ventral zones of neural cell proliferation. Our study provides strong evidence for the presence of vertebrate-type glial cells in amphioxus while highlighting the role played by segregated progenitor cell pools in CNS development. There are implications also for our understanding of glial cells in a broader evolutionary context and insights into patterns of precursor cell deployment in the chordate nerve cord.
Published: 2021

64. MicroRNAs regulatory networks governing the epigenetic landscape of MEN1 gastro‐entero‐pancreatic neuroendocrine tumor: A case report

Author: Luca Pandolfini, Simone Ciuffi, Maria Luisa Brandi, Ettore Luzi, Federico Cremisi, Francesca Marini, Gabriella Nesi, Luzi, Ettore, Pandolfini, Luca, Ciuffi, Simone, Marini, Francesca, Cremisi, Federico, Nesi, Gabriella, and Brandi, MARIA LUISA
Subjects: Medicine (General), Medicine (miscellaneous), MicroRNA, Gastro entero pancreatic, Duodenal Neoplasm, Biology, Bioinformatics, Letter to Editor, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Settore BIO/06 - Anatomia Comparata e Citologia, R5-920, Stomach Neoplasm, Gastrinoma, microRNA, Multiple Endocrine Neoplasia Type 1, Pancrea, Molecular Medicine, Female, Gene Regulatory Networks, MEN1, Epigenetics, Neuroendocrine Tumor, Human
Published: 2021
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65. Farmed Gilthead Sea Bream (Sparus aurata) by-Products Valorization: Viscera Oil ω-3 Enrichment by Short-Path Distillation and In Vitro Bioactivity Evaluation

Author: Concetta Maria Messina, Rosaria Arena, Vincenzo Alessandro Laudicella, Laura La Barbera, Giuseppe Renda, Gioacchino Fazio, Andrea Santulli, Simona Manuguerra, Giovanna Ficano, Messina C.M., Arena R., Manuguerra S., Renda G., Laudicella V.A., Ficano G., Fazio G., La Barbera L., and Santulli A.
Subjects: Antioxidant, 030309 nutrition & dietetics, Thiobarbituric acid, Fish farming, medicine.medical_treatment, Short path distillation, Pharmaceutical Science, Pilot Projects, nutraceutics, Antioxidants, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, Settore AGR/20 - Zoocolture, 3T3-L1 Cells, Fatty Acids, Omega-3, Drug Discovery, Adipocytes, TBARS, medicine, Animals, Peroxide value, Food science, Settore BIO/06 - Anatomia Comparata E Citologia, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), by-products, lcsh:QH301-705.5, Distillation, Waste Products, chemistry.chemical_classification, 0303 health sciences, Adipogenesis, omega-3 fatty acids, Fatty acid, 04 agricultural and veterinary sciences, 040401 food science, Sea Bream, fish oils, Oxidative Stress, Viscera, chemistry, aquaculture, lcsh:Biology (General), Bass, Polyunsaturated fatty acid
Abstract: This study shows a pilot scale protocol aimed to obtain an omega 3-enriched oil after the processing of farmed gilthead sea bream viscera (SBV), this was oil was tested in vitro for bioactivity, attesting to the possibility to turn waste into profit The quality of the oil, in terms of requirements for animal and human consumption, was assessed by determining some chemical parameters, such as peroxide value (PV), thiobarbituric acid reactive substances (TBARS), ρ-anisidine (ρ-AV) content, total oxidation value (TOTOX), and phospholipids and free fatty acid (%), both in crude viscera oil (CVO) and refined viscera oil (RVO). Among the extraction conditions, the higher CVO yields were obtained at 60 °C for 10 min (57.89%) and at 80 °C for 10 min (67.5%), and the resulting oxidation levels were low when utilizing both extraction conditions. RVO, obtained from CVO extracted at 60 °C, showed the highest quality on the basis of the assessed parameters. The ethyl esters of the total fatty acid (TFA) contents extracted from RVO were enriched in the ω-3 polyunsaturated fatty acid fraction (PUFAE) up to almost 56% via short path distillation (SPD). Antioxidant activities and adipogenic properties were tested in vitro. PUFAE protected 3T3 L1 cells from oxidative stress and exerted an anti-adipogenic effect in Dicentrarchus labrax pre-adipocytes, attesting to the beneficial properties for both farmed fish and human health. These results could stimulate the adoption of solutions aimed to recover and utilize aquaculture by-products at a higher scale, turning “waste into profit” and indicating a strategy to reach more sustainable business models in aquaculture resource utilization according to the principles of the circular economy.
Published: 2021

66. Inhibition of eIF6 Activity Reduces Hepatocellular Carcinoma Growth: An In Vivo and In Vitro Study

Author: Alessandra Scagliola, Annarita Miluzio, Giada Mori, Sara Ricciardi, Stefania Oliveto, Nicola Manfrini, and Stefano Biffo
Subjects: Carcinoma, Hepatocellular, Liver Neoplasms, Organic Chemistry, General Medicine, Catalysis, initiation, Computer Science Applications, Inorganic Chemistry, Mice, Settore BIO/06 - Anatomia Comparata e Citologia, fatty acid synthesis, eIF4E, uORFs, HCC, eIF6-60S binding inhibitors, Non-alcoholic Fatty Liver Disease, Peptide Initiation Factors, Animals, Humans, Eukaryotic Initiation Factors, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract: Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipids in the liver. Given the high prevalence of NAFLD, its evolution to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) is of global concern. Therapies for managing NASH-driven HCC can benefit from targeting factors that play a continuous role in NAFLD evolution to HCC. Recent work has shown that postprandial liver translation exacerbates lipid accumulation through the activity of a translation factor, eukaryotic initiation factor 6 (eIF6). Here, we test the effect of eIF6 inhibition on the progression of HCC. Mice heterozygous for eIF6 express half the level of eIF6 compared to wt mice and are resistant to the formation of HCC nodules upon exposure to a high fat/high sugar diet combined with liver damage. Histology showed that nodules in eIF6 het mice were smaller with reduced proliferation compared to wt nodules. By using an in vitro model of human HCC, we confirm that eIF6 depletion reduces the growth of HCC spheroids. We also tested three pharmacological inhibitors of eIF6 activity—eIFsixty-1, eIFsixty-4, and eIFsixty-6—and all three reduced eIF6 binding to 60S ribosomes and limited the growth of HCC spheroids. Thus, inhibition of eIF6 activity is feasible and limits HCC formation.
Published: 2022
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67. Enzymatic Spermine Metabolites Induce Apoptosis Associated with Increase of p53, caspase-3 and miR-34a in Both Neuroblastoma Cells, SJNKP and the N-Myc-Amplified Form IMR5

Author: Pasquale Fino, Gabriella Schiera, Gianluca Canettieri, Yuta Kanamori, Italia Di Liegro, Enzo Agostinelli, Patrizia Proia, Jessica Gasparello, Roberto Gambari, Alessia Finotti, Laura Di Magno, Carlo Maria Di Liegro, Paola Tirassa, Fabio Timeus, Tomoaki Tahara, Antonio Greco, Kanamori Y., Finotti A., Di Magno L., Canettieri G., Tahara T., Timeus F., Greco A., Tirassa P., Gasparello J., Fino P., Di Liegro C.M., Proia P., Schiera G., Di Liegro I., Gambari R., and Agostinelli E.
Subjects: 0301 basic medicine, Polyamine, neuroblastoma, apoptosis, microRNA, mitochondria, reactive oxygen species, oncotherapy, chemistry.chemical_compound, 0302 clinical medicine, Annexin, polyamine, Settore BIO/10 - Biochimica, Antineoplastic Combined Chemotherapy Protocols, Cytotoxic T cell, Settore BIO/06 - Anatomia Comparata E Citologia, Biology (General), Membrane Potential, Mitochondrial, N-Myc Proto-Oncogene Protein, Chemistry, Caspase 3, General Medicine, Blot, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Amine Oxidase (Copper-Containing), Signal Transduction, QH301-705.5, Article, NO, 03 medical and health sciences, Neuroblastoma, Cell Line, Tumor, medicine, Animals, Humans, Propidium iodide, Rats, Wistar, Cell Proliferation, Oncogene, Gene Amplification, medicine.disease, Molecular biology, MicroRNAs, 030104 developmental biology, Apoptosis, Spermine, Tumor Suppressor Protein p53
Abstract: Neuroblastoma (NB) is a common malignant solid tumor in children and accounts for 15% of childhood cancer mortality. Amplification of the N-Myc oncogene is a well-established poor prognostic marker in NB patients and strongly correlates with higher tumor aggression and resistance to treatment. New therapies for patients with N-Myc-amplified NB need to be developed. After treating NB cells with BSAO/SPM, the detection of apoptosis was determined after annexin V-FITC labeling and DNA staining with propidium iodide. The mitochondrial membrane potential activity was checked, labeling cells with the probe JC-1 dye. We analyzed, by real-time RT-PCR, the transcript of genes involved in the apoptotic process, to determine possible down- or upregulation of mRNAs after the treatment on SJNKP and the N-Myc-amplified IMR5 cell lines with BSAO/SPM. The experiments were carried out considering the proapoptotic genes Tp53 and caspase-3. After treatment with BSAO/SPM, both cell lines displayed increased mRNA levels for all these proapoptotic genes. Western blotting analysis with PARP and caspase-3 antibody support that BSAO/SPM treatment induces high levels of apoptosis in cells. The major conclusion is that BSAO/SPM treatment leads to antiproliferative and cytotoxic activity of both NB cell lines, associated with activation of apoptosis.
Published: 2021

68. A eutherian-specific microRNA controls the translation of Satb2 in a model of cortical differentiation

Author: Silvia Giulia Galfrè, Manuela Helmer-Citterich, Milena Rizzo, Robert Vignali, Laura Poliseno, Irene Appolloni, Keagan Dunville, Francesco Morandin, Paolo Malatesta, Manuella Martins, Andrea Marranci, Marco Pietrosanto, Luca Pandolfini, Marco Terrigno, Federico Cremisi, Alberto Mercatanti, Martins, Manuella, Galfrè, Silvia, Terrigno, Marco, Pandolfini, Luca, Appolloni, Irene, Dunville, Keagan, Marranci, Andrea, Rizzo, Milena, Mercatanti, Alberto, Poliseno, Laura, Morandin, Francesco, Pietrosanto, Marco, Helmer-Citterich, Manuela, Malatesta, Paolo, Vignali, Robert, and Cremisi, Federico
Subjects: 0301 basic medicine, Transcription Factor, Biochemistry, corpus callosum, neural stem cell, Mice, Settore BIO/06 - Anatomia Comparata e Citologia, 0302 clinical medicine, RNA interference, developmental timing, 3' Untranslated Regions, neural stem cells, Cerebral Cortex, cell fate, biology, microRNA, Settore BIO/11, Eutheria, Matrix Attachment Region Binding Protein, Gene Expression Regulation, Developmental, Translation (biology), Cell Differentiation, Neural stem cell, Cell biology, mammalian evolution, Corticogenesis, cortex, Human, in vitro corticogenesi, Neurogenesis, 3' Untranslated Region, Cell fate determination, post-transcriptional control, Article, Cell Line, 03 medical and health sciences, SATB2, cell identity, cortical layering, in vitro corticogenesis, miR-catch, Genetics, Animals, Humans, Progenitor cell, Post-transcriptional regulation, Animal, Tumor Suppressor Proteins, Matrix Attachment Region Binding Proteins, Cell Biology, Repressor Protein, Repressor Proteins, MicroRNAs, 030104 developmental biology, Cell fate, biology.protein, Neurogenesi, in vitro corticogenesis, TBR1, 030217 neurology & neurosurgery, Transcription Factors, Developmental Biology
Abstract: Summary Cerebral cortical development is controlled by key transcription factors that specify the neuronal identities in the different layers. The mechanisms controlling their expression in distinct cells are only partially known. We investigated the expression and stability of Tbr1, Bcl11b, Fezf2, Satb2, and Cux1 mRNAs in single developing mouse cortical cells. We observe that Satb2 mRNA appears much earlier than its protein and in a set of cells broader than expected, suggesting an initial inhibition of its translation, subsequently released during development. Mechanistically, Satb2 3′UTR modulates protein translation of GFP reporters during mouse corticogenesis. We select miR-541, a eutherian-specific miRNA, and miR-92a/b as the best candidates responsible for SATB2 inhibition, being strongly expressed in early and reduced in late progenitor cells. Their inactivation triggers robust and premature SATB2 translation in both mouse and human cortical cells. Our findings indicate RNA interference as a major mechanism in timing cortical cell identities., Graphical abstract, Highlights • mRNAs for key transcription factors are differentially stable during corticogenesis • miRNAs show a dynamic profile of expression in a model of mouse corticogenesis • miR-541 and miR-92a/b bind Satb2 3′UTR and prevent SATB2 translation • Antagonizing mir-541 and miR-92a/b anticipates SATB2 protein production, In this article, Cremisi and colleagues show that post-transcriptional mechanisms are involved in controlling key functional aspects of SATB2-expressing cortical neurons. They show that mir-541, a eutherian-specific miRNA, delays SATB2 protein production in an in vitro model of cortical cell differentiation. These results may explain the heterochronic shift of SATB2 appearance in the eutherian compared with the metatherian cortex.
Published: 2021

69. Interactive effects of increased temperature and gadolinium pollution in Paracentrotus lividus sea urchin embryos: a climate change perspectiveInteractive effects of increased temperature and gadolinium pollution in Paracentrotus lividus sea urchin embryos: a climate change perspective

Author: Martino C., Byrne M., Roccheri M. C., Chiarelli R., Martino C., Byrne M., Roccheri M.C., and Chiarelli R.
Subjects: Biomineralization, Metal contamination, Global warming, Autophagy, Apoptosis, Settore BIO/06 - Anatomia Comparata E Citologia, Cellular biomarkers
Abstract: Gradual ocean warming and marine heatwaves represent major threats for marine organisms already facing other anthropogenic-derived hazards, such as chemical contamination in coastal areas. In this study, the combined effects of thermal stress and exposure to gadolinium (Gd), a metal used as a contrasting agent in medical imaging which enters the aquatic environment, were investigated in the embryos and larvae of the sea urchin Paracentrotus lividus. Embryos were exposed to six treatments of three temperatures (18 °C, 21 °C, 24 °C) and two Gd concentrations (control: 0 μM; treated: 20 μM). With respect to developmental progression, increased temperature accelerated development and achievement of the larval stage, while Gd-exposed embryos at the control temperature (18 °C) showed a general delay in development at 24 h post-fertilization (hpf), and a stunting effect and impaired skeleton growth at 48 hpf. Elevated temperatures at near-future projections (+3 °C, 21 °C) reduced the negative effects of Gd on development with a lower percentage of abnormality and improved skeleton growth. Combined extreme warming at present-day marine heatwave conditions (+6 °C, 24 °C) and Gd treatment resulted in a lower proportion of embryos reaching the advanced larval stages compared to the 21 °C + Gd. At the molecular level, western blot analysis showed that Gd was the main driver for the induction of heat shock protein (HSP60, HSP70) expression. At 48 hpf, temperature increase was the main driver for activation of additional cellular stress response strategies such as autophagy and apoptosis. Combined treatments showed the induction of HSP60 at 24 hpf and autophagic and apoptotic processes at 48 hpf. Treatments having low levels of HSPs expression showed high levels of apoptosis, and vice versa, clearly demonstrating the antagonistic effects of HSPs expression and apoptosis. Detection of fragmented DNA in apoptotic nuclei showed selective apoptosis, likely in extremely damaged cells. Our results indicate that the negative effects of Gd-exposure on P. lividus larval development and biomineralization will be mitigated by a near-future ocean warming, up to a thermotolerance threshold when negative synergistic effects were evident. Our data highlight the use of biomarkers as sensitive tools to detect environmental impacts as well as the need for a better understanding of the interactions between the multiple stressors faced by marine species in coastal environments.
Published: 2021

70. Dall’approccio ecotossicologico a quello molecolare, dai test in vitro a quelli in vivo: la sfida per l’individuazione di biomarcatori per il monitoraggio dell’ambiente marino

Author: Messina Concetta Maria, Manuguerra Simona, Morghese Maria, Arena Rosaria, Renda Giuseppe, Espinosa Ruiz Cristobal, Santulli Andrea, Sprovieri, M, Cori, L, Bianchi, F, Cibella, F, De Gaetano, A, and Messina Concetta Maria, Manuguerra Simona, Morghese Maria, Arena Rosaria, Renda Giuseppe, Espinosa Ruiz Cristobal, Santulli Andrea
Subjects: Settore AGR/20 - Zoocolture, biomarkers, ambiente marino, Settore BIO/06 - Anatomia Comparata E Citologia, contaminanti
Abstract: Il presente lavoro riporta una selezione di alcuni risultati ottenuti impiegando sistemi modello rappresentati da colture cellulari di pesce, invertebrati e vertebrati marini, adottando biomarcatori finora poco indagati in organismi di questi ambienti, allo scopo di individuare sensori dello stato metabolico, la cui variazione, a lungo termine, è noto che porti a drammatiche variazioni dell’omeostasi, del ciclo cellulare e conseguenti alterazioni. Per semplificare la valutazione comparativa tra le risposte ottenute nei vari sistemi modello, riportiamo gli effetti determinati da una classe di contaminanti su cui si è concentrato, negli ultimi anni, l’interesse della ricerca in ambito ecotossicologico e ambientale, i poli-bromo-difenil-eteri (PBDE).
Published: 2021

71. Pyrazole[3,4-d]pyrimidine derivatives loaded into halloysite as potential CDK inhibitors

Author: Aldo Di Leonardo, Patrizia Cancemi, Silvia Schenone, Marina Massaro, Fabrizio Lo Celso, César Viseras Iborra, Serena Riela, Giancarlo Grossi, Viviana Barra, Giampaolo Barone, Università degli Studi di Palermo, Massaro M., Barone G., Barra V., Cancemi P., Di Leonardo A., Grossi G., Lo Celso F., Schenone S., Viseras Iborra C., and Riela S.
Subjects: Cell cycle checkpoint, Pyrimidine, Pharmaceutical Science, 02 engineering and technology, CDK inhibitors, Halloysite, Nanocomposites, Pyrazolo[3,4-d]pyrimidine derivatives, Cell Cycle Checkpoints, Cell Line, Tumor, Clay, Humans, Pyrazoles, Pyrimidines, Pyrazole, 030226 pharmacology & pharmacy, Cell Line, HeLa, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cyclin-dependent kinase, Pyrazolo[3, Settore BIO/06 - Anatomia Comparata E Citologia, Settore CHIM/02 - Chimica Fisica, Tumor, biology, Chemistry, Kinase, Cell growth, 4-d]pyrimidine derivatives, Settore CHIM/06 - Chimica Organica, Cell cycle, 021001 nanoscience & nanotechnology, biology.organism_classification, Settore BIO/18 - Genetica, Settore CHIM/03 - Chimica Generale E Inorganica, biology.protein, Cancer research, 0210 nano-technology
Abstract: Uncontrolled cell proliferation is a hallmark of cancer as a result of rapid and deregulated progression through the cell cycle. The inhibition of cyclin-dependent kinases (CDKs) activities is a promising therapeutic strategy to block cell cycle of tumor cells. In this work we reported a new example of nanocomposites based on halloysite nanotubes (HNTs)/pyrazolo[3,4-d]pyrimidine derivatives (Si306 and Si113) as anticancer agents and CDK inhibitors. HNTs/Si306 and HNTs/Si113 nanocomposites were synthesized and characterized. The release kinetics were also investigated. Antitumoral activity was evaluated on three cancer cell lines (HeLa, MDA-MB-231 and HCT116) and the effects on cell cycle arrest in HCT116 cells were evaluated. Finally, molecular dynamics simulations were performed of the complexes between Si113 or Si306 and the active site of both CDK 1 and 2., The work was financially supported by the University of Palermo. The work was carried out in the frame of the PON “AIM: Attrazione e Mobilità Internazionale” No. 1808223 project. SS and GG wish to acknowledge the AIRC project 2019 code 23725. The authors would thank Dr. Susanna Guernelli (University of Bologna) for TEM and SEM measurements.
Published: 2021

72. Mural granulosa cells of the human follicles indirectly show death molecular signals not depending on different ovarian stimulation protocols

Author: Ruvolo, G, Geraci, F, Roccheri, M C, Alessandro, R, Bosco, L, Ruvolo, G, Geraci, F, Roccheri, M C, Alessandro, R, and Bosco, L
Subjects: Granulosa cell, anti-apoptotic molecules, Settore BIO/06 - Anatomia Comparata E Citologia, follicle
Published: 2021

73. Vanadium induces calcium depletion and cell selective apoptosis during development of sea urchin embryos

Author: Roberto Chiarelli, Rosaria Scudiero, Patrizia Cancemi, Maria Carmela Roccheri, Chiara Martino, Roberto Chiarelli, Rosaria Scudiero, Patrizia Cancemi, Maria Carmela Roccheri, and Chiara Martino
Subjects: calcium, Stre, Vanadium, Settore BIO/06 - Anatomia Comparata E Citologia, apoptosi, sea urchin embryos
Abstract: Vanadium (V) is a metal widely distributed in soil, water and air. It has recently received growing interest because its compounds are often used in different applications, from industry to medicine.1 Here, using atomic absorption spectrometry, we demonstrate the predisposition of V to accumulate directly into embryonic cells, interfering with Ca uptake. At the morphological level, we observed dose- and time-dependent effects on phenotypes and on skeletal malformations. At the molecular level, V-exposed embryos showed the activation of the cellular stress response, inducing Hsp 60 and Hsp 70 synthesis and the activation of autophagy and apoptosis. The Hsps-mediated stress response to V appeared to counteract the damage induced by low (50 nM and 100 nM) and intermediate (500 nM and 1 µM) concentrations, while high cytotoxic doses (500 µM and 1 mM) induced more marked cell death mechanisms starting at 24 h of development, when the control embryos reached the gastrula stage.2 Only few cells showed nuclei with apoptotic DNA fragmentation, particularly in the ectodermal layer. Mesodermal and endodermal cells did not appear to be involved in this process of selective apoptosis.3 Microscopic fluorescence inspections indicated that primary mesenchyme cells (PMCs) were not involved in apoptotic processes, therefore their inability to carry on the skeletogenesis could be due to the Ca depletion. These results allow us to elect the sea urchin embryo as a suitable experimental model for studying the metal-correlated cellular/molecular responses.4,5
Published: 2021

74. Combination of Freezing, Low Sodium Brine and Cold Smoking on the Quality and Shelf-Life of Sea Bass (Dicentrarchus labrax L.) Fillets as a Strategy to Innovate the Market of Aquaculture Products

