584 results on '"zebra fish"'
Search Results
252. A new ergosterol analog, a new bis-anthraquinone and anti-obesity activity of anthraquinones from the marine sponge-associated fungus Talaromyces stipitatus KUFA 0207
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Luís Gales, Michael Lee, José Alberto Pereira, Vitor Vasconcelos, Anake Kijjoa, Suradet Buttachon, Madalena Pinto, Ralph Urbatzka, Artur M. S. Silva, Tida Dethoup, Sara Freitas, Jidapa Noinart, and CIIMAR - Centro Interdisciplinar de Investigação Marinha e Ambiental
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Models, Molecular ,Aquatic Organisms ,obesity ,anti-obesity ,Talaromyces ,Ethyl acetate ,Pharmaceutical Science ,Anthraquinones ,resveratrol ,01 natural sciences ,emodin ,Palmitic acid ,chemistry.chemical_compound ,citreorosein ,Stylissa flabelliformis ,Ergosterol ,bis-anthraquinone ,Drug Discovery ,zebra fish ,palmitic acid ,lcsh:QH301-705.5 ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Trichocomaceae ,Citreorosein ,ergosterol 5,8 endoperoxide ,Molecular Structure ,biology ,sterol derivative ,adult ,stereochemistry ,Porifera ,unclassified drug ,ergosta 4,6,8(14),22 tetraen 3 one ,Secalonic acid ,anthraquinone derivative ,rheoemodin ,crystal structure ,questinol ,Stereochemistry ,animal experiment ,embryo ,talarosterone ,Article ,ergosterol derivatives ,zebrafish Nile red assay ,Animals ,cyathisterone ,controlled study ,Talaromyces stipitatus ,anthraquinones ,secalonic acid A ,14. Life underwater ,fallacinol ,nonhuman ,010405 organic chemistry ,X ray crystallography ,biology.organism_classification ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,drug structure ,lcsh:Biology (General) ,chemistry ,sponge (Porifera) ,Anti-Obesity Agents ,Emodin - Abstract
A new ergosterol analog, talarosterone (1) and a new bis-anthraquinone derivative (3) were isolated, together with ten known compounds including palmitic acid, ergosta-4,6,8(14),22- tetraen-3-one, ergosterol-5,8-endoperoxide, cyathisterone (2), emodin (4a), questinol (4b), citreorosein (4c), fallacinol (4d), rheoemodin (4e) and secalonic acid A (5), from the ethyl acetate extract of the culture of the marine sponge-associated fungus Talaromyces stipitatus KUFA 0207. The structures of the new compounds were established based on extensive 1D and 2D spectral analysis, and in the case of talarosterone (1), the absolute configurations of its stereogenic carbons were determined by X-ray crystallographic analysis. The structure and stereochemistry of cyathisterone (2) was also confirmed by X-ray analysis. The anthraquinones 4a-e and secalonic acid A (5) were tested for their anti-obesity activity using the zebrafish Nile red assay. Only citreorosein (4c) and questinol (4b) exhibited significant anti-obesity activity, while emodin (4a) and secalonic acid A (5) caused toxicity (death) for all exposed zebrafish larvae after 24 h. © 2017 by the authors. Licensee MDPI. This work was partially supported through national funds provided by the FCT-Foundation for Science and Technology and European Regional Development Fund (ERDF) and COMPETE, under the projects PEst-C/MAR/LA0015/2013, PTDC/MAR-BIO/4694/2014, as well as by the project INNOVMAR - Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, within Research Line NOVELMAR/INSEAFOOD /ECOSERVICES), supported by the North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). J. Noitnart thanks the ALFABET project under the ERASMUS MUNDUS ACTION 2 with South East Asia, for a scholarship. We thank J?lia Bessa and Sara Cravo for technical support.
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- 2017
253. Generation and Characterization of Novel Zebrafish Models for Epileptogenesis
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Nguyen, Anna Thao Thanh
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chronic ,Zebra fish ,epilepsy ,epileptogenesis - Abstract
Epilepsy is one of the most common chronic neurological disorders affecting more than 50 million people worldwide. The disorder is considered a major health problem with increased risk of mortality and co-morbidities. The lack of a variety of reliable validated epilepsy models could possibly hinder or slow the progress in the discovery of better therapeutic options. The purpose of this study was to try and generate new models for epileptogenesis in zebrafish larvae to improve our understanding of epilepsy and how it develops, and that could be used for the discovery of new treatment options. with better outcome that could possibly prevent epilepsy from developing. A novel epileptic model was induced with valproate, but further studies are needed to validate for future drug discovery and to determine if the seizures are chronic. Epilepsy, zebrafish, epileptic model, seizure, epileptogenesis, models of epilepsy, chronic seizure, valproate, induced seizure, ginkgo biloba, epileptogenic, epileptiform activity, EEG, behavioural tracking, MTC, electrophysiological analysis, novel models, pharmacoresistant epilepsy, mortality, comorbidity
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- 2017
254. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy
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Juliette Legler, Jorke H. Kamstra, Valentina Davidoiu, P.H. Cenijn, Miriam J. B. Moester, Marjo J. den Broeder, Johannes F. de Boer, Leonie M. Kamminga, Freek Ariese, One Health Toxicologie, dIRAS RA-1, Chemistry and Biology, Institute for Environmental Studies, Biophotonics and Medical Imaging, LaserLaB - Biophotonics and Microscopy, and Amsterdam Neuroscience - Brain Imaging
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0301 basic medicine ,obesity ,Nonlinear Optical Microscopy ,fat droplet ,polymerase chain reaction ,Toxicology ,lcsh:Chemistry ,tributyltin ,3 dichloroisopropyl)phosphate ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Adipocyte ,zebra fish ,Cluster Analysis ,Obesogen ,TBT ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,lcsh:QH301-705.5 ,Zebrafish ,Spectroscopy ,biology ,messenger RNA ,article ,General Medicine ,Computer Science Applications ,unclassified drug ,TDCiPP ,Adipogenesis ,Environmental Pollutants ,tris(1 ,lipid diet ,toxicology ,stimulated raman scattering microscopy ,Tris ,medicine.medical_specialty ,animal structures ,organic compound ,laser microscopy ,Danio ,embryo ,030209 endocrinology & metabolism ,concentration (parameter) ,Diet, High-Fat ,adipocyte ,Catalysis ,SRS imaging ,tris(1,3 dichloroisopropyl)phosphate ,adipogenesis ,Inorganic Chemistry ,endocrinology ,03 medical and health sciences ,Organophosphorus Compounds ,larva ,obesogen ,SDG 3 - Good Health and Well-being ,In vivo ,zebrafish ,Internal medicine ,medicine ,Animals ,PPAR alpha ,controlled study ,SDG 14 - Life Below Water ,Obesity ,Physical and Theoretical Chemistry ,Liver X receptor ,Molecular Biology ,nonhuman ,Organic Chemistry ,fungi ,biology.organism_classification ,PPAR gamma ,cell differentiation ,Glucose ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,chemistry ,fertilization ,Tributyltin ,gene expression ,Trialkyltin Compounds - Abstract
Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio). We used label-free Stimulated Raman Scattering (SRS) microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf) and compared standard feed conditions (StF) to a high fat diet (HFD) or high glucose diet (HGD). We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM) or Tris(1,3-dichloroisopropyl)phosphate (TDCiPP, 0.5 µM) from 0–6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo. This research is financially supported by Netherlands Organisation for Scientific Research (NWO) VIDI/864.09.005, ASPASIA /015.006.018, VICI/918.10.628, NWO-Groot grant, and the European Union’s Horizon 2020 research and innovation program under grant agreement number 654148 LaserLaB Europe.
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- 2017
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255. A mixture of persistent organic pollutants and perfluorooctanesulfonic acid induces similar behavioural responses, but different gene expression profiles in Zebrafish larvae
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Khezri, Abdolrahman, Fraser, Thomas W. K., Nourizadeh-Lillabadi, Rasoul, Kamstra, Jorke H., Berg, Vidar, Zimmer, Karin E., Ropstad, Erik, One Health Toxicologie, and One Health Toxicologie
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0301 basic medicine ,Perfluorooctanesulfonic acid ,genetic structures ,hrh1 gene ,hdc gene ,nerve cell differentiation ,Toxicology ,chemistry.chemical_compound ,Gene expression ,zebra fish ,chrna7 gene ,manf gene ,Cluster Analysis ,Organic Chemicals ,swimming ,Zebrafish ,Spectroscopy ,persistent organic pollutant ,Fluorocarbons ,gabra1 gene ,Behavior, Animal ,messenger RNA ,crhb gene ,Dopaminergic ,Persistent organic pollutants ,article ,Embryo ,General Medicine ,perfluorooctanesulfonic acid ,persistent organic pollutants ,PFOS ,zebrafish larvae ,behavioural ,neurotoxicity ,Computer Science Applications ,Cell biology ,sertb gene ,Alkanesulfonic Acids ,real time polymerase chain reaction ,perfluoroundecanoic acid ,animal structures ,embryo ,Biology ,perfluorononanoic acid ,Serotonergic ,Catalysis ,perfluorohexanesulfonic acid ,Inorganic Chemistry ,03 medical and health sciences ,perfluorooctanoic acid ,larva ,Neurotoxicity ,Animals ,bdnf gene ,controlled study ,human ,Physical and Theoretical Chemistry ,Zebrafish larvae ,gene ,Molecular Biology ,nonhuman ,behavior ,Gene Expression Profiling ,Organic Chemistry ,perfluorodecanoic acid ,fungi ,Histaminergic ,genetic transcription ,biology.organism_classification ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,Fertilization ,gene expression ,Cholinergic ,Behavioural ,Transcriptome ,Water Pollutants, Chemical - Abstract
Persistent organic pollutants (POPs) are widespread in the environment and some may be neurotoxic. As we are exposed to complex mixtures of POPs, we aimed to investigate how a POP mixture based on Scandinavian human blood data affects behaviour and neurodevelopment during early life in zebrafish. Embryos/larvae were exposed to a series of sub-lethal doses and behaviour was examined at 96 h post fertilization (hpf). In order to determine the sensitivity window to the POP mixture, exposure models of 6 to 48 and 48 to 96 hpf were used. The expression of genes related to neurological development was also assessed. Results indicate that the POP mixture increases the swimming speed of larval zebrafish following exposure between 48 to 96 hpf. This behavioural effect was associated with the perfluorinated compounds, and more specifically with perfluorooctanesulfonic acid (PFOS). The expression of genes related to the stress response, GABAergic, dopaminergic, histaminergic, serotoninergic, cholinergic systems and neuronal maintenance, were altered. However, there was little overlap in those genes that were significantly altered by the POP mixture and PFOS. Our findings show that the POP mixture and PFOS can have a similar effect on behaviour, yet alter the expression of genes relevant to neurological development differently.
