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Zebrafish disease modelling

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https://www.readbyqxmd.com/read/28316026/zebrafish-as-a-model-to-evaluate-peptide-related-cancer-therapies
#1
REVIEW
Austin Y Shull, Chien-An A Hu, Yong Teng
Peptide-derived drug discovery has experienced a remarkable resurgence in the past decade since the failure of small-molecule modulators to effectively access the large binding surfaces of intracellular protein-protein interactions as well as "undruggable" residues of certain disease-driving proteins. However, the effectiveness of peptide-based cancer therapies is being questioned in light of declines in pharmaceutical R&D efficiency. As a model of whole organism, zebrafish provide a means to develop promising peptide and protein anticancer agents in an informative, cost-effective and time-efficient manner, which also allows for surveying mechanisms of drug action and optimization of drug delivery system...
March 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28304136/zebrafish-models-of-non-canonical-wnt-planar-cell-polarity-signalling-fishing-for-valuable-insight-into-vertebrate-polarized-cell-behavior
#2
REVIEW
Maria Jussila, Brian Ciruna
Planar cell polarity (PCP) coordinates the uniform orientation, structure and movement of cells within the plane of a tissue or organ system. It is beautifully illustrated in the polarized arrangement of bristles and hairs that project from specialized cell surfaces of the insect abdomen and wings, and pioneering genetic studies using the fruit fly, Drosophila melanogaster, have defined a core signalling network underlying PCP. This core PCP/non-canonical Wnt signalling pathway is evolutionarily conserved, and studies in zebrafish have helped transform our understanding of PCP from a peculiarity of polarized epithelia to a more universal cellular property that orchestrates a diverse suite of polarized cell behaviors that are required for normal vertebrate development...
March 17, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28289157/targeting-neutrophilic-inflammation-using-polymersome-mediated-cellular-delivery
#3
James D Robertson, Jon R Ward, Milagros Avila-Olias, Giuseppe Battaglia, Stephen A Renshaw
Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism...
March 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28285006/gata5-sumoylation-is-indispensable-for-zebrafish-cardiac-development
#4
Bin Wen, Hao Yuan, Xiaohui Liu, Haihong Wang, Saijuan Chen, Zhu Chen, Hugues de The, Jun Zhou, Jun Zhu
BACKGROUND: SUMOylation is a critical regulatory protein modification in eukaryotic cells and plays a pivotal role in cardiac development and disease. Several cardiac transcription factors are modified by SUMO, but little is known about the impact of SUMOylation on their function during cardiac development. METHODS: We used a zebrafish model to address the impact of SUMOylation on GATA5, an essential transcription factor in zebrafish cardiac development. GATA5 SUMOylation was probed by western blot, the subcellular localization and transcriptional activity of GATA5 mutants were examined by immunostaining and luciferase reporter assay...
March 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28281657/a-gcsfr-csf3r-zebrafish-mutant-models-the-persistent-basal-neutrophil-deficiency-of-severe-congenital-neutropenia
#5
Vahid Pazhakh, Sharon Clark, M Cristina Keightley, Graham J Lieschke
Granulocyte colony-stimulating factor (GCSF) and its receptor (GCSFR), also known as CSF3 and CSF3R, are required to maintain normal neutrophil numbers during basal and emergency granulopoiesis in humans, mice and zebrafish. Previous studies identified two zebrafish CSF3 ligands and a single CSF3 receptor. Transient antisense morpholino oligonucleotide knockdown of both these ligands and receptor reduces neutrophil numbers in zebrafish embryos, a technique widely used to evaluate neutrophil contributions to models of infection, inflammation and regeneration...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28278039/cardiovascular-toxicity-assessment-of-poly-ethylene-imine-based-cationic-polymers-on-zebrafish-model
#6
Qinglian Hu, Fengliang Guo, Fenghui Zhao, Guping Tang, Zhengwei Fu
Poly(ethylene imine)s (PEIs) have gained enormous attention in designing novel drug delivery systems for cancer treatment. High molecular weight of PEIs such as PEI 25 kD are promising for their drug carrying capacity. However, increased molecular weight is associated with toxicity. Currently, the toxicity evaluation of PEIs is mainly focused on the culture cell models, with very few studies investigating the risk assessment in vivo. Herein, the systemic evaluation of branched PEI 25 kD and PEI-CyD (PC) composed of low molecular PEI (Mw 600) and β-cyclodextrin (β-CyD) is performed in zebrafish model and endothelial cells...