Author: Maria Morghese, Concetta Maria Messina, Laura La Barbera, Giovanna Ficano, Rosaria Arena, Andrea Santulli, Messina C.M., Arena R., Ficano G., La Barbera L., Morghese M., and Santulli A.
Subjects: 0106 biological sciences, Fish farming, Food spoilage, fillets, Shelf life, 01 natural sciences, low-salt product, Article, 0404 agricultural biotechnology, Brining, Aquaculture, Settore AGR/20 - Zoocolture, 010608 biotechnology, lcsh:Zoology, Food science, sodium replacement, lcsh:QL1-991, Sea bass, Settore BIO/06 - Anatomia Comparata E Citologia, lcsh:Veterinary medicine, General Veterinary, biology, Dicentrachus labrax, business.industry, fish quality, 04 agricultural and veterinary sciences, biology.organism_classification, 040401 food science, shelf-life, aquaculture, Environmental science, lcsh:SF600-1100, Animal Science and Zoology, Dicentrarchus, business, Low sodium, cold smoking
Abstract: Aquaculture is playing a leading role in both meeting the growing demand for seafood and increasing the sustainability of the fish production sector. Thus, innovative technologies that improve its sustainability, competitiveness, and safety are necessary for growth in the sector. This study aimed to develop cold smoked sea bass fillets from aquaculture. The aptitude of frozen and fresh fillets for cold smoking was investigated by processing both fresh and thawed fillets kept previously at &minus, 20 &deg, C for 15, 30, 60, and 90 days. Moreover, to develop a low-salt product, fillets were immersed in low-sodium or standard brine. Sensory, biochemical, and physical-chemical analyses were performed on both the raw fillets and the smoked fillets during vacuum packaged storage for 35 days at 1 &plusmn, 0.5 &deg, C. Young modulus values, representative of texture and sensory evaluation, showed that the quality of fresh fillets was better compared to the thawed ones, thus affecting the quality of the final product as the correlation between parameters showed (principal component analysis). Cold smoking was effective in both maintaining the total volatile basic nitrogen (TVB-N) below the threshold for spoilage and preventing lipid peroxidation. Moreover, partial sodium replacement by potassium did not alter the sensory attributes of smoked fillets, which maintained high scores up to 21 days.
Published: 2021

