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Zebrafish disease modelling

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https://www.readbyqxmd.com/read/28719799/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-a-new-player-in-endoplasmic-reticulum-diseases-structure-biology-and-therapeutic-roles
#1
REVIEW
Yeawon Kim, Sun-Ji Park, Ying Maggie Chen
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28714182/rare-coding-variants-in-mapk7-predispose-to-adolescent-idiopathic-scoliosis
#2
Wenjie Gao, Chong Chen, Taifeng Zhou, Shulan Yang, Bo Gao, Hang Zhou, Chengjie Lian, Zizhao Wu, Xianjian Qiu, Xiaoming Yang, Esam Alattar, Wentao Liu, Deying Su, Silong Sun, Yulan Chen, Kenneth M C Cheung, Youqiang Song, Keith K D Luk, Danny Chan, Pak Chung Sham, Chao Xing, Chiea Chuen Khor, Gabriel Liu, Junlin Yang, Yubin Deng, Dingjun Hao, Dongsheng Huang, Quan-Zhen Li, Caixia Xu, Peiqiang Su
Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder characterized by three-dimensional spinal curvatures, affecting 2-3% of school age children, yet the causes underlying AIS are not well understood. Here, we firstly conducted a whole-exome sequencing and linkage analysis on a three-generation Chinese family with autosomal dominant (AD) AIS, then performed targeted sequencing in a discovery cohort comprising 20 AD-AIS families and 86 simplex patients, and finally identified three disease-associated missense variants (c...
July 17, 2017: Human Mutation
https://www.readbyqxmd.com/read/28710811/insights-from-zebrafish-on-human-pigment-cell-disease-and-treatment
#3
REVIEW
Cynthia D Cooper
Black pigment cells, melanocytes, arise early during development from multipotent neural crest cells. Melanocytes protect human skin from DNA damaging sunrays and provide color for hair, eyes and skin. Several disorders and diseases originate from these cells, including the deadliest skin cell cancer, melanoma. Thus, melanocytes are critical for a healthy life and for protecting humans from disease. Due to the ease of visualizing pigment cells through transparent larvae skin and conserved roles for zebrafish melanophore genes to mammalian melanocyte genes, zebrafish larvae offer a biologically relevant model for understanding pigment cell development and disease in humans...
July 14, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28707266/6-ohda-lesioned-adult-zebrafish-as-a-useful-parkinson-s-disease-model-for-dopaminergic-neuroregeneration
#4
Yuganthini Vijayanathan, Fei Tieng Lim, Siong Meng Lim, Chiau Ming Long, Maw Pin Tan, Abu Bakar Abdul Majeed, Kalavathy Ramasamy
Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6...
July 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28705258/fate-bias-during-neural-regeneration-adjusts-dynamically-without-recapitulating-developmental-fate-progression
#5
Jeremy Ng Chi Kei, Peter David Currie, Patricia Regina Jusuf
BACKGROUND: Regeneration of neurons in the central nervous system is poor in humans. In other vertebrates neural regeneration does occur efficiently and involves reactivation of developmental processes. Within the neural retina of zebrafish, Müller glia are the main stem cell source and are capable of generating progenitors to replace lost neurons after injury. However, it remains largely unknown to what extent Müller glia and neuron differentiation mirror development. METHODS: Following neural ablation in the zebrafish retina, dividing cells were tracked using a prolonged labelling technique...
July 13, 2017: Neural Development
https://www.readbyqxmd.com/read/28705044/the-genetics-of-hair-cell-function-in-zebrafish
#6
Teresa Nicolson
Our ears are remarkable sensory organs, providing the important senses of balance and hearing. The complex structure of the inner ear, or 'labyrinth', along with the assorted neuroepithelia, have evolved to detect head movements and sounds with impressive sensitivity. The rub is that the inner ear is highly vulnerable to genetic lesions and environmental insults. According to National Institute of Health estimates, hearing loss is one of the most commonly inherited or acquired sensorineural diseases. To understand the causes of deafness and balance disorders, it is imperative to understand the underlying biology of the inner ear, especially the inner workings of the sensory receptors...
July 13, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28698482/studying-autophagy-in-zebrafish
#7
REVIEW
Benan John Mathai, Annemarie H Meijer, Anne Simonsen
Autophagy is an evolutionarily conserved catabolic process which allows lysosomal degradation of complex cytoplasmic components into basic biomolecules that are recycled for further cellular use. Autophagy is critical for cellular homeostasis and for degradation of misfolded proteins and damaged organelles as well as intracellular pathogens. The role of autophagy in protection against age-related diseases and a plethora of other diseases is now coming to light; assisted by several divergent eukaryotic model systems ranging from yeast to mice...