March 6, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28271062/gap-junction-in-the-teleost-fish-lineage-duplicated-connexins-may-contribute-to-skin-pattern-formation-and-body-shape-determination
#7
REVIEW
Masakatsu Watanabe
Gap junctions are intercellular channels that allow passage of ions and small molecules between adjacent cells. Gap junctions in vertebrates are composed of connexons, which are an assembly of six proteins, connexins. Docking of two connexons on the opposite cell surfaces forms a gap junction between the cytoplasm of two neighboring cells. Connexins compose a family of structurally related four-pass transmembrane proteins. In mammals, there are ~20 connexins, each of which contributes to unique permeability of gap junctions, and mutations of some connexin-encoding genes are associated with human diseases...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28271061/identification-and-expression-analysis-of-the-complete-family-of-zebrafish-pkd-genes
#8
Samantha J England, Paul C Campbell, Santanu Banerjee, Annika J Swanson, Katharine E Lewis
Polycystic kidney disease (PKD) proteins are trans-membrane proteins that have crucial roles in many aspects of vertebrate development and physiology, including the development of many organs as well as left-right patterning and taste. They can be divided into structurally-distinct PKD1-like and PKD2-like proteins and usually one PKD1-like protein forms a heteromeric polycystin complex with a PKD2-like protein. For example, PKD1 forms a complex with PKD2 and mutations in either of these proteins cause Autosomal Dominant Polycystic Kidney Disease (ADPKD), which is the most frequent potentially-lethal single-gene disorder in humans...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28264986/a-truncating-mutation-in-cep55-is-the-likely-cause-of-march-a-novel-syndrome-affecting-neuronal-mitosis
#9
Patrick Frosk, Heleen H Arts, Julien Philippe, Carter S Gunn, Emma L Brown, Bernard Chodirker, Louise Simard, Jacek Majewski, Somayyeh Fahiminiya, Chad Russell, Yangfan P Liu, Robert Hegele, Nicholas Katsanis, Conrad Goerz, Marc R Del Bigio, Erica E Davis
BACKGROUND: Hydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. The goals of this work are to describe a novel autosomal-recessive syndrome that includes hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH)); to identify its genetic cause(s) and to provide functional insight into pathomechanism. METHODS: We used homozygosity mapping and exome sequencing to identify recessive mutations in a single family with three affected fetuses...
March 6, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28263972/the-pre-rrna-processing-factor-def-is-rate-limiting-for-the-pathogenesis-of-mycn-driven-neuroblastoma
#10
T Tao, S B Sondalle, H Shi, S Zhu, A R Perez-Atayde, J Peng, S J Baserga, A T Look
The nucleolar factor, digestive organ expansion factor (DEF), has a key role in ribosome biogenesis, functioning in pre-ribosomal RNA (pre-rRNA) processing as a component of the small ribosomal subunit (SSU) processome. Here we show that the peripheral sympathetic nervous system (PSNS) is very underdeveloped in def-deficient zebrafish, and that def haploinsufficiency significantly decreases disease penetrance and tumor growth rate in a MYCN-driven transgenic zebrafish model of neuroblastoma that arises in the PSNS...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28262634/francisella-noatunensis-ssp-noatunensis-iglc-deletion-mutant-protects-adult-zebrafish-challenged-with-acute-mortality-dose-of-wild-type-strain
#11
Elisabeth O Lampe, Julia I Tandberg, Anne-Lise Rishovd, Hanne C Winther-Larsen
The intracellular fish pathogen Francisella noatunensis remains an unsolved problem for aquaculture worldwide and an efficient vaccine is needed. In Francisella sp., IglC is an important virulence factor necessary for intracellular growth and escape from phagolysosomes. Deletion of the intracellular growth locus C (iglC) in Francisella sp. causes attenuation, but vaccine potential has only been attributed to ΔiglC from Francisella noatunensis ssp. orientalis, a warm-water fish pathogen. A ΔiglC mutant was constructed in the cold-water fish pathogen F...