75. Autophagy

Author: Klionsky, Daniel J., Abdel-Aziz, Amal Kamal, Abdelfatah, Sara, Abdellatif, Mahmoud, Abdoli, Asghar, Abel, Steffen, Abeliovich, Hagai, Abildgaard, Marie H., Abudu, Yakubu Princely, Acevedo-Arozena, Abraham, Adamopoulos, Iannis E., Adeli, Khosrow, Adolph, Timon E., Adornetto, Annagrazia, Aflaki, Elma, Agam, Galila, Agarwal, Anupam, Aggarwal, Bharat B., Agnello, Maria, Agostinis, Patrizia, Agrewala, Javed N., Agrotis, Alexander, Aguilar, Patricia V., Ahmad, S. Tariq, Ahmed, Zubair M., Ahumada-Castro, Ulises, Aits, Sonja, Aizawa, Shu, Akkoc, Yunus, Akoumianaki, Tonia, Akpinar, Hafize Aysin, Al-Abd, Ahmed M., Al-Akra, Lina, Al-Gharaibeh, Abeer, Alaoui-Jamali, Moulay A., Alberti, Simon, Alcocer-Gómez, Elísabet, Alessandri, Cristiano, Ali, Muhammad, Alim Al-Bari, M. Abdul, Aliwaini, Saeb, Alizadeh, Javad, Almacellas, Eugènia, Almasan, Alexandru, Alonso, Alicia, Alonso, Guillermo D., Altan-Bonnet, Nihal, Altieri, Dario C., Álvarez, Élida M. C., Alves, Sara, Alves da Costa, Cristine, Alzaharna, Mazen M., Amadio, Marialaura, Amantini, Consuelo, Amaral, Cristina, Ambrosio, Susanna, Amer, Amal O., Ammanathan, Veena, An, Zhenyi, Andersen, Stig U., Andrabi, Shaida A., Andrade-Silva, Magaiver, Andres, Allen M., Angelini, Sabrina, Ann, David, Anozie, Uche C., Ansari, Mohammad Y., Antas, Pedro, Antebi, Adam, Antón, Zuriñe, Anwar, Tahira, Apetoh, Lionel, Apostolova, Nadezda, Araki, Toshiyuki, Araki, Yasuhiro, Arasaki, Kohei, Araújo, Wagner L., Araya, Jun, Arden, Catherine, Arévalo, Maria-Angeles, Arguelles, Sandro, Arias, Esperanza, Arikkath, Jyothi, Arimoto, Hirokazu, Ariosa, Aileen R., Armstrong-James, Darius, Arnauné-Pelloquin, Laetitia, Aroca, Angeles, Arroyo, Daniela S., Arsov, Ivica, Artero, Rubén, Asaro, Dalia Maria Lucia, Aschner, Michael, Ashrafizadeh, Milad, Ashur-Fabian, Osnat, Atanasov, Atanas G., Au, Alicia K., Auberger, Patrick, Auner, Holger W., Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Ávalos, Yenniffer, Aveic, Sanja, Aveleira, Célia Alexandra, Avin-Wittenberg, Tamar, Aydin, Yucel, Ayton, Scott, Ayyadevara, Srinivas, Azzopardi, Maria, Baba, Misuzu, Backer, Jonathan M., Backues, Steven K., Bae, Dong-Hun, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric H., Baek, Ahruem, Baek, Seung-Hoon, Baek, Sung Hee, Bagetta, Giacinto, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xiyuan, Bai, Yidong, Bairagi, Nandadulal, Baksi, Shounak, Balbi, Teresa, Baldari, Cosima T., Balduini, Walter, Ballabio, Andrea, Ballester, Maria, Balazadeh, Salma, Balzan, Rena, Bandopadhyay, Rina, Banerjee, Sreeparna, Banerjee, Sulagna, Bánréti, Ágnes, Bao, Yan, Baptista, Mauricio S., Baracca, Alessandra, Barbati, Cristiana, Bargiela, Ariadna, Barilà, Daniela, Barlow, Peter G., Barmada, Sami J., Barreiro, Esther, Barreto, George E., Bartek, Jiri, Bartel, Bonnie, Bartolome, Alberto, Barve, Gaurav R., Basagoudanavar, Suresh H., Bassham, Diane C., Bast, Robert C., Basu, Alakananda, Batoko, Henri, Batten, Isabella, Baulieu, Etienne E., Baumgarner, Bradley L., Bayry, Jagadeesh, Beale, Rupert, Beau, Isabelle, Beaumatin, Florian, Bechara, Luiz R.G., Beck, George R., Beers, Michael F., Begun, Jakob, Behrends, Christian, Behrens, Georg M.N., Bei, Roberto, Bejarano, Eloy, Bel, Shai, Behl, Christian, Belaid, Amine, Belgareh-Touzé, Naïma, Bellarosa, Cristina, Belleudi, Francesca, Belló Pérez, Melissa, Bello-Morales, Raquel, Beltran, Jackeline Soares de Oliveira, Beltran, Sebastián, Benbrook, Doris Mangiaracina, Bendorius, Mykolas, Benitez, Bruno A., Benito-Cuesta, Irene, Bensalem, Julien, Berchtold, Martin W., Berezowska, Sabina, Bergamaschi, Daniele, Bergami, Matteo, Bergmann, Andreas, Berliocchi, Laura, Berlioz-Torrent, Clarisse, Bernard, Amélie, Berthoux, Lionel, Besirli, Cagri G., Besteiro, Sebastien, Betin, Virginie M., Beyaert, Rudi, Bezbradica, Jelena S., Bhaskar, Kiran, Bhatia-Kissova, Ingrid, Bhattacharya, Resham, Bhattacharya, Sujoy, Bhattacharyya, Shalmoli, Bhuiyan, Md. Shenuarin, Bhutia, Sujit Kumar, Bi, Lanrong, Bi, Xiaolin, Biden, Trevor J., Bijian, Krikor, Billes, Viktor A., Binart, Nadine, Bincoletto, Claudia, Birgisdottir, Asa B., Bjorkoy, Geir, Blanco, Gonzalo, Blas-Garcia, Ana, Blasiak, Janusz, Blomgran, Robert, Blomgren, Klas, Blum, Janice S., Boada-Romero, Emilio, Boban, Mirta, Boesze-Battaglia, Kathleen, Boeuf, Philippe, Boland, Barry, Bomont, Pascale, Bonaldo, Paolo, Bonam, Srinivasa Reddy, Bonfili, Laura, Bonifacino, Juan S., Boone, Brian A., Bootman, Martin D., Bordi, Matteo, Borner, Christoph, Bornhauser, Beat C., Borthakur, Gautam, Bosch, Jürgen, Bose, Santanu, Botana, Luis M., Botas, Juan, Boulanger, Chantal M., Boulton, Michael E., Bourdenx, Mathieu, Bourgeois, Benjamin, Bourke, Nollaig M., Bousquet, Guilhem, Boya, Patricia, Bozhkov, Peter V., Bozi, Luiz H. M., Bozkurt, Tolga O., Brackney, Doug E., Brandts, Christian H., Braun, Ralf J., Braus, Gerhard H., Bravo-Sagua, Roberto, Bravo-San Pedro, José M., Brest, Patrick, Bringer, Marie-Agnès, Briones-Herrera, Alfredo, Broaddus, V. Courtney, Brodersen, Peter, Brodsky, Jeffrey L., Brody, Steven L., Bronson, Paola G., Bronstein, Jeff M., Brown, Carolyn N., Brown, Rhoderick E., Brum, Patricia C., Brumell, John H., Brunetti-Pierri, Nicola, Bruno, Daniele, Bryson-Richardson, Robert J., Bucci, Cecilia, Buchrieser, Carmen, Bueno, Marta, Buitrago-Molina, Laura Elisa, Buraschi, Simone, Buch, Shilpa, Buchan, J. Ross, Buckingham, Erin M., Budak, Hikmet, Budini, Mauricio, Bultynck, Geert, Burada, Florin, Burgoyne, Joseph R., Burón, M. Isabel, Bustos, Victor, Büttner, Sabrina, Butturini, Elena, Byrd, Aaron, Cabas, Isabel, Cabrera-Benitez, Sandra, Cadwell, Ken, Cai, Jingjing, Cai, Lu, Cai, Qian, Cairó, Montserrat, Calbet, Jose A., Caldwell, Guy A., Caldwell, Kim A., Call, Jarrod A., Calvani, Riccardo, Calvo, Ana C., Calvo-Rubio Barrera, Miguel, Camara, Niels OS, Camonis, Jacques H., Camougrand, Nadine, Campanella, Michelangelo, Campbell, Edward M., Campbell-Valois, François-Xavier, Campello, Silvia, Campesi, Ilaria, Campos, Juliane C., Camuzard, Olivier, Cancino, Jorge, Candido de Almeida, Danilo, Canesi, Laura, Caniggia, Isabella, Canonico, Barbara, Cantí, Carles, Cao, Bin, Caraglia, Michele, Caramés, Beatriz, Carchman, Evie H., Cardenal-Muñoz, Elena, Cardenas, Cesar, Cardenas, Luis, Cardoso, Sandra M., Carew, Jennifer S., Carle, Georges F., Carleton, Gillian, Carloni, Silvia, Carmona-Gutierrez, Didac, Carneiro, Leticia A., Carnevali, Oliana, Carosi, Julian M., Carra, Serena, Carrier, Alice, Carrier, Lucie, Carroll, Bernadette, Carter, A. Brent, Carvalho, Andreia Neves, Casanova, Magali, Casas, Caty, Casas, Josefina, Cassioli, Chiara, Castillo, Eliseo F., Castillo, Karen, Castillo-Lluva, Sonia, Castoldi, Francesca, Castori, Marco, Castro, Ariel F., Castro-Caldas, Margarida, Castro-Hernandez, Javier, Castro-Obregon, Susana, Catz, Sergio D., Cavadas, Claudia, Cavaliere, Federica, Cavallini, Gabriella, Cavinato, Maria, Cayuela, Maria L., Cebollada Rica, Paula, Cecarini, Valentina, Cecconi, Francesco, Cechowska-Pasko, Marzanna, Cenci, Simone, Ceperuelo-Mallafré, Victòria, Cerqueira, João J., Cerutti, Janete M., Cervia, Davide, Cetintas, Vildan Bozok, Cetrullo, Silvia, Chae, Han-Jung, Chagin, Andrei S., Chai, Chee-Yin, Chakrabarti, Gopal, Chakrabarti, Oishee, Chakraborty, Tapas, Chakraborty, Trinad, Chami, Mounia, Chamilos, Georgios, Chan, David W., Chan, Edmond Y. W., Chan, Edward D., Chan, H.Y. Edwin, Chan, Helen H., Chan, Hung, Chan, Matthew T.V., Chan, Yau Sang, Chandra, Partha K., Chang, Chih-Peng, Chang, Chunmei, Chang, Hao-Chun, Chang, Kai, Chao, Jie, Chapman, Tracey, Charlet-Berguerand, Nicolas, Chatterjee, Samrat, Chaube, Shail K., Chaudhary, Anu, Chauhan, Santosh, Chaum, Edward, Checler, Frédéric, Cheetham, Michael E., Chen, Chang-Shi, Chen, Guang-Chao, Chen, Jian-Fu, Chen, Liam L., Chen, Leilei, Chen, Lin, Chen, Mingliang, Chen, Mu-Kuan, Chen, Ning, Chen, Quan, Chen, Ruey-Hwa, Chen, Shi, Chen, Wei, Chen, Weiqiang, Chen, Xin-Ming, Chen, Xiong-Wen, Chen, Xu, Chen, Yan, Chen, Ye-Guang, Chen, Yingyu, Chen, Yongqiang, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Zhefan Stephen, Chen, Zhi, Chen, Zhi-Hua, Chen, Zhijian J., Chen, Zhixiang, Cheng, Hanhua, Cheng, Jun, Cheng, Shi-Yuan, Cheng, Wei, Cheng, Xiaodong, Cheng, Xiu-Tang, Cheng, Yiyun, Cheng, Zhiyong, Chen, Zhong, Cheong, Heesun, Cheong, Jit Kong, Chernyak, Boris V., Cherry, Sara, Cheung, Chi Fai Randy, Cheung, Chun Hei Antonio, Cheung, King-Ho, Chevet, Eric, Chi, Richard J., Chiang, Alan Kwok Shing, Chiaradonna, Ferdinando, Chiarelli, Roberto, Chiariello, Mario, Chica, Nathalia, Chiocca, Susanna, Chiong, Mario, Chiou, Shih-Hwa, Chiramel, Abhilash I., Chiurchiù, Valerio, Cho, Dong-Hyung, Choe, Seong-Kyu, Choi, Augustine M.K., Choi, Mary E., Choudhury, Kamalika Roy, Chow, Norman S., Chu, Charleen T., Chua, Jason P., Chua, John Jia En, Chung, Hyewon, Chung, Kin Pan, Chung, Seockhoon, Chung, So-Hyang, Chung, Yuen-Li, Cianfanelli, Valentina, Ciechomska, Iwona A., Cifuentes, Mariana, Cinque, Laura, Cirak, Sebahattin, Cirone, Mara, Clague, Michael J., Clarke, Robert, Clementi, Emilio, Coccia, Eliana M., Codogno, Patrice, Cohen, Ehud, Cohen, Mickael M., Colasanti, Tania, Colasuonno, Fiorella, Colbert, Robert A., Colell, Anna, Čolić, Miodrag, Coll, Nuria S., Collins, Mark O., Colombo, María I., Colón-Ramos, Daniel A., Combaret, Lydie, Comincini, Sergio, Cominetti, Márcia R., Consiglio, Antonella, Conte, Andrea, Conti, Fabrizio, Contu, Viorica Raluca, Cookson, Mark R., Coombs, Kevin M., Coppens, Isabelle, Corasaniti, Maria Tiziana, Corkery, Dale P., Cordes, Nils, Cortese, Katia, Costa, Maria do Carmo, Costantino, Sarah, Costelli, Paola, Coto-Montes, Ana, Crack, Peter J., Crespo, Jose L., Criollo, Alfredo, Crippa, Valeria, Cristofani, Riccardo, Csizmadia, Tamas, Cuadrado, Antonio, Cui, Bing, Cui, Jun, Cui, Yixian, Cui, Yong, Culetto, Emmanuel, Cumino, Andrea C., Cybulsky, Andrey V., Czaja, Mark J., Czuczwar, Stanislaw J., D’Adamo, Stefania, D’Amelio, Marcello, D’Arcangelo, Daniela, D’Lugos, Andrew C., D’Orazi, Gabriella, da Silva, James A., Dafsari, Hormos Salimi, Dagda, Ruben K., Dagdas, Yasin, Daglia, Maria, Dai, Xiaoxia, Dai, Yun, Dai, Yuyuan, Dal Col, Jessica, Dalhaimer, Paul, Dalla Valle, Luisa, Dallenga, Tobias, Dalmasso, Guillaume, Damme, Markus, Dando, Ilaria, Dantuma, Nico P., Darling, April L., Das, Hiranmoy, Dasarathy, Srinivasan, Dasari, Santosh K., Dash, Srikanta, Daumke, Oliver, Dauphinee, Adrian N., Davies, Jeffrey S., Dávila, Valeria A., Davis, Roger J., Davis, Tanja, Dayalan Naidu, Sharadha, De Amicis, Francesca, De Bosscher, Karolien, De Felice, Francesca, De Franceschi, Lucia, De Leonibus, Chiara, de Mattos Barbosa, Mayara G., De Meyer, Guido R.Y., De Milito, Angelo, De Nunzio, Cosimo, De Palma, Clara, De Santi, Mauro, De Virgilio, Claudio, De Zio, Daniela, Debnath, Jayanta, DeBosch, Brian J., Decuypere, Jean-Paul, Deehan, Mark A., Deflorian, Gianluca, DeGregori, James, Dehay, Benjamin, Del Rio, Gabriel, Delaney, Joe R., Delbridge, Lea M. D., Delorme-Axford, Elizabeth, Delpino, M. Victoria, Demarchi, Francesca, Dembitz, Vilma, Demers, Nicholas D., Deng, Hongbin, Deng, Zhiqiang, Dengjel, Joern, Dent, Paul, Denton, Donna, DePamphilis, Melvin L., Der, Channing J., Deretic, Vojo, Descoteaux, Albert, Devis, Laura, Devkota, Sushil, Devuyst, Olivier, Dewson, Grant, Dharmasivam, Mahendiran, Dhiman, Rohan, di Bernardo, Diego, Di Cristina, Manlio, Di Domenico, Fabio, Di Fazio, Pietro, Di Fonzo, Alessio, Di Guardo, Giovanni, Di Guglielmo, Gianni M., Di Leo, Luca, Di Malta, Chiara, Di Nardo, Alessia, Di Rienzo, Martina, Di Sano, Federica, Diallinas, George, Diao, Jiajie, Diaz-Araya, Guillermo, Díaz-Laviada, Inés, Dickinson, Jared M., Diederich, Marc, Dieudé, Mélanie, Dikic, Ivan, Ding, Shiping, Ding, Wen-Xing, Dini, Luciana, Dinić, Jelena, Dinic, Miroslav, Dinkova-Kostova, Albena T., Dionne, Marc S., Distler, Jörg H.W., Diwan, Abhinav, Dixon, Ian M.C., Djavaheri-Mergny, Mojgan, Dobrinski, Ina, Dobrovinskaya, Oxana, Dobrowolski, Radek, Dobson, Renwick C.J., Đokić, Jelena, Dokmeci Emre, Serap, Donadelli, Massimo, Dong, Bo, Dong, Xiaonan, Dong, Zhiwu, 2nd Dorn, Gerald W., Dotsch, Volker, Dou, Huan, Dou, Juan, Dowaidar, Moataz, Dridi, Sami, Drucker, Liat, Du, Ailian, Du, Caigan, Du, Guangwei, Du, Hai-Ning, Du, Li-Lin, du Toit, André, Duan, Shao-Bin, Duan, Xiaoqiong, Duarte, Sónia P., Dubrovska, Anna, Dunlop, Elaine A., Dupont, Nicolas, Durán, Raúl V., Dwarakanath, Bilikere S., Dyshlovoy, Sergey A., Ebrahimi-Fakhari, Darius, Eckhart, Leopold, Edelstein, Charles L., Efferth, Thomas, Eftekharpour, Eftekhar, Eichinger, Ludwig, Eid, Nabil, Eisenberg, Tobias, Eissa, N. Tony, Eissa, Sanaa, Ejarque, Miriam, El Andaloussi, Abdeljabar, El-Hage, Nazira, El-Naggar, Shahenda, Eleuteri, Anna Maria, El-Shafey, Eman S., Elgendy, Mohamed, Eliopoulos, Aristides G., Elizalde, María M., Elks, Philip M., Elsasser, Hans-Peter, Elsherbiny, Eslam S., Emerling, Brooke M., Emre, N. C. Tolga, Eng, Christina H., Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelsen, Agnete S.T., Enserink, Jorrit M., Escalante, Ricardo, Esclatine, Audrey, Escobar-Henriques, Mafalda, Eskelinen, Eeva-Liisa, Espert, Lucile, Eusebio, Makandjou-Ola, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Facchiano, Francesco, Fadeel, Bengt, Fader, Claudio, Faesen, Alex C., Fairlie, W. Douglas, Falcó, Alberto, Falkenburger, Bjorn H., Fan, Daping, Fan, Jie, Fan, Yanbo, Fang, Evandro F., Fang, Yanshan, Fang, Yognqi, Fanto, Manolis, Farfel-Becker, Tamar, Faure, Mathias, Fazeli, Gholamreza, Fedele, Anthony O., Feldman, Arthur M., Feng, Du, Feng, Jiachun, Feng, Lifeng, Feng, Yibin, Feng, Yuchen, Feng, Wei, Fenz Araujo, Thais, Ferguson, Thomas A., Fernández, Álvaro F., Fernandez-Checa, Jose C., Fernández-Veledo, Sonia, Fernie, Alisdair R., Ferrante, Anthony W., Ferraresi, Alessandra, Ferrari, Merari F., Ferreira, Julio C.B., Ferro-Novick, Susan, Figueras, Antonio, Filadi, Riccardo, Filigheddu, Nicoletta, Filippi-Chiela, Eduardo, Filomeni, Giuseppe, Fimia, Gian Maria, Fineschi, Vittorio, Finetti, Francesca, Finkbeiner, Steven, Fisher, Edward A., Fisher, Paul B., Flamigni, Flavio, Fliesler, Steven J., Flo, Trude H., Florance, Ida, Florey, Oliver, Florio, Tullio, Fodor, Erika, Follo, Carlo, Fon, Edward A., Forlino, Antonella, Fornai, Francesco, Fortini, Paola, Fracassi, Anna, Fraldi, Alessandro, Franco, Brunella, Franco, Rodrigo, Franconi, Flavia, Frankel, Lisa B., Friedman, Scott L., Fröhlich, Leopold F., Frühbeck, Gema, Fuentes, Jose M., Fujiki, Yukio, Fujita, Naonobu, Fujiwara, Yuuki, Fukuda, Mitsunori, Fulda, Simone, Furic, Luc, Furuya, Norihiko, Fusco, Carmela, Gack, Michaela U., Gaffke, Lidia, Galadari, Sehamuddin, Galasso, Alessia, Galindo, Maria F., Gallolu Kankanamalage, Sachith, Galluzzi, Lorenzo, Galy, Vincent, Gammoh, Noor, Gan, Boyi, Ganley, Ian G., Gao, Feng, Gao, Hui, Gao, Minghui, Gao, Ping, Gao, Shou-Jiang, Gao, Wentao, Gao, Xiaobo, Garcera, Ana, Garcia, Maria Noé, Garcia, Verónica E., García-Del Portillo, Francisco, Garcia-Escudero, Vega, Garcia-Garcia, Aracely, Garcia-Macia, Marina, García-Moreno, Diana, Garcia-Ruiz, Carmen, García-Sanz, Patricia, Garg, Abhishek D., Gargini, Ricardo, Garofalo, Tina, Garry, Robert F., Gassen, Nils C., Gatica, Damian, Ge, Liang, Ge, Wanzhong, Geiss-Friedlander, Ruth, Gelfi, Cecilia, Genschik, Pascal, Gentle, Ian E., Gerbino, Valeria, Gerhardt, Christoph, Germain, Kyla, Germain, Marc, Gewirtz, David A., Ghasemipour Afshar, Elham, Ghavami, Saeid, Ghigo, Alessandra, Ghosh, Manosij, Giamas, Georgios, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibson, Gary E., Gibson, Spencer B., Ginet, Vanessa, Giniger, Edward, Giorgi, Carlotta, Girao, Henrique, Girardin, Stephen E., Giridharan, Mridhula, Giuliano, Sandy, Giulivi, Cecilia, Giuriato, Sylvie, Giustiniani, Julien, Gluschko, Alexander, Goder, Veit, Goginashvili, Alexander, Golab, Jakub, Goldstone, David C., Golebiewska, Anna, Gomes, Luciana R., Gomez, Rodrigo, Gómez-Sánchez, Rubén, Gomez-Puerto, Maria Catalina, Gomez-Sintes, Raquel, Gong, Qingqiu, Goni, Felix M., González-Gallego, Javier, Gonzalez-Hernandez, Tomas, Gonzalez-Polo, Rosa A., Gonzalez-Reyes, Jose A., González-Rodríguez, Patricia, Goping, Ing Swie, Gorbatyuk, Marina S., Gorbunov, Nikolai V., Görgülü, Kıvanç, Gorojod, Roxana M., Gorski, Sharon M., Goruppi, Sandro, Gotor, Cecilia, Gottlieb, Roberta A., Gozes, Illana, Gozuacik, Devrim, Graef, Martin, Gräler, Markus H., Granatiero, Veronica, Grasso, Daniel, Gray, Joshua P., Green, Douglas R., Greenhough, Alexander, Gregory, Stephen L., Griffin, Edward F., Grinstaff, Mark W., Gros, Frederic, Grose, Charles, Gross, Angelina S., Gruber, Florian, Grumati, Paolo, Grune, Tilman, Gu, Xueyan, Guan, Jun-Lin, Guardia, Carlos M., Guda, Kishore, Guerra, Flora, Guerri, Consuelo, Guha, Prasun, Guillén, Carlos, Gujar, Shashi, Gukovskaya, Anna, Gukovsky, Ilya, Gunst, Jan, Günther, Andreas, Guntur, Anyonya R., Guo, Chuanyong, Guo, Chun, Guo, Hongqing, Guo, Lian-Wang, Guo, Ming, Gupta, Pawan, Gupta, Shashi Kumar, Gupta, Swapnil, Gupta, Veer Bala, Gupta, Vivek, Gustafsson, Asa B., Gutterman, David D., H.B., Ranjitha, Haapasalo, Annakaisa, Haber, James E., Hać, Aleksandra, Hadano, Shinji, Hafrén, Anders J., Haidar, Mansour, Hall, Belinda S., Halldén, Gunnel, Hamacher-Brady, Anne, Hamann, Andrea, Hamasaki, Maho, Han, Weidong, Hansen, Malene, Hanson, Phyllis I., Hao, Zijian, Harada, Masaru, Harhaji-Trajkovic, Ljubica, Hariharan, Nirmala, Haroon, Nigil, Harris, James, Hasegawa, Takafumi, Hasima Nagoor, Noor, Haspel, Jeffrey A., Haucke, Volker, Hawkins, Wayne D., Hay, Bruce A., Haynes, Cole M., Hayrabedyan, Soren B., Hays, Thomas S., He, Congcong, He, Qin, He, Rong-Rong, He, You-Wen, He, Yu-Ying, Heakal, Yasser, Heberle, Alexander M., Hejtmancik, J. Fielding, Helgason, Gudmundur Vignir, Henkel, Vanessa, Herb, Marc, Hergovich, Alexander, Herman-Antosiewicz, Anna, Hernández, Agustín, Hernandez, Carlos, Hernandez-Diaz, Sergio, Hernandez-Gea, Virginia, Herpin, Amaury, Herreros, Judit, Hervás, Javier H., Hesselson, Daniel, Hetz, Claudio, Heussler, Volker T., Higuchi, Yujiro, Hilfiker, Sabine, Hill, Joseph A., Hlavacek, William S., Ho, Emmanuel A., Ho, Idy H.T., Ho, Philip Wing-Lok, Ho, Shu-Leong, Ho, Wan Yun, Hobbs, G. Aaron, Hochstrasser, Mark, Hoet, Peter H.M., Hofius, Daniel, Hofman, Paul, Höhn, Annika, Holmberg, Carina I., Hombrebueno, Jose R., Yi-Ren Hong, Chang-Won Hong, Hooper, Lora V., Hoppe, Thorsten, Horos, Rastislav, Hoshida, Yujin, Hsin, I-Lun, Hsu, Hsin-Yun, Hu, Bing, Hu, Dong, Hu, Li-Fang, Hu, Ming Chang, Hu, Ronggui, Hu, Wei, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Jinlian, Hua, Yingqi, Huan, Chongmin, Huang, Canhua, Huang, Chuanshu, Huang, Chuanxin, Huang, Chunling, Huang, Haishan, Huang, Kun, Huang, Michael L.H., Huang, Rui, Huang, Shan, Huang, Tianzhi, Huang, Xing, Huang, Yuxiang Jack, Huber, Tobias B., Hubert, Virginie, Hubner, Christian A., Hughes, Stephanie M., Hughes, William E., Humbert, Magali, Hummer, Gerhard, Hurley, James H., Hussain, Sabah, Hussain, Salik, Hussey, Patrick J., Hutabarat, Martina, Hwang, Hui-Yun, Hwang, Seungmin, Ieni, Antonio, Ikeda, Fumiyo, Imagawa, Yusuke, Imai, Yuzuru, Imbriano, Carol, Imoto, Masaya, Inman, Denise M., Inoki, Ken, Iovanna, Juan, Iozzo, Renato V., Ippolito, Giuseppe, Irazoqui, Javier E., Iribarren, Pablo, Ishaq, Mohd, Ishikawa, Makoto, Ishimwe, Nestor, Isidoro, Ciro, Ismail, Nahed, Issazadeh-Navikas, Shohreh, Itakura, Eisuke, Ito, Daisuke, Ivankovic, Davor, Ivanova, Saška, Iyer, Anand Krishnan V., Izquierdo, José M., Izumi, Masanori, Jäättelä, Marja, Jabir, Majid Sakhi, Jackson, William T., Jacobo-Herrera, Nadia, Jacomin, Anne-Claire, Jacquin, Elise, Jadiya, Pooja, Jaeschke, Hartmut, Jagannath, Chinnaswamy, Jakobi, Arjen J., Jakobsson, Johan, Janji, Bassam, Jansen-Dürr, Pidder, Jansson, Patric J., Jantsch, Jonathan, Januszewski, Sławomir, Jassey, Alagie, Jean, Steve, Jeltsch-David, Hélène, Jendelova, Pavla, Jenny, Andreas, Jensen, Thomas E., Jessen, Niels, Jewell, Jenna L., Ji, Jing, Jia, Lijun, Jia, Rui, Jiang, Liwen, Jiang, Qing, Jiang, Richeng, Jiang, Teng, Jiang, Xuejun, Jiang, Yu, Jimenez-Sanchez, Maria, Jin, Eun-Jung, Jin, Fengyan, Jin, Hongchuan, Jin, Li, Jin, Luqi, Jin, Meiyan, Jin, Si, Jo, Eun-Kyeong, Joffre, Carine, Johansen, Terje, Johnson, Gail V.W., Johnston, Simon A., Jokitalo, Eija, Jolly, Mohit Kumar, Joosten, Leo A.B., Jordan, Joaquin, Joseph, Bertrand, Ju, Dianwen, Ju, Jeong-Sun, Ju, Jingfang, Juárez, Esmeralda, Judith, Delphine, Juhász, Gábor, Jun, Youngsoo, Jung, Chang Hwa, Jung, Sung-Chul, Jung, Yong Keun, Jungbluth, Heinz, Jungverdorben, Johannes, Just, Steffen, Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kaganovich, Daniel, Kahana, Alon, Kain, Renate, Kajimura, Shinjo, Kalamvoki, Maria, Kalia, Manjula, Kalinowski, Danuta S., Kaludercic, Nina, Kalvari, Ioanna, Kaminska, Joanna, Kaminskyy, Vitaliy O., Kanamori, Hiromitsu, Kanasaki, Keizo, Kang, Chanhee, Kang, Rui, Kang, Sang Sun, Kaniyappan, Senthilvelrajan, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanthasamy, Anumantha G., Kanthasamy, Arthi, Kantorow, Marc, Kapuy, Orsolya, Karamouzis, Michalis V., Karim, Md. Razaul, Karmakar, Parimal, Katare, Rajesh G., Kato, Masaru, Kaufmann, Stefan H.E., Kauppinen, Anu, Kaushal, Gur P., Kaushik, Susmita, Kawasaki, Kiyoshi, Kazan, Kemal, Ke, Po-Yuan, Keating, Damien J., Keber, Ursula, Kehrl, John H., Keller, Kate E., Keller, Christian W., Kemper, Jongsook Kim, Kenific, Candia M., Kepp, Oliver, Kermorgant, Stephanie, Kern, Andreas, Ketteler, Robin, Keulers, Tom G., Khalfin, Boris, Khalil, Hany, Khambu, Bilon, Khan, Shahid Y., Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha, Kho, Widuri, Khobrekar, Noopur V., Khuansuwan, Sataree, Khundadze, Mukhran, Killackey, Samuel A., Kim, Dasol, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Dong-Eun, Kim, Eun Young, Kim, Eun-Kyoung, Kim, Hak-Rim, Kim, Hee-Sik, Hyung-Ryong Kim, Kim, Jeong Hun, Kim, Jin Kyung, Kim, Jin-Hoi, Kim, Joungmok, Kim, Ju Hwan, Kim, Keun Il, Kim, Peter K., Kim, Seong-Jun, Kimball, Scot R., Kimchi, Adi, Kimmelman, Alec C., Kimura, Tomonori, King, Matthew A., Kinghorn, Kerri J., Kinsey, Conan G., Kirkin, Vladimir, Kirshenbaum, Lorrie A., Kiselev, Sergey L., Kishi, Shuji, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kitsis, Richard N., Kittler, Josef T., Kjaerulff, Ole, Klein, Peter S., Klopstock, Thomas, Klucken, Jochen, Knævelsrud, Helene, Knorr, Roland L., Ko, Ben C.B., Ko, Fred, Ko, Jiunn-Liang, Kobayashi, Hotaka, Kobayashi, Satoru, Koch, Ina, Koch, Jan C., Koenig, Ulrich, Kögel, Donat, Koh, Young Ho, Koike, Masato, Kohlwein, Sepp D., Kocaturk, Nur M., Komatsu, Masaaki, König, Jeannette, Kono, Toru, Kopp, Benjamin T., Korcsmaros, Tamas, Korkmaz, Gözde, Korolchuk, Viktor I., Korsnes, Mónica Suárez, Koskela, Ali, Kota, Janaiah, Kotake, Yaichiro, Kotler, Monica L., Kou, Yanjun, Koukourakis, Michael I., Koustas, Evangelos, Kovacs, Attila L., Kovács, Tibor, Koya, Daisuke, Kozako, Tomohiro, Kraft, Claudine, Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna D., Kretz-Remy, Carole, Kroemer, Guido, Ktistakis, Nicholas T., Kuchitsu, Kazuyuki, Kuenen, Sabine, Kuerschner, Lars, Kukar, Thomas, Kumar, Ajay, Kumar, Ashok, Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad, Kume, Shinji, Kumsta, Caroline, Kundu, Chanakya N., Kundu, Mondira, Kunnumakkara, Ajaikumar B., Kurgan, Lukasz, Kutateladze, Tatiana G., Kutlu, Ozlem, Kwak, SeongAe, Kwon, Ho Jeong, Kwon, Taeg Kyu, Kwon, Yong Tae, Kyrmizi, Irene, La Spada, Albert, Labonté, Patrick, Ladoire, Sylvain, Laface, Ilaria, Lafont, Frank, Lagace, Diane C., Lahiri, Vikramjit, Lai, Zhibing, Laird, Angela S., Lakkaraju, Aparna, Lamark, Trond, Lan, Sheng-Hui, Landajuela, Ane, Lane, Darius J. R., Lane, Jon D., Lang, Charles H., Lange, Carsten, Langel, Ülo, Langer, Rupert, Lapaquette, Pierre, Laporte, Jocelyn, LaRusso, Nicholas F., Lastres-Becker, Isabel, Lau, Wilson Chun Yu, Laurie, Gordon W., Lavandero, Sergio, Law, Betty Yuen Kwan, Law, Helen Ka-wai, Layfield, Rob, Le, Weidong, Le Stunff, Herve, Leary, Alexandre Y., Lebrun, Jean-Jacques, Leck, Lionel Y.W., Leduc-Gaudet, Jean-Philippe, Lee, Changwook, Lee, Chung-Pei, Lee, Da-Hye, Lee, Edward B., Lee, Erinna F., Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu, Lee, Jae Man, Lee, Jason S., Lee, Jin-A, Lee, Joo-Yong, Lee, Jun Hee, Lee, Michael, Lee, Min Goo, Lee, Min Jae, Lee, Myung-Shik, Lee, Sang Yoon, Lee, Seung-Jae, Lee, Stella Y., Lee, Sung Bae, Lee, Won Hee, Lee, Ying-Ray, Lee, Yong-ho, Lee, Youngil, Lefebvre, Christophe, Legouis, Renaud, Lei, Yu L., Lei, Yuchen, Leikin, Sergey, Leitinger, Gerd, Lemus, Leticia, Leng, Shuilong, Lenoir, Olivia, Lenz, Guido, Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda, Leopoldino, Andréia M., Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth, Leung, Chi-Ting, Leung, Po Sing, Leventhal, Jeremy S., Levine, Beth, Lewis, Patrick A., Ley, Klaus, Li, Bin, Li, Da-Qiang, Li, Jianming, Li, Jing, Li, Jiong, Li, Ke, Li, Liwu, Li, Mei, Li, Min, Li, Ming, Li, Mingchuan, Li, Pin-Lan, Li, Ming-Qing, Li, Qing, Li, Sheng, Li, Tiangang, Li, Wei, Li, Wenming, Li, Xue, Li, Yi-Ping, Li, Yuan, Li, Zhiqiang, Li, Zhiyong, Li, Zhiyuan, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng, Liang, Yongheng, Liang, YongTian, Liao, Guanghong, Liao, Lujian, Liao, Mingzhi, Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl P. Y., Lilly, Mary A., Lim, Hyunjung J., Lima, Thania R.R., Limana, Federica, Lin, Chao, Lin, Chih-Wen, Lin, Dar-Shong, Lin, Fu-Cheng, Lin, Jiandie D., Lin, Kurt M., Lin, Kwang-Huei, Lin, Liang-Tzung, Lin, Pei-Hui, Lin, Qiong, Lin, Shaofeng, Lin, Su-Ju, Lin, Wenyu, Lin, Xueying, Lin, Yao-Xin, Lin, Yee-Shin, Linden, Rafael, Lindner, Paula, Ling, Shuo-Chien, Lingor, Paul, Linnemann, Amelia K., Liou, Yih-Cherng, Lipinski, Marta M., Lipovšek, Saška, Lira, Vitor A., Lisiak, Natalia, Liton, Paloma B., Liu, Chao, Liu, Ching-Hsuan, Liu, Chun-Feng, Liu, Cui Hua, Liu, Fang, Liu, Hao, Liu, Hsiao-Sheng, Liu, Hua-feng, Liu, Huifang, Liu, Jia, Liu, Jing, Liu, Julia, Liu, Leyuan, Liu, Longhua, Liu, Meilian, Liu, Qin, Liu, Wei, Liu, Wende, Liu, Xiao-Hong, Liu, Xiaodong, Liu, Xingguo, Liu, Xu, Liu, Xuedong, Liu, Yanfen, Liu, Yang, Liu, Yueyang, Liu, Yule, Livingston, J. 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Patrick, Murthy, Aditya, Myöhänen, Timo T., Mysorekar, Indira U., Mytych, Jennifer, Nabavi, Seyed Mohammad, Nabissi, Massimo, Nagy, Péter, Nah, Jihoon, Nahimana, Aimable, Nakagawa, Ichiro, Nakamura, Ken, Nakatogawa, Hitoshi, Nandi, Shyam S., Nanjundan, Meera, Nanni, Monica, Napolitano, Gennaro, Nardacci, Roberta, Narita, Masashi, Nassif, Melissa, Nathan, Ilana, Natsumeda, Manabu, Naude, Ryno J., Naumann, Christin, Naveiras, Olaia, Navid, Fatemeh, Nawrocki, Steffan T., Nazarko, Taras Y., Nazio, Francesca, Negoita, Florentina, Neill, Thomas, Neisch, Amanda L., Neri, Luca M., Netea, Mihai G., Neubert, Patrick, Neufeld, Thomas P., Neumann, Dietbert, Neutzner, Albert, Newton, Phillip T., Ney, Paul A., Nezis, Ioannis P., Ng, Charlene C.W., Ng, Tzi Bun, Nguyen, Hang T. T., Nguyen, Long T., Ni, Hong-Min, Ní Cheallaigh, Clíona, Ni, Zhenhong, Nicolao, M. 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Bishr, Önal, Gizem, Ondrej, Martin, Ong, Sang-Bing, Ong, Sang-Ging, Onnis, Anna, Orellana, Juan A., Orellana-Muñoz, Sara, Ortega-Villaizan, Maria Del Mar, Ortiz-Gonzalez, Xilma R., Ortona, Elena, Osiewacz, Heinz D., Osman, Abdel-Hamid K., Osta, Rosario, Otegui, Marisa S., Otsu, Kinya, Ott, Christiane, Ottobrini, Luisa, Ou, Jing-hsiung James, Outeiro, Tiago F., Oynebraten, Inger, Ozturk, Melek, Pagès, Gilles, Pahari, Susanta, Pajares, Marta, Pajvani, Utpal B., Pal, Rituraj, Paladino, Simona, Pallet, Nicolas, Palmieri, Michela, Palmisano, Giuseppe, Palumbo, Camilla, Pampaloni, Francesco, Pan, Lifeng, Pan, Qingjun, Pan, Wenliang, Pan, Xin, Panasyuk, Ganna, Pandey, Rahul, Pandey, Udai B., Pandya, Vrajesh, Paneni, Francesco, Pang, Shirley Y., Panzarini, Elisa, Papademetrio, Daniela L., Papaleo, Elena, Papinski, Daniel, Papp, Diana, Park, Eun Chan, Park, Hwan Tae, Park, Ji-Man, Park, Jong-In, Park, Joon Tae, Park, Junsoo, Park, Sang Chul, Park, Sang-Youel, Parola, Abraham H., Parys, Jan B., Pasquier, Adrien, Pasquier, Benoit, Passos, João F., Pastore, Nunzia, Patel, Hemal H., Patschan, Daniel, Pattingre, Sophie, Pedraza-Alva, Gustavo, Pedraza-Chaverri, Jose, Pedrozo, Zully, Pei, Gang, Pei, Jianming, Peled-Zehavi, Hadas, Pellegrini, Joaquín M., Pelletier, Joffrey, Peñalva, Miguel A., Peng, Di, Peng, Ying, Penna, Fabio, Pennuto, Maria, Pentimalli, Francesca, Pereira, Cláudia MF, Pereira, Gustavo J.S., Pereira, Lilian C., Pereira de Almeida, Luis, Perera, Nirma D., Pérez-Lara, Ángel, Perez-Oliva, Ana B., Pérez-Pérez, María Esther, Periyasamy, Palsamy, Perl, Andras, Perrotta, Cristiana, Perrotta, Ida, Pestell, Richard G., Petersen, Morten, Petrache, Irina, Petrovski, Goran, Pfirrmann, Thorsten, Pfister, Astrid S., Philips, Jennifer A., Pi, Huifeng, Picca, Anna, Pickrell, Alicia M., Picot, Sandy, Pierantoni, Giovanna M., Pierdominici, Marina, Pierre, Philippe, Pierrefite-Carle, Valérie, Pierzynowska, Karolina, Pietrocola, Federico, Pietruczuk, Miroslawa, Pignata, Claudio, Pimentel-Muiños, Felipe X., Pinar, Mario, Pinheiro, Roberta O., Pinkas-Kramarski, Ronit, Pinton, Paolo, Pircs, Karolina, Piya, Sujan, Pizzo, Paola, Plantinga, Theo S., Platta, Harald W., Plaza-Zabala, Ainhoa, Plomann, Markus, Plotnikov, Egor Y., Plun-Favreau, Helene, Pluta, Ryszard, Pocock, Roger, Pöggeler, Stefanie, Pohl, Christian, Poirot, Marc, Poletti, Angelo, Ponpuak, Marisa, Popelka, Hana, Popova, Blagovesta, Porta, Helena, Porte Alcon, Soledad, Portilla-Fernandez, Eliana, Post, Martin, Potts, Malia B., Poulton, Joanna, Powers, Ted, Prahlad, Veena, Prajsnar, Tomasz K., Praticò, Domenico, Prencipe, Rosaria, Priault, Muriel, Proikas-Cezanne, Tassula, Promponas, Vasilis J., Proud, Christopher G., Puertollano, Rosa, Puglielli, Luigi, Pulinilkunnil, Thomas, Puri, Deepika, Puri, Rajat, Puyal, Julien, Qi, Xiaopeng, Qi, Yongmei, Qian, Wenbin, Qiang, Lei, Qiu, Yu, Quadrilatero, Joe, Quarleri, Jorge, Raben, Nina, Rabinowich, Hannah, Ragona, Debora, Ragusa, Michael J., Rahimi, Nader, Rahmati, Marveh, Raia, Valeria, Raimundo, Nuno, Rajasekaran, Namakkal-Soorappan, Ramachandra Rao, Sriganesh, Rami, Abdelhaq, Ramírez-Pardo, Ignacio, Ramsden, David B., Randow, Felix, Rangarajan, Pundi N., Ranieri, Danilo, Rao, Hai, Rao, Lang, Rao, Rekha, Rathore, Sumit, Ratnayaka, J. Arjuna, Ratovitski, Edward A., Ravanan, Palaniyandi, Ravegnini, Gloria, Ray, Swapan K., Razani, Babak, Rebecca, Vito, Reggiori, Fulvio, Régnier-Vigouroux, Anne, Reichert, Andreas S., Reigada, David, Reiling, Jan H., Rein, Theo, Reipert, Siegfried, Rekha, Rokeya Sultana, Ren, Hongmei, Ren, Jun, Ren, Weichao, Renault, Tristan, Renga, Giorgia, Reue, Karen, Rewitz, Kim, Ribeiro de Andrade Ramos, Bruna, Riazuddin, S. Amer, Ribeiro-Rodrigues, Teresa M., Ricci, Jean-Ehrland, Ricci, Romeo, Riccio, Victoria, Richardson, Des R., Rikihisa, Yasuko, Risbud, Makarand V., Risueño, Ruth M., Ritis, Konstantinos, Rizza, Salvatore, Rizzuto, Rosario, Roberts, Helen C., Roberts, Luke D., Robinson, Katherine J., Roccheri, Maria Carmela, Rocchi, Stephane, Rodney, George G., Rodrigues, Tiago, Rodrigues Silva, Vagner Ramon, Rodriguez, Amaia, Rodriguez-Barrueco, Ruth, Rodriguez-Henche, Nieves, Rodriguez-Rocha, Humberto, Roelofs, Jeroen, Rogers, Robert S., Rogov, Vladimir V., Rojo, Ana I., Rolka, Krzysztof, Romanello, Vanina, Romani, Luigina, Romano, Alessandra, Romano, Patricia S., Romeo-Guitart, David, Romero, Luis C., Romero, Montserrat, Roney, Joseph C., Rongo, Christopher, Roperto, Sante, Rosenfeldt, Mathias T., Rosenstiel, Philip, Rosenwald, Anne G., Roth, Kevin A., Roth, Lynn, Roth, Steven, Rouschop, Kasper M.A., Roussel, Benoit D., Roux, Sophie, Rovere-Querini, Patrizia, Roy, Ajit, Rozieres, Aurore, Ruano, Diego, Rubinsztein, David C., Rubtsova, Maria P., Ruckdeschel, Klaus, Ruckenstuhl, Christoph, Rudolf, Emil, Rudolf, Rüdiger, Ruggieri, Alessandra, Ruparelia, Avnika Ashok, Rusmini, Paola, Russell, Ryan R., Russo, Gian Luigi, Russo, Maria, Russo, Rossella, Ryabaya, Oxana O., Ryan, Kevin M., Ryu, Kwon-Yul, Sabater-Arcis, Maria, Sachdev, Ulka, Sacher, Michael, Sachse, Carsten, Sadhu, Abhishek, Sadoshima, Junichi, Safren, Nathaniel, Saftig, Paul, Sagona, Antonia P., Sahay, Gaurav, Sahebkar, Amirhossein, Sahin, Mustafa, Sahin, Ozgur, Sahni, Sumit, Saito, Nayuta, Saito, Shigeru, Saito, Tsunenori, Sakai, Ryohei, Sakai, Yasuyoshi, Sakamaki, Jun-Ichi, Saksela, Kalle, Salazar, Gloria, Salazar-Degracia, Anna, Salekdeh, Ghasem H., Saluja, Ashok K., Sampaio-Marques, Belém, Sanchez, Maria Cecilia, Sanchez-Alcazar, Jose A., Sanchez-Vera, Victoria, Sancho-Shimizu, Vanessa, Sanderson, J. Thomas, Sandri, Marco, Santaguida, Stefano, Santambrogio, Laura, Santana, Magda M., Santoni, Giorgio, Sanz, Alberto, Sanz, Pascual, Saran, Shweta, Sardiello, Marco, Sargeant, Timothy J., Sarin, Apurva, Sarkar, Chinmoy, Sarkar, Sovan, Sarrias, Maria-Rosa, Sarkar, Surajit, Sarmah, Dipanka Tanu, Sarparanta, Jaakko, Sathyanarayan, Aishwarya, Sathyanarayanan, Ranganayaki, Scaglione, K. Matthew, Scatozza, Francesca, Schaefer, Liliana, Schafer, Zachary T., Schaible, Ulrich E., Schapira, Anthony H.V., Scharl, Michael, Schatzl, Hermann M., Schein, Catherine H., Scheper, Wiep, Scheuring, David, Schiaffino, Maria Vittoria, Schiappacassi, Monica, Schindl, Rainer, Schlattner, Uwe, Schmidt, Oliver, Schmitt, Roland, Schmidt, Stephen D., Schmitz, Ingo, Schmukler, Eran, Schneider, Anja, Schneider, Bianca E., Schober, Romana, Schoijet, Alejandra C., Schott, Micah B., Schramm, Michael, Schröder, Bernd, Schuh, Kai, Schüller, Christoph, Schulze, Ryan J., Schürmanns, Lea, Schwamborn, Jens C., Schwarten, Melanie, Scialo, Filippo, Sciarretta, Sebastiano, Scott, Melanie J., Scotto, Kathleen W., Scovassi, A. Ivana, Scrima, Andrea, Scrivo, Aurora, Sebastian, David, Sebti, Salwa, Sedej, Simon, Segatori, Laura, Segev, Nava, Seglen, Per O., Seiliez, Iban, Seki, Ekihiro, Selleck, Scott B., Sellke, Frank W., Selsby, Joshua T., Sendtner, Michael, Senturk, Serif, Seranova, Elena, Sergi, Consolato, Serra-Moreno, Ruth, Sesaki, Hiromi, Settembre, Carmine, Setty, Subba Rao Gangi, Sgarbi, Gianluca, Sha, Ou, Shacka, John J., Shah, Javeed A., Shang, Dantong, Shao, Changshun, Shao, Feng, Sharbati, Soroush, Sharkey, Lisa M., Sharma, Dipali, Sharma, Gaurav, Sharma, Kulbhushan, Sharma, Pawan, Sharma, Surendra, Shen, Han-Ming, Shen, Hongtao, Shen, Jiangang, Shen, Ming, Shen, Weili, Shen, Zheni, Sheng, Rui, Sheng, Zhi, Sheng, Zu-Hang, Shi, Jianjian, Shi, Xiaobing, Shi, Ying-Hong, Shiba-Fukushima, Kahori, Shieh, Jeng-Jer, Shimada, Yohta, Shimizu, Shigeomi, Shimozawa, Makoto, Shintani, Takahiro, Shoemaker, Christopher J., Shojaei, Shahla, Shoji, Ikuo, Shravage, Bhupendra V., Shridhar, Viji, Shu, Chih-Wen, Shu, Hong-Bing, Shui, Ke, Shukla, Arvind K., Shutt, Timothy E., Sica, Valentina, Siddiqui, Aleem, Sierra, Amanda, Sierra-Torre, Virginia, Signorelli, Santiago, Sil, Payel, Silva, Bruno J. de Andrade, Silva, Johnatas D., Silva-Pavez, Eduardo, Silvente-Poirot, Sandrine, Simmonds, Rachel E., Simon, Anna Katharina, Simon, Hans-Uwe, Simons, Matias, Singh, Anurag, Singh, Lalit P., Singh, Rajat, Singh, Shivendra V., Singh, Shrawan K., Singh, Sudha B., Singh, Sunaina, Singh, Surinder Pal, Sinha, Debasish, Sinha, Rohit Anthony, Sinha, Sangita, Sirko, Agnieszka, Sirohi, Kapil, Sivridis, Efthimios L., Skendros, Panagiotis, Skirycz, Aleksandra, Slaninová, Iva, Smaili, Soraya S., Smertenko, Andrei, Smith, Matthew D., Soenen, Stefaan J., Sohn, Eun Jung, Sok, Sophia P. 