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Zebrafish drug screen

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https://www.readbyqxmd.com/read/27927697/absence-of-11-keto-reduction-of-cortisone-and-11-ketotestosterone-in-the-model-organism-zebrafish
#1
Maria Tsachaki, Arne Meyer, Benjamin Weger, Denise V Kratschmar, Janina Tokarz, Jerzy Adamski, Heinz-Georg Belting, Markus Affolter, Thomas Dickmeis, Alex Odermatt
Zebrafish are widely used as model organism. Their suitability for endocrine studies, drug screening and toxicity assessements depends on the extent of conservation of specific genes and biochemical pathways between zebrafish and human. Glucocorticoids consist of inactive 11-keto (cortisone, 11-dehydrocorticosterone) and active 11β-hydroxyl forms (cortisol, corticosterone). In mammals, two 11β-hydroxysteroid dehydrogenases (11β-HSD1, 11β-HSD2) interconvert active and inactive glucocorticoids, allowing tissue-specific regulation of glucocorticoid action...
December 7, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27919782/understanding-zebrafish-cognition
#2
REVIEW
Darya A Meshalkina, Marina N Kizlyk, Elana V Kysil, Adam D Collier, David J Echevarria, Murilo S Abreu, Leonardo J G Barcellos, Cai Song, Allan V Kalueff
Zebrafish (Danio rerio) are rapidly becoming a popular model organism in translational and cognitive neuroscience research. Both larval and adult zebrafish continue to increase our understanding of cognitive mechanisms and their genetic and pharmacological modulation. Here, we discuss the developing utility of zebrafish in understanding cognitive phenotypes and their deficits, relevant to a wide range human brain disorders. We also discuss the potential of zebrafish models for high-throughput genetic mutant and small molecule screening (e...
December 2, 2016: Behavioural Processes
https://www.readbyqxmd.com/read/27916716/effects-of-a-non-competitive-n-methyl-d-aspartate-nmda-antagonist-tiletamine-in-adult-zebrafish
#3
Tatiana O Kolesnikova, Sergey L Khatsko, Vadim A Shevyrin, Yuri Yu Morzherin, Allan V Kalueff
Tiletamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. However, the neurotropic profile of tiletamine remains poorly understood, necessitating novel models and in-vivo screens, including non-mammalian species...
December 1, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27896850/zebrafish-larva-as-a-reliable-model-for-in-vivo-assessment-of-membrane-remodeling-involvement-in-the-hepatotoxicity-of-chemical-agents
#4
Normand Podechard, Martine Chevanne, Morgane Fernier, Arnaud Tête, Aurore Collin, Doris Cassio, Olivier Kah, Dominique Lagadic-Gossmann, Odile Sergent
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury...
November 28, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27896487/natural-compounds-as-occult-ototoxins-ginkgo-biloba-flavonoids-moderately-damage-lateral-line-hair-cells
#5
Sarah Neveux, Nicole K Smith, Anna Roche, Bruce E Blough, Wimal Pathmasiri, Allison B Coffin
Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine...
November 28, 2016: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/27895047/innovative-approaches-to-establish-and-characterize-primary-cultures-an-ex-vivo-3d-system-and-the-zebrafish-model
#6
Chiara Liverani, Federico La Manna, Arwin Groenewoud, Laura Mercatali, Gabri Van Der Pluijm, Federica Pieri, Davide Cavaliere, Alessandro De Vita, Chiara Spadazzi, Giacomo Miserocchi, Alberto Bongiovanni, Federica Recine, Nada Riva, Dino Amadori, Ennio Tasciotti, Ewa Snaar-Jagalska, Toni Ibrahim
Patient-derived specimens are an invaluable resource to investigate tumor biology. However, in vivo studies on primary cultures are often limited by the small amount of material available, while conventional in vitro systems might alter the features and behavior that characterize cancer cells. We present our data obtained on primary dedifferentiated liposarcoma cells cultured in a 3D scaffold-based system and injected into a zebrafish model. Primary cells were characterized in vitro for their morphological features, sensitivity to drugs and biomarker expression, and in vivo for their engraftment and invasiveness abilities...
November 28, 2016: Biology Open
https://www.readbyqxmd.com/read/27888069/vertebrate-embryos-as-tools-for-anti-angiogenic-drug-screening-and-function
#7
Shaunna L Beedie, Alexandra J Diamond, Lucas Rosa Fraga, William D Figg, Neil Vargesson
The development of new angiogenic inhibitors highlights a need for robust screening assays that adequately capture the complexity of vessel formation, and allow for the quantitative evaluation of the teratogenicity of new anti-angiogenic agents. This review discusses the use of screening assays in vertebrate embryos, specifically focusing upon chicken and zebrafish embryos, for the detection of anti-angiogenic agents.