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- 2017
256. Análisis de los efectos teratogénicos del ácido valproico en el desarrollo del tubo neural del pez cebra y los efectos protectores de la vitamina C
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González Arias, Ana, Folgueira Otero, Mónica, and Universidade da Coruña. Facultade de Ciencias
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Neural tube ,Tubo neural ,Vitamina C ,Ácido valproico ,Zebra fish ,Valproic acid ,Pez cebra ,Vitamin C ,Peixe cebra - Abstract
[Resumen:] El ácido valproico (VPA) es el principal anticonvulsionante utilizado contra la epilepsia. Sin embargo, durante la gestación actúa como teratógeno en las etapas iniciales del embarazo, principalmente ocasionando malformaciones en el sistema nervioso central (SNC). Esto es debido a un aumento de las especies reactivas del oxígeno, pudiéndose contrarrestar añadiendo un antioxidante natural. El objetivo de este proyecto es determinar si la vitamina C disminuye el efecto teratógeno sobre el tubo neural del VPA en embriones de pez cebra transgénicos tratados con diferentes concentraciones de este anticonvulsionante. A las 96 horas post-fecundación se realizará un análisis de la morfología del tubo neural bajo el estereomicroscopio. También se realizará una técnica de inmunofluorescencia para la detección de la proteína Zonula Occludens-1 (ZO-1) para poder observar la morfología del ventrículo del tubo neural. Esto permitirá una mejor observación de malformaciones bajo el microscopio de fluorescencia tras las exposiciones al anticonvulsionante y al agente antioxidante. [Resumo:] O ácido valproico (VPA) é o principal antionvulsionante empregado contra a epilepsia. Sin embargo, durante a xestación actúa como teratóxeno nas etapas iniciais do embarazo, principalmente ocasionando malformacións no sistema nervioso central (SNC). Isto é debido a un aumento das especies reactivas do osíxeno, sendo posible contrarrestar engadindo un antioxidante natural. O obxetivo de este proxecto é determinar si a vitamina C disminue o efecto teratóxeno sobre o tubo neural do VPA en embrións de peixe cebra tranxénicos tratados con diferentes concentracións de este anticonculsionante. Ás 96 horas post-fecundación realizarase un estudo baixo o estereomicroscopio. Tamén realizaremos unha técnica de inmunofluorescencia para a detección da proteína Zonula Occludens-1 (ZO-1) para poder observar a morfoloxía do ventrículo do tubo neural. Esto permitirá una mellor observación de malformacións baixo o microscopio de fluorescencia tras as exposicións ó anticonvulsionante e ó axente oxidante. [Abstract:] Valproic acid (VPA) is the main anticonvulsant used for epilepsy. However, it acts as a tetarogenic agent during early pregnancy, causing malformations in the central nervous system of the embryo (CNS). This teratogenic effect is caused by the increase in reactive oxygen species, which can be countered with the supplementation of vitamin C. The aim of this proyect is to determine if vitamin C 5 minimizes the tetarogenic effect of VPA in in the neural tube of of transgenic zebrafish embryos treated with different concentrations of this anticonvulsant. At 96 hours post-fertilization, we will study the larvae under a stereomicrosope. In addition, we will perform an immunofluorescent staining against the Zonula Occludens-1 (ZO-1) protein in order to observe ventricular surface of the neural tube. This will allow a better analysis of neural malformations under the fluorescence microscope after the exposure to the anticonvulsant and the antioxidant agent. Traballo fin de grao (UDC.CIE). Bioloxía. Curso 2016/2017
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- 2017
257. Functional Comparison of Human and Zebra Fish FKBP52 Confirms the Importance of the Proline-Rich Loop for Regulation of Steroid Hormone Receptor Activity
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Yenni A. Garcia, Veronica W Rowlett, Ashley N Payan, Diondra C. Harris, Cheryl Storer Samaniego, Marc B. Cox, Tatsuya Maehigashi, and Nina R. Ortiz
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0301 basic medicine ,Mutant ,steroid hormone receptor ,progesterone receptor ,Hsp70 ,lcsh:Chemistry ,Mice ,0302 clinical medicine ,Glucocorticoid receptor ,androgen receptor ,zebra fish ,glucocorticoid receptor ,Threonine ,Receptor ,lcsh:QH301-705.5 ,Spectroscopy ,Mice, Knockout ,Alanine ,Chemistry ,General Medicine ,3. Good health ,Computer Science Applications ,Cell biology ,Receptors, Androgen ,Gain of Function Mutation ,Proline-Rich Protein Domains ,Signal Transduction ,endocrine system ,animal structures ,Steroid hormone receptor ,Saccharomyces cerevisiae ,Molecular Dynamics Simulation ,Article ,Catalysis ,Tacrolimus Binding Proteins ,Inorganic Chemistry ,03 medical and health sciences ,Receptors, Glucocorticoid ,stomatognathic system ,Animals ,Humans ,HSP90 Heat-Shock Proteins ,Homology modeling ,Physical and Theoretical Chemistry ,Molecular Biology ,cochaperone ,Danio rerio ,fungi ,Organic Chemistry ,Fibroblasts ,Zebrafish Proteins ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,FKBP52 ,Steroid hormone receptor activity ,heat shock protein 90 (Hsp90) ,proline-rich loop ,030217 neurology & neurosurgery - Abstract
Previous studies demonstrated that the 52-kDa FK506-binding protein (FKBP52) proline-rich loop is functionally relevant in the regulation of steroid hormone receptor activity. While zebra fish (Danio rerio, Dr) FKBP52 contains all of the analogous domains and residues previously identified as critical for FKBP52 potentiation of receptor activity, it fails to potentiate activity. Thus, we used a cross-species comparative approach to assess the residues that are functionally critical for FKBP52 function. Random selection of gain-of-function DrFKBP52 mutants in Saccharomyces cerevisiae identified two critical residues, alanine 111 (A111) and threonine 157 (T157), for activation of receptor potentiation by DrFKBP52. In silico homology modeling suggests that alanine to valine substitution at position 111 in DrFKBP52 induces an open conformation of the proline-rich loop surface similar to that observed on human FKBP52, which may allow for sufficient surface area and increased hydrophobicity for interactions within the receptor&ndash, chaperone complex. A second mutation in the FKBP12-like domain 2 (FK2), threonine 157 to arginine (T157R), also enhanced potentiation, and the DrFKBP52-A111V/T157R double mutant potentiated receptor activity similar to human FKBP52. Collectively, these results confirm the functional importance of the FKBP52 proline-rich loop, suggest that an open conformation on the proline-rich loop surface is a predictor of activity, and highlight the importance of an additional residue within the FK2 domain.
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- 2019
258. An overview of organic matters in municipal wastewater: Removal via self-assembly flocculating mechanism and the molecular level characterization.
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Vimala, R.T.V., Lija Escaline, J., Murugan, Kadarkarai, and Sivaramakrishnan, S.
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ORGANIC compounds , *PARTICLE size distribution , *SEWAGE , *PHTHALIC acid , *ZETA potential , *DISSOLVED organic matter - Abstract
On considering the critical issues in attaining stringent water quality standards and not creating any environmental impacts, we focused for the first time the economically feasible, emerging technology known as Self-assembly flocculating (Saf process). In which, the study investigated the applicability of bioflocculant (a biopolymer-self-assembly in nature) act as a surrogates on relying the removal of broad spectrum of substances under optimized conditions (Dosage: 90 mg/L; pH: 7; CaCl 2). On using different techniques, the results have proved in removing the organic matter such as pharmaceuticals (Gentamycin, Cholecalciferol, Fluvoxamine, 3-OH Desogestrel, and Pheniramine), endocrine disturbing compounds [Phthalic acid, Benzene, 1, 2, 4 -Trimethoxy-5-(1-Propenyl)-, Benzene, 1, 2-Dimethoxy-4-(2-Propenyl)-, 1, 2-Benzenedicarboxylic Acid, 3-Cyclohexen-1-ol], fluorescent components (Polysaccharide like material), and others. The toxicological assessment of self-assembly bioflocculant implemented on zebra fish were statistically correlated [r = 0.95, p < 0.01 and 0.05 for P 1 WW; r = 0.91, p < 0.01 and 0.05 for P 2 WW] and [r = 0.7 5, p < 0.05 for P 1 WT; r = 0.095, p < 0.01 and 0.05 for P 2 WT]. This integrated approach supplemented further information of zeta potential (−16 mV in P 1 WW and −14.6 mV in P 2 WW decreased to −1.05 mV and −1.56 mV) with particle size distribution to explain via Saf process. In this research, the new insight has established non-toxic, self-assembly, biodegradable, bioflocculant for effective bioremediation. Image 1 • Removal efficiency of the self-assembly bioflocculant in removing the organic matters from the municipal wastewater were analyzed using advanced level techniques. • Bio-toxicity assessment was performed in zebra fish exposed to municipal and treated water. • The correlatory relationship between particle size distribution and zeta potential was explained. [ABSTRACT FROM AUTHOR]
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- 2020
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259. Toxicity of Carlina Oxide—A Natural Polyacetylene from the Carlina acaulis Roots—In Vitro and in Vivo Study.
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Wnorowski, Artur, Wnorowska, Sylwia, Wojas-Krawczyk, Kamila, Grenda, Anna, Staniak, Michał, Michalak, Agnieszka, Woźniak, Sylwia, Matosiuk, Dariusz, Biała, Grażyna, Wójciak, Magdalena, Sowa, Ireneusz, Krawczyk, Paweł, and Strzemski, Maciej
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PROGRAMMED cell death 1 receptors , *ACUTE toxicity testing , *NUCLEAR magnetic resonance spectroscopy , *ANTIPARASITIC agents , *OXIDES , *CELL lines - Abstract
There are several reports indicating that the roots of the Carlina acaulis L. used to be commonly applied as a treatment measure in skin diseases and as an antiparasitic agent, starting from antiquity to the 19th century; however, nowadays, it has lost its importance. Currently, numerous studies are being conducted assessing the possibility of reintroducing C. acaulis-derived extracts to phytotherapy. Determining the safety profile of the main constituents of the plant material is crucial for achieving this goal. Here, we aimed to determine the toxicity profile of carlina oxide, one of the most abundant components of the C. acaulis root extract. We obtained the carlina oxide by distillation of C. acaulis roots in the Deryng apparatus. The purity of the standard was evaluated using GC-MS, and the identity was confirmed by IR, Raman, and NMR spectroscopy. In vitro cytotoxicity was assessed using a panel of human cell lines of skin origin, including BJ normal fibroblasts and UACC-903, UACC-647, and C32 melanoma cells. This was accompanied by an in vivo zebrafish acute toxicity test (ZFET). In vitro studies showed a toxic effect of carlina oxide, as demonstrated by an induction of apoptosis and necrosis in both normal and melanoma cells. Decreased expression of AKT kinase and extracellular signal-regulated kinase 1/2 (ERK1/2) was noted in the UACC-647 melanoma cell line. It was also observed that carlina oxide modified the expression of programmed cell death-ligand 1 (PD-L1) in tested cell lines. Carlina oxide exhibited high in vivo toxicity, with LC50 = 10.13 µg/mL upon the 96 h of exposure in the ZFET test. Here, we demonstrate that carlina oxide displays toxic effects to cells in culture and to living organisms. The data indicate that C. acaulis-based extracts considered for therapeutic use should be completely deprived of carlina oxide. [ABSTRACT FROM AUTHOR]
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- 2020
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260. Impact of nanomaterials on ecosystems: Mechanistic aspects in vivo.
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Bakshi, Mandeep Singh
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PLANT surfaces , *SUSTAINABLE design , *BIOLOGICAL systems , *AQUATIC plants , *GOLD nanoparticles , *ECOSYSTEMS - Abstract
Nanotechnologies are becoming increasingly popular in modern era of human development in every aspect of life. Their impact on our ecosystem in air, soil, and water is largely unknown because of the limited amount of information available, and hence, they require considerable attention. This account highlights the important routes of nanomaterials toxicity in air, soil, and water, their possible impact on the ecosystem and aquatic life. The mechanistic aspects have been focused on the size, shape, and surface modifications of nanomaterials. The preventive measures and future directions along with appropriate designs and implementation of nanotechnologies have been proposed so as to minimize the interactions of nanomaterials with terrestrial flora and aquatic life. Specifically, the focus largely remains on the toxicity of metallic nanoparticles such as gold (Au) and silver (Ag) because of their applications in diverse fields. The account lists some prominent mechanistic routes of nanotoxicity along with in vivo experimental results based on the fundamental understanding that how nanometallic surfaces interact with plant as well as animal biological systems. The appropriate modifications of the nanometallic surfaces with biocompatible molecules are considered to be the most effective preventive measures to reduce the nanotoxicity. Image 1 • The realistic modes of analyses (mostly in vivo studies) of understanding the nanomaterials toxicity. •Influence of size, shape, and surface modifications of nanomaterials on environmental nanotoxicity. •The possible future directions require design and implementation of sustainable nanotechnologies with minimum nanotoxicity. [ABSTRACT FROM AUTHOR]
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- 2020
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261. Synthesis, in vitro, and in vivo (Zebra fish) antitubercular activity of 7,8-dihydroquinolin-5(6H)-ylidenehydrazinecarbothioamides.
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Marvadi, Sandeep kumar, Krishna, Vagolu Siva, Surineni, Goverdhan, Srilakshmi Reshma, Rudraraju, Sridhar, Balasubramanian, Sriram, Dharmarajan, and Kantevari, Srinivas
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ZEBRAS , *MYCOBACTERIUM tuberculosis , *FISHES , *HYDROGEN bonding , *STARVATION , *AMMONIUM acetate , *HYDRAZINE derivatives - Abstract
• Twenty-two dihydroquinolinylidenehydrazinecarbothioamides 4a–v was synthesized. • Five compounds 4a , 4e , 4g , 4j and 4k were resulted as the potent Mtb inhibitors. • Hydrazinecarbothioamide derivatives 4a–k exhibited enhanced activity than 3a–k. • The in vivo (Zebra fish) antimycobacterial screening led to the hit compound 4j. • 4j exhibited significant activity in Mtb nutrient starvation model. We, herein, describe the synthesis of a series of novel aryl tethered 7,8-dihydroquinolin-5(6 H)-ylidenehydrazinecarbothioamides 4a–v , which showed in vitro and in vivo antimycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Rv. The intermediates dihydro-6 H- quinolin-5-ones 3a–v were synthesized from β-enaminones, reacting with cyclochexane-1,3-dione/5,5-dimethylcyclohexane-1,3-dione and ammonium acetate using a modified Bohlmann-Rahtz reaction conditions. They were further reacted with thiosemicarbazide to give the respective hydrazine carbothioamides 4a–v. All the new analogues 4a–v , were characterized by their NMR and mass spectral data analysis. Among the twenty-two compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294), two compounds, 4e and 4j , exhibited the highest inhibition with an MIC of 0.39 µg/mL. Compounds 4a, 4g , and 4k were found to inhibit Mtb at an MIC of 0.78 µg/mL. Hydrazinecarbothioamides 4a–k , exhibited enhanced activity than dihydroquinolinones 3a–k. The observed increase in potency provides a clear evidence that hydrazinecarbothioamide is a potential pharmacophore, collectively imparting synergistic effect in enhancing antitubercular activity of the dihydroquinolinone core. The in vivo (Zebra fish) antimycobacterial screening of the in vitro active molecules led to the identification of a hit compound, 4j , with significant activity in the Mtb nutrient starvation model (2.2-fold reduction). Docking studies of 4j showed a hydrogen bond with the P156 residue of the protein. [ABSTRACT FROM AUTHOR]
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- 2020
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262. Discriminating Cys from GSH/H2S in vitro and in vivo with a NIR fluorescent probe.