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M., St. Clair, Daret, Stagni, Venturina, Staiano, Leopoldo, Stalnecker, Clint A., Stankov, Metodi V., Stathopulos, Peter B., Stefan, Katja, Stefan, Sven Marcel, Stefanis, Leonidas, Steffan, Joan S., Steinkasserer, Alexander, Stenmark, Harald, Sterneckert, Jared, Stevens, Craig, Stoka, Veronika, Storch, Stephan, Stork, Björn, Strappazzon, Flavie, Strohecker, Anne Marie, Stupack, Dwayne G., Su, Huanxing, Su, Ling-Yan, Su, Longxiang, Suarez-Fontes, Ana M., Subauste, Carlos S., Subbian, Selvakumar, Subirada, Paula V., Sudhandiran, Ganapasam, Sue, Carolyn M., Sui, Xinbing, Summers, Corey, Sun, Guangchao, Sun, Jun, Sun, Kang, Sun, Meng-xiang, Sun, Qiming, Sun, Yi, Sun, Zhongjie, Sunahara, Karen K.S., Sundberg, Eva, Susztak, Katalin, Sutovsky, Peter, Suzuki, Hidekazu, Sweeney, Gary, Symons, J. David, Sze, Stephen Cho Wing, Szewczyk, Nathaniel J., Tabęcka-Łonczynska, Anna, Tabolacci, Claudio, Tacke, Frank, Taegtmeyer, Heinrich, Tafani, Marco, Tagaya, Mitsuo, Tai, Haoran, Tait, Stephen W. G., Takahashi, Yoshinori, Takats, Szabolcs, Talwar, Priti, Tam, Chit, Tam, Shing Yau, Tampellini, Davide, Tamura, Atsushi, Tan, Chong Teik, Tan, Eng-King, Tan, Ya-Qin, Tanaka, Masaki, Tanaka, Motomasa, Tang, Daolin, Tang, Jingfeng, Tang, Tie-Shan, Tanida, Isei, Tao, Zhipeng, Taouis, Mohammed, Tatenhorst, Lars, Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory A., Taylor, Joan M., Tchetina, Elena, Tee, Andrew R., Tegeder, Irmgard, Teis, David, Teixeira, Natercia, Teixeira-Clerc, Fatima, Tekirdag, Kumsal A., Tencomnao, Tewin, Tenreiro, Sandra, Tepikin, Alexei V., Testillano, Pilar S., Tettamanti, Gianluca, Tharaux, Pierre-Louis, Thedieck, Kathrin, Thekkinghat, Arvind A., Thellung, Stefano, Thinwa, Josephine W., Thirumalaikumar, V.P., Thomas, Sufi Mary, Thomes, Paul G., Thorburn, Andrew, Thukral, Lipi, Thum, Thomas, Thumm, Michael, Tian, Ling, Tichy, Ales, Till, Andreas, Timmerman, Vincent, Titorenko, Vladimir I., Todi, Sokol V., Todorova, Krassimira, Toivonen, Janne M., Tomaipitinca, Luana, Tomar, Dhanendra, Tomas-Zapico, Cristina, Tomić, Sergej, Tong, Benjamin Chun-Kit, Tong, Chao, Tong, Xin, Tooze, Sharon A., Torgersen, Maria L., Torii, Satoru, Torres-López, Liliana, Torriglia, Alicia, Towers, Christina G., Towns, Roberto, Toyokuni, Shinya, Trajkovic, Vladimir, Tramontano, Donatella, Tran, Quynh-Giao, Travassos, Leonardo H., Trelford, Charles B., Tremel, Shirley, Triola, Gemma, Trougakos, Ioannis P., Tsao, Betty P., Tschan, Mario P., Tse, Hung-Fat, Tse, Tak Fu, Tsugawa, Hitoshi, Tsvetkov, Andrey S., Tumbarello, David A., Tumtas, Yasin, Tuñón, María J., Turcotte, Sandra, Turk, Boris, Turk, Vito, Turner, Bradley J., Tuxworth, Richard I., Tyler, Jessica K., Tyutereva, Elena V., Uchiyama, Yasuo, Ugun-Klusek, A, Uhlig, Holm H., Ułamek-Kozioł, Marzena, Ulasov, Ilya V., Umekawa, Midori, Ungermann, Christian, Unno, Rei, Urbe, Sylvie, Uribe-Carretero, Elisabet, Üstün, Suayib, Uversky, Vladimir N, Vaccari, Thomas, Vaccaro, Maria I., Vahsen, Björn F., Vakifahmetoglu-Norberg, Helin, Valdor, Rut, Valente, Maria J., Valko, Ayelén, Vallee, Richard B., Valverde, Angela M., Van den Berghe, Greet, van der Veen, Stijn, Van Kaer, Luc, van Loosdregt, Jorg, van Wijk, Sjoerd J.L., Vandenberghe, Wim, Vanhorebeek, Ilse, Vannier-Santos, Marcos A., Vannini, Nicola, Vanrell, M. 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Lindsay, Whitworth, Alexander J., Wiktorska, Katarzyna, Wildenberg, Manon E., Wileman, Tom, Wilkinson, Simon, Willbold, Dieter, Williams, Brett, Williams, Robin S.B., Williams, Roger L., Williamson, Peter R., Wilson, Richard A., Winner, Beate, Winsor, Nathaniel J., Witkin, Steven S., Wodrich, Harald, Woehlbier, Ute, Wollert, Thomas, Wong, Esther, Wong, Jack Ho, Wong, Richard W., Wong, Vincent Kam Wai, Wong, W. 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Liliana, Schafer, Zachary T, Schaible, Ulrich E, Schapira, Anthony H V, Scharl, Michael, Schatzl, Hermann M, Schein, Catherine H, Scheper, Wiep, Scheuring, David, Schiaffino, Maria Vittoria, Schiappacassi, Monica, Schindl, Rainer, Schlattner, Uwe, Schmidt, Oliver, Schmitt, Roland, Schmidt, Stephen D, Schmitz, Ingo, Schmukler, Eran, Schneider, Anja, Schneider, Bianca E, Schober, Romana, Schoijet, Alejandra C, Schott, Micah B, Schramm, Michael, Schröder, Bernd, Schuh, Kai, Schüller, Christoph, Schulze, Ryan J, Schürmanns, Lea, Schwamborn, Jens C, Schwarten, Melanie, Scialo, Filippo, Sciarretta, Sebastiano, Scott, Melanie J, Scotto, Kathleen W, Scovassi, A Ivana, Scrima, Andrea, Scrivo, Aurora, Sebastian, David, Sebti, Salwa, Sedej, Simon, Segatori, Laura, Segev, Nava, Seglen, Per O, Seiliez, Iban, Seki, Ekihiro, Selleck, Scott B, Sellke, Frank W, Selsby, Joshua T, Sendtner, Michael, Senturk, Serif, Seranova, Elena, Sergi, Consolato, Serra-Moreno, Ruth, Sesaki, Hiromi, Settembre, Carmine, 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Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de biogenèse membranaire (LBM), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université du Québec à Trois-Rivières (UQTR), Laboratory of Pathogen Host Interactions [Montpellier] (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut NeuroMyoGène (INMG), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Université Paris 13 (UP13)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), OEil, nutrition et signalisation cellulaire [CSGA], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), 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 Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Marseille (CRCM), 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), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Métabolisme, Cancer et Immunité (CRC - UMR_S 1138), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Karolinska Institutet [Stockholm], Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - 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 Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologia Celular [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire d'Optique et Biosciences (LOB), École polytechnique (X)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), SFR Biosciences, Laboratoire de Génétique et Pathologie des Mollusques Marins (LGPMM), Santé, Génétique et Microbiologie des Mollusques (SGMM), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS), Université de Strasbourg (UNISTRA), Sanofi [Vitry-sur-Seine], SANOFI Recherche, Micro-environnement tumoral et résistance aux traitements, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Immunologie de Marseille - Luminy (CIML), Universidade de Aveiro, Shanghai Jiao Tong University [Shanghai], Biochimie membranaire et transport / Membrane Biochemistry and Transport, Institut Pasteur [Paris] (IP), Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), National Institute of General Medical Sciences [GM131919], Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-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 Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), University of South Carolina Upstate (USC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Physiologie et physiopathologie endocriniennes, 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), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris]-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)-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), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-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)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Génétique et Pathologie des Mollusques Marins, 17390 La Tremblade, France. (LGPMM), Santé, Génétique et Microbiologie des Mollusques (IFREMER SG2M), Institut Français de Recherche pour l'Exploitation de la Mer - Atlantique (IFREMER Atlantique), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer - Atlantique (IFREMER Atlantique), Institut d’Etudes Avancées de l’Université de Strasbourg (USIAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan System-University of Michigan System, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences. Johannes Gutenberg University, Division of Cardiology, Medical University of Graz, Department of Hepatitis and HIV, Pasteur Institute of Iran, Department of Molecular Signal Processing, Leibniz Institute for Plant Biochemistry, Department of Biochemistry and Food Science, The Hebrew University of Jerusalem (HUJ), RNA and Autophagy Group, Danish Cancer Society Research Center, Biotech Research and Innovation Centre (BRIC), University of Copenhagen = Københavns Universitet (KU), Department of Medical Biology, The Arctic University of Norway (UiT), CIBERNED and Universidad de La Laguna, ITB, Hospital Universitario De Canarias, UC Davis Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California, Department of Biochemistry [University of Toronto], University of Toronto, Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria., Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Protein Structure and Function Section, National Institutes of Health, National Eye institute, Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Faculty of Health Sciences, Division of Nephrology and Birmingham VA Medical Center, University of Alabama at Birmingham [ Birmingham] (UAB), Inflammation Research Center, Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli studi di Palermo - University of Palermo, Cell Death Research & Therapy (CDRT) Lab, Department of Cellular & Molecular Medicine, Center for Cancer Biology, Indian Institute of Technology, The MRC Protein Phosphorylation and Ubiquitylation Unit [Dundee, UK] (School of Life Sciences), University of Dundee, Department of Pathology [Dallas], University of Texas Southwestern Medical Center [Dallas], Department of Biology, Colby College, Departments of Otorhinolaryngology Head & Neck Surgery, Ophthalmology and Visual Science, University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Center for Integrative Biology, and Geroscience Center for Brain Health and Metabolism, Universidad Mayor [Santiago de Chile], Department of Experimental Medical Science, Cell Death, Lysosomes and Artificial Intelligence Group, Lund University [Lund], College of Bioresource Sciences, Nihon University, Department of Molecular Biology and Genetics and KUTTAM Research Center for Translational Medicine, Koc University, School of Medicine, Istanbul, School of Medicine. Laboratory of Clinical Microbiology and Microbial Pathogenesis, University of Crete [Heraklion] (UOC), Institute of Molecular Biology and Biotechnology (IMBB-FORTH), Foundation for Research and Technology - Hellas (FORTH), Cancer Therapeutics Unit, The Institute of Cancer Research, London, UK., Pharmaceutical Sciences Department, College of Pharmacy, Gulf Medical University [Ajman, UAE], Department of Pathology and Bosch Institute, University of Sydney, The University of Sydney, Department of Research, Insight Institute of Neurosurgery & Neuroscience, Departments of Medicine and Oncology and Segal Cancer Centre, McGill University = Université McGill [Montréal, Canada], Center for Molecular and Cellular Bioengineering [TU Dresden, Germany] (CMCB), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Departamento de Psicología Experimental, Universidad de Sevilla, Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Johns Hopkins University School of Medicine [Baltimore], Department of Pharmacy, Faculty of Science, University of Rajshahi, Rajshahi, Bangladesh, Islamic University of Gaza (IUG - IU Gaza), University of Manitoba [Winnipeg], University of Barcelona, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Cleveland Clinic, University of the Basque Country [Bizkaia] (UPV/EHU), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, 'Dr. Héctor N. Torres' [Buenos Aires] (INGEBI), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas y Naturales [Buenos Aires] (FCEyN), Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Universidad de Buenos Aires [Buenos Aires] (UBA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), The Wistar Institute, University of Buenos Aires [Argentina], Universidade do Porto, Excellence Laboratory LabEx DISTALZ, University of Pavia, University of Camerino, Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina (TIGEM), Ohio State University [Columbus] (OSU), University of California [San Francisco] (UCSF), Aarhus University [Aarhus], Federal University of Sao Paulo (Unifesp), Nove de Julho University [Bauru] (UNINOVE ), Cedars-Sinai Medical Center, University of Bologna, City of Hope Comprehensive Cancer Center [Duarte], The University of Tennessee [Knoxville], Northeastern Ohio Medical University (NEOMED), Chronic Diseases Research Center (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA)-Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA), Max planck Institute for Biology of Ageing [Cologne], School of Biochemistry, University of Bristol, University of Helsinki, Inserm U1231 University UBFC Dijon, University of Valencia, National Center of Neurology and Psychiatry [Tokyo, Japan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), 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 Côte d'Azur (UCA), UMR 1195 Inserm, Université Paris Sud (Paris 11), Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the National Institute of General Medical Sciences [GM131919]. Due to space and other limitations, it is not possible to include all other sources of financial support., Debosch, Brian J, Degregori, Jame, Depamphilis, Melvin L, Hyung-Ryong Kim, Null, Kwak, Seongae, Larusso, Nicholas F, Liang, Yongtian, Lleonart, Matilde E, Macdougald, Ormond A, Macintosh, Gustavo C, Mackeigan, Jeffrey P, Mccarty, Nami, Mcdonald, Christine, Mcgill, Mitchell R, Mckenna, Sharon L, Mclaughlin, Bethann, Mcloughlin, Fionn, Mcniven, Mark A, Mcwilliams, Thomas G, Xu, Jinrong, Klionsky D.J., Abdel-Aziz A.K., Abdelfatah S., Abdellatif M., Abdoli A., Abel S., Abeliovich H., Abildgaard M.H., Abudu Y.P., Acevedo-Arozena A., Adamopoulos I.E., Adeli K., Adolph T.E., Adornetto A., Aflaki E., Agam G., Agarwal A., Aggarwal B.B., Agnello M., Agostinis P., Agrewala J.N., Agrotis A., Aguilar P.V., Ahmad S.T., Ahmed Z.M., Ahumada-Castro U., Aits S., Aizawa S., Akkoc Y., Akoumianaki T., Akpinar H.A., Al-Abd A.M., Al-Akra L., Al-Gharaibeh A., Alaoui-Jamali M.A., Alberti S., Alcocer-Gomez E., Alessandri C., Ali M., Alim Al-Bari M.A., Aliwaini S., Alizadeh J., Almacellas E., Almasan A., Alonso A., Alonso G.D., Altan-Bonnet N., Altieri D.C., Alvarez E.M.C., Alves S., Alves da Costa C., Alzaharna M.M., Amadio M., Amantini C., Amaral C., Ambrosio S., Amer A.O., Ammanathan V., An Z., Andersen S.U., Andrabi S.A., Andrade-Silva M., Andres A.M., Angelini S., Ann D., Anozie U.C., Ansari M.Y., Antas P., Antebi A., Anton Z., Anwar T., Apetoh L., Apostolova N., Araki T., Araki Y., Arasaki K., Araujo W.L., Araya J., Arden C., Arevalo M.-A., Arguelles S., Arias E., Arikkath J., Arimoto H., Ariosa A.R., Armstrong-James D., Arnaune-Pelloquin L., Aroca A., Arroyo D.S., Arsov I., Artero R., Asaro D.M.L., Aschner M., Ashrafizadeh M., Ashur-Fabian O., Atanasov A.G., Au A.K., Auberger P., Auner H.W., Aurelian L., Autelli R., Avagliano L., Avalos Y., Aveic S., Aveleira C.A., Avin-Wittenberg T., Aydin Y., Ayton S., Ayyadevara S., Azzopardi M., Baba M., Backer J.M., Backues S.K., Bae D.-H., Bae O.-N., Bae S.H., Baehrecke E.H., Baek A., Baek S.-H., Baek S.H., Bagetta G., Bagniewska-Zadworna A., Bai H., Bai J., Bai X., Bai Y., Bairagi N., Baksi S., Balbi T., Baldari C.T., Balduini W., Ballabio A., Ballester M., Balazadeh S., Balzan R., Bandopadhyay R., Banerjee S., Banreti A., Bao Y., Baptista M.S., Baracca A., Barbati C., Bargiela A., Barila D., Barlow P.G., Barmada S.J., Barreiro E., Barreto G.E., Bartek J., Bartel B., Bartolome A., Barve G.R., Basagoudanavar S.H., Bassham D.C., Bast R.C., Basu A., Batoko H., Batten I., Baulieu E.E., Baumgarner B.L., Bayry J., Beale R., Beau I., Beaumatin F., Bechara L.R.G., Beck G.R., Beers M.F., Begun J., Behrends C., Behrens G.M.N., Bei R., Bejarano E., Bel S., Behl C., Belaid A., Belgareh-Touze N., Bellarosa C., Belleudi F., Bello Perez M., Bello-Morales R., Beltran J.S.D.O., Beltran S., Benbrook D.M., Bendorius M., Benitez B.A., Benito-Cuesta I., Bensalem J., Berchtold M.W., Berezowska S., Bergamaschi D., Bergami M., Bergmann A., Berliocchi L., Berlioz-Torrent C., Bernard A., Berthoux L., Besirli C.G., Besteiro S., Betin V.M., Beyaert R., Bezbradica J.S., Bhaskar K., Bhatia-Kissova I., Bhattacharya R., Bhattacharya S., Bhattacharyya S., Bhuiyan M.S., Bhutia S.K., Bi L., Bi X., Biden T.J., Bijian K., Billes V.A., Binart N., Bincoletto C., Birgisdottir A.B., Bjorkoy G., Blanco G., Blas-Garcia A., Blasiak J., Blomgran R., Blomgren K., Blum J.S., Boada-Romero E., Boban M., Boesze-Battaglia K., Boeuf P., Boland B., Bomont P., Bonaldo P., Bonam S.R., Bonfili L., Bonifacino J.S., Boone B.A., Bootman M.D., Bordi M., Borner C., Bornhauser B.C., Borthakur G., Bosch J., Bose S., Botana L.M., Botas J., Boulanger C.M., Boulton M.E., Bourdenx M., Bourgeois B., Bourke N.M., Bousquet G., Boya P., Bozhkov P.V., Bozi L.H.M., Bozkurt T.O., Brackney D.E., Brandts C.H., Braun R.J., Braus G.H., Bravo-Sagua R., Bravo-San Pedro J.M., Brest P., Bringer M.-A., Briones-Herrera A., Broaddus V.C., Brodersen P., Brodsky J.L., Brody S.L., Bronson P.G., Bronstein J.M., Brown C.N., Brown R.E., Brum P.C., Brumell J.H., Brunetti-Pierri N., Bruno D., Bryson-Richardson R.J., Bucci C., Buchrieser C., Bueno M., Buitrago-Molina L.E., Buraschi S., Buch S., Buchan J.R., Buckingham E.M., Budak H., Budini M., Bultynck G., Burada F., Burgoyne J.R., Buron M.I., Bustos V., Buttner S., Butturini E., Byrd A., Cabas I., Cabrera-Benitez S., Cadwell K., Cai J., Cai L., Cai Q., Cairo M., Calbet J.A., Caldwell G.A., Caldwell K.A., Call J.A., Calvani R., Calvo A.C., Calvo-Rubio Barrera M., Camara N.O.S., Camonis J.H., Camougrand N., Campanella M., Campbell E.M., Campbell-Valois F.-X., Campello S., Campesi I., Campos J.C., Camuzard O., Cancino J., Candido de Almeida D., Canesi L., Caniggia I., Canonico B., Canti C., Cao B., Caraglia M., Carames B., Carchman E.H., Cardenal-Munoz E., Cardenas C., Cardenas L., Cardoso S.M., Carew J.S., Carle G.F., Carleton G., Carloni S., Carmona-Gutierrez D., Carneiro L.A., Carnevali O., Carosi J.M., Carra S., Carrier A., Carrier L., Carroll B., Carter A.B., Carvalho A.N., Casanova M., Casas C., Casas J., Cassioli C., Castillo E.F., Castillo K., Castillo-Lluva S., Castoldi F., Castori M., Castro A.F., Castro-Caldas M., Castro-Hernandez J., Castro-Obregon S., Catz S.D., Cavadas C., Cavaliere F., Cavallini G., Cavinato M., Cayuela M.L., Cebollada Rica P., Cecarini V., Cecconi F., Cechowska-Pasko M., Cenci S., Ceperuelo-Mallafre V., Cerqueira J.J., Cerutti J.M., Cervia D., Cetintas V.B., Cetrullo S., Chae H.-J., Chagin A.S., Chai C.-Y., Chakrabarti G., Chakrabarti O., Chakraborty T., Chami M., Chamilos G., Chan D.W., Chan E.Y.W., Chan E.D., Chan H.Y.E., Chan H.H., Chan H., Chan M.T.V., Chan Y.S., Chandra P.K., Chang C.-P., Chang C., Chang H.-C., Chang K., Chao J., Chapman T., Charlet-Berguerand N., Chatterjee S., Chaube S.K., Chaudhary A., Chauhan S., Chaum E., Checler F., Cheetham M.E., Chen C.-S., Chen G.-C., Chen J.-F., Chen L.L., Chen L., Chen M., Chen M.-K., Chen N., Chen Q., Chen R.-H., Chen S., Chen W., Chen X.-M., Chen X.-W., Chen X., Chen Y., Chen Y.-G., Chen Y.-J., Chen Y.-Q., Chen Z.S., Chen Z., Chen Z.-H., Chen Z.J., Cheng H., Cheng J., Cheng S.-Y., Cheng W., Cheng X., Cheng X.-T., Cheng Y., Cheng Z., Cheong H., Cheong J.K., Chernyak B.V., Cherry S., Cheung C.F.R., Cheung C.H.A., Cheung K.-H., Chevet E., Chi R.J., Chiang A.K.S., Chiaradonna F., Chiarelli R., Chiariello M., Chica N., Chiocca S., Chiong M., Chiou S.-H., Chiramel A.I., Chiurchiu V., Cho D.-H., Choe S.-K., Choi A.M.K., Choi M.E., Choudhury K.R., Chow N.S., Chu C.T., Chua J.P., Chua J.J.E., Chung H., Chung K.P., Chung S., Chung S.-H., Chung Y.-L., Cianfanelli V., Ciechomska I.A., Cifuentes M., Cinque L., Cirak S., Cirone M., Clague M.J., Clarke R., Clementi E., Coccia E.M., Codogno P., Cohen E., Cohen M.M., Colasanti T., Colasuonno F., Colbert R.A., Colell A., Colic M., Coll N.S., Collins M.O., Colombo M.I., Colon-Ramos D.A., Combaret L., Comincini S., Cominetti M.R., Consiglio A., Conte A., Conti F., Contu V.R., Cookson M.R., Coombs K.M., Coppens I., Corasaniti M.T., Corkery D.P., Cordes N., Cortese K., Costa M.D.C., Costantino S., Costelli P., Coto-Montes A., Crack P.J., Crespo J.L., Criollo A., Crippa V., Cristofani R., Csizmadia T., Cuadrado A., Cui B., Cui J., Cui Y., Culetto E., Cumino A.C., Cybulsky A.V., Czaja M.J., Czuczwar S.J., D'Adamo S., D'Amelio M., D'Arcangelo D., D'Lugos A.C., D'Orazi G., da Silva J.A., Dafsari H.S., Dagda R.K., Dagdas Y., Daglia M., Dai X., Dai Y., Dal Col J., Dalhaimer P., Dalla Valle L., Dallenga T., Dalmasso G., Damme M., Dando I., Dantuma N.P., Darling A.L., Das H., Dasarathy S., Dasari S.K., Dash S., Daumke O., Dauphinee A.N., Davies J.S., Davila V.A., Davis R.J., Davis T., Dayalan Naidu S., De Amicis F., De Bosscher K., De Felice F., De Franceschi L., De Leonibus C., de Mattos Barbosa M.G., De Meyer G.R.Y., De Milito A., De Nunzio C., De Palma C., De Santi M., De Virgilio C., De Zio D., Debnath J., DeBosch B.J., Decuypere J.-P., Deehan M.A., Deflorian G., DeGregori J., Dehay B., Del Rio G., Delaney J.R., Delbridge L.M.D., Delorme-Axford E., Delpino M.V., Demarchi F., Dembitz V., Demers N.D., Deng H., Deng Z., Dengjel J., Dent P., Denton D., DePamphilis M.L., Der C.J., Deretic V., Descoteaux A., Devis L., Devkota S., Devuyst O., Dewson G., Dharmasivam M., Dhiman R., di Bernardo D., Di Cristina M., Di Domenico F., Di Fazio P., Di Fonzo A., Di Guardo G., Di Guglielmo G.M., Di Leo L., Di Malta C., Di Nardo A., Di Rienzo M., Di Sano F., Diallinas G., Diao J., Diaz-Araya G., Diaz-Laviada I., Dickinson J.M., Diederich M., Dieude M., Dikic I., Ding S., Ding W.-X., Dini L., Dinic J., Dinic M., Dinkova-Kostova A.T., Dionne M.S., Distler J.H.W., Diwan A., Dixon I.M.C., Djavaheri-Mergny M., Dobrinski I., Dobrovinskaya O., Dobrowolski R., Dobson R.C.J., Dokic J., Dokmeci Emre S., Donadelli M., Dong B., Dong X., Dong Z., Dorn II G.W., Dotsch V., Dou H., Dou J., Dowaidar M., Dridi S., Drucker L., Du A., Du C., Du G., Du H.-N., Du L.-L., du Toit A., Duan S.-B., Duan X., Duarte S.P., Dubrovska A., Dunlop E.A., Dupont N., Duran R.V., Dwarakanath B.S., Dyshlovoy S.A., Ebrahimi-Fakhari D., Eckhart L., Edelstein C.L., Efferth T., Eftekharpour E., Eichinger L., Eid N., Eisenberg T., Eissa N.T., Eissa S., Ejarque M., El Andaloussi A., El-Hage N., El-Naggar S., Eleuteri A.M., El-Shafey E.S., Elgendy M., Eliopoulos A.G., Elizalde M.M., Elks P.M., Elsasser H.-P., Elsherbiny E.S., Emerling B.M., Emre N.C.T., Eng C.H., Engedal N., Engelbrecht A.-M., Engelsen A.S.T., Enserink J.M., Escalante R., Esclatine A., Escobar-Henriques M., Eskelinen E.-L., Espert L., Eusebio M.-O., Fabrias G., Fabrizi C., Facchiano A., Facchiano F., Fadeel B., Fader C., Faesen A.C., Fairlie W.D., Falco A., Falkenburger B.H., Fan D., Fan J., Fan Y., Fang E.F., Fang Y., Fanto M., Farfel-Becker T., Faure M., Fazeli G., Fedele A.O., Feldman A.M., Feng D., Feng J., Feng L., Feng Y., Feng W., Fenz Araujo T., Ferguson T.A., Fernandez A.F., Fernandez-Checa J.C., Fernandez-Veledo S., Fernie A.R., Ferrante A.W., Ferraresi A., Ferrari M.F., Ferreira J.C.B., Ferro-Novick S., Figueras A., Filadi R., Filigheddu N., Filippi-Chiela E., Filomeni G., Fimia G.M., Fineschi V., Finetti F., Finkbeiner S., Fisher E.A., Fisher P.B., Flamigni F., Fliesler S.J., Flo T.H., Florance I., Florey O., Florio T., Fodor E., Follo C., Fon E.A., Forlino A., Fornai F., Fortini P., Fracassi A., Fraldi A., Franco B., Franco R., Franconi F., Frankel L.B., Friedman S.L., Frohlich L.F., Fruhbeck G., Fuentes J.M., Fujiki Y., Fujita N., Fujiwara Y., Fukuda M., Fulda S., Furic L., Furuya N., Fusco C., Gack M.U., Gaffke L., Galadari S., Galasso A., Galindo M.F., Gallolu Kankanamalage S., Galluzzi L., Galy V., Gammoh N., Gan B., Ganley I.G., Gao F., Gao H., Gao M., Gao P., Gao S.-J., Gao W., Gao X., Garcera A., Garcia M.N., Garcia V.E., Garcia-Del Portillo F., Garcia-Escudero V., Garcia-Garcia A., Garcia-Macia M., Garcia-Moreno D., Garcia-Ruiz C., Garcia-Sanz P., Garg A.D., Gargini R., Garofalo T., Garry R.F., Gassen N.C., Gatica D., Ge L., Ge W., Geiss-Friedlander R., Gelfi C., Genschik P., Gentle I.E., Gerbino V., Gerhardt C., Germain K., Germain M., Gewirtz D.A., Ghasemipour Afshar E., Ghavami S., Ghigo A., Ghosh M., Giamas G., Giampietri C., Giatromanolaki A., Gibson G.E., Gibson S.B., Ginet V., Giniger E., Giorgi C., Girao H., Girardin S.E., Giridharan M., Giuliano S., Giulivi C., Giuriato S., Giustiniani J., Gluschko A., Goder V., Goginashvili A., Golab J., Goldstone D.C., Golebiewska A., Gomes L.R., Gomez R., Gomez-Sanchez R., Gomez-Puerto M.C., Gomez-Sintes R., Gong Q., Goni F.M., Gonzalez-Gallego J., Gonzalez-Hernandez T., Gonzalez-Polo R.A., Gonzalez-Reyes J.A., Gonzalez-Rodriguez P., Goping I.S., Gorbatyuk M.S., Gorbunov N.V., Gorgulu K., Gorojod R.M., Gorski S.M., Goruppi S., Gotor C., Gottlieb R.A., Gozes I., Gozuacik D., Graef M., Graler M.H., Granatiero V., Grasso D., Gray J.P., Green D.R., Greenhough A., Gregory S.L., Griffin E.F., Grinstaff M.W., Gros F., Grose C., Gross A.S., Gruber F., Grumati P., Grune T., Gu X., Guan J.-L., Guardia C.M., Guda K., Guerra F., Guerri C., Guha P., Guillen C., Gujar S., Gukovskaya A., Gukovsky I., Gunst J., Gunther A., Guntur A.R., Guo C., Guo H., Guo L.-W., Guo M., Gupta P., Gupta S.K., Gupta S., Gupta V.B., Gupta V., Gustafsson A.B., Gutterman D.D., H.B R., Haapasalo A., Haber J.E., Hac A., Hadano S., Hafren A.J., Haidar M., Hall B.S., Hallden G., Hamacher-Brady A., Hamann A., Hamasaki M., Han W., Hansen M., Hanson P.I., Hao Z., Harada M., Harhaji-Trajkovic L., Hariharan N., Haroon N., Harris J., Hasegawa T., Hasima Nagoor N., Haspel J.A., Haucke V., Hawkins W.D., Hay B.A., Haynes C.M., Hayrabedyan S.B., Hays T.S., He C., He Q., He R.-R., He Y.-W., He Y.-Y., Heakal Y., Heberle A.M., Hejtmancik J.F., Helgason G.V., Henkel V., Herb M., Hergovich A., Herman-Antosiewicz A., Hernandez A., Hernandez C., Hernandez-Diaz S., Hernandez-Gea V., Herpin A., Herreros J., Hervas J.H., Hesselson D., Hetz C., Heussler V.T., Higuchi Y., Hilfiker S., Hill J.A., Hlavacek W.S., Ho E.A., Ho I.H.T., Ho P.W.-L., Ho S.-L., Ho W.Y., Hobbs G.A., Hochstrasser M., Hoet P.H.M., Hofius D., Hofman P., Hohn A., Holmberg C.I., Hombrebueno J.R., Yi-Ren Hong C.-W.H., Hooper L.V., Hoppe T., Horos R., Hoshida Y., Hsin I.-L., Hsu H.-Y., Hu B., Hu D., Hu L.-F., Hu M.C., Hu R., Hu W., Hu Y.-C., Hu Z.-W., Hua F., Hua J., Hua Y., Huan C., Huang C., Huang H., Huang K., Huang M.L.H., Huang R., Huang S., Huang T., Huang X., Huang Y.J., Huber T.B., Hubert V., Hubner C.A., Hughes S.M., Hughes W.E., Humbert M., Hummer G., Hurley J.H., Hussain S., Hussey P.J., Hutabarat M., Hwang H.-Y., Hwang S., Ieni A., Ikeda F., Imagawa Y., Imai Y., Imbriano C., Imoto M., Inman D.M., Inoki K., Iovanna J., Iozzo R.V., Ippolito G., Irazoqui J.E., Iribarren P., Ishaq M., Ishikawa M., Ishimwe N., Isidoro C., Ismail N., Issazadeh-Navikas S., Itakura E., Ito D., Ivankovic D., Ivanova S., Iyer A.K.V., Izquierdo J.M., Izumi M., Jaattela M., Jabir M.S., Jackson W.T., Jacobo-Herrera N., Jacomin A.-C., Jacquin E., Jadiya P., Jaeschke H., Jagannath C., Jakobi A.J., Jakobsson J., Janji B., Jansen-Durr P., Jansson P.J., Jantsch J., Januszewski S., Jassey A., Jean S., Jeltsch-David H., Jendelova P., Jenny A., Jensen T.E., Jessen N., Jewell J.L., Ji J., Jia L., Jia R., Jiang L., Jiang Q., Jiang R., Jiang T., Jiang X., Jiang Y., Jimenez-Sanchez M., Jin E.-J., Jin F., Jin H., Jin L., Jin M., Jin S., Jo E.-K., Joffre C., Johansen T., Johnson G.V.W., Johnston S.A., Jokitalo E., Jolly M.K., Joosten L.A.B., Jordan J., Joseph B., Ju D., Ju J.-S., Ju J., Juarez E., Judith D., Juhasz G., Jun Y., Jung C.H., Jung S.-C., Jung Y.K., Jungbluth H., Jungverdorben J., Just S., Kaarniranta K., Kaasik A., Kabuta T., Kaganovich D., Kahana A., Kain R., Kajimura S., Kalamvoki M., Kalia M., Kalinowski D.S., Kaludercic N., Kalvari I., Kaminska J., Kaminskyy V.O., Kanamori H., Kanasaki K., Kang C., Kang R., Kang S.S., Kaniyappan S., Kanki T., Kanneganti T.-D., Kanthasamy A.G., Kanthasamy A., Kantorow M., Kapuy O., Karamouzis M.V., Karim M.R., Karmakar P., Katare R.G., Kato M., Kaufmann S.H.E., Kauppinen A., Kaushal G.P., Kaushik S., Kawasaki K., Kazan K., Ke P.-Y., Keating D.J., Keber U., Kehrl J.H., Keller K.E., Keller C.W., Kemper J.K., Kenific C.M., Kepp O., Kermorgant S., Kern A., Ketteler R., Keulers T.G., Khalfin B., Khalil H., Khambu B., Khan S.Y., Khandelwal V.K.M., Khandia R., Kho W., Khobrekar N.V., Khuansuwan S., Khundadze M., Killackey S.A., Kim D., Kim D.R., Kim D.-H., Kim D.-E., Kim E.Y., Kim E.-K., Kim H.-R., Kim H.-S., Hyung-Ryong Kim, Kim J.H., Kim J.K., Kim J.-H., Kim J., Kim K.I., Kim P.K., Kim S.-J., Kimball S.R., Kimchi A., Kimmelman A.C., Kimura T., King M.A., Kinghorn K.J., Kinsey C.G., Kirkin V., Kirshenbaum L.A., Kiselev S.L., Kishi S., Kitamoto K., Kitaoka Y., Kitazato K., Kitsis R.N., Kittler J.T., Kjaerulff O., Klein P.S., Klopstock T., Klucken J., Knaevelsrud H., Knorr R.L., Ko 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L., Tomar D., Tomas-Zapico C., Tomic S., Tong B.C.-K., Tong C., Tong X., Tooze S.A., Torgersen M.L., Torii S., Torres-Lopez L., Torriglia A., Towers C.G., Towns R., Toyokuni S., Trajkovic V., Tramontano D., Tran Q.-G., Travassos L.H., Trelford C.B., Tremel S., Trougakos I.P., Tsao B.P., Tschan M.P., Tse H.-F., Tse T.F., Tsugawa H., Tsvetkov A.S., Tumbarello D.A., Tumtas Y., Tunon M.J., Turcotte S., Turk B., Turk V., Turner B.J., Tuxworth R.I., Tyler J.K., Tyutereva E.V., Uchiyama Y., Ugun-Klusek A., Uhlig H.H., Ulamek-Koziol M., Ulasov I.V., Umekawa M., Ungermann C., Unno R., Urbe S., Uribe-Carretero E., Ustun S., Uversky V.N., Vaccari T., Vaccaro M.I., Vahsen B.F., Vakifahmetoglu-Norberg H., Valdor R., Valente M.J., Valko A., Vallee R.B., Valverde A.M., Van den Berghe G., van der Veen S., Van Kaer L., van Loosdregt J., van Wijk S.J.L., Vandenberghe W., Vanhorebeek I., Vannier-Santos M.A., Vannini N., Vanrell M.C., Vantaggiato C., Varano G., Varela-Nieto I., Varga M., Vasconcelos M.H., 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Yan S., Yan S.-J., Yan Z., Yanagi Y., Yang C., Yang D.-S., Yang H., Yang H.-T., Yang J.-M., Yang J., Yang L., Yang M., Yang P.-M., Yang Q., Yang S., Yang S.-F., Yang W., Yang W.Y., Yang X., Yang Y., Yao H., Yao S., Yao X., Yao Y.-G., Yao Y.-M., Yasui T., Yazdankhah M., Yen P.M., Yi C., Yin X.-M., Yin Y., Yin Z., Ying M., Ying Z., Yip C.K., Yiu S.P.T., Yoo Y.H., Yoshida K., Yoshii S.R., Yoshimori T., Yousefi B., Yu B., Yu H., Yu J., Yu L., Yu M.-L., Yu S.-W., Yu V.C., Yu W.H., Yu Z., Yuan J., Yuan L.-Q., Yuan S., Yuan S.-S.F., Yuan Y., Yuan Z., Yue J., Yue Z., Yun J., Yung R.L., Zacks D.N., Zaffagnini G., Zambelli V.O., Zanella I., Zang Q.S., Zanivan S., Zappavigna S., Zaragoza P., Zarbalis K.S., Zarebkohan A., Zarrouk A., Zeitlin S.O., Zeng J., Zeng J.-D., Zerovnik E., Zhan L., Zhang B., Zhang D.D., Zhang H., Zhang H.-L., Zhang J., Zhang J.-P., Zhang K.Y.B., Zhang L.W., Zhang L., Zhang M., Zhang P., Zhang S., Zhang W., Zhang X., Zhang X.-W., Zhang X.D., Zhang Y., Zhang Y.-D., Zhang Y.-Y., Zhang Z., Zhao H., Zhao L., Zhao S., Zhao T., Zhao X.-F., Zhao Y., Zheng G., Zheng K., Zheng L., Zheng S., Zheng X.-L., Zheng Y., Zheng Z.-G., Zhivotovsky B., Zhong Q., Zhou A., Zhou B., Zhou C., Zhou G., Zhou H., Zhou J., Zhou K., Zhou R., Zhou X.-J., Zhou Y., Zhou Z.-Y., Zhou Z., Zhu B., Zhu C., Zhu G.-Q., Zhu H., Zhu W.-G., Zhu Y., Zhuang H., Zhuang X., Zientara-Rytter K., Zimmermann C.M., Ziviani E., Zoladek T., Zong W.-X., Zorov D.B., Zorzano A., Zou W., Zou Z., Zuryn S., Zwerschke W., Brand-Saberi B., Dong X.C., Kenchappa C.S., Lin Y., Oshima S., Rong Y., Sluimer J.C., Stallings C.L., Tong C.-K., 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)-Université Côte d'Azur (UCA), 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., Agrewala, J. N., Agrotis, A., Aguilar, P. V., Ahmad, S. T., Ahmed, Z. M., Ahumada-Castro, U., Aits, S., Aizawa, S., Akkoc, Y., Akoumianaki, T., Akpinar, H. A., Al-Abd, A. M., Al-Akra, L., Al-Gharaibeh, A., Alaoui-Jamali, M. A., Alberti, S., Alcocer-Gomez, E., Alessandri, C., Ali, M., Alim Al-Bari, M. A., Aliwaini, S., Alizadeh, J., Almacellas, E., Almasan, A., Alonso, A., Alonso, G. D., Altan-Bonnet, N., Altieri, D. C., Alvarez, E. M. C., Alves, S., Alves da Costa, C., Alzaharna, M. M., Amadio, M., Amantini, C., Amaral, C., Ambrosio, S., Amer, A. O., Ammanathan, V., An, Z., Andersen, S. U., Andrabi, S. A., Andrade-Silva, M., Andres, A. M., Angelini, S., Ann, D., Anozie, U. C., Ansari, M. 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E., Chung, H., Chung, K. P., Chung, S., Chung, S. -H., Chung, Y. -L., Cianfanelli, V., Ciechomska, I. A., Cifuentes, M., Cinque, L., Cirak, S., Cirone, M., Clague, M. J., Clarke, R., Clementi, E., Coccia, E. M., Codogno, P., Cohen, E., Cohen, M. M., Colasanti, T., Colasuonno, F., Colbert, R. A., Colell, A., Colic, M., Coll, N. S., Collins, M. O., Colombo, M. I., Colon-Ramos, D. A., Combaret, L., Comincini, S., Cominetti, M. R., Consiglio, A., Conte, A., Conti, F., Contu, V. R., Cookson, M. R., Coombs, K. M., Coppens, I., Corasaniti, M. T., Corkery, D. P., Cordes, N., Cortese, K., Costa, M. D. C., Costantino, S., Costelli, P., Coto-Montes, A., Crack, P. J., Crespo, J. L., Criollo, A., Crippa, V., Cristofani, R., Csizmadia, T., Cuadrado, A., Cui, B., Cui, J., Cui, Y., Culetto, E., Cumino, A. C., Cybulsky, A. V., Czaja, M. J., Czuczwar, S. J., D'Adamo, S., D'Amelio, M., D'Arcangelo, D., D'Lugos, A. C., D'Orazi, G., da Silva, J. A., Dafsari, H. S., Dagda, R. 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J., Deretic, V., Descoteaux, A., Devis, L., Devkota, S., Devuyst, O., Dewson, G., Dharmasivam, M., Dhiman, R., di Bernardo, D., Di Cristina, M., Di Domenico, F., Di Fazio, P., Di Fonzo, A., Di Guardo, G., Di Guglielmo, G. M., Di Leo, L., Di Malta, C., Di Nardo, A., Di Rienzo, M., Di Sano, F., Diallinas, G., Diao, J., Diaz-Araya, G., Diaz-Laviada, I., Dickinson, J. M., Diederich, M., Dieude, M., Dikic, I., Ding, S., Ding, W. -X., Dini, L., Dinic, J., Dinic, M., Dinkova-Kostova, A. T., Dionne, M. S., Distler, J. H. W., Diwan, A., Dixon, I. M. C., Djavaheri-Mergny, M., Dobrinski, I., Dobrovinskaya, O., Dobrowolski, R., Dobson, R. C. J., Dokic, J., Dokmeci Emre, S., Donadelli, M., Dong, B., Dong, X., Dong, Z., Dorn II, G. W., Dotsch, V., Dou, H., Dou, J., Dowaidar, M., Dridi, S., Drucker, L., Du, A., Du, C., Du, G., Du, H. -N., Du, L. -L., du Toit, A., Duan, S. -B., Duan, X., Duarte, S. P., Dubrovska, A., Dunlop, E. A., Dupont, N., Duran, R. V., Dwarakanath, B. S., Dyshlovoy, S. 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Yu, L, Yu, M, Yu, S, Yu, V, Yu, W, Yu, Z, Yuan, J, Yuan, L, Yuan, S, Yuan, Y, Yuan, Z, Yue, J, Yue, Z, Yun, J, Yung, R, Zacks, D, Zaffagnini, G, Zambelli, V, Zanella, I, Zang, Q, Zanivan, S, Zappavigna, S, Zaragoza, P, Zarbalis, K, Zarebkohan, A, Zarrouk, A, Zeitlin, S, Zeng, J, Žerovnik, E, Zhan, L, Zhang, B, Zhang, D, Zhang, H, Zhang, J, Zhang, K, Zhang, L, Zhang, M, Zhang, P, Zhang, S, Zhang, W, Zhang, X, Zhang, Y, Zhang, Z, Zhao, H, Zhao, L, Zhao, S, Zhao, T, Zhao, X, Zhao, Y, Zheng, G, Zheng, K, Zheng, L, Zheng, S, Zheng, X, Zheng, Y, Zheng, Z, Zhivotovsky, B, Zhong, Q, Zhou, A, Zhou, B, Zhou, C, Zhou, G, Zhou, H, Zhou, J, Zhou, K, Zhou, R, Zhou, X, Zhou, Y, Zhou, Z, Zhu, B, Zhu, C, Zhu, G, Zhu, H, Zhu, W, Zhu, Y, Zhuang, H, Zhuang, X, Zientara-Rytter, K, Zimmermann, C, Ziviani, E, Zoladek, T, Zong, W, Zorov, D, Zorzano, A, Zou, W, Zou, Z, Zuryn, S, Zwerschke, W, Brand-Saberi, B, Kenchappa, C, Oshima, S, Rong, Y, Sluimer, J, and Stallings, C
Subjects: macroautophagy, autophagy, Autophagosome, [SDV]Life Sciences [q-bio], cance, LC3, macroautophagy, autophagosome, neurodegeneration, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Autophagy, Autophagosome, NO, stress vacuole, stress, autophagic processes, stre, rflux, LC3, cancer, guidelines, flux, lysosome, phagophore, vacuole, Settore BIO/06 - Anatomia Comparata E Citologia, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, Medaka oryzias latipes, QH, Autophagosome, cancer, flux, LC3, lysosome, macroautophagy, neurodegeneration, phagophore, stress vacuole, Settore BIO/17 - ISTOLOGIA, RC
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field. doi: 10.1080/15548627.2020.1797280 ispartof: Autophagy vol:17 issue:1 pages:1-382 ispartof: location:United States status: published
Published: 2021
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76. Establishment and Preliminary Characterization of Three Astrocytic Cells Lines Obtained from Primary Rat Astrocytes by Sub-Cloning