November 22, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27885812/a-whole-animal-chemical-screen-approach-to-identify-modifiers-of-intestinal-neutrophilic-inflammation
#8
Stefan H Oehlers, Maria Vega Flores, Christopher J Hall, Liuyang Wang, Dennis C Ko, Kathryn E Crosier, Philip S Crosier
By performing two high-content small molecule screens on DSS- and TNBS-induced zebrafish enterocolitis models of inflammatory bowel disease, we have identified novel anti-inflammatory drugs from the John Hopkins Clinical Compound Library that suppress neutrophilic inflammation. Live imaging of neutrophil distribution was used to assess the level of acute inflammation and concurrently screen for off-target drug effects. Supporting the validity of our screening strategy, most of the anti-inflammatory drug hits were known antibiotics or anti-inflammatory agents...
November 25, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27857842/zebrafish-models-of-prader-willi-syndrome-fast-track-to-pharmacotherapeutics
#9
Emma D Spikol, Caroline E Laverriere, Maya Robnett, Gabriela Carter, Erin Wolfe, Eric Glasgow
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed...
March 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/27831568/arqiv-hts-a-versatile-whole-organism-screening-platform-enabling-in-vivo-drug-discovery-at-high-throughput-rates
#10
David T White, Arife Unal Eroglu, Guohua Wang, Liyun Zhang, Sumitra Sengupta, Ding Ding, Surendra K Rajpurohit, Steven L Walker, Hongkai Ji, Jiang Qian, Jeff S Mumm
The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed 'ARQiv-HTS'. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification...
December 2016: Nature Protocols
https://www.readbyqxmd.com/read/27831560/manipulating-the-air-filled-zebrafish-swim-bladder-as-a-neutrophilic-inflammation-model-for-acute-lung-injury
#11
Yuefei Zhang, Hongcui Liu, Junlin Yao, Yanfeng Huang, Shenlu Qin, Zheng Sun, Yingchun Xu, Shu Wan, Hongqiang Cheng, Chunqi Li, Xue Zhang, Yuehai Ke
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are life-threatening diseases that are associated with high mortality rates due to treatment limitations. Neutrophils play key roles in the pathogenesis of ALI/ARDS by promoting the inflammation and injury of the alveolar microenvironment. To date, in vivo functional approaches have been limited by the inaccessibility to the alveolar sacs, which are located at the anatomical terminal of the respiratory duct in mammals...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27821862/manipulation-of-zebrafish-s-orientation-using-artificial-cilia-in-a-microchannel-with-actively-adaptive-wall-design
#12
Karthick Mani, Tsung-Chun Chang Chien, Bivas Panigrahi, Chia-Yuan Chen
The zebrafish is a powerful genetic model organism especially in the biomedical chapter for new drug discovery and development. The genetic toolbox which this vertebrate possesses opens a new window to investigate the etiology of human diseases with a high degree genetic similarity. Still, the requirements of laborious and time-consuming of contemporary zebrafish processing assays limit the procedure in carrying out such genetic screen at high throughput. Here, a zebrafish control scheme was initiated which includes the design and validation of a microfluidic platform to significantly increase the throughput and performance of zebrafish larvae manipulation using the concept of artificial cilia actuation...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27818143/an-autophagic-flux-probe-that-releases-an-internal-control
#13
Takeshi Kaizuka, Hideaki Morishita, Yutaro Hama, Satoshi Tsukamoto, Takahide Matsui, Yuichiro Toyota, Akihiko Kodama, Tomoaki Ishihara, Tohru Mizushima, Noboru Mizushima
Macroautophagy is an intracellular degradation system that utilizes the autophagosome to deliver cytoplasmic components to the lysosome. Measuring autophagic activity is critically important but remains complicated and challenging. Here, we have developed GFP-LC3-RFP-LC3ΔG, a fluorescent probe to evaluate autophagic flux. This probe is cleaved by endogenous ATG4 proteases into equimolar amounts of GFP-LC3 and RFP-LC3ΔG. GFP-LC3 is degraded by autophagy, while RFP-LC3ΔG remains in the cytosol, serving as an internal control...