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Zhu, Linlin, Zhang, Tiange, Ma, Yanyan, and Lin, Weiying
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FLUORESCENT probes , *CYSTEINE , *SINGLE molecules , *CHEMICAL properties , *DETECTION limit , *INFRARED absorption , *CHEMICAL structure , *NEAR infrared radiation - Abstract
• We developed a near infrared fluorescent probe (NN) for discriminating Cys from GSH/H 2 S in vivo for the first time. It is also the first time to discriminating biolthiols in vivo. • The probe NN exhibited excellent selectivity, stability, low cytotoxicity as well as low detection limit (0.05 μM for Cys, 0.11 μM for GSH and 0.02 μM for H 2 S) • Significantly, probe NN can distinguish Cys from GSH/H 2 S in vivo for the first time. • Furthermore, the success of the differentiation of Cys from GSH/H 2 S in vivo lays the experimental foundation for further exploring the role of these mercaptans in living systems. • Discriminating Cys from GSH/H 2 S in vitro and in vivo with a NIR fluorescent probe. Biothiols play a prominent role in physiological and pathological processes as reactive sulfur species (RSS), which are closely related to the pathways of metabolism of living animals. By reason of their similar chemical structure and properties, it is challenging to distinguish biological mercaptans from each other in living systems. Herein, a NIR probe (NN) for effectively distinguishing cysteine (Cys) from glutathione (GSH)/hydrogen sulfide (H 2 S) using a dual-channel responsive mode in vitro and in vivo were developed. NN performs no fluorescence characteristics in the visible to NIR range. Upon treatment with Cys, the system generates significant fluorescence enhancement in both green and near infrared emission bands, while encounter of GSH/H 2 S generates the increasing of fluorescence only in the near infrared region. In addition, the probe NN also exhibits excellent selectivity, stability, low cytotoxicity as well as low detection limit (0.05 μM for Cys, 0.11 μM for GSH and 0.02 μM for H 2 S). More importantly, integrating these excellent attributes into a single molecule make it possible to discriminate Cys from GSH/H 2 S in vivo for the first time. [ABSTRACT FROM AUTHOR]
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- 2020
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263. A rapid and sensitive fluorescent probe for detecting hydrogen polysulfides in living cells and zebra fish.
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Fang, Qian, Yue, Xiuxiu, Han, Shaohui, Wang, Benhua, and Song, Xiangzhi
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FLUORESCENT probes , *ZEBRAS , *POLYSULFIDES , *FISHES , *COUMARINS , *DETECTION limit , *HYDROGEN , *FLUORESCENCE - Abstract
Hydrogen polysulfides (H 2 S n , n>1) plays crucial roles in many biological processes, while it remains a challenge for rapid and selective detection of H 2 S n. We designed and synthesized a turn-on fluorescent probe (JCCF) for detecting H 2 S n based on a new julolidine-coumarinocoumarin scaffold. H 2 S n could trigger a dramatic fluorescence enhancement (52-fold) with a fast response time and a low detection limit of 98.3 nM (S/N = 3). Moreover, JCCF was successfully applied to image H 2 S n in living cells and zebra fish with low cytotoxicity. A rapid (within 2 min) fluorescent probe was developed for the sensitive and selective detection of hydrogen polysulfides (H 2 S 2) with a low detection limit (98.3 nM). This probe was successfully applied to detect H 2 S 2 in both living cells and zebra fish with low cytotoxicity. Unlabelled Image • A Julolidine-coumarin based fluorescent probe was developed for selective and sensitive detection of H 2 S n. • This probe exhibited a rapid response (within 2 min) and a low detection limit (9.83 × 10−8 M) toward H 2 S n. • This probe was successfully applied to image H 2 S n in living cells and zebra fish. [ABSTRACT FROM AUTHOR]
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- 2020
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264. Development of a two-photon fluorescent probe to monitor the changes of viscosity in living cells, zebra fish and mice.
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Peng, Min, Yin, Junling, and Lin, Weiying
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VISCOSITY , *ZEBRAS , *FLUORESCENT probes , *FISHES , *MICE , *CELLS - Abstract
The detection of viscosity is of great significance for medical research. Herein, we have developed a two-photon fluorescent probe CB-V for monitoring micro-viscosity changes. The fluorescence emission intensity of CB-V increased 9.6-fold from methanol to glycerol exhibiting an excellent fluorescence response. With excellent properties of CB-V , monitoring the viscosity variations has been achieved not only in living cells but also in zebra fish and mice. A two-photon fluorescent probe CB-V with near infrared emission has been developed to measure the viscosity changes in living cells, zebra fish and mice. Unlabelled Image • A fluorescent probe for detecting viscosity has been constructed. • The probe CB-V exhibit two-photon excitation, near infrared emission, high selectivity, and excellent biocompatibility. • The probe CB-V successfully achieved viscosity detection not only in cells but also in zebra fish and in inflamed mice. [ABSTRACT FROM AUTHOR]
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- 2020
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265. Functional Comparison of Human and Zebra Fish FKBP52 Confirms the Importance of the Proline-Rich Loop for Regulation of Steroid Hormone Receptor Activity.
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Harris, Diondra C., Garcia, Yenni A., Samaniego, Cheryl Storer, Rowlett, Veronica W., Ortiz, Nina R., Payan, Ashley N., Maehigashi, Tatsuya, and Cox, Marc B.
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STEROID receptors , *HORMONE regulation , *ZEBRAS , *FISHES , *HEAT shock proteins , *MOLECULAR chaperones - Abstract
Previous studies demonstrated that the 52-kDa FK506-binding protein (FKBP52) proline-rich loop is functionally relevant in the regulation of steroid hormone receptor activity. While zebra fish (Danio rerio; Dr) FKBP52 contains all of the analogous domains and residues previously identified as critical for FKBP52 potentiation of receptor activity, it fails to potentiate activity. Thus, we used a cross-species comparative approach to assess the residues that are functionally critical for FKBP52 function. Random selection of gain-of-function DrFKBP52 mutants in Saccharomyces cerevisiae identified two critical residues, alanine 111 (A111) and threonine 157 (T157), for activation of receptor potentiation by DrFKBP52. In silico homology modeling suggests that alanine to valine substitution at position 111 in DrFKBP52 induces an open conformation of the proline-rich loop surface similar to that observed on human FKBP52, which may allow for sufficient surface area and increased hydrophobicity for interactions within the receptor–chaperone complex. A second mutation in the FKBP12-like domain 2 (FK2), threonine 157 to arginine (T157R), also enhanced potentiation, and the DrFKBP52-A111V/T157R double mutant potentiated receptor activity similar to human FKBP52. Collectively, these results confirm the functional importance of the FKBP52 proline-rich loop, suggest that an open conformation on the proline-rich loop surface is a predictor of activity, and highlight the importance of an additional residue within the FK2 domain. [ABSTRACT FROM AUTHOR]
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- 2019
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266. Genotoxic impact of emerging contaminant amoxicillin residue on zebra fish ( Danio rerio ) embryos.
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Chowdhury J, Mandal TK, and Mondal S
- Abstract
The widest-spectrum, most-consumed β-lactam antibiotic amoxicillin (AMX) is used to treat bovine mastitis that is caused primarily by many bacteria. Excessive use of antibiotics can lead to established residual contamination of the milk even after pasteurization. The amount of antibiotic residue above Maximum Residue Limit (MRL) has a negative impact on both public health and the environment. Therefore, the objective of this study is to determine the concentration of amoxicillin residue (AMXR) in raw and pasteurized milk samples of cow suffered from mastitis, by the standard methods of HPLC compared to pure AMX drug and effect of the said residue on the developmental toxicity and genotoxicity of zebra fish at 72 hpf and 48 hpf embryo, respectively. Results obtained by HPLC showed that AMXR exhibits 574.89 and 250.75 times higher concentration in the raw and pasteurized milk than MRL in compare to pure AMX drug. This current study showed that AMXR decreased the body length and yolk sac region, while the pure AMX drug-treated group showed increased height and length of the yolk sac and shorter body length relative to the other groups. The Comet Assay measured the DNA damage caused by AMXR. The group where AMXR were applied showed the highest percentage of tail DNA and tail moment relative to other groups. So, here AMXR is considered as the genotoxic contaminant that is emerging and affect on public health., (© 2020 The Authors.)
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- 2020
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267. Quantitative Nucleic Acid Histochemistry of the Yolk Sac Syncytium of Oviparous Teleosts: Implications for Hypotheses of Yolk Utilization
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Bachop, W. E., Schwartz, F. J., and Blaxter, John H. S., editor
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- 1974
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268. Neurones sous-tendant la locomotion chez le poisson zèbre
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Sternberg, Jenna, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris VI, Hugues Pascal-Mousselard, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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Spinal cord ,Zebra fish ,Botulinum neurotoxin ,Comportement ,Toxine botulique ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Poisson zèbre ,Moelle épinière ,PKD2L1 ,Locomotion - Abstract
The neural networks that underlie locomotion are complex and require integration of sensory input and physiological state. However, how these networks function during active locomotion to incorporate sensory input from the environment and the internal state of the animal remains poorly understand. The zebrafish larva is an ideal vertebrate to study these questions thanks to its simple locomotor repertoire, transparency, and amenability to genetic manipulation. In Chapter 1, I describe a program to track behavior at high speeds and automatically characterize locomotor patterns in a high-throughput manner. V2a interneurons are excitatory interneurons in the spinal cord and hindbrain identified by the chx10 transcription factor. In Chapter 2, I validated the use of a genetically-encoded botulinum toxin to silence the chx10 population in vivo. Using fictive locomotor recordings and calcium imaging, I demonstrated that silencing V2as leads to decreased activity in primary motor neurons during fast swimming, corresponding to a lower swimming frequency in V2a-silenced larvae. Cerebrospinal fluid-contacting neurons (CSF-cNs) are intraspinal neurons that relay sensory information to motor circuits. CSF-cNs in diverse species express GABA and the transient receptor potential channel PKD2L1. In Chapter 3, I used genetic targeting, calcium imaging, pharmacology, and electrophysiology to investigate the role of spontaneous activity in CSF-cNs. I showed that single channel opening of PKD2L1 represents an intrinsic source of spontaneous activity in CSF-cNs. These tools and results will allow a more complete picture of how dynamic interactions shape locomotor output in vivo.; Les circuits neuronaux sous-tendant la locomotion requièrent d'intégrer à la fois des stimuli sensoriels et l'état physiologique. Cependant, la manière dont ces circuits fonctionnent pendant la locomotion active reste peu comprise. La larve de poisson zèbre est un organisme vertébré idéal pour étudier cette question de part son répertoire locomoteur simple et son accessibilité à la manipulation génétique. Dans le Chapitre 1, je décris le logiciel que nous avons développé afin de nous permettre de traquer les comportements et caractériser automatiquement les modules locomoteurs à haut débit. Les interneurones V2a sont des neurones excitateurs de la moelle épinière et du cerveau postérieur caractérisés par l'expression du facteur de transcription chx10. Afin de tester leur implication dans la locomotion, j'ai, dans le Chapitre 2, validé l'utilisation d'une toxine génétiquement encodée dans le but d'inhiber la population chx10 positive in vivo. Par analyse comportementale, enregistrements de locomotion fictive et imagerie calcique, nous avons montré que les V2as sont impliqués différemment dans la locomotion lente et rapide. Les neurones contactant le liquide céphalorachidien (NcLCRs) relaient des informations sensorielles aux circuits moteurs. Par ciblage génétique, imagerie calcique, pharmacologie et électrophysiologie, j'ai, dans le Chapitre 3, investigué le rôle de l'activité spontanée dans les NcLCRs. J'ai montré que l'ouverture de canaux PKD2L1 représentait une source intrinsèque d'activité spontanée dans les NcLCRs. Ces résultats offrent une meilleure compréhension de la manière dont les interactions dynamiques structurent les sorties locomotrices in vivo.