Author: Riccardo Mormino, Carlo Maria Di Liegro, Simona Maria Angela Rizzo, Vincenzo Vitale, Italia Di Liegro, Gabriella Schiera, Tiziana Ferrara, Fabio Caradonna, Pietro D'Oca, Ilenia Cruciata, Caradonna, Fabio, Schiera, Gabriella, Di Liegro, Carlo Maria, Vitale, Vincenzo, Cruciata, Ilenia, Ferrara, Tiziana, D'Oca, Pietro, Mormino, Riccardo, Rizzo, Simona Maria Angela, and Di Liegro, Italia
Subjects: 0301 basic medicine, lcsh:QH426-470, Somatic cell, Primary Cell Culture, Article, 03 medical and health sciences, Cytogenetics, 0302 clinical medicine, Glioma, Settore BIO/10 - Biochimica, Parenchyma, Genetics, medicine, Animals, Epigenetics, Settore BIO/06 - Anatomia Comparata E Citologia, Genetics (clinical), Cell Line, Transformed, Cloning, biology, medicine.disease, Cell biology, Clone Cells, Rats, gliomas, linker histone H1.0, lcsh:Genetics, Settore BIO/18 - Genetica, astrocyte cell lines, 030104 developmental biology, medicine.anatomical_structure, Histone, epigenetic alterations, Cell culture, 030220 oncology & carcinogenesis, Astrocytes, biology.protein, Astrocyte
Abstract: Gliomas are complex and heterogeneous tumors that originate from the glial cells of the brain. The malignant cells undergo deep modifications of their metabolism, and acquire the capacity to invade the brain parenchyma and to induce epigenetic modifications in the other brain cell types. In spite of the efforts made to define the pathology at the molecular level, and to set novel approaches to reach the infiltrating cells, gliomas are still fatal. In order to gain a better knowledge of the cellular events that accompany astrocyte transformation, we developed three increasingly transformed astrocyte cell lines, starting from primary rat cortical astrocytes, and analyzed them at the cytogenetic and epigenetic level. In parallel, we also studied the expression of the differentiation-related H1.0 linker histone variant to evaluate its possible modification in relation with transformation. We found that the most modified astrocytes (A-FC6) have epigenetic and chromosomal alterations typical of cancer, and that the other two clones (A-GS1 and A-VV5) have intermediate properties. Surprisingly, the differentiation-specific somatic histone H1.0 steadily increases from the normal astrocytes to the most transformed ones. As a whole, our results suggest that these three cell lines, together with the starting primary cells, constitute a potential model for studying glioma development.
Published: 2020