July 9, 2017: Cells
https://www.readbyqxmd.com/read/28697314/grainyhead-like-transcription-factors-in-craniofacial-development
#8
M R Carpinelli, M E de Vries, S M Jane, S Dworkin
Craniofacial development in vertebrates involves the coordinated growth, migration, and fusion of several facial prominences during embryogenesis, processes governed by strict genetic and molecular controls. A failure in any of the precise spatiotemporal sequences of events leading to prominence fusion often leads to anomalous facial, skull, and jaw formation-conditions termed craniofacial defects (CFDs). Affecting approximately 0.1% to 0.3% of live births, CFDs are a highly heterogeneous class of developmental anomalies, which are often underpinned by genetic mutations...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28694436/expression-and-regulation-of-drug-transporters-in-vertebrate-neutrophils
#9
Matthew J Foulkes, Katherine M Henry, Julien Rougeot, Edward Hooper-Greenhill, Catherine A Loynes, Phil Jeffrey, Angeleen Fleming, Caroline O Savage, Annemarie H Meijer, Simon Jones, Stephen A Renshaw
There remains a need to identify novel pro-resolution drugs for treatment of inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory treatments in clinical use, perhaps due to our lack of understanding of how drugs access this complex cell type. Here we present the first comprehensive description and expression of both major classes of drug transporters, SLC and ABC, in resting human blood neutrophils. Moreover, we have studied the expression of these carriers in the tractable model system, the zebrafish (Danio rerio), additionally examining the evolutionary relationship between drug transporters in zebrafish and humans...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687604/calpain-inhibition-is-protective-in-machado-joseph-disease-zebrafish-due-to-induction-of-autophagy
#10
Maxinne Watchon, Kristy C Yuan, Nick Mackovski, Adam J Svahn, Nicholas J Cole, Claire Goldsbury, Silke Rinkwitz, Thomas S Becker, Garth A Nicholson, Angela S Laird
The neurodegenerative disease Machado-Joseph disease (MJD), also known as spinocerebellar ataxin-3, affects neurons of the brain and spinal cord, disrupting control of the movement of muscles. We have successfully established the first transgenic zebrafish (Danio rerio) model of MJD, which express human ataxin-3 protein containing either 23 glutamines (23Q, wild-type) or 84Q (MJD-causing), within neurons. Phenotypic characterization of the zebrafish (male and female) revealed that the ataxin-3-84Q zebrafish have decreased survival compared to ataxin-3-23Q and develop ataxin-3 neuropathology, ataxin-3 cleavage fragments and motor impairment...
July 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28684310/selective-inhibition-of-plasma-membrane-calcium-atpase-4-improves-angiogenesis-and-vascular-reperfusion
#11
Sathishkumar Kurusamy, Dolores López-Maderuelo, Robert Little, David Cadagan, Aaron M Savage, Jude C Ihugba, Rhiannon R Baggott, Farjana B Rowther, Sara Martínez-Martínez, Pablo Gómez-Del Arco, Clare Murcott, Weiguang Wang, J Francisco Nistal, Delvac Oceandy, Ludwig Neyses, Robert N Wilkinson, Elizabeth J Cartwright, Juan Miguel Redondo, Angel Luis Armesilla
AIMS: Ischaemic cardiovascular disease is a major cause of morbidity and mortality worldwide. Despite promising results from pre-clinical animal models, VEGF-based strategies for therapeutic angiogenesis have yet to achieve successful reperfusion of ischaemic tissues in patients. Failure to restore efficient VEGF activity in the ischaemic organ remains a major problem in current pro-angiogenic therapeutic approaches. Plasma membrane calcium ATPase 4 (PMCA4) negatively regulates VEGF-activated angiogenesis via inhibition of the calcineurin/NFAT signalling pathway...
July 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28682135/using-zebrafish-as-a-model-to-study-the-role-of-epigenetics-in-hearing-loss
#12
Yingzi He, Beier Bao, Huawei Li
The rapid progress of bioinformatics and high-throughput screening techniques in recent years has led to the identification of many candidate genes and small-molecule drugs that have the potential to make significant contributions to our understanding of the developmental and pathological processes of hearing, but it remains unclear how these genes and regulatory factors are coordinated. Increasing evidence suggests that epigenetic mechanisms are essential for establishing gene expression profiles and likely play an important role in the development of inner ear and in the pathology of hearing-associated diseases...
July 6, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28668389/inducible-liver-specific-overexpression-of-gankyrin-in-zebrafish-results-in-spontaneous-intrahepatic-cholangiocarcinoma-and-hepatocellular-carcinoma-formation
#13
Shin-Jie Huang, Chih-Lun Cheng, Jim-Ray Chen, Hong-Yi Gong, Wangta Liu, Jen-Leih Wu
Liver cancer is the second leading cause of death worldwide. As such, establishing animal models of the disease is important for both basic and translational studies that move toward developing new therapies. Gankyrin is a critical oncoprotein in the genetic control of liver pathology. In order to evaluate the oncogenic role of gankyrin without cancer cell inoculation and drug treatment, we overexpressed gankyrin under the control of the fabp10a promoter. A Tet-Off system was used to drive expression in hepatocytes...