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- 2016
269. Axonal target specificity in the CRISPR/Cas9 era : a new role for Reelin in vertebrate visual sytem development
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Di Donato, Vincenzo, Génétique et Biologie du Développement, Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris VI, Filippo Del Bene, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and STAR, ABES
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Vertebrate vsiual system ,Système visual ,nervous system ,Ciblage axonal ,Zebra fish ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Mutagénèse conditionelle ,Poisson zèbre ,Reelin ,CRISPR/Cas9 - Abstract
Neuronal connections in the visual system are arranged in synaptic laminae. Understanding the basis of lamina-specific axonal targeting is critical to gain deeper insights on how complex neural networks form. In a first study we investigated the role of the ECM protein Reelin during zebrafish retinotectal circuit formation in vivo. Here retinal ganglion cells (RGCs) convey the visual information to the brain by projecting their axons to different layers of the optic tectum. We demonstrated that Reelin secreted by a specific class of tectal superficial inhibitory neurons is spatially distributed in a superficial-to-deep gradient within the tectal neuropil. Induced gene disruption for all the components of the canonical Reelin pathway expressed in the retinotectal system resulted in aberrant layering of RGC axons suggesting a role for Reelin pathway in axonal sublaminar segregation. Altogether our findings elucidate a new role for Reelin in vertebrate visual system development, during which it acts as molecular cue by imparting positional information for ingrowing RGCs.In a second study we took advantage of the CRISPR/Cas9 technology to develop a novel approach for conditional mutagenesis in zebrafish. Our results provide evidence that tissue-specific gene disruption can be achieved by driving Cas9 expression with the Gal4/UAS system. We established a tool to induce loss-of-function mutations in cell clones or single cells that can be followed by genetic labeling, enabling their phenotypic analysis. Our technique has the potential to be applied to a wide-range of model organisms, allowing systematic mutagenesis and labeling on a genome-wide scale., Les connexions neuronales du système visuel forment des synapses spatialement distribuées en couches discrètes. Comprendre la base du ciblage spécifique axonale est critique pour déchiffrer la formation des réseaux neuronaux complexes. Dans une première étude, nous avons investigué le rôle de la protéine de la matrice extracellulaire Reelin dans la formation in vivo du circuit rétinotectal chez le poisson zèbre. Ce circuit se compose de cellules ganglionnaires de la rétine (CGRs) transmettant l’information visuelle au cerveau via la projection de leur axone dans les différentes couches du tectum optique. Nous avons démontré que la Reelin secrétée par de neurones inhibiteurs localisés dans les couches supérieures du tectum optique forme un gradient. L’induction de mutations délétères dans la voie de signalisation canonicale de la Reelin à l’aide d’outils génétiques a conduit à des défauts de ciblage des axones de CGRs. Nos résultats démontrent un nouveau rôle de la Reelin lors du développement du système visuel et la décrivent comme signature moléculaire nécessaire au ciblage et au positionnement précis des axones de CGRs.Dans une seconde étude, nous avons utilisé la technique CRISPR/Cas9 pour développer une nouvelle approche de mutagénèse conditionnelle chez le poisson zèbre. Nos résultats démontrent que la perturbation de gènes dans des tissues spécifiques peut être effectué par l’induction de l’expression de la protéine Cas9 via le système Gal4/UAS. Nous avons établis un outil pour induire l’apparition de mutations délétères dans des clones de cellules mais aussi dans des cellules individuelles, tous pouvant être suivit distinctement grâce à un marquage génétique.
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- 2016
270. Topology and dynamics of the zebrafish segmentation clock core circuit
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Schröter, Christian, Ares, Saúl, Morelli, Luis G., Isakova, Alina, Hens, Korneel, Soroldoni, Daniele, Gajewski, Martin, Jülicher, Frank, Maerkl, Sebastian J., Deplancke, Bart, Oates, Andrew C., and University of Zurich
- Subjects
core circuit ,Transcription, Genetic ,protein antibody ,Biochemistry ,Substrate Specificity ,purl.org/becyt/ford/1 [https] ,somitogenesis ,SX00 SystemsX.ch ,2400 General Immunology and Microbiology ,zebra fish ,Protein Interaction Mapping ,Molecular Cell Biology ,Basic Helix-Loop-Helix Transcription Factors ,Protein Interaction Maps ,SX05 DynamiX ,Biology (General) ,segmentation clock ,Promoter Regions, Genetic ,Mathematical Computing ,Zebrafish ,embryonic structures ,Feedback, Physiological ,her7 gene ,messenger RNA ,Protein Stability ,molecular clock ,Gene Expression Regulation, Developmental ,2800 General Neuroscience ,protein function ,unclassified drug ,Phenotype ,Somites ,messenger RNA synthesis ,transcription factor Her1 ,Synopsis ,transcription factor Her6 ,transcription regulation ,transcription factor Her7 ,Dimerization ,her1 gene ,CIENCIAS NATURALES Y EXACTAS ,SX20 Research, Technology and Development Projects ,QH301-705.5 ,homodimer ,transcription factor Her6 antibody ,Otras Ciencias Biológicas ,animal experiment ,embryo ,1100 General Agricultural and Biological Sciences ,Molecular dynamics ,protein DNA binding ,Models, Biological ,Article ,animal tissue ,Ciencias Biológicas ,Model Organisms ,Biological Clocks ,1300 General Biochemistry, Genetics and Molecular Biology ,Two-Hybrid System Techniques ,Genetics ,Animals ,controlled study ,mutant ,RNA, Messenger ,gene ,purl.org/becyt/ford/1.6 [https] ,her6 gene ,Biology ,Body Patterning ,Vertebrata ,Danio rerio ,nonhuman ,embryo segmentation ,genetic network ,embryo development ,Zebrafish Proteins ,Repressor Proteins ,basic helix loop helix transcription factor ,570 Life sciences ,biology ,Prediction ,Mathematics ,Transcription Factors ,Developmental Biology - Abstract
During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a "dimer cloud" that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. © 2012 Schröter et al. Fil: Schroter, Christian. University of Cambridge; Estados Unidos Fil: Ares, Saúl. Max Planck Institute For The Physics Of Complex Systems; Alemania Fil: Morelli, Luis Guillermo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Isakova, Alina. Ecole Polytechnique Federale de Lausanne; Francia Fil: Hens, Korneel. Ecole Polytechnique Federale de Lausanne; Francia Fil: Soroldoni, Daniele. Max Planck Institute Of Molecular Cell Biology And Genetics; Alemania Fil: Gajewski, Martin. Universitat zu Köln; Alemania Fil: Jülicher, Frank. Max Planck Institute For The Physics Of Complex Systems; Alemania Fil: Maerkl, Sebastian J.. Ecole Polytechnique Federale de Lausanne; Francia Fil: Deplancke, Bart. Ecole Polytechnique Federale de Lausanne; Francia Fil: Oates, Andrew C.. Max Planck Institute Of Molecular Cell Biology And Genetics; Alemania
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- 2016
271. Editorial: Ontogeny and Phylogeny of Brain Barrier Mechanisms
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Shane A. Liddelow, Helen B. Stolp, and Norman R. Saunders
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0301 basic medicine ,tight junctions ,Mammalian Embryos ,Central nervous system ,Choroid plexus ,influx mechanisms ,Development ,Biology ,Blood–brain barrier ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,efflux mechanisms ,Phylogenetics ,zebra fish ,medicine ,Genetics ,Tight junctions ,development ,Blood-brain barrier ,choroid plexus ,Tight junction ,Zebra fish ,General Neuroscience ,blood-brain barrier ,Influx mechanisms ,Spinal cord ,030104 developmental biology ,medicine.anatomical_structure ,Editorial ,Drosophila ,Neuroscience ,030217 neurology & neurosurgery ,Efflux mechanisms - Abstract
The protective barriers of the central nervous system, positioned at interfaces between the brain, spinal cord and the periphery, are often considered as gatekeepers—restricting entry of unwanted molecules and ensuring an effective maintenance of the delicate microenvironment of the central nervous system. While there is truth in this depiction, it does not fully capture the highly dynamic nature of these brain barrier systems; the specific regulation of transporters, the signaling between endothelial cells and other components of the neurovascular unit; or the precise regulation of cerebrospinal fluid composition via the choroid plexus, that changes appropriately both during development and throughout aging.
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- 2016
272. Loss-Of-Function Mutations In Elmo2 Cause Intraosseous Vascular Malformation By Impeding Rac1 Signaling
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Halil Ibrahim Canter, Simone Laupheimer, Bayram Yuksel, Mireia Perez Camps, Ibrahim Vargel, Lorenzo D. Botto, Sevket Ruacan, Nicola Longo, Elif Uz, Mahmut Şamil Sağıroğlu, Ahmad Alzahrani, Bruno Reversade, Omer F. Gerdan, Tokiharu Takahashi, Eeswari Paramalingam, Jingwei Rachel Xiong, Kemal Kosemehmetoglu, Arda Cetinkaya, Zeliha Gormez, Ekim Z. Taskiran, Nurten A. Akarsu, Tıbbi Genetik, Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Moleküler Biyoloji ve Genetik Bölümü., Uz, Elif, Acibadem University Dspace, Amsterdam Cardiovascular Sciences, Amsterdam Reproduction & Development (AR&D), and Center for Reproductive Medicine
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Male ,Pathology ,Vascular smooth muscle ,Tooth extraction ,DOCK1 protein, human ,Signal transduction ,Gene ,Craniofacial region ,Intracranial hypertension ,Gene inactivation ,Skull malformation ,Facial bone ,0302 clinical medicine ,Genetics(clinical) ,Gingiva bleeding ,Species difference ,Phylogeny ,Genetics & Heredity ,Adaptor proteins, signal transducing ,Cell migration ,Cell motion ,Anatomy ,Rac1 protein ,030220 oncology & carcinogenesis ,Hemorrhagic shock ,Deficiency ,Mechanism ,Human ,medicine.medical_specialty ,Vascular malformations ,Clinical article ,Bone malformation ,Spinal cord compression ,Article ,03 medical and health sciences ,Signal transducing adaptor protein ,Complex ,Alkaline phosphatase ,Skin biopsy ,Genetics ,Humans ,Animal model ,Animal experiment ,Alleles ,Actin ,Autosomal recessive disorder ,Zebra fish ,Animal ,Magnetic resonance angiography ,medicine.disease ,Cytoskeletal proteins ,ELMO2 gene ,030104 developmental biology ,Jaw ,Mutation ,Loss of function mutation ,Lesions ,Protein expression ,Angiogenesis ,Familial disease ,Artificial embolization ,0301 basic medicine ,Physiology ,Brain hernia ,Caldesmon ,Growth ,Bone deformation ,Face asymmetry ,Intravascular hemolysis ,Animal tissue ,Homozygosity ,Desmin ,Brain ventricle peritoneum shunt ,Primary Intraosseous Vascular Malformation ,Skull ,Parietal Bone ,Bone and bones ,Exophthalmos ,Integrin-linked kinase ,Sequencing data ,Zebrafish ,Genetics (clinical) ,Priority journal ,Allele ,Vascular malformation ,Homozygote ,Lactate dehydrogenase ,ELMO2 protein, human ,Rac GTP-Binding Proteins ,Lymphatic system ,Phenotype ,Intramembranous ossification ,Fibroblast ,Female ,Rac GTP-binding proteins ,North American ,Adult ,Evolution, molecular ,Umbilical hernia ,Myosin ,Biology ,RAC1 protein, human ,Saudi ,Cell movement ,Rac protein ,Sclerotherapy ,medicine ,Cell-migration ,Animals ,Human tissue ,Bone ,Species specificity ,Tooth disease ,Paraplegia ,Bone biopsy ,Rac1 GTP-binding protein ,Vertebrate ,Vascularization ,Smooth muscle actin ,biology.organism_classification ,Nonhuman ,Metabolism ,Congenital blood vessel malformation ,Turk (people) ,Molecular evolution ,Controlled study ,Cytoskeleton protein - Abstract
Çalışmada 21 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. Vascular malformations are non-neoplastic expansions of blood vessels that arise due to errors during angiogenesis. They are a heterogeneous group of sporadic or inherited vascular disorders characterized by localized lesions of arteriovenous, capillary, or lymphatic origin. Vascular malformations that occur inside bone tissue are rare. Herein, we report loss-of-function mutations in ELMO2 (which translates extracellular signals into cellular movements) that are causative for autosomal-recessive intraosseous vascular malformation (VMOS) in five different families. Individuals with VMOS suffer from life-threatening progressive expansion of the jaw, craniofacial, and other intramembranous bones caused by malformed blood vessels that lack a mature vascular smooth muscle layer. Analysis of primary fibroblasts from an affected individual showed that absence of ELMO2 correlated with a significant downregulation of binding partner DOCK1, resulting in deficient RAC1-dependent cell migration. Unexpectedly, elmo2-knockout zebrafish appeared phenotypically normal, suggesting that there might be human-specific ELMO2 requirements in bone vasculature homeostasis or genetic compensation by related genes. Comparative phylogenetic analysis indicated that elmo2 originated upon the appearance of intramembranous bones and the jaw in ancestral vertebrates, implying that elmo2 might have been involved in the evolution of these novel traits. The present findings highlight the necessity of ELMO2 for maintaining vascular integrity, specifically in intramembranous bones. CRANIRARE consortium - R07197KS Strategic Positioning Fund for Genetic Orphan Diseases Agency for Science Technology & Research (A*STAR) Hacettepe Üniversitesi- 00-02-101-009 / 03-D07-101-001
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- 2016
273. iLIR database: A web resource for LIR motif-containing proteins in eukaryotes
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Jacomin, A. -C, Samavedam, S., Promponas, Vasilis J., Nezis, I. P., and Promponas, Vasilis J. [0000-0003-3352-4831]