77. Histone Deacetylase Inhibitors from Marine Invertebrates

Author: Claudio Luparello, Manuela Mauro, Vincenzo Arizza, Mirella Vazzana, Luparello, Claudio, Mauro, Manuela, Arizza, Vincenzo, and Vazzana, Mirella
Subjects: 0301 basic medicine, Gene isoform, biomedical applications, marine invertebrates, Settore BIO/05 - Zoologia, Computational biology, Review, histone deacetylase inhibitors, General Biochemistry, Genetics and Molecular Biology, Chromatin remodeling, anticancer compound, 03 medical and health sciences, Cnidaria, 0302 clinical medicine, Non-histone protein, marine invertebrate, Gene expression, Epigenetics, Settore BIO/06 - Anatomia Comparata E Citologia, histone deacetylase inhibitor, lcsh:QH301-705.5, General Immunology and Microbiology, biology, Marine invertebrates, anticancer compounds, Porifera, 030104 developmental biology, Histone, lcsh:Biology (General), 030220 oncology & carcinogenesis, biology.protein, biomedical application, Histone deacetylase, General Agricultural and Biological Sciences, Echinodermata
Abstract: Simple Summary Histone deacetylases (HDACs) are enzymes that control gene expression and are involved in the onset of serious human pathologies, including cancer; hence, their inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of molecules showing active pharmacological properties and an extensive spectrum of biomedical applications. This review is focused on the description of the molecular, biochemical, and, where available, physiological aspects of marine invertebrate-derived compounds that possess HDACi properties, taking into consideration their possible utilization as treatment agents against different pathological states. Abstract Histone deacetylases (HDACs) are key components of the epigenetic machinery controlling gene expression. They are involved in chromatin remodeling events via post-translational histone modifications but may also act on nonhistone proteins, influencing many fundamental cellular processes. Due to the key involvement of HDACs in serious human pathologies, including cancer, HDAC inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of secondary metabolites showing active pharmacological properties and an extensive spectrum of biomedical applications. The aim of this review is to gather selected studies that report the extraction and identification of marine invertebrate-derived compounds that possess HDACi properties, grouping the producing species according to their taxonomic hierarchy. The molecular, biochemical, and/or physiological aspects, where available, and modes of action of these naturally occurring HDACis will be recapitulated, taking into consideration their possible utilization for the future design of analogs with increased bioavailability and efficacy, less toxicity, and, also, higher isoform selectivity.
Published: 2020

78. Role of Natural Bioactive Compounds in the Rise and Fall of Cancers

Author: Claudio Luparello and Luparello, Claudio
Subjects: Cancer Research, n/a, cancer, bioactive factors, Editorial, Oncology, business.industry, Cancer research, Medicine, Cancer development, Settore BIO/06 - Anatomia Comparata E Citologia, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, business, lcsh:RC254-282
Abstract: Recent years have seen the idea of a close association between nutrition and the modulation of cancer development/progression reinforced. In fact, an increasing number of experimental and epidemiological evidence have been produced supporting the concept that many different bioactive components of food (e.g. polyphenols, mono- and polyunsaturated fatty acids, methyl-group donors….) may be implicated in either the promotion of or the protection against carcinogenesis. At cellular level, such compounds can have an impact on different but sometimes intertwined processes, such as growth and differentiation, DNA repair, programmed cell death, and oxidative stress. In addition, compelling evidence is starting to build up of the existence of primary epigenetic targets of dietary compounds, such as oncogenic/oncosuppressor miRNAs or DNA-modifying enzymes, which in turn impair gene expression and function. This editorial aims to summarize the themes of the 31 papers (20 original articles and 11 reviews) published in the special issue “Role of Natural Bioactive Compounds in the Rise and Fall of Cancers” presenting the latest findings on the intracellular pathways and mechanisms affected by selected natural molecules influencing the fine-tuning of cancer phenotype.
Published: 2020

79. BDE-47 exposure modulates cellular responses, oxidative stress and biotransformation related-genes in Mytilus galloprovincialis

Author: Francesco Regoli, Andrea Santulli, Fabio D'Agostino, Cristobal Espinosa Ruiz, Concetta Maria Messina, Giuseppe Avellone, Mario Sprovieri, Simona Manuguerra, Messina C.M., Espinosa Ruiz C., Regoli F., Manuguerra S., D'Agostino F., Avellone G., Sprovieri M., and Santulli A.
Subjects: 0301 basic medicine, Gill, animal structures, Time Factors, Gene Expression, Aquatic Science, PBDE, medicine.disease_cause, Andrology, 03 medical and health sciences, Random Allocation, Polybrominated diphenyl ethers, Biotransformation, Settore AGR/20 - Zoocolture, Detoxification, Gene expression, medicine, Halogenated Diphenyl Ethers, Environmental Chemistry, Mussels, Animals, Tissue Distribution, Settore BIO/06 - Anatomia Comparata E Citologia, Mytilus, biology, Dose-Response Relationship, Drug, fungi, Cell Cycle, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, Bioaccumulation, Drug Resistance, Multiple, Oxidative Stress, 030104 developmental biology, Toxicity, Inactivation, Metabolic, 040102 fisheries, 0401 agriculture, forestry, and fisheries, Oxidative stress, Water Pollutants, Chemical
Abstract: Polybrominated diphenyl ethers (PBDEs) are flame retardants, characterized by elevated stability in the marine environment, where are accumulated by organisms, inducing a wide panel of negative effects. In this study, some biochemical patterns related to toxicity, biotransformation and oxidative stress, were studied in the marine model system, Mytilus galloprovincialis, exposed to BDE-47. Mussels were fed with microalgae, previously treated with increasing concentrations of PBDEs (maximum dose 100 ng L-1 of BDE-47 per day). After 15 days of treatment, mussels were fed with the same diet without BDE-47, for additional 15 days. Gills and digestive glands were analyzed at T 0, at 15 and 30 days. Histopathological lesions were assessed in digestive glands of contaminated mussels, while expression of genes, related to cell cycle, multidrug resistance, oxidative stress and detoxification was evaluated on both gills and digestive glands. After 15 days, BDE-47 exposure significantly affected the cell activity in digestive gland and, at 30 days, only mussels exposed to the lower doses showed a certain recovery. Regarding the gene expression, both gills and digestive glands showed a significant down-regulation of the target genes at 15 days, although most of them were up-regulated at 30 days in digestive gland. The results on BDE-47 accumulation in mussels revealed a dose-dependent concentration in tissues, which remained elevated after further 15 days of depuration. This trend supports the responses of the biomarkers, indicating that exposure, at environmentally realistic concentrations of BDE-47, strongly modulates oxidative stress and related patterns of gene expression, suggesting concerns for long-term effect in the biota.
Published: 2020

80. Molecular Alterations in Spermatozoa of a Family Case Living in the Land of Fires. A First Look at Possible Transgenerational Effects of Pollutants

Author: Luigi Montano, Tiziana Notari, Antonella Giarra, Federica Marra, Marina Piscopo, Marina Prisco, Liana Bosco, Claudia Moriello, Gennaro Lettieri, Marco Trifuoggi, Lettieri, G., Marra, F., Moriello, C., Prisco, M., Notari, T., Trifuoggi, M., Giarra, A., Bosco, L., Montano, L., Piscopo, M., Lettieri G., Marra F., Moriello C., Prisco M., Notari T., Trifuoggi M., Giarra A., Bosco L., Montano L., and Piscopo M.
Subjects: 0301 basic medicine, Male, Protamine, protein-DNA binding, 010501 environmental sciences, 01 natural sciences, Antioxidants, lcsh:Chemistry, Oxidative damage, Histones, chemistry.chemical_compound, Protamines, Settore BIO/06 - Anatomia Comparata E Citologia, Land of Fires, heavy metals, lcsh:QH301-705.5, Spectroscopy, Genetics, biology, Sperm Count, Sperm Motility, Nuclear Protein, human protamines, transgenerational effects, Human protamine, Nuclear Proteins, General Medicine, Middle Aged, Spermatozoa, Computer Science Applications, DNA oxidative damage, Histone, Heavy metal, Sperm Motility, Environmental Pollutants, Antioxidant, Adolescent, DNA damage, Semen, EMSA, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Transgenerational epigenetics, Humans, Physical and Theoretical Chemistry, Molecular Biology, Environmental Pollutant, Land of Fire, Infertility, Male, 0105 earth and related environmental sciences, Pollutant, Organic Chemistry, Transgenerational effect, Environmental Exposure, Hydrogen Peroxide, human spermatozoa, Semen Analysis, 030104 developmental biology, Fertility, lcsh:Biology (General), lcsh:QD1-999, chemistry, biology.protein, DNA, DNA Damage
Abstract: In our previous work, we reported alterations in protamines/histones ratio, in DNA binding of these proteins and their involvement in DNA oxidative damage in 84% of the young men living in the Land of Fires. In the present work, we extended our findings, evaluating any alterations in spermatozoa of a family case, a father and son, living in this area, to also give a first look at the possibility of transgenerational inherited effects of environmental contaminants on the molecular alterations of sperm nuclear basic proteins (SNBP), DNA and semen parameters. In the father and son, we found a diverse excess of copper and chromium in the semen, different alterations in SNBP content and low DNA binding affinity of these proteins. In addition, DNA damage, in the presence of CuCl2 and H2O2, increased by adding both the father and son SNBP. Interestingly, son SNBP, unlike his father, showed an unstable DNA binding and were able to produce DNA damage even without external addition of CuCl2, in line with a lower seminal antioxidant activity than the father. The peculiarity of some characteristics of son semen could be a basis for possible future studies on transgenerational effects of pollutants on fertility.
Published: 2020

81. Antitumoral compounds from vertebrate sister group: A review of Mediterranean ascidians

Author: Valentina Lazzara, Vincenzo Arizza, Manuela Mauro, Mirella Vazzana, Diletta Punginelli, and Manuela Mauro, Valentina Lazzara, Diletta Punginelli, Vincenzo Arizza, Mirella Vazzana
Subjects: Mediterranean climate, Immunology, Population, Biodiversity, Settore BIO/05 - Zoologia, Zoology, Antineoplastic Agents, Drug development, Biology, Peptides, Cyclic, 01 natural sciences, Antitumoral, chemistry.chemical_compound, Depsipeptides, Neoplasms, biology.animal, Mediterranean Sea, Animals, Humans, Urochordata, Invertebrate, Settore BIO/06 - Anatomia Comparata E Citologia, education, Cancer, Biological Products, education.field_of_study, 010405 organic chemistry, fungi, Vertebrate, Bioactive compound, 0104 chemical sciences, Marine biodiversity, 010404 medicinal & biomolecular chemistry, chemistry, Sister group, Tunicates, Trabectedin, Developmental Biology
Abstract: Among the diseases that afflict the human population, cancer is one for which many drug treatments are not yet known or effective. Moreover, the pharmacological treatments used often create serious side effects in sick patients and for this reason, it is essential to find effective and less harmful treatments. To date, marine biodiversity is a real source of metabolites with antitumoral activity and among invertebrates' ascidians have been the main source to obtain them. Mediterranean area is the richest in biodiversity and contains several ascidian species used in drugs development during the years. However, many more Mediterranean ascidian species have not been studied and could be a source of useful bioactive compounds. This review aims to summarize the scientific studies that analyzed the antitumor compounds obtained from different Mediterranean ascidians species, encouraging them to search further compounds in other new species to improve pharmacological treatments and human population life.
Published: 2020

82. Gene Expression of Disease-related Genes in Alzheimer's Disease is Impaired by Tau Aggregation

Author: K. Dunville, Maria Claudia Caiazza, Martina Varisco, Antonino Cattaneo, C. Di Primio, A. Scarlatti, Laura Pancrazi, Giacomo Siano, Mario Costa, F. Cremisi, Siano, G., Varisco, M., Scarlatti, A., Caiazza, M. C., Dunville, K., Cremisi, F., Costa, M., Pancrazi, L., Di Primio, C., and Cattaneo, A.
Subjects: Amyloid, Amino Acid Transport System X-AG, Active Transport, Cell Nucleus, Prefrontal Cortex, tau Proteins, Biology, Neurotransmission, tauopathie, Protein Aggregation, Pathological, 03 medical and health sciences, Glutamatergic, Settore BIO/06 - Anatomia Comparata e Citologia, Mice, 0302 clinical medicine, Downregulation and upregulation, VGluT1, Structural Biology, Alzheimer Disease, Gene expression, Animals, Humans, Prefrontal cortex, Molecular Biology, Embryonic Stem Cells, 030304 developmental biology, Neurons, 0303 health sciences, prefrontal cortex, tau aggregation, Glutamate receptor, Brain, Cell biology, Gene Expression Regulation, Tauopathies, Synapses, Vesicular Glutamate Transport Protein 1, gene expression, Glutamatergic synapse, 030217 neurology & neurosurgery
Abstract: Neuronal hyperexcitability linked to an increase in glutamate signalling is a peculiar trait of the early stages of Alzheimer's disease (AD) and tauopathies, however, a progressive reduction in glutamate release follows in advanced stages. We recently reported that in the early phases of the neurodegenerative process, soluble, non-aggregated Tau accumulates in the nucleus and modulates the expression of disease-relevant genes directly involved in glutamatergic transmission, thus establishing a link between Tau instability and altered neurotransmission. Here we report that while the nuclear translocation of Tau in cultured cells is not impaired by its own aggregation, the nuclear amyloid inclusions of aggregated Tau abolish Tau-dependent increased expression of the glutamate transporter. Remarkably, we observed that in the prefrontal cortex (PFC) of AD patient brain, the glutamate transporter is upregulated at early stages and is downregulated at late stages. The Gene Set Enrichment Analysis indicates that the modulation of Tau-dependent gene expression along the disease progression can be extended to all protein pathways of the glutamatergic synapse. Together, this evidence links the altered glutamatergic function in the PFC during AD progression to the newly discovered function of nuclear Tau.
Published: 2020