March 6, 2017: Diseases of Aquatic Organisms
https://www.readbyqxmd.com/read/28257660/induction-of-intrinsic-apoptosis-in-leukaemia-stem-cells-and-in-vivo-zebrafish-model-by-betulonic-acid-isolated-from-walsura-pinnata-hassk-meliaceae
#12
Kok Hoong Leong, Mohamad Azrul Mahdzir, Mohd Fadzli Md Din, Khalijah Awang, Yuka Tanaka, Kasem Kulkeaw, Tohru Ishitani, Daisuke Sugiyama
BACKGROUND: Leukaemia stem cells (LSC) have been associated with disease relapse and chemotherapy resistance. Betulonic acid (BA), a pentacyclic lupane-type triterpenoid, was reported to exhibit cytotoxicity toward various cancer cells and to be capable of inducing intrinsic apoptosis in solid tumours. However, the in vitro and in vivo apoptotic effects of BA against LSC remain unknown. HYPOTHESIS/PURPOSE: We aimed to determine whether BA isolated from bark of Walsura pinnata Hassk (Meliaceae) has pro-apoptotic effects on LSC in in vitro and in vivo models...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28255526/retinal-degeneration-and-regeneration-lessons-from-fishes-and-amphibians
#13
REVIEW
Divya Ail, Muriel Perron
PURPOSE OF REVIEW: Retinal degenerative diseases have immense socio-economic impact. Studying animal models that recapitulate human eye pathologies aids in understanding the pathogenesis of diseases and allows for the discovery of novel therapeutic strategies. Some non-mammalian species are known to have remarkable regenerative abilities and may provide the basis to develop strategies to stimulate self-repair in patients suffering from these retinal diseases. RECENT FINDINGS: Non-mammalian organisms, such as zebrafish and Xenopus, have become attractive model systems to study retinal diseases...
2017: Current Pathobiology Reports
https://www.readbyqxmd.com/read/28253259/scalable-design-of-paired-crispr-guide-rnas-for-genomic-deletion
#14
Carlos Pulido-Quetglas, Estel Aparicio-Prat, Carme Arnan, Taisia Polidori, Toni Hermoso, Emilio Palumbo, Julia Ponomarenko, Roderic Guigo, Rory Johnson
CRISPR-Cas9 technology can be used to engineer precise genomic deletions with pairs of single guide RNAs (sgRNAs). This approach has been widely adopted for diverse applications, from disease modelling of individual loci, to parallelized loss-of-function screens of thousands of regulatory elements. However, no solution has been presented for the unique bioinformatic design requirements of CRISPR deletion. We here present CRISPETa, a pipeline for flexible and scalable paired sgRNA design based on an empirical scoring model...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28252672/acute-podocyte-injury-is-not-a-stimulus-for-podocytes-to-migrate-along-the-glomerular-basement-membrane-in-zebrafish-larvae
#15
Florian Siegerist, Antje Blumenthal, Weibin Zhou, Karlhans Endlich, Nicole Endlich
Podocytes have a unique 3D structure of major and interdigitating foot processes which is the prerequisite for renal blood filtration. Loss of podocytes leads to chronic kidney disease ending in end stage renal disease. Until now, the question if podocytes can be replaced by immigration of cells along the glomerular basement membrane (GBM) is under debate. We recently showed that in contrast to former theories, podocytes are stationary in the zebrafish pronephros and neither migrate nor change their branching pattern of major processes over 23 hours...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28252024/evolution-of-complexity-in-the-zebrafish-synapse-proteome
#16
Àlex Bayés, Mark O Collins, Rita Reig-Viader, Gemma Gou, David Goulding, Abril Izquierdo, Jyoti S Choudhary, Richard D Emes, Seth G N Grant
The proteome of human brain synapses is highly complex and is mutated in over 130 diseases. This complexity arose from two whole-genome duplications early in the vertebrate lineage. Zebrafish are used in modelling human diseases; however, its synapse proteome is uncharacterized, and whether the teleost-specific genome duplication (TSGD) influenced complexity is unknown. We report the characterization of the proteomes and ultrastructure of central synapses in zebrafish and analyse the importance of the TSGD...