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0301 basic medicine ,Autophagosome ,LRS ,Proteome ,Arabidopsis thaliana ,ved/biology.organism_classification_rank.species ,Amino Acid Motifs ,computer.software_genre ,protein database ,Recognition sequence ,cell membrane protein ,eukaryote ,zebra fish ,Data Mining ,AIM ,rat ,light chain 3 protein ,database ,receptor protein ,Mammals ,LC3-interacting region motif ,Database ,Eukaryota ,iLIR database ,Cell biology ,unclassified drug ,Databases as Topic ,protein protein interaction ,LIR containing protein ,ATG8 ,Resource ,In silico ,proteome ,LIR-containing protein ,animal experiment ,LIRCP ,Gallus gallus ,Saccharomyces cerevisiae ,Biology ,Models, Biological ,Article ,myosin light chain ,03 medical and health sciences ,atg8 protein ,Autophagy ,Animals ,Humans ,Mus musculus ,controlled study ,Amino Acid Sequence ,human ,cell protein ,Model organism ,protein motif ,Caenorhabditis elegans ,Molecular Biology ,Gene ,mouse ,selective autophagy ,Internet ,nonhuman ,ved/biology ,LIR ,Cell Biology ,prediction ,data mining ,Rattus norvegicus ,amino acid sequence ,030104 developmental biology ,Gene Ontology ,protein analysis ,gene ontology ,computer model ,computer ,Biogenesis - Abstract
Atg8-family proteins are the best-studied proteins of the core autophagic machinery. They are essential for the elongation and closure of the phagophore into a proper autophagosome. Moreover, Atg8-family proteins are associated with the phagophore from the initiation of the autophagic process to, or just prior to, the fusion between autophagosomes with lysosomes. In addition to their implication in autophagosome biogenesis, they are crucial for selective autophagy through their ability to interact with selective autophagy receptor proteins necessary for the specific targeting of substrates for autophagic degradation. In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database (https://ilir.warwick.ac.uk) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy. © 2016 The Author(s). Published with license by Taylor & Francis. © Anne-Claire Jacomin, Siva Samavedam, Vasilis Promponas, and Ioannis P. Nezis. 12 1945 1953 Cited By :3
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- 2016
274. Activation of NF-κB Protein Prevents the Transition from Juvenile Ovary to Testis and Promotes Ovarian Development in Zebrafish*
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Scott A. Ochsner, Hazem Khalaf, Neil J. McKenna, Marie Karlsson, Per-Erik Olsson, Jesper Karlsson, Jarno Koskinen, László Orbán, Rajini Sreenivasan, and Ajay Pradhan
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Male ,Gonad ,Sex Differentiation ,Hot Temperature ,Blotting, Western ,Ovary ,Apoptosis ,Zebra Fish ,Development ,Biochemistry ,Cell Line ,Transcriptome ,Gene expression ,Gonad Transformation ,Testis ,medicine ,Escherichia coli ,Animals ,Gene Regulatory Networks ,Molecular Biology ,Zebrafish ,Oligonucleotide Array Sequence Analysis ,Inflammation ,Sexual differentiation ,biology ,Models, Genetic ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,fungi ,Sex Reversal ,NF-kappa B ,Cell Biology ,Sex Determination ,Zebrafish Proteins ,biology.organism_classification ,Molecular biology ,Cell biology ,Gene expression profiling ,medicine.anatomical_structure ,Female ,Developmental biology ,Developmental Biology ,Signal Transduction ,Deoxycholic Acid - Abstract
Background: NF-κB is a key regulator of anti-apoptotic processes and plays a role in gonad formation in mammals. Results: NF-κB activation leads to female-biased sex differentiation in zebrafish. Conclusion: Anti-apoptotic signaling during the juvenile ovary stage is needed for the maintenance of oocytes in zebrafish. Significance: Unraveling the regulation of apoptotic processes during gonadal transformation will facilitate understanding the molecular mechanism of zebrafish sex differentiation., Testis differentiation in zebrafish involves juvenile ovary to testis transformation initiated by an apoptotic wave. The molecular regulation of this transformation process is not fully understood. NF-κB is activated at an early stage of development and has been shown to interact with steroidogenic factor-1 in mammals, leading to the suppression of anti-Müllerian hormone (Amh) gene expression. Because steroidogenic factor-1 and Amh are important for proper testis development, NF-κB-mediated induction of anti-apoptotic genes could, therefore, also play a role in zebrafish gonad differentiation. The aim of this study was to examine the potential role of NF-κB in zebrafish gonad differentiation. Exposure of juvenile zebrafish to heat-killed Escherichia coli activated the NF-κB pathways and resulted in an increased ratio of females from 30 to 85%. Microarray and quantitative real-time-PCR analysis of gonads showed elevated expression of NF-κB-regulated genes. To confirm the involvement of NF-κB-induced anti-apoptotic effects, zebrafish were treated with sodium deoxycholate, a known inducer of NF-κB or NF-κB activation inhibitor (NAI). Sodium deoxycholate treatment mimicked the effect of heat-killed bacteria and resulted in an increased proportion of females from 25 to 45%, whereas the inhibition of NF-κB using NAI resulted in a decrease in females from 45 to 20%. This study provides proof for an essential role of NF-κB in gonadal differentiation of zebrafish and represents an important step toward the complete understanding of the complicated process of sex differentiation in this species and possibly other cyprinid teleosts as well.
- Published
- 2012
275. Survival Dynamics and Colonization of Exogenous Probiotic Bacteria Bacillus subtilis in Aquaculture Water and Intestine of Zebra Fish (Danio rerio)
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Jiehao Xu, Song Li, Lin He, Sunjian Lv, Haisheng Xu, Yuyin Chena, Jiehao Xu, Song Li, Lin He, Sunjian Lv, Haisheng Xu, and Yuyin Chena
- Abstract
Adaptability of probiotic bacteria is an important trait for the survival and colonization in water or fish intestine and the performance of their bio-control function. Bacillus is a widely used genus of probiotic bacteria in aquaculture. However, its survival dynamics and effect on water or fish intestine is still unclear. In this study, we assessed the survival dynamics of exogenous Bacillus subtilis Bst51 and its effect on the microbial community structure in water and fish intestine by using green fluorescent protein (GFP) labeling and bacteriological methods. Results showed that GFP labeling was an efficient method for detection of the survival of B. subtilis in the water column and fish intestine. Our results showed that when administered only once, the concentration of Bst51 in water declined to one-tenth of the original concentration and reached a stable state after 24 h. This confirmed that Bst51 strain was able to survive and colonize in aquaculture water with concentrations higher than 103 CFU (Colony Forming Units)/mL. The concentration of Bst51 cells in zebra fish intestine decreased slightly and remained constant at around 5×106 CFU/g after only one treatment. The results confirmed that if Bst51 cells have a concentration of over 109 CFU/mL they can survive and colonize in zebra fish intestine.
- Published
- 2016
276. Evolutionary plasticity of segmentation clock networks
- Author
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Olivier Tassy, Andrew C. Oates, Arcady Mushegian, Earl F. Glynn, Gaye Hattem, Daniela Roellig, Aurélie J. Krol, Mary-Lee Dequéant, and Olivier Pourquié
- Subjects
biological rhythm ,phenotypic plasticity ,Polymerase Chain Reaction ,Mice ,0302 clinical medicine ,Receptors ,zebra fish ,Segmentation ,Molecular clock ,Zebrafish ,Research Articles ,Oligonucleotide Array Sequence Analysis ,Genetics ,0303 health sciences ,Receptors, Notch ,biology ,Wnt signaling pathway ,molecular clock ,Vertebrate ,oscillation ,medicine.anatomical_structure ,priority journal ,signal transduction ,Mesoderm ,Notch ,Evolution ,chicken ,animal experiment ,Notch signaling pathway ,embryo ,Article ,animal tissue ,Evolution, Molecular ,03 medical and health sciences ,Biological Clocks ,Notch receptor ,biology.animal ,fibroblast growth factor ,mesoderm ,Paraxial mesoderm ,medicine ,Animals ,controlled study ,Molecular Biology ,mouse ,gene identification ,030304 developmental biology ,Vertebrata ,Danio rerio ,nonhuman ,fungi ,Molecular ,zebrafish ,biology.organism_classification ,Wnt protein ,Fibroblast Growth Factors ,Wnt Proteins ,Evolutionary biology ,in situ hybridization ,Chickens ,transcriptome ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The vertebral column is a conserved anatomical structure that defines the vertebrate phylum. The periodic or segmental pattern of the vertebral column is established early in development when the vertebral precursors, the somites, are rhythmically produced from presomitic mesoderm (PSM). This rhythmic activity is controlled by a segmentation clock that is associated with the periodic transcription of cyclic genes in the PSM. Comparison of the mouse, chicken and zebrafish PSM oscillatory transcriptomes revealed networks of 40 to 100 cyclic genes mostly involved in Notch, Wnt and FGF signaling pathways. However, despite this conserved signaling oscillation, the identity of individual cyclic genes mostly differed between the three species, indicating a surprising evolutionary plasticity of the segmentation networks. © 2011. Published by The Company of Biologists Ltd.
- Published
- 2011
277. Genotoxic damages in zebrafish submitted to a polymetallic gradient displayed by the Lot River (France)
- Author
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Jean-Paul Bourdineaud, Jacqueline Garnier-Laplace, Patrice Gonzalez, Sébastien Cambier, Nicolas Orieux, Christelle Adam, Bénédicte Morin, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), Laboratoire de Radioécologie et d'Ecotoxicologie (DEI/SECRE/LRE), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
- Subjects
DNA Repair ,polymerase chain reaction ,river ,[SDV]Life Sciences [q-bio] ,Health, Toxicology and Mutagenesis ,environmental exposure ,Gene Expression ,010501 environmental sciences ,medicine.disease_cause ,01 natural sciences ,sensitivity analysis ,pollutant source ,random amplified polymorphic DNA ,zebra fish ,Lot River ,Zebrafish ,water pollution ,0303 health sciences ,Cadmium ,quantitative analysis ,Ecology ,8 hydroxydeoxyguanosine ,article ,General Medicine ,Pollution ,cyprinid ,Random Amplified Polymorphic DNA Technique ,Zinc ,bioaccumulation ,8-Hydroxy-2'-Deoxyguanosine ,Bioaccumulation ,Environmental chemistry ,Pisces ,Comet Assay ,France ,Environmental Monitoring ,metal ,chemistry.chemical_element ,Biology ,ecotoxicology ,animal tissue ,03 medical and health sciences ,Rivers ,medicine ,Cyprinidae ,Animals ,Ecotoxicology ,controlled study ,14. Life underwater ,intermethod comparison ,030304 developmental biology ,0105 earth and related environmental sciences ,nonhuman ,Danio rerio ,concentration (parameters) ,genotoxicity ,pollution exposure ,Public Health, Environmental and Occupational Health ,Deoxyguanosine ,assay ,biology.organism_classification ,Comet assay ,chemistry ,13. Climate action ,Zinc toxicity ,pollution effect ,Water Pollutants, Chemical ,Genotoxicity ,DNA Damage ,Mutagens - Abstract
Genotoxic effects of a polymetallic pollution gradient displayed by the Lot River and one of its tributary have been assessed on zebrafish Danio rerio. Three methods were compared: RAPD-PCR, the comet assay, and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) formation. The fishes were exposed for 14 days to waters collected from three stations: Joanis, a site polluted by cadmium (Cd) and zinc (Zn) (mean concentrations: 15. γg Cd/L and 550. γg Zn/L), Bouillac (mean concentrations: 0.55. γg Cd/L and 80. γg Zn/L), and Boisse-Penchot, a reference station (mean concentrations
- Published
- 2011
278. Histological Changes Induced in Gonads, Liver and Kidney of Zebra Fish (Danio Rerio) Under the Effect Octylphenol (OP)
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Gabi Dumitrescu, Liliana Petculescu Ciochina, Sorin Voia, Dorel Dronca, and Liliana Boca
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histology ,lcsh:Agriculture ,kidney ,lcsh:T ,zebra fish ,octhylphenol ,lcsh:S ,gonads ,lcsh:Q ,liver ,lcsh:Science ,lcsh:Technology - Abstract
World-wide researches during the last years are focused upon the negative effects caused by the natural chemical compounds and anthropogenic compounds, already being demonstrated that a great part of them change the endocrine control over reproduction at different species. The issue studied by our team is concerned with the histological changes that appear within liver, kidney and gonadal development at the zebra fish (Danio rerio), exposed to octylphenol from 21-115 days, and within 21-75 days of life. In order to achieve the histological preparations, for each period under study, fishes were divided into three groups of 30 individuals, namely: Lot 1 - Control, respectively lots 2 and 3, at which the administrated octylphenol concentrations were of 60 μg L-1, respectively 100 μg L-1. Fishes of the six groups were raised in 30-liters aquariums (30 fish / aquarium). Fragments of liver, kidney and gonads were processed histologically, colored with the Mallory thrichromic staining method and examined with the optical microscope. Histopathological study revealed changes in the three organs, namely this fine granulation hepatocytes, peritubular edema and vascular ectasia in renal parenchyma and their differentiation in the gonads to sex predominantly female, issues that demonstrate the estrogenic effect of the octylphenol. Those microscopical aspects observed in the kidney and liver of the specimens exposed to action of octhylphenol, suggest that the octhlyphenol is bind to the estrogenic receptors on the membrane of hepatic cells, inducing vitellogenin synthesis.