83. New Synthetic Nitro-Pyrrolomycins as Promising Antibacterial and Anticancer Agents

Author: Alessandro Presentato, Rosa Alduina, Maria Valeria Raimondi, Miriam Buttacavoli, Giovanna Li Petri, Agnese Ribaudo, Patrizia Cancemi, Viviana De Caro, and Maria Valeria Raimondi, Alessandro Presentato, Giovanna Li Petri, Miriam Buttacavoli, Agnese Ribaudo, Viviana De Caro, Rosa Alduina, Patrizia Cancemi
Subjects: 0301 basic medicine, Microbiology (medical), Staphylococcus aureus, medicine.drug_class, Antibiotics, pyrrolomycin, medicine.disease_cause, Settore BIO/19 - Microbiologia Generale, 01 natural sciences, Biochemistry, Microbiology, pyrrolic nucleus, HCT116, Article, 03 medical and health sciences, antibacterial activity, MCF 7, medicine, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, Settore BIO/06 - Anatomia Comparata E Citologia, Cytotoxicity, heterocycles, Minimum bactericidal concentration, antitumoral activity, 010405 organic chemistry, Chemistry, Pseudomonas aeruginosa, lcsh:RM1-950, MCF7, Biological activity, Settore CHIM/08 - Chimica Farmaceutica, 0104 chemical sciences, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, Infectious Diseases, MCF-7, Nitro
Abstract: Pyrrolomycins (PMs) are polyhalogenated antibiotics known as powerful biologically active compounds, yet featuring high cytotoxicity. The present study reports the antibacterial and antitumoral properties of new chemically synthesized PMs, where the three positions of the pyrrolic nucleus were replaced by nitro groups, aiming to reduce their cytotoxicity while maintaining or even enhancing the biological activity. Indeed, the presence of the nitro substituent in diverse positions of the pyrrole determined an improvement of the minimal bactericidal concentration (MBC) against Gram-positive (i.e., Staphylococcus aureus) or -negative (i.e., Pseudomonas aeruginosa) pathogen strains as compared to the natural PM-C. Moreover, some new nitro-PMs were as active as or more than PM-C in inhibiting the proliferation of colon (HCT116) and breast (MCF 7) cancer cell lines and were less toxic towards normal epithelial (hTERT RPE-1) cells. Altogether, our findings contribute to increase the knowledge of the mode of action of these promising molecules and provide a basis for their rationale chemical or biological manipulation.
Published: 2020

84. Collective Locomotion of Human Cells, Wound Healing and Their Control by Extracts and Isolated Compounds from Marine Invertebrates

Author: Valentina Lazzara, Manuela Mauro, Claudio Luparello, Mirella Vazzana, and Claudio Luparello *, Manuela Mauro, Valentina Lazzara, Mirella Vazzana
Subjects: marine invertebrates, cell migration, Morphogenesis, Pharmaceutical Science, wound healing, Review, Biology, Analytical Chemistry, lcsh:QD241-441, Cnidaria, 03 medical and health sciences, 0302 clinical medicine, lcsh:Organic chemistry, Cell Movement, marine invertebrate, In vivo, Drug Discovery, Animals, Settore BIO/06 - Anatomia Comparata E Citologia, Physical and Theoretical Chemistry, 030304 developmental biology, 0303 health sciences, Plant Extracts, Regeneration (biology), Organic Chemistry, Cell migration, Marine invertebrates, In vitro, Porifera, Cell biology, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, Molecular Medicine, Identification (biology), Wound healing
Abstract: The collective migration of cells is a complex integrated process that represents a common theme joining morphogenesis, tissue regeneration, and tumor biology. It is known that a remarkable amount of secondary metabolites produced by aquatic invertebrates displays active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of crude extracts or isolated compounds that exert a modulatory effect on collective cell locomotion and/or skin tissue reconstitution and recapitulate the molecular, biochemical, and/or physiological aspects, where available, which are associated to the substances under examination, grouping the producing species according to their taxonomic hierarchy. Taken all of the collected data into account, marine invertebrates emerge as a still poorly-exploited valuable resource of natural products that may significantly improve the process of skin regeneration and restrain tumor cell migration, as documented by in vitro and in vivo studies. Therefore, the identification of the most promising invertebrate-derived extracts/molecules for the utilization as new targets for biomedical translation merits further and more detailed investigations.
Published: 2020

85. Cell-Free Coelomic Fluid Extracts of the Sea Urchin Arbacia lixula Impair Mitochondrial Potential and Cell Cycle Distribution and Stimulate Reactive Oxygen Species Production and Autophagic Activity in Triple-Negative MDA-MB231 Breast Cancer Cells

Author: Dalia Maria Lucia Asaro, Mirella Vazzana, Valentina Lazzara, Debora Ragona, Federica Affranchi, Claudio Luparello, Vincenzo Arizza, and Claudio Luparello *, Debora Ragona, Dalia Maria Lucia Asaro, Valentina Lazzara, Federica Affranchi, Vincenzo Arizza, Mirella Vazzana
Subjects: Cell, Settore BIO/05 - Zoologia, Ocean Engineering, 03 medical and health sciences, lcsh:Oceanography, 0302 clinical medicine, breast cancer, lcsh:VM1-989, biology.animal, medicine, Viability assay, lcsh:GC1-1581, Settore BIO/06 - Anatomia Comparata E Citologia, Arbacia lixula, Sea urchin, 030304 developmental biology, Water Science and Technology, Civil and Structural Engineering, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, biology, lcsh:Naval architecture. Shipbuilding. Marine engineering, Cell cycle, biology.organism_classification, echinoderm, medicine.anatomical_structure, chemistry, Apoptosis, 030220 oncology & carcinogenesis, Cancer research, cytotoxicity, Breast carcinoma
Abstract: Triple-negative breast cancer (TNBC) is a highly malignant tumor histotype which lacks effective targeted therapies, thereby being considered as the most aggressive form of breast carcinoma. To identify novel compounds which could counteract TNBC cell growth, we explored the in vitro effects of crude extracts and &lt, 10 kDa-filtered fractions of the coelomic fluid obtained from the sea urchin Arbacia lixula on TNBC MDA-MB231 cells. We examined cell viability, cycle distribution, apoptotic/autophagic activity, and mitochondrial polarization/cell redox status. Here, we report the first data demonstrating an anti-TNBC effect by A. lixula-derived coelomic fluid extracts. Thus, identification of the water-soluble bioactive component(s) contained in the extracts deserve(s) further investigation aimed to devise novel promising prevention and/or treatment agents effective against highly malignant breast tumors.
Published: 2020

86. Mirtazapine for Rett syndrome: a candidate to improve quality of life

Author: FLORES GUTIÉRREZ, JAVIER, FLORES GUTIÉRREZ, Javier, and TONGIORGI, Enrico
Subjects: Settore BIO/06 - Anatomia Comparata e Citologia, Patient, Rett syndrome, Patients, Mirtazapine, Mouse model, Brain physiology
Abstract: Rett syndrome (RTT) is a progressive non degenerative neurodevelopmental disease affecting mainly females, with an incidence of 1 out 10.000 newborn girls. Its symptomatology is very variable and may include: motor deficits, intellectual disability, cardiorespiratory alterations and epilepsy, among other alterations. RTT diagnosis is complex and mainly based on clinical evaluations. All patients apparently develop normally until approximately the first year of life. Then, a developmental stagnation occurs, followed by a regression period in which patients lose acquired skills. In most cases, RTT is due to loss-of-function mutations in the MECP2 gene, which encodes the methyl-CpG-binding protein 2 (MeCP2), a widespread chromatin organizer that controls the transcription of hundreds of genes. Even if experiments performed in a mouse model showed a reversion of RTT-like phenotypes after the re-expression of murine Mecp2, at present there is no a cure for RTT. Pharmacological and physical therapies are the only available techniques to alleviate RTT symptomatology. Regarding drugs, all treatments used on RTT patients are used only for specific symptoms. Since monoaminergic systems are downregulated in both RTT patients and mouse models, antidepressants have been proposed as candidate drugs to treat this disease. Among them, mirtazapine (MTZ) has showed an excellent safety profile through years and the ability to rescue several behavioural, physiological and neuroanatomical phenotypes in a male mouse model of RTT. The present project aimed to complete and to extend these results, as well as to find some mechanisms of action of MTZ. To do this, we used Mecp2tm1.1Bird female mice, a RTT model with a verified face validity, and treated them at different ages and for different durations. First, we verified the safety of MTZ, as we did not observe any adverse effects, even when we treated young female mice with a high dosage of MTZ for one month. Second, we found several improvements in motor, somatosensory and cognitive domains. In one case, we were able to propose a mechanism for the behavioural rescue, as MTZ normalized parvalbumin expression in a related brain area. Results in female mice were completed by a retrospective analysis of a heterogeneous cohort of adult RTT patients that had been treated with MTZ for long periods. Only 2 out 11 patients showed adverse effects and were discontinued, while others showed an improvement of several clinical features in the motor domain, as well as in multiple behavioural alterations. In summary, results obtained in this thesis strongly supports MTZ as a promising treatment for RTT. They represent a robust proof-of-concept and will constitute the base of a dossier aimed to obtain the ethical authorization to initiate a randomized clinical trial. In this way, it will be possible to verify whether MTZ can effectively alleviate RTT symptomatology and, thus, improve quality of life of affected people and their families.
Published: 2020

87. Mining extraction in the ocean depths: a baseline to understand and reduce acoustic impact on biodiversity

Author: Manuela Mauro, VAZZANA, Mirella, and GERMANA', Maria
Subjects: ZOOLOGIA, biology, Holothuria tubulosa, noise pollution, Zoology, physiological responses, Physiological responses, Juvenile fish, biology.organism_classification, Chromis chromis, Deep Sea Mining, biochemical parameter, Deep sea mining, Biochemical parameters, Habitat destruction, Noise pollution, biology.animal, FISICA APLICADA, behavioural response, Behavioural responses, Settore BIO/06 - Anatomia Comparata E Citologia, Arbacia lixula, Sea urchin, Invertebrate
Abstract: [ES] A lo largo de la historia, el hombre ha explotado los recursos minerales de la tierra para su supervivencia y desarrollo tecnológico sin un equilibrio con su regeneración. Dado el crecimiento de la población mundial y la reducción de recursos, el hombre comenzó a buscar nuevos depósitos que se encontraron en la década de 1960 en las profundidades de los océanos. Con estos, la humanidad empezò a pensar en extraer los minerales de estos depósitos y esto llevò al nacimiento de Deep Sea Mining (DSM). Las consecuencias de las actividades mineras en las profundidades del mar no se conocen realmente y los efectos pueden ser diferentes: contaminación acústica, contaminación lumínica, contaminación química, destrucción del hábitat, fragmentación del hábitat y pérdida de especies que son la base de muchos sistemas vitales. El impacto acústico de estas actividades puede tener importantes consecuencias en las especies marinas, aunque este es el tema más ignorado. El propósito de este proyecto de doctorado fue proporcionar una comprensión básica de los posibles impactos acústicos del DSM en la biodiversidad antes de que comiencen estas actividades. Para hacer esto, el proyecto de doctorado se organizó en varios pasos. Primero, durante un experimento indoor, se analizaron las respuestas bioquímicas en invertebrados sometidos a estrés acústico, Arbacia lixula y Mytilus galloprovincialis. Los resultados demostraron efectos significativos en la actividad de citotoxicidad, expresión de heat shock protein (HSPs) y actividades enzimáticas (esterasas, fosfatasas alcalinas, peroxidasas) en el líquido celomático de los erizos de mar sometidos a estrés acústico. También se observaron efectos significativos en el nivel de glucosa, la citotoxicidad y las actividades enzimáticas (esterasa, fosfatasa alcalina, peroxidasa) de la glándula digestiva del mejillón. En segundo lugar, se analizaron las respuestas bioquímicas de vertebrados e invertebrados sometidos in-situ a la emisión de watergun: Chromis chromis, Holothuria tubulosa y Arbacia lixula. Se encontraron efectos significativos sobre los niveles de cortisol en peces y las actividades enzimáticas (esterasas, fosfatasas alcalinas, peroxidasas y superoxide dismutasas) en membrana peristomial de erizo de mar. Además, las respuestas bioquímicas enzimáticas analizadas en los fluidos celómicos de los equinodermos fue significativa solo por A. lixula y solo en la activade peroxidasica. Tercero se estudiaron los cambios de comportamiento en las condiciones experimentales en juveniles de Sparus aurata sometidos a 4 frecuencias de emisión acústica diferentes. Este experimento demostró que solo las bajas frecuencias tuvieron efectos en todas las respuestas comportamental: altura de natación, motilidad y dispersión del grupo. Sobre la base de los datos de comportamiento obtenidos in vivo en peces jóvenes, se creó un modelo numérico para predecir los impactos de diferentes frecuencias de emisión acústica. Utilizando los resultados obtenidos y la bibliografía científica, se propuso un primer estándar técnico que es útil para la minería., [CA] A lo llarc de l'historia, l'home ha explotat els recursos minerals de la terra per a la seua supervivencia i desenroll tecnologic sense un equilibri en la seua regeneracio. Donat el creiximent de la poblacio mundial i la reduccio de recursos, l'home escomençà a buscar nous deposits que se trobaren en la decada de 1960 en les fondaries dels oceans. En estos, l'humanitat empezò a pensar en extraure els minerals d'estos deposits i aço llevò al naiximent de Deep Sea Mining (DSM). Les conseqüencies de les activitats mineres en les fondaries del mar no se coneixen realment i els efectes poden ser diferents: contaminacio acustica, contaminacio lluminica, contaminacio quimica, destruccio de l'habitat, fragmentacio de l'habitat i perdua d'especies que son la base de molts sistemes vitals. L'impacte acustic d'estes activitats pot tindre importants conseqüencies en les especies marines, encara que este es el tema mes ignorat. El proposit d'este proyecte de doctorat fon proporcionar una comprensio basica dels possibles impactes acustics del DSM en la biodiversidad abans de que escomencen estes activitats. Per a fer aço, el proyecte de doctorat s'organisà en varis passos. Primer, durant un experiment indoor, s'analisaren les respostes bioquimiques en invertebrats somesos a estrés acustic, Arbacia lixula i Mytilus galloprovincialis. Els resultats demostraren efectes significatius en l'activitat de citotoxicidad, expressio d'heat shock protein (HSPS) i activitats enzimáticas (esterasa, fosfatasas alcalina, peroxidasas) en el liquit celomático dels capellanets de mar somesos a estrés acustic. Tambe s'observaren efectes significatius en el nivell de glucosa, la citotoxicidad i les activitats enzimáticas (esterasa, fosfatasa alcalina, peroxidasas) de la glandula digestiva de la clochina. En segon lloc, s'analisaren les respostes bioquimiques de vertebrats i invertebrats somesos in-situ a l'emissio de watergun: Chromis chromis, Holothuria tubulosa i Arbacia lixula. se trobaren efectes significatius sobre els nivells de cortisol en peixos i les activitats enzimáticas (esterasas, fosfatasas alcalines, peroxidasas y superoxide dimutases) en peristomes de capellanet de mar. Ademes, les respostes bioquimiques enzimáticas analisades en els decorreguts celómicos dels equinoderms fon significativa nomes per A. lixula i nomes en l'activade peroxidasica. Tercer s'estudiaren els canvis de comportament en les condicions experimentals en jovenils de Sparus aurata somesos a 4 freqüencies d'emissio acustica diferents. Este experiment demostrà que nomes les baixes freqüencies tingueren efectes en totes les respostes comportamental: alçada de natacio, motilidad i escampada del grup. Sobre la base de les senyes de comportament obtinguts in vivo en peixos jovens, se creó un model numeric per a predecir els impactes de diferents freqüencies d'emissio acustica. Utilisant els resultats obtinguts i la bibliografia cientifica, se propongue un primer estandart tecnic que es util per a la mineria., [EN] Throughout history, man has exploited the earth's mineral resources for its survival and for technological development without regard for their regeneration. Given the growth of the world population and given the fall in resources, man started looking for new deposits, which were found in 1960s in the ocean depths. Humankind then began to consider extracting minerals from these deposits and this gave origin to Deep Sea Mining (DSM). The consequences of mining activities in the deep sea are not entirely known and the effects can be varied: noise pollution, light pollution, chemical pollution, habitat destruction, habitat fragmentation and the loss of species which we consider the basis of many life systems. The acoustic impact of these activities could have significant consequences on marine species; nevertheless, this has been the most overlooked issue to date. The aim of this PhD project was to provide baseline knowledge of possible acoustic impacts of DSM on biodiversity before mining begins. In order to do this, the PhD project was organised into 3 different stages. First, during an indoor experiment, the biochemical responses of invertebrates Arbacia lixula and Mytilus galloprovincialis subjected to acoustic stress were analysed. The results showed significant changes in cytotoxicity activity, expression of heat shock proteins (HSPs), and enzyme activities (esterases, alkaline phosphatases, peroxidases) in the coelomic fluid of sea urchins subjected to acoustic stress. Significant effects were also observed in glucose levels, cytotoxicity and enzyme activities (esterase, alkaline phosphatase, peroxidase) in the digestive gland of the mussel. Second, the biochemical responses of vertebrates and invertebrates subjected in-situ to watergun emission were analysed: Chromis chromis, Holothuria tubulosa and Arbacia lixula. Significant effects on fish cortisol levels and on enzyme activities in sea urchin peristomes were found. Furthermore, the enzyme biochemical responses analysed in the coelomic fluids of echinoderms showed significant effects only in A. lixula sea urchin and only in peroxidase activity. Third, behavioural changes in experimental conditions were studied in juveniles of Sparus aurata subjected to 4 different acoustic emission frequencies. This experiment showed that only low frequencies had effects on all the behavioural responses analysed: swimming height, motility and dispersion of the group. Based on behavioural data obtained in vivo on juvenile fish, a numerical model was created to predict the impacts of different acoustic emission frequencies. Using the results obtained and literature, a first technical standard useful for mining activities was drawn up., The study of the Section 3.3 was supported by grants from MIUR (Ministry of Education, University and Research), Fondo Finalizzato alla Ricerca di Ateneo (FFR, 2018-2021) to M.V. and by the CNR research project: IMPLEMENTATION OF THE SOS CONVENTION - Offshore Platforms & Impacts between MATTM and CNR-DTA, (Capo Granitola, Campobello di Mazara) Work Package E: Indepth technical and scientific evaluation of the effects on marine ecosystems of airgun technologies and the effects of a watergun The study of the Section 3.4 study was conducted in the framework of the PhD program in Mediterranean Biodiversity XXXII cycle (International) of the University of Palermo. I. Perez-Arjona, M. Bou-Cabo and V. Espinosa acknowledge the financial support of the European Comission -project 11.0661/2018794607/SUB/ENV.C2. Risk-based Approaches to Good Environmental Status (RAGES). The other founding supports come from PhD Innovative with Industrial Characterization PON 2014-2020 and the projects CAIMAR Joint Laboratory Italy-Argentina (Laboratori Congiunti Bilaterali Internazionali of the Italian National Reseach Council, 2017-2019) and BOSS – Study of bioacoustics and applications for the sustainable exploitation of marine resources (Projects of major importance in the Scientific and Technological Collaboration Executive Programmes, funded by the Italian Ministry of Foreign Affairs and International Cooperation).
Published: 2020

88. Chitosan Film Functionalized with Grape Seed Oil—Preliminary Evaluation of Antimicrobial Activity

Author: Manuela Mauro, Paola Pinto, Luca Settanni, Valeria Puccio, Mirella Vazzana, Branwen L. Hornsby, Antonio Fabbrizio, Vita Di Stefano, Giampaolo Barone, Vincenzo Arizza, and Manuela Mauro, Paola Pinto, Luca Settanni, Valeria Puccio, Mirella Vazzana, Branwen L. Hornsby,Antonio Fabbrizio, Vita Di Stefano, Giampaolo Barone, Vincenzo Arizza
Subjects: Settore CHIM/10 - Chimica Degli Alimenti, Renewable Energy, Sustainability and the Environment, Geography, Planning and Development, Settore BIO/05 - Zoologia, food and beverages, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Management, Monitoring, Policy and Law, bioactive molecule, crustacean, marine invertebrate, shelf life, Settore CHIM/03 - Chimica Generale E Inorganica, Settore BIO/06 - Anatomia Comparata E Citologia, Settore AGR/16 - Microbiologia Agraria
Abstract: Although the fishing and wine industries undoubtedly contribute significantly to the economy, they also generate large waste streams with considerable repercussions on both economic and environmental levels. Scientific literature has shown products can be extracted from these streams which have properties of interest to the cosmetics, pharmaceutical and food industries. Antimicrobial activity is undoubtedly among the most interesting of these properties, and particularly useful in the production of food packaging to increase the shelf life of food products. In this study, film for food packaging was produced for the first time using chitosan extracted from the exoskeletons of red shrimp (Aristomorpha foliacea) and oil obtained from red grape seeds (Vitis vinifera). The antimicrobial activity of two films was analyzed: chitosan-only film and chitosan film with the addition of red grape seed oil at two different concentrations (0.5 mL and 1 mL). Our results showed noteworthy antimicrobial activity resulting from functionalized chitosan films; no activity was observed against pathogen and spoilage Gram-positive and Gram-negative bacteria, although the antimicrobial effects observed were species-dependent. The preliminary results of this study could contribute to developing the circular economy, helping to promote the reuse of waste to produce innovative films for food packaging.
Published: 2022
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89. Valorization of Side Stream Products from Sea Cage Fattened Bluefin Tuna (Thunnus thynnus): Production and In Vitro Bioactivity Evaluation of Enriched ω-3 Polyunsaturated Fatty Acids

Author: Concetta Maria Messina, Rosaria Arena, Simona Manuguerra, Laura La Barbera, Eleonora Curcuraci, Giuseppe Renda, Andrea Santulli, Messina C.M., Arena R., Manuguerra S., La Barbera L., Curcuraci E., Renda G., and Santulli A.
Subjects: side streams, food and beverages, biomarkers, Pharmaceutical Science, ω-3 fatty acids, eye diseases, adipogenesis, SAF-1 cell line, Settore AGR/20 - Zoocolture, tuna fish oils, lipid metabolism, Drug Discovery, lipids (amino acids, peptides, and proteins), Settore BIO/06 - Anatomia Comparata E Citologia, human activities, Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Abstract: The valorization of side streams from fishery and aquaculture value-chains is a valuable solution to address one of the challenges of the circular economy: turning wastes into profit. Side streams produced after filleting of sea cage fattened bluefin tuna (Thunnus thynnus) were analyzed for proximate composition and fatty acid profile to evaluate the possibility of producing tuna oil (TO) as a valuable source of ω-3 polyunsaturated fatty acids (PUFA) and testing its bioactivity in vitro. Ethyl esters of total fatty acids (TFA), obtained from TO, were pre-enriched by urea complexation (PUFA-Ue) and then enriched by short path distillation (SPD) up to almost 85% of the PUFA fraction (PUFA-SPe). The bioactivity of TFA, PUFA-SPe, and ethyl esters of depleted PUFA (PUFA-SPd) were tested in vitro, through analysis of lipid metabolism genes, in gilthead sea bream (Sparus aurata) fibroblast cell line (SAF-1) exposed to oils. TFA and PUFA-SPd upregulated transcription factors (pparβ and pparγ) and lipid metabolism-related genes (D6D, fas, fabp, fatp1, and cd36), indicating the promotion of adipogenesis. PUFA-SPe treated cells were similar to control. PUFA-SPe extracted from farmed bluefin tuna side streams could be utilized in fish feed formulations to prevent excessive fat deposition, contributing to improving both the sustainability of aquaculture and the quality of its products.
Published: 2022
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90. Vanadium Toxicity Monitored by Fertilization Outcomes and Metal Related Proteolytic Activities in Paracentrotus lividus Embryos

Author: Roberto Chiarelli, Chiara Martino, Maria Carmela Roccheri, Fabiana Geraci, Chiarelli, Roberto, Martino, Chiara, Roccheri, Maria Carmela, and Geraci, Fabiana
Subjects: sea urchin embryo, Chemical Health and Safety, Health, Toxicology and Mutagenesis, gelatinase, Settore BIO/06 - Anatomia Comparata E Citologia, Toxicology, sodium orthovanadate, metalloproteinases, sea urchin embryos, gelatinases
Abstract: Metal pharmaceutical residues often represent emerging toxic pollutants of the aquatic environment, as wastewater treatment plants do not sufficiently remove these compounds. Recently, vanadium (V) derivatives have been considered as potential therapeutic factors in several diseases, however, only limited information is available about their impact on aquatic environments. This study used sea urchin embryos (Paracentrotus lividus) to test V toxicity, as it is known they are sensitive to V doses from environmentally relevant to very cytotoxic levels (50 nM; 100 nM; 500 nM; 1 µM; 50 µM; 100 µM; 500 µM; and 1 mM). We used two approaches: The fertilization test (FT) and a protease detection assay after 36 h of exposure. V affected the fertilization percentage and increased morphological abnormalities of both egg and fertilization envelope, in a dose-dependent manner. Moreover, a total of nine gelatinases (with apparent molecular masses ranging from 309 to 22 kDa) were detected, and their proteolytic activity depended on the V concentration. Biochemical characterization shows that some of them could be aspartate proteases, whereas substrate specificity and the Ca2+/Zn2+ requirement suggest that others are similar to mammalian matrix metalloproteinases (MMPs).
Published: 2022
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91. Influence of salt of different origin on the microbiological characteristics, histamine generation and volatile profile of salted anchovies (Engraulis encrasicolus L.)