June 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28657312/molecular-dynamics-flexible-fitting-simulations-identify-new-models-of-the-closed-state-of-the-cystic-fibrosis-transmembrane-conductance-regulator-protein
#14
Luba Simhaev, Nael A McCarty, Robert C Ford, Hanoch Senderowitz
Cystic fibrosis (CF) is a lethal, genetic disease found in particular in humans of European origin which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The search for CF therapies acting by modulating the impaired function of mutant CFTR will be greatly advanced by high resolution structures of CFTR in different states. To date, two medium resolution electron microscopy (EM) structures of CFTR are available (one of a distant zebrafish (Danio rerio) CFTR ortholog and one of human CFTR)...
July 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28656156/the-effects-of-aging-on-amyloid-%C3%AE-42-induced-neurodegeneration-and-regeneration-in-adult-zebrafish-brain
#15
Prabesh Bhattarai, Alvin Kuriakose Thomas, Yixin Zhang, Caghan Kizil
Alzheimer disease is the most prevalent neurodegenerative disease and is associated with aggregation of Amyloid-β42 peptides. In mammals, Amyloid-β42 causes impaired neural stem/progenitor cell (NSPC) proliferation and neurogenesis, which exacerbate with aging. The molecular programs necessary to enhance NSPC proliferation and neurogenesis in our brains to mount successful regeneration are largely unknown. Therefore, to identify the molecular basis of effective brain regeneration, we previously established an Amyloid-β42 model in adult zebrafish that displayed Alzheimer-like phenotypes reminiscent of humans...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28654864/wolf-hirschhorn-syndrome-candidate-1-whsc1-functions-as-a-tumor-suppressor-by-governing-cell-differentiation
#16
Chuan Yu, Xiaomin Yao, Linjie Zhao, Ping Wang, Qian Zhang, Chengjian Zhao, Shaohua Yao, Yuquan Wei
Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone 3 lysine 36 (H3K36) specific methyltransferase that is frequently deleted in Wolf-Hirschhorn syndrome (WHS). Whsc1 is also found mutated in a subgroup of B-cell derived malignant diseases by genomic translocation or point mutation, both of which resulted in hyperactivity of WHSC1 mediated H3K36 methylation and uncontrolled cell proliferation, suggesting that whsc1 functions as an oncogene. However, here we provided evidences to show that whsc1 also has tumor suppressor functions...
June 24, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28652704/rhein-attenuates-inflammation-through-inhibition-of-nf-%C3%AE%C2%BAb-and-nalp3-inflammasome-in-vivo-and-in-vitro
#17
Hui Ge, Hao Tang, Yanbing Liang, Jingguo Wu, Qing Yang, Lijin Zeng, Zhongfu Ma
Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28652318/a-framework-for-quantification-and-physical-modeling-of-cell-mixing-applied-to-oscillator-synchronization-in-vertebrate-somitogenesis
#18
Koichiro Uriu, Rajasekaran Bhavna, Andrew C Oates, Luis G Morelli
In development and disease, cells move as they exchange signals. One example is found in vertebrate development, where the timing of segment formation is set by a "segmentation clock" in which oscillating gene expression is synchronized across a population of cells by Delta-Notch signaling. Delta-Notch signaling requires local cell-cell contact, but in the zebrafish embryonic tailbud oscillating cells move rapidly, exchanging neighbors. Previous theoretical studies proposed that this relative movement or cell mixing might alter signaling and thereby enhance synchronization...
June 26, 2017: Biology Open
https://www.readbyqxmd.com/read/28647853/are-podocytes-motile
#19
REVIEW
Nicole Endlich, Florian Siegerist, Karlhans Endlich
Podocytes, the postmitotic and highly branched epithelial cells of the glomerulus, play a pivotal role for the function of the glomerular filtration barrier and the development of chronic kidney disease. It has long been discussed whether podocytes in vivo are motile and can laterally migrate in a coordinated way along the capillaries until they reach the position of naked glomerular basement membrane often found in podocytopathies. Such motility would also be the prerequisite for the replacement of lost podocytes by progenitor cells...
June 24, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28637666/nr4a-orphan-nuclear-receptor-family-members-nr4a2-and-nr4a3-regulate-neutrophil-number-and-survival
#20
Lynne R Prince, Svenja Dannewitz Prosseda, Kathryn Higgins, Jennifer Carlring, Elizabeth C Prestwich, Nikolay V Ogryzko, Atiqur Rahman, Alexander Basran, Francesco Falciani, Philip Taylor, Stephen A Renshaw, Moira K B Whyte, Ian Sabroe
Neutrophil lifespan is plastic and highly responsive to factors that regulate cellular survival. Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signaling, which positively regulates neutrophil survival. The aim of this study was to define transcriptional responses to PKA activation and to delineate the roles of these factors in neutrophil function and survival...
June 21, 2017: Blood
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