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- 2010
279. Parental exposure to gamma radiation causes progressively altered transcriptomes linked to adverse effects in zebrafish offspring
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Hurem, Selma, Martín, Leonardo Martín, Lindeman, Leif, Brede, Dag Anders, Salbu, Brit, Lyche, Jan Ludvig, Aleström, Peter, Kamstra, Jorke H., One Health Toxicologie, and One Health Toxicologie
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Male ,0301 basic medicine ,ATM protein ,Health, Toxicology and Mutagenesis ,polymerase chain reaction ,prenatal exposure ,radiation exposure ,reactive oxygen metabolite ,Toxicology ,Radioecology ,Transcriptome ,transcriptomics ,Pregnancy ,Radiation, Ionizing ,genetic variability ,hatching ,zebra fish ,Zebrafish ,biology ,Reproduction ,article ,Embryo ,General Medicine ,Pollution ,Maternal Exposure ,Prenatal Exposure Delayed Effects ,Female ,signal transduction ,Ionizing radiation ,Offspring ,DNA damage ,cytochrome P450 ,animal experiment ,embryo death ,mRNA sequencing ,embryo ,RNA sequence ,gametogenesis ,Andrology ,Biological pathway ,03 medical and health sciences ,Animals ,transferrin ,controlled study ,gastrulation ,Gametogenesis ,nonhuman ,gamma radiation ,biology.organism_classification ,030104 developmental biology ,MRNA Sequencing ,Gamma Rays ,gene expression ,chromatin ,Biomarkers - Abstract
Ionizing radiation causes a variety of effects, including DNA damage associated to cancers. However, the effects in progeny from irradiated parents is not well documented. Using zebrafish as a model, we previously found that parental exposure to ionizing radiation is associated with effects in offspring, such as increased hatching rates, deformities, increased DNA damage and reactive oxygen species. Here, we assessed short (one month) and long term effects (one year) on gene expression in embryonic offspring (5.5 h post fertilization) from zebrafish exposed during gametogenesis to gamma radiation (8.7 or 53 mGy/h for 27 days, total dose 5.2 or 31 Gy) using mRNA sequencing. One month after exposure, a global change in gene expression was observed in offspring from the 53 mGy/h group, followed by embryonic death at late gastrula, whereas offspring from the 8.7 mGy/h group was unaffected. Interestingly, one year after exposure newly derived embryos from the 8.7 mGy/h group exhibited 2390 (67.7% downregulated) differentially expressed genes. Overlaps in differentially expressed genes and enriched biological pathways were evident between the 53 mGy/h group one month and 8.7 mGy/h one year after exposure, but were oppositely regulated. Pathways could be linked to effects in adults and offspring, such as DNA damage (via Atm signaling) and reproduction (via Gnrh signaling). Comparison with gene expression analysis in directly exposed embryos indicate transferrin a and cytochrome P450 2x6 as possible biomarkers for radiation response in zebrafish. Our results indicate latent effects following ionizing radiation exposure from the lower dose in parents that can be transmitted to offspring and warrants monitoring effects over subsequent generations. This work shows that the effects of ionizing radiation in offspring of exposed parents are mediated by altered transcriptomes and that in time these effects are progressively increased in offspring.
- Published
- 2018
280. Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis
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Simon Trowitzsch, Karla M. Neugebauer, Reinhard Lührmann, Magdalena Strzelecka, Gert Weber, and Andrew C. Oates
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RNA splicing ,Biology ,Lethal ,environment and public health ,Article ,macromolecule ,small nuclear RNA ,coiled body ,Small Nuclear ,Structural Biology ,zebra fish ,Animals ,Humans ,snRNP ,Histone locus body ,Molecular Biology ,Ribonucleoprotein ,SnRNP Biogenesis ,Genetics ,Danio rerio ,nonhuman ,urogenital system ,Nuclear Proteins ,coilin ,embryo development ,fish protein ,Ribonucleoproteins, Small Nuclear ,zebrafish ,Recombinant Proteins ,unclassified drug ,Cell biology ,cell proliferation ,Genes ,priority journal ,Ribonucleoproteins ,Cajal body ,Gene Knockdown Techniques ,Genes, Lethal ,Coilin ,Small nuclear RNA - Abstract
Spliceosomal small nuclear ribonucleoproteins (snRNPs), comprised of small nuclear RNAs (snRNAs) in complex with snRNP-specific proteins, are essential for pre-mRNA splicing. Coilin is not a snRNP protein but concentrates snRNPs and their assembly intermediates in Cajal bodies (CBs). Here we show that depletion of coilin in zebrafish embryos leads to CB dispersal, deficits in snRNP biogenesis and expression of spliced mRNA, as well as reduced cell proliferation followed by developmental arrest. Notably, injection of purified mature human snRNPs restored mRNA expression and viability. snRNAs were necessary but not sufficient for rescue, showing that only assembled snRNPs can bypass the requirement for coilin. Thus, coilin's essential function in embryos is to promote macromolecular assembly of snRNPs, likely by concentrating snRNP components in CBs to overcome rate-limiting assembly steps. © 2010 Nature America, Inc. All rights reserved.
- Published
- 2010
281. Zili Inhibits Transforming Growth Factor-β Signaling by Interacting with Smad4
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Huaqin Sun, Shu Chen, Dachang Tao, Wenqian Deng, Yongxin Ma, Yanyan Liu, Mei Zeng, Xiaolin Liao, Na Li, and Dan Li
- Subjects
TGF-β ,Male ,Cytokines/TGF-β ,Embryo, Nonmammalian ,Nodal Protein ,Blotting, Western ,Nodal signaling ,Piwi-interacting RNA ,Biochemistry ,Development Differentiation ,Germ cell proliferation ,Transforming Growth Factor beta ,Two-Hybrid System Techniques ,Animals ,Immunoprecipitation ,Gene Regulation ,Molecular Biology ,Zebrafish ,Smad/Transcription Factor ,In Situ Hybridization ,Body Patterning ,Smad4 Protein ,Piwil2 ,biology ,Zebra fish ,Mechanisms of Signal Transduction ,Gene Expression Regulation, Developmental ,RNA-Binding Proteins ,Zili ,Epistasis, Genetic ,Cell Biology ,Transforming growth factor beta ,Oligonucleotides, Antisense ,Zebrafish Proteins ,biology.organism_classification ,Smad Proteins, Receptor-Regulated ,Molecular biology ,Cell biology ,Bone Morphogenetic Proteins ,Mesoderm formation ,biology.protein ,Female ,Ectopic expression ,Smad4 ,NODAL ,Receptors, Transforming Growth Factor beta ,Protein Binding ,Signal Transduction - Abstract
Piwi proteins are required for germ cell proliferation, differentiation, and germ line stem cell maintenance. In normal tissues, human and mouse Piwil2 are primarily expressed in testis but widely expressed in tumors. However, the underlying mechanism remains largely unknown. In vertebrates, transforming growth factor (TGF)-beta signaling plays an important role in patterning embryo and control of cell growth and differentiation. A previous study has shown a role for Zili, a Piwil2 gene in zebrafish, in germ cells in zebrafish. Here we report that zili functions in patterning the early embryo and inhibits TGF-beta signaling. Whole mount expression analysis shows that zili expresses not only in PGCs but also in axis. Ectopic expression of zili causes fusion of the eyes and reduction of mesodermal marker genes expression, suggesting that zili functions to inhibit Nodal signaling and mesoderm formation. Genetic interaction shows that zili inhibits Nodal and bone morphogenetic protein signaling. The results of protein interaction assays identify that Zili binds to Smad4 via its N-terminal domain and prevents the formation of Smad2/3/4 and Smad1/5/9/4 complexes to antagonize TGF-beta signaling. This work shows that zili plays a role in early embryogenesis beyond germ line as a novel negative regulator of TGF-beta signaling, extending the function of Piwi proteins in vertebrates.
- Published
- 2010
282. Extracellular Nanovesicle Enhanced Gene Transfection Using Polyethyleneimine in HEK293T Cells and Zebrafish Embryos.
- Author
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Zhang Z, Wen K, Zhang C, Laroche F, Wang Z, Zhou Q, Liu Z, Abrahams JP, and Zhou X
- Abstract
It is a hot topic to improve efficiency and decrease toxicity of gene transfection reagents. The extracellular nanovesicles (EVs) that are released by cells play an important role in intercellular communication and are naturally designed for genetic exchange between cells. Here, we show that the EVs have a large beneficial effect in polyethyleneimine (PEI)-mediated transfection of a GFP-encoding plasmid into HEK293T cells. An improvement of transfection efficiency of ~500% and a decrease in toxicity were observed in a specific concentration range of PEI. The EVs also greatly improved the transfection of the same plasmid into zebrafish embryos. To verify the generality of this gene transfection approach, we also tested the cell viability and gene transfection efficiency using two other plasmids (EpTEN and ELuc) and in another cell line (A549). The measured increase in transfection efficiency makes EV a promising candidate for enhancement of the quality of current PEI-based transfection technique., (Copyright © 2020 Zhang, Wen, Zhang, Laroche, Wang, Zhou, Liu, Abrahams and Zhou.)
- Published
- 2020
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- View/download PDF
283. Some Plant Defense Stimulators can induce IL-1β production in human immune cells in vitro .
- Author
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Teyssier L, Sorci G, Chluba J, Aimé S, Wendehenne D, Lamotte O, and Connat JL
- Abstract
Among Plant Protection Products (PPP), a new emerging category of pesticides act by stimulating plant defense in order to improve plant resistance against microbial pathogens. Given that these compounds, the so-called Plant Defense Stimulators (PDS) act on innate immunity, we tested, using an in vitro approach on human mononuclear leucocytes (PBMC), the potential toxicity (XTT assay) and inflammatory effects (production of IL-1β) of 4 PPP belonging to different chemical families. We found that two products (LBG-01F34® and Regalis®) did not induce any cytotoxicity or IL-1 β production. The product BION-50 WG®, that contains Acibenzolar-S-methyl (ASM) and silica particles did not present any cytotoxicity but induced a significant increase in the production of the inflammatory cytokine IL-1 β. Finally, Vacciplant® that contains laminarin, was highly cytotoxic and pro-inflammatory. It induced a strong production of IL-1 β when used at a concentration in the culture medium, as low as 0.02 mg/mL. We also tested the potential toxic effect of these 4 PPP on 4 days old zebra fish larvae. After 24 h of exposure, our results indicate that Vacciplant® induced zebra fish larvae mortality at concentration of 20 μg/mL. LBG did not induced significant mortality at concentrations up to 1 mg/mL whereas Regalis was lethal for 0,3 mg/mL concentrations and BION-50 WG began to induce mortality at 2,5 mg/mL. Our results indicate possible effects of PDS on IL-1β production in human cells and fish survival, calling for more studies on the potential noxious side effects of these compounds., Competing Interests: There are no conflicts of interest to declare., (© 2020 The Authors. Published by Elsevier B.V.)
- Published
- 2020
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284. Lessons, insights and newly developed tools emerging from behavioral phenotyping core facilities.
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Bikovski L, Robinson L, Konradsson-Geuken A, Kullander K, Viereckel T, Winberg S, Roman E, and Tsoory M
- Abstract
Scientific investigations, in general, and research in neuroscience, in particular, are becoming ever more complex and require the integration of different techniques. Behavioral assays, which are among the most frequently used methodologies in neuroscience, nowadays rely on advanced, sophisticated technologies that require proficient application. Therefore, behavioral core facilities are becoming essential support units, as they provide the specialized expert research services needed to conduct advanced neuroscience. We here review the lessons learned and insights gathered from managing behavioral core facilities in different academic research institutes. This review addresses several issues, including: the advantages of behavioral core facilities, considerations for establishing a behavioral core facility, and the methodological advances made through calibration and standardization of assay protocols and the development of new assays. Collectively, the review highlights the benefits of both working within and collaborating with behavioral core facility units and emphasizes the potential progress in neuro-phenotyping that such facilities provide., (Copyright © 2020. Published by Elsevier B.V.)
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- 2020
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285. Zebra Fish in Toxicology Research: Streptavidin Conjugated Peroxidase Assay in the Development Phase of Zebrafish Embryos to Study Liver Toxicities.
- Author
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Bala A, Mondal C, and KantiHaldar P
- Subjects
- Animals, Bacterial Proteins metabolism, Dexamethasone toxicity, Embryo, Nonmammalian, Enzyme Assays methods, Horseradish Peroxidase metabolism, Liver pathology, Zebrafish, Chemical and Drug Induced Liver Injury etiology, Liver drug effects, Toxicity Tests, Acute methods
- Abstract
Background: Zebrafish have similar hepatic anatomy and cellular architecture just like mammals. Therefore, a number of investigators are using zebrafish to study liver pathologies. However, the evaluation model specific to liver toxicities in zebra fish was not clearly stated earlier., Aims and Objectives: The present study was designed to develop a model of embryonic liver toxicity using dexamethasone (DEXA, 0-20 μM) as a standard hepatotoxic agent., Methods: such toxicities are easily measured by streptavidin-conjugated peroxidase assay after 48- hour post-fertilization (hpf) of DEXA treatment., Results: In addition to morphological toxicities at different hpf, DEXA showed significant (*p< 0.05 &**p<0.01) reduction of peroxidase-chromogenic dye reaction in the assay as compared to DEXA untreated embryos at 10 & 20 μM concentration that concluded the hepatocellular toxicity of dexamethasone., Conclusion: Hopefully, the developed model for hepatotoxicity evaluation will be a promising model for the evaluation of new drugs or chemicals as an easy vertebrate model before the commencement of another animal model., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2020
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286. Interkingdom Genetic Mix-and-Match To Produce Novel Sunscreens.