Author: Michele Matraxia, Filippo Saiano, Giancarlo Moschetti, Marcella Barbera, Francesco Rallo, Raimondo Gaglio, Andrea Santulli, Nicola Francesca, Antonio Alfonzo, Alfonzo, Antonio, Gaglio, Raimondo, Francesca, Nicola, Barbera, Marcella, Saiano, Filippo, Santulli, Andrea, Matraxia, Michele, Rallo, Francesco, and Moschetti, Giancarlo
Subjects: 0106 biological sciences, 0301 basic medicine, Taste, Salt, Settore AGR/13 - Chimica Agraria, 030106 microbiology, Salt (chemistry), 01 natural sciences, Sensory analysis, 03 medical and health sciences, chemistry.chemical_compound, Engraulis, 010608 biotechnology, Anchovie, Food science, Settore BIO/06 - Anatomia Comparata E Citologia, Staphylococcaceae, chemistry.chemical_classification, biology, Chemistry, VOC, Ripening, biology.organism_classification, Lactic acid, Composition (visual arts), Bacterial community, Histamine, Settore AGR/16 - Microbiologia Agraria, Food Science, Biotechnology
Abstract: The effect of six salts of different geographical areas on the quality of salted anchovies was evaluated. The crude salts were chemically characterized by determination of inorganic and volatile organic compounds (VOCs). Salted anchovies, corresponding to six experimental trials, were subjected to microbiological, chemical (including histamine content) and sensory analysis during the entire period of ripening (150 days). The salts were characterized by marked differences in terms of major cations and trace element amounts. Among the 27 VOCs detected, octadecane was the most abundant compound and the main differences of the salts were registered for alkanes and alcohols. During maturation, significant microbiological differences between the salts were found for the levels of total aerobic mesophilic microorganisms, lactic acid bacteria, Staphylococcaceae and Enterobacteriaceae counts. All salted anchovies contained histamine below the thresholds allowed by current regulations, but statistical differences were registered for the concentrations of the different trials. Consistent differences were also revealed for their sensory profiles, in particular concerning odour and taste and overall acceptability. Several differences were also detected for dryness, brown colour, putrid odour, rancid and raw blood taste sensory attributes. Especially the differences in the composition (chemical and VOC's) of the raw salts used for the production of salted anchovies has a significant effect on the sensory characteristics of the final product.
Published: 2018
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92. Asymmetry in the Cytoarchitecture of the Area 44 Homolog of the Brain of the Chimpanzee Pan troglodytes

Author: Graic, J. -M., Peruffo, A., Corain, L., Centelleghe, C., Granato, Alberto, Zanellato, E., Cozzi, B., Granato A. (ORCID:0000-0003-3755-1036), Graic, J. -M., Peruffo, A., Corain, L., Centelleghe, C., Granato, Alberto, Zanellato, E., Cozzi, B., and Granato A. (ORCID:0000-0003-3755-1036)
Abstract: The evolution of the brain in apes and man followed a joint pathway stemming from common ancestors 5–10 million years ago. However, although apparently sharing similar organization and neurochemical properties, association areas of the isocortex remain one of the cornerstones of what sets humans aside from other primates. Brodmann’s area 44, the area of Broca, is known for its implication in speech, and thus indirectly is a key mark of human uniqueness. This latero-caudal part of the frontal lobe shows a marked functional asymmetry in humans, and takes part in other complex functions, including learning and imitation, tool use, music and contains the mirror neuron system (MNS). Since the main features in the cytoarchitecture of Broca’s area remains relatively constant in hominids, including in our closest relative, the chimpanzee Pan troglodytes, investigations on the finer structure, cellular organization, connectivity and eventual asymmetry of area 44 have a direct bearing on the understanding of the neural mechanisms at the base of our language. The semi-automated image analysis technology that we employed in the current study showed that the structure of the cortical layers of the chimpanzee contains elements of asymmetry that are discussed in relation to the corresponding human areas and the putative resulting disparity of function.
Published: 2020

93. Gene Expression and Apoptosis Levels in Cumulus Cells of Patients with Polymorphisms of FSHR and LHB Undergoing in Vitro Fertilization Program

Author: Monica Lispi, Maria Carmela Roccheri, Elena Sarcina, Claudio Luparello, Domenico Valerio, Stefania Ferrari, Liana Bosco, Daniele Santi, Giovanni Ruvolo, Paola Piomboni, Bosco, L., Ruvolo, G., Luparello, C., Ferrari, S., Valerio, D., Santi, D., Piomboni, P., Sarcina, E., Lispi, M., and Roccheri, M.
Subjects: 0301 basic medicine, Apoptosis, Cumulus cells, FSHR, Gene expression, LH, Polymorphism, Physiology, lcsh:Physiology, Gonadotropin-Releasing Hormone, 0302 clinical medicine, Gene Frequency, lcsh:QD415-436, Settore BIO/06 - Anatomia Comparata E Citologia, Cells, Cultured, In Situ Hybridization, Fluorescence, 030219 obstetrics & reproductive medicine, lcsh:QP1-981, Caspase 3, medicine.anatomical_structure, Cumulus cell, Receptors, FSH, DNA fragmentation, Female, Signal Transduction, Adult, Heterozygote, medicine.medical_specialty, endocrine system, Genotype, Granulosa cell, DNA Fragmentation, Fertilization in Vitro, Biology, Real-Time Polymerase Chain Reaction, Buserelin, Polymorphism, Single Nucleotide, lcsh:Biochemistry, 03 medical and health sciences, Follicle, Internal medicine, medicine, Humans, Apoptosi, Heterozygote advantage, Luteinizing Hormone, beta Subunit, Oocyte, 030104 developmental biology, Endocrinology, Haplotypes, Multivariate Analysis, Oocytes, Follicle-stimulating hormone receptor, Proto-Oncogene Proteins c-akt
Abstract: Background/Aims: FSH receptor (FSHR) Ala307Thr and Asn680Ser and LHβ chain (LHB) Trp28Arg and Ile35Thr polymorphisms affect the response to pharmacological ovarian stimulation with r-FSH in women undergoing assisted reproductive treatment (ART). Here, we evaluated the expression level of selected genes involved in follicle maturation and the possible onset of apoptosis in cumulus cells of patients with single and double FSHR and LHB polymorphisms, as potential markers of oocyte competence. Methods: Cumulus cells from 36 stimulated patients were collected and SNP genotyping performed by PCR. Gene expression was evaluated through real-time PCR, and apoptosis estimated via TUNEL assay, and cleaved caspase-3 and pAKT immunostaining. Results: The cumulative data show significant correlations indicating that the genetic alteration of FSHR and/or LHB genes may lead to perturbations of the signaling network programmed to granulosa cell survival and follicle development. Notably, when double heterozygotes were compared to the rest of the patients, a higher level of apoptosis in terms of both DNA fragmentation index and amount of active caspase-3 was observed in cumulus cells. Conclusions: These results may help to define personalized stimulation protocols in ART programs, to increase the success rate of ICSI procedures in accordance with the polymorphic condition of the individual patient.
Published: 2017

94. Underwater high frequency noise: Biological responses in sea urchin Arbacia lixula (Linnaeus, 1758)

Author: Elena Papale, Mirella Vazzana, Maria Dioguardi, Giuseppa Buscaino, Luigi Inguglia, Francesco Beltrame, Manuela Mauro, Salvatore Mazzola, Maria Ceraulo, Vincenzo Arizza, and Vazzana, M., Mauro, M., Ceraulo, M., Dioguardi, M., Papale, E., Mazzola, S., Arizza, V., Beltrame, F., Inguglia, L., Buscaino,G.
Subjects: 0106 biological sciences, Physiology, Phosphatase, Zoology, 01 natural sciences, Biochemistry, Esterase, Hemolysis, 03 medical and health sciences, biology.animal, Animals, Homeostasis, HSP70 Heat-Shock Proteins, Mating, Settore BIO/06 - Anatomia Comparata E Citologia, Molecular Biology, Sea urchin, Arbacia lixula, HSP70, 030304 developmental biology, Invertebrate, Cell Proliferation, Peroxidase, Arbacia, 0303 health sciences, biology, Echinoderm, 010604 marine biology & hydrobiology, Esterases, Marine invertebrate, Marine invertebrates, biology.organism_classification, Alkaline Phosphatase, Acoustic stimulu, Enzyme assay, Coelomomyces, Body Fluids, biology.protein, Metabolome, Physiological stress, Noise
Abstract: Marine life is extremely sensitive to the effects of environmental noise due to its reliance on underwater sounds for basic life functions, such as searching for food and mating. However, the effects on invertebrate species are not yet fully understood. The aim of this study was to determine the biochemical responses of Arbacia lixula exposed to high-frequency noise. Protein concentration, enzyme activity (esterase, phosphatase and peroxidase) and cytotoxicity in coelomic fluid were compared in individuals exposed for three hours to consecutive linear sweeps of 100 to 200 kHz lasting 1 s, and control specimens. Sound pressure levels ranged between 145 and 160 dB re 1μPa. Coelomic fluid was extracted and the gene and protein expression of HSP70 with RT-PCR was evaluated on coelomocytes. A significant change was found in enzyme activity and in the expression of the HSP70 gene and protein compared to the control. These results suggested that high-frequency stimuli elicit a noise-induced physiological stress response in A. lixula, confirming the vulnerability of this species to acoustic exposure. Furthermore, these findings provide the first evidence that cell-free coelomic fluid can be used as a signal to evaluate noise exposure in marine invertebrates.
Published: 2020

95. Dietary administration effects of exopolysaccharide from potential probiotic strains on immune and antioxidant status and nutritional value of European sea bass (Dicentrarchus labrax L.)

Author: Concetta Maria Messina, Andrea Santulli, Hatem Majdoub, Ridha El Mzoughi, María Ángeles Esteban, Rosaria Arena, Abdelkarim Mahdhi, Cristóbal Espinosa-Ruíz, Ibtissem Chakroun, Mahdhi A., Chakroun I., Espinosa-Ruiz C., Messina C.M., Arena R., Majdoub H., Santulli A., Mzoughi R., and Esteban M.A.
Subjects: Antioxidant, 040301 veterinary sciences, medicine.medical_treatment, Aquaculture, Antioxidants, law.invention, 0403 veterinary science, European sea ba, 03 medical and health sciences, Probiotic, Immune system, law, Exopolysaccharide, Settore AGR/20 - Zoocolture, medicine, Animals, Food science, Sea bass, Settore BIO/06 - Anatomia Comparata E Citologia, 030304 developmental biology, chemistry.chemical_classification, Innate immunity, 0303 health sciences, General Veterinary, biology, Probiotics, Fatty Acids, Polysaccharides, Bacterial, Fatty acid, 04 agricultural and veterinary sciences, biology.organism_classification, Animal Feed, Eicosapentaenoic acid, Diet, chemistry, Docosahexaenoic acid, Animal Nutritional Physiological Phenomena, Bass, Dicentrarchus, Gene expression, Nutritive Value
Abstract: The use of biological immunostimulants is considered a valuable practice to improve culture conditions in aquaculture sector that may help to increase production and maintain healthy environment. We undertook this study in order to evaluate the potential effect of the administration of two exopolysaccharides (EPS) "EPLB" and "EPB" derived from potential probiotic strains on immune and antioxidant status of European sea bass (Dicentrarchus labrax L.) larvae. In order to find out if the EPSs have an effect on the biochemical composition during the trial period, the nutritional value has been evaluated. The results revealed that expression levels of immune-relevant genes (infg, Il1b, Il8, Il6 and tcr-β) in the gut and head kidney and the scavenging enzymes (cat, sod, gr) genes in the liver were modulated. In fact, the dietary supplementation with the tested EPSs, significantly enhances the expression of immune-associated genes in the head-kidney, particularly infg and tcrβ, as well as catalase gene in liver. During the period of study, EPSs administration did not affect the fatty acid profiles of larvae, which is balanced. This is confirmed by the Docosahexaenoic acid / Eicosapentaenoic acid ratio and demonstrates that EPLB and EPB can be administrated without any negative effect on biochemical composition of European sea bass. The present findings provided evidence that the tested EPSs with antibacterial and antioxidant activities can enhance immune response without negative effect on the biochemical composition. The used EPSs can be considered as a good source of natural functional aquafeed ingredients for European sea bass.
Published: 2020

96. Asymmetry in the Cytoarchitecture of the Area 44 Homolog of the Brain of the Chimpanzee Pan troglodytes

Author: Cinzia Centelleghe, Bruno Cozzi, Jean-Marie Graïc, Livio Corain, Emanuela Zanellato, Antonella Peruffo, and Alberto Granato
Subjects: 0301 basic medicine, cytoarchitecture, media_common.quotation_subject, Neuroscience (miscellaneous), Biology, lcsh:RC321-571, lcsh:QM1-695, pan troglodytes, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Common descent, medicine, area 44, Association (psychology), lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Mirror neuron, media_common, Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA, lcsh:Human anatomy, asymmetry, Broca area, cerebral cortex, 030104 developmental biology, medicine.anatomical_structure, Frontal lobe, Cytoarchitecture, Cerebral cortex, Evolution of the brain, Anatomy, Imitation, Neuroscience, 030217 neurology & neurosurgery
Abstract: The evolution of the brain in apes and man followed a joint pathway stemming from common ancestors 5–10 million years ago. However, although apparently sharing similar organization and neurochemical properties, association areas of the isocortex remain one of the cornerstones of what sets humans aside from other primates. Brodmann’s area 44, the area of Broca, is known for its implication in speech, and thus indirectly is a key mark of human uniqueness. This latero-caudal part of the frontal lobe shows a marked functional asymmetry in humans, and takes part in other complex functions, including learning and imitation, tool use, music and contains the mirror neuron system (MNS). Since the main features in the cytoarchitecture of Broca’s area remains relatively constant in hominids, including in our closest relative, the chimpanzee Pan troglodytes, investigations on the finer structure, cellular organization, connectivity and eventual asymmetry of area 44 have a direct bearing on the understanding of the neural mechanisms at the base of our language. The semi-automated image analysis technology that we employed in the current study showed that the structure of the cortical layers of the chimpanzee contains elements of asymmetry that are discussed in relation to the corresponding human areas and the putative resulting disparity of function.
Published: 2020

97. Naphthalimide imidazolium-based supramolecular hydrogels as bioimaging and theranostic soft materials

Author: Francesca D'Anna, Carla Rizzo, Patrizia Cancemi, Salvatore Marullo, Leonardo Mattiello, Rizzo C., Cancemi P., Mattiello L., Marullo S., and D'Anna F.
Subjects: Materials science, Cell Survival, Macromolecular Substances, Surface Properties, Scanning electron microscope, imidazolium salts, 010402 general chemistry, 01 natural sciences, Theranostic Nanomedicine, chemistry.chemical_compound, bioimaging, fluorescence, naphthalimide, supramolecular hydrogels, Cell Line, Tumor, Phase (matter), Humans, General Materials Science, Particle Size, Settore BIO/06 - Anatomia Comparata E Citologia, Alkyl, Fluorescent Dyes, chemistry.chemical_classification, Molecular Structure, 010405 organic chemistry, Dimethyl sulfoxide, Optical Imaging, Imidazoles, Hydrogels, Biological activity, Settore CHIM/06 - Chimica Organica, Resonance (chemistry), Combinatorial chemistry, Fluorescence, 0104 chemical sciences, Naphthalimides, chemistry, Self-healing hydrogels
Abstract: 1,8-Naphthalimide-based imidazolium salts differing for the alkyl chain length and the nature of the anion were synthesized and characterized to obtain fluorescent probes for bioimaging applications. First, their self-assembly behavior and gelling ability were investigated in water and water/dimethyl sulfoxide binary mixtures. Only salts having longer alkyl chains were able to give supramolecular hydrogels, whose properties were investigated by using a combined approach of fluorescence, resonance light scattering, and rheology measurements. Morphological information was obtained by scanning electron microscopy. In addition, conductive properties of organic salts in solution and gel state were analyzed. Imidazolium salts were successfully tested for their possible application as bioimaging and cytotoxic agents toward three cancer cell lines and a nontumoral epithelial cell line. Characterization of their behavior was performed by MTT and cell-based assays. Finally, the biological activity of hydrogels was also investigated. Collectively, our findings showed that naphthalimide-based imidazolium salts are promising theranostic agents and they were able to preserve their biological properties also in the gel phase.
Published: 2020

98. Sperm DNA integrity and human papillomavirus (HPV) infections: a controversy that could be resolved by a new molecular approach

Author: schillaci R, Notari T, Capra G, Ragusa MA, Roccheri MC, Perino A, Ferrigno A, Bosco L, schillaci R, Notari T, Capra G, Ragusa MA, Roccheri MC, Perino A, Ferrigno A, and Bosco L
Subjects: HPV, Spermatozoa, Settore MED/07 - Microbiologia E Microbiologia Clinica, Settore BIO/11 - Biologia Molecolare, Settore BIO/06 - Anatomia Comparata E Citologia, TUNEL
Abstract: Study question: The aim was to determine if HPVs affect spermatozoa DNA integrity. To resolve the discrepancy regarding the association between HPV infections and sperm DNA damage. Summary answer: To elucidate if HPV impairs DNA integrity, we suggest to investigate HPV DNA positivity in spermatozoa by a differential lysis procedure before TUNEL assay.
Published: 2020

99. Histone Deacetylase Inhibitors

Author: Luparello C, Vazzana M, Luparello C, and Vazzana M
Subjects: anticancer compound, Cnidaria, marine invertebrate, biomedical application, Settore BIO/06 - Anatomia Comparata E Citologia, histone deacetylase inhibitor, Porifera, Echinodermata
Abstract: Histone deacetylases (HDACs) are key components of the epigenetic machinery controlling gene expression. They are involved in chromatin remodeling events via post-translational histone modifications but may also act on nonhistone proteins, influencing many fundamental cellular processes. Due to the key involvement of HDACs in serious human pathologies, including cancer, HDAC inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of secondary metabolites showing active pharmacological properties and an extensive spectrum of biomedical applications. Some of these compounds possess HDACi properties.
Published: 2020

100. Allograft Inflammatory Factor AIF-1: early immune response in the Mediterranean sea urchin Paracentrotus lividus

Author: Mirella Vazzana, Vinicius Queiroz, Marco Chiaramonte, Manuela Mauro, Luigi Inguglia, Simona La Rosa, Vincenzo Arizza, Chiaramonte M., Arizza V., La Rosa S., Queiroz V., Mauro M., Vazzana M., and Inguglia L.
Subjects: 0106 biological sciences, 0301 basic medicine, Lipopolysaccharides, Lipopolysaccharide, Population, Settore BIO/05 - Zoologia, LPS treatment, 010603 evolutionary biology, 01 natural sciences, Paracentrotus lividus, 03 medical and health sciences, chemistry.chemical_compound, Immune system, Immunity, biology.animal, Animals, Amino Acid Sequence, RNA, Messenger, Immune response, Settore BIO/06 - Anatomia Comparata E Citologia, education, Coelomocyte, Sea urchin, education.field_of_study, biology, Base Sequence, Echinoderm, Proteins, biology.organism_classification, Cell biology, 030104 developmental biology, chemistry, Gene Expression Regulation, Allograft inflammatory factor 1, Paracentrotus, Animal Science and Zoology, AIF-1
Abstract: Echinoderms are a phylum of deuterostomic invertebrates that play a key role in maintaining the biodiversity of marine ecosystems. They represent a good study model for immunity because their coelomic fluid contains different types of cells involved in the inflammatory response: the coelomocytes. In the case of the sea urchin Paracentrotus lividus, the coelomocyte population is mainly represented by amoebocytes and uncoloured spherulocytes that implement a defence program through phagocytosis, encapsulation, cytotoxicity, and production of antimicrobial agents. The purpose of this study was to find evidence of a possible modulating effect of lipopolysaccharide LPS on the expression of the AIF-1 gene and therefore to determine whether or not there is a correlation between the P. lividus immune response and the expression of this gene when the homeostasis of the animals is disturbed by a bacterial infection which, in this case, was simulated with treatment with LPS. AIF-1 (Allograft Inflammatory Factor 1) is a 17 kDa calcium-binding protein that, in vertebrates, is involved in the activation of macrophages. Similarly, in Echinoids and in general in invertebrates, the expression of this gene increases considerably after a bacterial attack and this suggests that it plays a key role during the immune responses.
Published: 2020

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