November 17, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27812327/social-preference-deficits-in-juvenile-zebrafish-induced-by-early-chronic-exposure-to-sodium-valproate
#14
Xiuyun Liu, Yinglan Zhang, Jia Lin, Qiaoxi Xia, Ning Guo, Qiang Li
Prenatal exposure to sodium valproate (VPA), a widely used anti-epileptic drug, is related to a series of dysfunctions, such as deficits in language and communication. Clinical and animal studies have indicated that the effects of VPA are related to the concentration and to the exposure window, while the neurobehavioral effects of VPA have received limited research attention. In the current study, to analyze the neurobehavioral effects of VPA, zebrafish at 24 h post-fertilization (hpf) were treated with early chronic exposure to 20 μM VPA for 7 h per day for 6 days or with early acute exposure to 100 μM VPA for 7 h...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27811851/establishment-of-a-congenital-amegakaryocytic-thrombocytopenia-model-and-a-thrombocyte-specific-reporter-line-in-zebrafish
#15
Q Lin, Y Zhang, R Zhou, Y Zheng, L Zhao, M Huang, X Zhang, A Y H Leung, W Zhang, Y Zhang
Mutations in the human myeloproliferative leukemia protein gene (MPL) are known to cause congenital amegakaryocytic thrombocytopenia (CAMT). The prognosis of this heritable disorder is poor and bone marrow transplantation is the only effective treatment. Here, by using transcription activator-like effect or nucleases (TALEN) technology, we created a zebrafish mpl mutant to model human CAMT. Disruption of zebrafish mpl leaded to a severe reduction in thrombocytes and a high bleeding tendency, as well as deficiencies in adult HSPCs...
November 4, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27802373/innate-color-preference-of-zebrafish-and-its-use-in-behavioral-analyses
#16
Jong-Su Park, Jae-Ho Ryu, Tae-Ik Choi, Young-Ki Bae, Suman Lee, Hae Jin Kang, Cheol-Hee Kim
Although innate color preference of motile organisms may provide clues to behavioral biases, it has remained a longstanding question. In this study, we investigated innate color preference of zebrafish larvae. A cross maze with different color sleeves around each arm was used for the color preference test (R; red, G; green, B; blue, Y; yellow). The findings showed that 5 dpf zebrafish larvae preferred blue over other colors (B > R > G > Y). To study innate color recognition further, tyrosinase mutants were generated using CRISPR/Cas9 system...
October 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27798206/screening-of-anti-mycobacterial-compounds-in-a-naturally-infected-zebrafish-larvae-model
#17
J P Dalton, B Uy, K S Okuda, C J Hall, W A Denny, P S Crosier, S Swift, S Wiles
OBJECTIVES: Mycobacterium tuberculosis is a deadly human pathogen that causes the lung disease TB. M. tuberculosis latently infects a third of the world's population, resulting in ∼1.5 million deaths per year. Due to the difficulties and expense of carrying out animal drug trials using M. tuberculosis and rodents, infections of the zebrafish Danio rerio with Mycobacterium marinum have become a useful surrogate. However, the infection methods described to date require specialized equipment and a high level of operator expertise...
October 24, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27792754/characterization-of-zebrafish-models-of-marinesco-sj%C3%A3-gren-syndrome
#18
Genri Kawahara, Yukiko K Hayashi
SIL1 is a nucleotide exchange factor for the endoplasmic reticulum chaperone, BiP. Mutations in the SIL1 gene cause Marinesco-Sjögren syndrome (MSS), an autosomal recessive disease characterized by cerebellar ataxia, mental retardation, congenital cataracts, and myopathy. To create novel zebrafish models of MSS for therapeutic drug screening, we analyzed phenotypes in sil1 knock down fish by two different antisense oligo morpholinos. Both sil1 morphants had abnormal formation of muscle fibers and irregularity of the myosepta...
2016: PloS One
https://www.readbyqxmd.com/read/27779463/a-zebrafish-live-imaging-model-reveals-differential-responses-of-microglia-toward-glioblastoma-cells-in-vivo
#19
Lloyd Hamilton, Katy R Astell, Gergana Velikova, Dirk Sieger
Glioblastoma multiforme is the most common and deadliest form of brain cancer. Glioblastomas are infiltrated by a high number of microglia, which promote tumor growth and surrounding tissue invasion. However, it is unclear how microglia and glioma cells physically interact and if there are differences, depending on glioma cell type. Hence, we have developed a novel live imaging assay to study microglia-glioma interactions in vivo in the zebrafish brain. We transplanted well-established human glioblastoma cell lines, U87 and U251, into transgenic zebrafish lines with labelled macrophages/microglia...
December 2016: Zebrafish
https://www.readbyqxmd.com/read/27764767/muscle-dysfunction-in-a-zebrafish-model-of-duchenne-muscular-dystrophy
#20
Jeffrey J Widrick, Matthew Alexander, Benjamin Sanchez, Devin Gibbs, Genri Kawahara, Alan Beggs, Louis Kunkel
Sapje zebrafish lack the protein dystrophin and are the smallest vertebrate model of Duchenne muscular dystrophy (DMD). Their small size makes them ideal for large-scale drug discovery screens. However, the extent that sapje mimic the muscle dysfunction of higher vertebrate models of DMD is unclear. We used an optical birefringence assay to differentiate affected dystrophic sapje larvae from their unaffected siblings and then studied trunk muscle contractility at 4-7 days post fertilization. Preparation cross-sectional area (CSA) was similar for affected and unaffected larvae, yet tetanic forces of affected preparations were only 30-60% of normal...
October 7, 2016: Physiological Genomics
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