- Author
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Osborn AR and Mahmud T
- Subjects
- Amino Acids chemistry, Animals, Anthozoa drug effects, Benzophenones adverse effects, Benzophenones pharmacology, Cinnamates adverse effects, Cinnamates pharmacology, Cyclohexanols chemistry, Plasmids genetics, Skin Cream chemistry, Ultraviolet Rays, Metabolic Engineering methods, Rhodococcus genetics, Streptomyces genetics, Streptomyces coelicolor metabolism, Sunscreening Agents chemical synthesis, Zebrafish genetics
- Abstract
Sunscreen-containing skincare products protect the skin from damage caused by sun exposure. However, many of them contain oxybenzone and/or octinoxate, which have been reported to be toxic to juvenile coral and to cause coral bleaching. Thus, there is a growing need for new sunscreen compounds that are less harmful to the environment. Here, we report an engineered biosynthetic pathway employing genes from a vertebrate and two Gram-(+) bacteria that forms novel sunscreen compounds with hybrid structures of gadusol and mycosporine-like amino acids, both of which are found in marine environments. These compounds, named gadusporines, have unique UV absorbance at 340 nm, expanding the range of mycosporine- and gadusol-based sunscreen products. The synthesis of gadusporines in Streptomyces coelicolor establishes a platform for the design and production of novel sunscreens.
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- 2019
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287. Spatio-temporal distribution of gap junctions in zebra fish embryo.
- Author
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Dasgupta, J. and Singh, Udai
- Abstract
The distribution of gap junctions in zebra fish embryo is a dynamic process. They appear during cleavage stages and are uniformly distributed between deep cells in early blastula. By mid-blastula stage their density increases all over the embryo. At this stage lightly stained L cells and densely stained D cells (Dasgupta and Singh 1981; Wilhelm Roux's Arch Dev Biol 190:358) develop some differences in their surface properties due to which the frequencies of gap junctions between homologous (L-L and D-D) cells are two- to threefold higher than between heterologous (L-D) cells. Before the initiation of epipoly the gap junction occurrence increases in the envelopinglayer (EVL) and then decreases. The possible functional significance of the organization of these junctions is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1982
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288. Early differentiation in zebra fish blastula: Role of yolk syncytial layer.
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Dasgupta, Jai and Singh, Udai
- Abstract
The blastomeres of the zebra fish embryo can be classified into two types-cells stained densely (D) or lightly (L) with a mixture of toluidine and methylene (T-M) blue. The dense staining of D cells is largely due to the high density of mitochondria, rough endoplasmic reticulum and polyribosomes. The presence of partially dense stained cells during early blastula stage shows that L cells are transformed into D cells. That the yolk syncytial layer (YSL) plays some role in this transformation is suggested by the proximity of these cells to the YSL and by their distinct spatial orientation with densely stained cytoplasmic regions always facing towards the interior of the embryo. [ABSTRACT FROM AUTHOR]
- Published
- 1981
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289. STUDY REGARDING THE LIGHT INFLUENCES ON EMBRYO DEVELOPMENT IN ZEBRA FISH (Danio rerio)
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MIHAELA BĂDILIŢĂ, A. GROZEA, and I. BĂNĂŢEAN-DUNEA
- Subjects
lcsh:Agriculture ,lcsh:T ,zebra fish ,lcsh:S ,embryo development ,lcsh:Q ,light ,lcsh:Science ,lcsh:Technology - Abstract
The aim of this paper is to emphasize the main aspects of the ways in which lightinfluences the development of zebra fish (Danio rerio) embryos.During the experiments 3 variants with natural light, continuous light and totally darkwere used to monitor the development of zebra fish embryos in 40 ml Nunk culturedishes at optimum density (1 embryo/ 3 ml) and at 28,5oC temperature.It could be noticed that most embryos died in continuous light medium (57%). Thismeans that such mediums are not suitable to embryos’ development. For the controlvariant (natural light) it was recorded the lowest mortality rate of only 17% and intotally dark variant the mortality was of 40%.Researches on the influence of light on zebra fish embryo development showed that themost suited medium for supporting, growing and developing the Danio rerio embryosit the medium having natural light.
- Published
- 2007
290. STUDY ON EMBRYO DEVELOPMENT IN ZEBRA FISH (Danio rerio) DEPENDING ON DIFFERENT pH LEVELS
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MIHAELA BĂDILIŢĂ, A. GROZEA, and I. BĂNĂŢEAN-DUNEA
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lcsh:Agriculture ,ph ,lcsh:T ,zebra fish ,lcsh:S ,embryo development ,lcsh:Q ,lcsh:Science ,lcsh:Technology - Abstract
The aim of this paper is to emphasize the main aspects of the ways in whichdifferent pH levels influence the development of zebra fish (Danio rerio) embryos.During the experiments there have been used 6 variants with different pH levels inorder to monitor the development of zebra fish embryos in 40 ml Nunk culturedishes at optimum density (1 embryo/ 3 ml) and at an optimal temperature of28.5oC.It could be noticed that most embryos died in a pH=6 medium (70%). This meansthat such a medium is not suitable to embryo’s development. For the controlvariant (pH=7) it has been recorded the lowest mortality rate of only 23% and inthe case of other variants the mortality was of 30-40%.The studies of the pH influence upon the zebra fish embryo development haveunderlined the fact that little digressions from the optimal conditions can led toirreversible modifications within the roe which sometimes are even lethal.
- Published
- 2007
291. Overexpression a novel zebra fish spermatogenesis-associated gene 17 (SPATA17) induces apoptosis in GC-1 cells
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Nie, Dongsong, Liu, Y., and Xiang, Y.
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- 2011
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292. Functionally conserved effects of rapamycin exposure on zebrafish
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Ceren Sucularli, Dilay Ciglidag Dungul, Huma Shehwana, Hilal Özdağ, Ozlen Konu, and Cem Kuscu
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0301 basic medicine ,Cell viability ,Cancer Research ,Mouse ,Unclassified drug ,Drug exposure ,Dickkopf 1b protein ,Cytochrome P450 ,Apoptosis ,Microarray ,Steady state ,Biochemistry ,Zebrafish protein ,Transcriptome ,Cytochrome P450 26B1 ,Mice ,0302 clinical medicine ,Species difference ,Zebrafish ,Cell proliferation ,Aromatic levo amino acid decarboxylase ,Gene expression regulation ,Regulation of gene expression ,Embryo growth ,Pigmentation ,Messenger RNA ,TOR Serine-Threonine Kinases ,Target of rapamycin kinase ,Body size ,Cell cycle ,Transcription factor FOXM1 ,Cell biology ,Fibroblast culture ,Oncology ,Embryo ,030220 oncology & carcinogenesis ,mTOR ,Molecular Medicine ,Genetic conservation ,Animal cell ,WNT inhibitory factor 1 ,Dickkopf 1 protein ,Down regulation ,Biology ,Article ,Cell Line ,Ribosome subunit ,03 medical and health sciences ,Species Specificity ,Upregulation ,Genetics ,Animals ,Oxidative phosphorylation ,Rapamycin ,Animal experiment ,Mitochondrion ,Molecular Biology ,Mechanistic target of rapamycin ,PI3K/AKT/mTOR pathway ,Sirolimus ,Cell metabolism ,Drug effects ,Real-time qPCR ,Proteasome ,DNA synthesis ,Zebra fish ,Animal ,Microarray analysis techniques ,Protein ,Microarray analysis ,Zebrafish Proteins ,Nonhuman ,biology.organism_classification ,Molecular biology ,Drug effect ,Meta-analysis ,Metabolism ,030104 developmental biology ,Gene Expression Regulation ,biology.protein ,ZF4 ,Gene expression ,Comparative study ,Transcription factor ,Protein synthesis ,Controlled study ,Endoplasmic reticulum ,Phenylalanine 4 monooxygenase ,Animal cell culture - Abstract
Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase important in cell proliferation, growth and protein translation. Rapamycin, a well-known anti-cancer agent and immunosuppressant drug, inhibits mTOR activity in different taxa including zebrafish. In the present study, the effect of rapamycin exposure on the transcriptome of a zebrafish fibroblast cell line, ZF4, was investigated. Microarray analysis demonstrated that rapamycin treatment modulated a large set of genes with varying functions including protein synthesis, assembly of mitochondrial and proteasomal machinery, cell cycle, metabolism and oxidative phosphorylation in ZF4 cells. A mild however, coordinated reduction in the expression of proteasomal and mitochondrial ribosomal subunits was detected, while the expression of numerous ribosomal subunits increased. Meta-analysis of heterogeneous mouse rapamycin microarray datasets enabled the comparison of zebrafish and mouse pathways modulated by rapamycin, using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway analysis. The analyses demonstrated a high degree of functional conservation between zebrafish and mice in response to rapamycin. In addition, rapamycin treatment resulted in a marked dose-dependent reduction in body size and pigmentation in zebrafish embryos. The present study is the first, to the best of our knowledge, to evaluate the conservation of rapamycin-modulated functional pathways between zebrafish and mice, in addition to the dose-dependent growth curves of zebrafish embryos upon rapamycin exposure.
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- 2015
293. Pkd2 affects the architecture of zebrafish left-right organizer
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R Jacinto, M Roxo-Rosa, Susana S. Lopes, Pedro Sampaio, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Centro de Estudos de Doenças Crónicas (CEDOC)
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fluid flow ,Morphogenesis ,morphogenesis ,Biology ,urologic and male genital diseases ,Article ,Extracellular matrix ,zebra fish ,controlled study ,education ,Zebrafish ,Ion channel ,Genetics ,education.field_of_study ,nonhuman ,polycystin 2 ,urogenital system ,Cell Biology ,protein function ,biology.organism_classification ,female genital diseases and pregnancy complications ,Cell biology ,Polycystin 2 ,priority journal ,dorsal anterior clustering ,Poster Presentation ,Motile cilium ,cell component ,NODAL ,Developmental biology ,cell structure - Abstract
Background Dorsal anterior clustering (DAC) of motile cilia in the left-right organizer (LRO) is crucial for normal fluid flow dynamics and correct laterality in zebrafish [1]. We directly demonstrated that charon/dand5 transcription is negatively regulated by strong flow in zebrafish LRO [1] which suggests that LRO cells have the ability to sense fluid flow and influence gene expression patterns, but how? Pkd2 ion channel is a good candidate because it participates in a mechanosensory complex that senses fluid flow and induces a calcium inward flux in kidney cells [2] and in nodal cells [3]. In agreement, mouse and zebrafish mutants for Pkd2 have LR defects [4,5]. However, Pkd2 is also involved in cell polarity during migration [6] and in extracellular matrix deposition [7] implying a role for Pkd2 in cell morphogenesis.
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- 2015
294. Arl13b interferes with α-tubulin acetylation
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Petra Pintado, Cecília Seixas, Susana S. Lopes, Duarte C. Barral, Centro de Estudos de Doenças Crónicas (CEDOC), and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
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Kupffer cell ,animal cell ,Article ,Arl13b protein ,Downregulation and upregulation ,acyltransferase ,zebra fish ,medicine ,Mec 17 protein ,controlled study ,Receptor ,protein expression ,Zebrafish ,nonhuman ,biology ,Cilium ,Vesicle ,protein acetylation ,Cell Biology ,protein function ,biology.organism_classification ,unclassified drug ,Cell biology ,alpha tubulin ,Tubulin ,medicine.anatomical_structure ,guanine nucleotide binding protein ,priority journal ,Acetylation ,protein protein interaction ,cilia length ,Poster Presentation ,biology.protein ,cellular parameters ,upregulation - Abstract
Methods We used the zebrafish Kupffer’s vesicle as a dynamic ciliary growth system and performed a seven hour timecourse experiment comparing the length of cilia measured by Arl13b-GFP or by acetylated a-tubulin. In order to evaluate the specificity of the alterations in a-tubulin acetylation pattern, we overexpressed different ciliary proteins that were also reported to increase cilia length.
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- 2015
295. The Influence of Infective Dose on the Virulence of a Generalist Pathogen in Rainbow Trout (Oncorhynchus mykiss) and Zebra Fish (Danio rerio)
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biology ,zebra fish ,ta1181 ,rainbow trout ,pathogen - Published
- 2015
296. Zebrafish as a model for developmental toxicity assessment
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Teixidó Condomines, Elisabet, Piqué Benages, Maria Esther, Boix Sabrià, Núria, Llobet Mallafré, Joan M. (Joan Maria), Gómez Catalán, Jesús, and Universitat de Barcelona
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animal structures ,Peix zebra ,Zebra fish ,embryonic structures ,Toxicologia ,Toxicology - Abstract
Podeu consultar el llibre complet a: http://hdl.handle.net/2445/67430, The zebrafish embryo has emerged as promising alternative model for traditional in vivo developmental toxicological screening due to their advantageous characteristics as their small size and transparency. In this paper, we reviewed the applicability of the zebrafish embryo model in some relevant areas to human t oxicology as developmental toxicity, cardiovascular toxicity and neurotoxicity (behavioral assessment). Despite the promising results, further optimization and testing of more substances as well as a harmonized methodology is needed to streamline the metho ds and make the assay conducive to medium - throughput.
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- 2015
297. Are zebrafish larvae suitable for assessing the hepatotoxicity potential of drug candidates?
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Mesens, N., Crawfordb, A.D., Menke, A., Hung, P.D., Goethem, F. van, Nuyts, R., Hansen, E., Wolterbeek, A., Gompel, J. van, Witte, P. de, and Esguerra, C.V.