March 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28251883/tomm22-knockdown-mediated-hepatocyte-damages-elicit-both-the-formation-of-hybrid-hepatocytes-and-biliary-conversion-to-hepatocytes-in-zebrafish-larvae
#17
Jianchen Wu, Tae-Young Choi, Donghun Shin
The liver has a highly regenerative capacity. In the normal liver, hepatocytes proliferate to restore lost liver mass.However, when hepatocyte proliferation is impaired, biliary epithelial cells (BECs) activate and contribute to hepatocytes. We previously reported in zebrafish that upon severe hepatocyte ablation, BECs extensively contribute to regenerated hepatocytes. It was also speculated that BECdriven liver regeneration might occur in another zebrafish liver injury model in which temporary knockdown of the mitochondrial import gene <i>tomm22</i> by morpholino antisense oligonucleotides (MO) induces hepatocyte death...
March 1, 2017: Gene Expression
https://www.readbyqxmd.com/read/28249360/heart-function-and-hemodynamics-analysis-for-zebrafish-embryos
#18
REVIEW
Huseyin C Yalcin, Armin Amindari, Jonathan T Butcher, Asma Althani, Magdi Yacoub
The zebrafish has emerged to become a powerful vertebrate animal model for cardiovascular research in recent years. Its advantages include easy genetic manipulation, transparency, small size, low cost, and the ability to survive without active circulation at early stages of development. Sequencing the whole genome and identifying orthologue genes with human genome enabled to induce clinically relevant cardiovascular defects via genetic approaches. Heart function and disturbed hemodynamics need to be assessed in a reliable manner for these disease models in order to reveal mechanobiology of induced defects...
March 1, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28247754/small-sized-mpeg-plga-nanoparticles-of-schisantherin-a-with-sustained-release-for-enhanced-brain-uptake-and-anti-parkinsonian-activity
#19
Tongkai Chen, Chuwen Li, Ye Li, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism natural product. However, its poor water solubility and rapid serum clearance impose significant barriers to delivery of SA to the brain. This work aimed to develop SA in a nanoparticle formulation that extended SA circulation in the bloodstream and consequently an increased brain uptake and thus to be potentially efficacious for the treatment of Parkinson's disease (PD). Spherical SA nanoparticles with a mean particle size of 70 nm were prepared by encapsulating SA into methoxy poly(ethylene glycol)-block-poly(d,l)-lactic-co-glycolic acid (mPEG-PLGA) nanoparticles (SA-NPs) with an encapsulation efficiency of ∼91% and drug loading of ∼28%...
March 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28247347/using-transgenic-zebrafish-to-study-muscle-stem-progenitor-cells
#20
Phong D Nguyen, Peter D Currie
Understanding muscle stem cell behaviors can potentially provide insights into how these cells act and respond during normal growth and diseased contexts. The zebrafish is an ideal model organism to examine these behaviors in vivo where it would normally be technically challenging in other mammalian models. This chapter will describe the procedures required to successfully conduct live imaging of zebrafish transgenics that has specifically been adapted for skeletal muscle.
2017: Methods in Molecular Biology
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