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Male ,Steatosis ,Unclassified drug ,RAPID - Risk Analysis for Products in Development ,Amiodarone ,Cell vacuole ,Animal tissue ,Liver cell ,Life ,Drug safety ,Cholestasis ,Glycogen analysis ,Screening assay ,Buspirone ,Fatty acid binding protein 10a ,Paracetamol ,Tacrine ,Liver size ,DILI ,Female ,In situ hybridization ,Healthy Living ,Glycogen ,Liver level ,Adult ,animal structures ,Diclofenac ,Histology ,Liver toxicity ,Heart rate ,Histopathology ,Concentration response ,Rosiglitazone ,Troglitazone ,Lfabp10a ,Fatty acid binding protein ,Nefazodone ,Food and Nutrition ,Zebrafish larvae ,Nutrition ,Danio rerio ,Mitochondrial toxicity ,Larval stage ,Zebra fish ,fungi ,Hepatotoxicity ,Molecular cloning ,Bosentan ,Tetracycline ,Nonhuman ,Zolpidem ,Alpidem ,Tamoxifen ,Circulation ,Toxicity testing ,Protein expression ,ELSS - Earth, Life and Social Sciences ,Ketorolac ,Reactive oxygen metabolite ,Controlled study ,Mitochondrial membrane - Abstract
Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other organ toxicities and the immature larval stage of the zebrafish might complicate accurate and fast analysis. We investigated whether expression analysis of liver-specific fatty acid binding protein 10a (lfabp10a) was an appropriate endpoint for assessing hepatotoxic effects in zebrafish larvae. It was found that expression analysis of lfabp10a was a valid marker, as after treatment with hepatotoxicants, dose-response curves could be obtained and statistically significant abnormal lfabp10 expression levels correlated with hepatocellular histopathological changes in the liver. However, toxicity in other vital organs such as the heart could impact liver outgrowth and thus had to be assessed concurrently. Whether zebrafish larvae were suitable for assessing human relevant drug-induced hepatotoxicity was assessed with hepatotoxicants and non-hepatotoxicants that have been marketed for human use and classified according to their mechanism of toxicity. The zebrafish larva showed promising predictivity towards a number of mechanisms and was capable of distinguishing between hepatotoxic and non-hepatotoxic chemical analogues, thus implying its applicability as a potential screening model for DILI. © 2015 John Wiley & Sons, Ltd.
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- 2015
298. Are zebrafish larvae suitable for assessing the hepatotoxicity potential of drug candidates?
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Male ,Steatosis ,Unclassified drug ,RAPID - Risk Analysis for Products in Development ,Amiodarone ,Cell vacuole ,Animal tissue ,Liver cell ,Life ,Drug safety ,Cholestasis ,Glycogen analysis ,Screening assay ,Buspirone ,Fatty acid binding protein 10a ,Paracetamol ,Tacrine ,Liver size ,DILI ,Female ,In situ hybridization ,Healthy Living ,Glycogen ,Liver level ,Adult ,animal structures ,Diclofenac ,Histology ,Liver toxicity ,Heart rate ,Histopathology ,Concentration response ,Rosiglitazone ,Troglitazone ,Lfabp10a ,Fatty acid binding protein ,Nefazodone ,Food and Nutrition ,Life and Social Sciences ,Zebrafish larvae ,Nutrition ,Danio rerio ,Mitochondrial toxicity ,Larval stage ,Zebra fish ,fungi ,Hepatotoxicity ,Molecular cloning ,Bosentan ,Tetracycline ,ELSS - Earth ,Nonhuman ,Zolpidem ,Alpidem ,Tamoxifen ,Circulation ,Toxicity testing ,Protein expression ,Ketorolac ,Reactive oxygen metabolite ,Controlled study ,Mitochondrial membrane - Abstract
Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other organ toxicities and the immature larval stage of the zebrafish might complicate accurate and fast analysis. We investigated whether expression analysis of liver-specific fatty acid binding protein 10a (lfabp10a) was an appropriate endpoint for assessing hepatotoxic effects in zebrafish larvae. It was found that expression analysis of lfabp10a was a valid marker, as after treatment with hepatotoxicants, dose-response curves could be obtained and statistically significant abnormal lfabp10 expression levels correlated with hepatocellular histopathological changes in the liver. However, toxicity in other vital organs such as the heart could impact liver outgrowth and thus had to be assessed concurrently. Whether zebrafish larvae were suitable for assessing human relevant drug-induced hepatotoxicity was assessed with hepatotoxicants and non-hepatotoxicants that have been marketed for human use and classified according to their mechanism of toxicity. The zebrafish larva showed promising predictivity towards a number of mechanisms and was capable of distinguishing between hepatotoxic and non-hepatotoxic chemical analogues, thus implying its applicability as a potential screening model for DILI. © 2015 John Wiley & Sons, Ltd.
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- 2015
299. Mutations in RAD21 Disrupt Regulation of APOB in Patients With Chronic Intestinal Pseudo-Obstruction
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Dustin Dowless, Mauro D'Amato, Ludmila Francescatto, Greger Lindberg, Lina Cordeddu, Kivanc Cefle, Tommaso Pippucci, Giovanni Romeo, Zeynel Mungan, Sukru Ozturk, Vincenzo Stanghellini, Claudio Graziano, Roberto De Giorgio, Sukru Palanduz, Asuman Gedikbasi, Michael J. Bamshad, Nicholas Katsanis, Giovanni Barbara, Francesca Bianco, Umberto Volta, Rosanna Cogliandro, Elena Bonora, Tayfun Ozcelik, Giacomo Caio, Alessandra Gori, Marco Seri, Bonora, E, Bianco, F, Cordeddu, L, Bamshad, M, Francescatto, L, Dowless, D, Stanghellini, V, Cogliandro, Rf, Lindberg, G, Mungan, Z, Cefle, K, Ozcelik, T, Palanduz, S, Ozturk, S, Gedikbasi, A, Gori, A, Pippucci, T, Graziano, C, Volta, U, Caio, G, Barbara, G, D'Amato, M, Seri, M, Katsanis, N, Romeo, G, and De Giorgio, R.
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Male ,Apolipoprotein B ,Morpholino ,Genomic DNA ,Cell Cycle Proteins ,Gene mutation ,Enteric Nervous System ,Chromosome 11 ,Intestinal Motility ,Gene expression ,Haplotype ,Child ,Nuclear Protein ,Mutation ,Messenger RNA ,Gastroenterology ,Complementary DNA ,Immunohistochemistry ,Reverse transcription polymerase chain reaction ,Zebrafish Protein ,Human ,Genotype ,Sporadic and Familial Chronic Intestinal Pseudoobstruction ,Article ,RAD21 protein ,Humans ,RNA, Messenger ,Segregation analysis ,Aged ,Zebra fish ,Animal ,Intestinal Pseudo-Obstruction ,Gene frequency ,Sporadic and Familial Chronic Intestinal Pseudo-obstruction ,Human cell ,Case-Control Studies ,Gene Knockdown Technique ,Epistasis ,Protein expression ,Animal Model ,Gastrointestinal Motility ,Unclassified drug ,Sporadic and Familial Chronic Intestinal Pseudoobstruction, Intestinal Motility, Animal Model, Genetic Analysis ,Transcription factor RUNX1 ,medicine.disease_cause ,Homozygosity ,Western blotting ,HEK293 Cell ,Cell Cycle Protein ,Exome ,Intestine pseudoobstruction ,Regulatory mechanism ,Middle aged ,Zebrafish ,Genetic transfection ,Priority journal ,Allele ,Lamina propria ,biology ,Promoter region ,Nuclear Proteins ,Genetic Analysis ,Middle Aged ,Nerve cell ,DNA-Binding Proteins ,Phenotype ,Real-time polymerase chain reaction ,Embryo ,Gene Knockdown Techniques ,HEK293 cell line ,Phosphoprotein ,Apolipoprotein B-100 ,Core Binding Factor Alpha 2 Subunit ,Female ,Case-Control Studie ,Adult ,Down regulation ,NO ,Young Adult ,Lymphoblastoid cell ,Next generation sequencing ,medicine ,Animals ,Immunoprecipitation ,Chromosome 8 ,Hepatology ,Protein ,Gene Expression Profiling ,In vitro study ,Sequence Analysis, DNA ,Zebrafish Proteins ,Phosphoproteins ,Nonhuman ,biology.organism_classification ,Molecular biology ,Single nucleotide polymorphism ,HEK293 Cells ,Binding affinity ,Young adult ,Preschool child ,Chronic Disease ,Cancer research ,biology.protein ,Genetic Analysi ,Genetic variability ,Controlled study - Abstract
BACKGROUND & AIMS: Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. METHODS: We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. RESULTS: We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. CONCLUSIONS: Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons. Background Aims Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. Methods We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. Results We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. Conclusions Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons.
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- 2015
300. TAF1 Variants are associated with dysmorphic features, intellectual disability, and neurological manifestations
- Author
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Maria Kousi, Kay Metcalfe, Laura T. Jiménez-Barrón, Christopher Smith, Jane L. Schuette, Jean Baptiste Rivière, Sara Ellingwood, Erica E. Davis, Sander Stegmann, Alfonso Caro-Llopis, Maria Tzetis, David Mittelman, Sophia Kitsiou-Tzeli, Edith H. Wang, Vera M. Kalscheuer, A. Micheil Innes, Konstantina Kosma, Jillian S. Parboosingh, P.Y. Billie Au, Kristin G. Monaghan, Carlos E. Prada, Rosemarie Smith, Laurence Faivre, Sandra Monfort, Alan F. Rope, Jonathan Crain, Mónica Roselló, Yiyang Wu, Reid J. Robison, Jeffrey Swensen, Francisco Martínez, Max Dorfel, Carmen Orellana, Robert B. Hufnagel, Gareth Highnam, Kai Wang, Sungjin Moon, Tjitske Kleefstra, Edward Yang, Nicholas Katsanis, Sandra Ospina, Nicolette S. den Hollander, Catherine E. Keegan, Gholson J. Lyon, Jason O'Rawe, Silvestre Oltra, Han Fang, and Agathe Roubertie
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Proband ,Male ,Gene Mutation ,Neurologic Features ,Developmental Disabilities ,Intellectual Impairment ,Inheritance Patterns ,Intergluteal Crease ,Tata-Binding Protein Associated Factors ,E-Box Elements ,Gene Duplication ,Recessive Inheritance ,Pathology ,Genetics(clinical) ,Child ,Gene knockdown ,Clinical Article ,Genetic Screening ,Neurodegeneration ,Pedigree ,developmental delay ,Dystonia ,Child, Preschool ,Priority Journal ,dystonia ,Transcription Factor Iid ,Human ,Disease Model ,Article ,Rna Sequence ,Unclassified Drug ,Histone Acetyltransferase ,Intellectual Disability ,Genetics ,Humans ,Family ,Degenerative Disease ,TATA-Binding Protein Associated Factors ,Face Dysmorphia ,Phenotypic Variation ,School Child ,Animal ,Infant ,Transcription Factor Tfiid ,facial dysmorphology ,medicine.disease ,Tata-Binding Protein Associated Factor 25 Kda ,Nerve Degeneration ,Mutation ,intergluteal crease ,Single Nucleotide Polymorphism ,Transcription Factor TFIID ,Developmental Disorder ,Transcription Factor ,Facial Dysmorphology ,Zebra Fish ,Clinical Evaluation ,Family Assessment ,Abnormal Gait ,Intellectual disability ,neurologic features ,Down Regulation ,Global developmental delay ,Preschool Child ,Zebrafish ,Tata Binding Protein Associated Factor ,Genetics (clinical) ,Histone Acetyltransferases ,Inheritance ,Neurodegenerative Diseases ,Neurologic Disease ,Phenotype ,intellectual disability ,Muscle Hypotonia ,transcription ,Transcription ,Genetic Association ,Signal Transduction ,Adolescent ,E Box Element ,Biology ,Enfermedades genéticas en los niños ,Young Adult ,Report ,medicine ,Genetic Disorder ,TAF1 ,Taf1 ,Animals ,Gene ,Developmental Delay ,abnormal gait ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Protein ,Facies ,Ginecología & otras especialidades médicas ,Clinical Feature ,biology.organism_classification ,Disease Models, Animal ,Metabolism ,E Box Protein ,Gene Expression Regulation ,Clinical Assessment ,Anormalidades de los cromosomas sexuales en niños - Abstract
Contains fulltext : 152777.pdf (Publisher’s version ) (Open Access) We describe an X-linked genetic syndrome associated with mutations in TAF1 and manifesting with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male individuals. Simultaneous studies using diverse strategies led to the identification of nine families with overlapping clinical presentations and affected by de novo or maternally inherited single-nucleotide changes. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring single-nucleotide changes, but they also demonstrated a severe neurodegeneration phenotype. Functional analysis with RNA-seq for one of the families suggested that the phenotype is associated with downregulation of a set of genes notably enriched with genes regulated by E-box proteins. In addition, knockdown and mutant studies of this gene in zebrafish have shown a quantifiable, albeit small, effect on a neuronal phenotype. Our results suggest that mutations in TAF1 play a critical role in the development of this X-linked ID syndrome.
- Published
- 2015
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