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https://www.readbyqxmd.com/read/29228025/a-defect-in-the-inner-kinetochore-protein-cenpt-causes-a-new-syndrome-of-severe-growth-failure
#1
Christina Y Hung, Barbara Volkmar, James D Baker, Johann W Bauer, Emanuela Gussoni, Stefan Hainzl, Alfred Klausegger, Jose Lorenzo, Ivana Mihalek, Olaf Rittinger, Mustafa Tekin, Julia E Dallman, Olaf A Bodamer
Primordial growth failure has been linked to defects in the biology of cell division and replication. The complex processes involved in microtubule spindle formation, organization and function have emerged as a dominant patho-mechanism in these conditions. The majority of reported disease genes encode for centrosome and centriole proteins, leaving kinetochore proteins by which the spindle apparatus interacts with the chromosomes largely unaccounted for. We report a novel disease gene encoding the constitutive inner kinetochore member CENPT, which is involved in kinetochore targeting and assembly, resulting in severe growth failure in two siblings of a consanguineous family...
2017: PloS One
https://www.readbyqxmd.com/read/29226803/quantitative-missense-variant-effect-prediction-using-large-scale-mutagenesis-data
#2
Vanessa E Gray, Ronald J Hause, Jens Luebeck, Jay Shendure, Douglas M Fowler
Large datasets describing the quantitative effects of mutations on protein function are becoming increasingly available. Here, we leverage these datasets to develop Envision, which predicts the magnitude of a missense variant's molecular effect. Envision combines 21,026 variant effect measurements from nine large-scale experimental mutagenesis datasets, a hitherto untapped training resource, with a supervised, stochastic gradient boosting learning algorithm. Envision outperforms other missense variant effect predictors both on large-scale mutagenesis data and on an independent test dataset comprising 2,312 TP53 variants whose effects were measured using a low-throughput approach...
December 1, 2017: Cell Systems
https://www.readbyqxmd.com/read/29225165/cross-talk-between-tp53-and-c-myc-in-the-pathophysiology-of-diamond-blackfan-anemia-evidence-from-rpl11-deficient-in-vivo-and-in-vitro-models
#3
Anirban Chakraborty, Tamayo Uechi, Yukari Nakajima, Hanna T Gazda, Marie-Françoise O'Donohue, Pierre-Emmanuel Gleizes, Naoya Kenmochi
Mutations in genes encoding ribosomal proteins have been identified in Diamond-Blackfan anemia (DBA), a rare genetic disorder that presents with a prominent erythroid phenotype. TP53 has been implicated in the pathophysiology of DBA with ribosomal protein (RP) L11 playing a crucial role in the TP53 response. Interestingly, RPL11 also controls the transcriptional activity of c-Myc, an oncoprotein that positively regulates ribosome biogenesis. In the present study, we analyzed the consequences of rpl11 depletion on erythropoiesis and ribosome biogenesis in zebrafish...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29225039/a-massively-parallel-reporter-assay-of-3-utr-sequences-identifies-in%C3%A2-vivo-rules-for-mrna-degradation
#4
Michal Rabani, Lindsey Pieper, Guo-Liang Chew, Alexander F Schier
The stability of mRNAs is regulated by signals within their sequences, but a systematic and predictive understanding of the underlying sequence rules remains elusive. Here we introduce UTR-seq, a combination of massively parallel reporter assays and regression models, to survey the dynamics of tens of thousands of 3' UTR sequences during early zebrafish embryogenesis. UTR-seq revealed two temporal degradation programs: a maternally encoded early-onset program and a late-onset program that accelerated degradation after zygotic genome activation...
November 30, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29224359/a-reduced-transcriptome-approach-to-assess-environmental-toxicants-using-zebrafish-embryo-test
#5
Pingping Wang, Pu Xia, Jianghua Yang, Zhihao Wang, Ying Peng, Wei Shi, Daniel L Villeneuve, Hongxia Yu, Xiaowei Zhang
Omics approaches can monitor responses and alterations of biological pathways at genome-scale, which are useful to predict potential adverse effects by environmental toxicants. However, high throughput application of transcriptomics in chemical assessment is limited due to the high cost and lack of "standardized" toxicogenomic methods. Here, a reduced zebrafish transcriptome (RZT) approach was developed to represent the whole transcriptome and to profile bioactivity of chemical and environmental mixtures in zebrafish embryo...
December 11, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29221954/total-particulate-matter-from-cigarette-smoke-disrupts-vascular-development-in-zebrafish-brain-danio-rerio
#6
Andrey Massarsky, G L Prasad, Richard T Di Giulio
Several studies have demonstrated zebrafish as a useful high-throughput in-vivo model to study the effects of cigarette smoke on early development. It has been shown previously that exposure of zebrafish to cigarette smoke total particulate matter (TPM) leads to several adverse physiological aberrations, including heart deformities and improper angiogenesis. Consequently, this study investigated the effects of TPM on cardiovascular development in zebrafish that were exposed to increasing concentrations of TPM based upon nicotine content from 6h post fertilization (hpf) up to 72hpf...
December 5, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29221193/steroidogenic-factor-1-hypermethylation-in-maternal-rat-blood-could-serve-as-a-biomarker-for-intrauterine-growth-retardation
#7
Dong-Mei Wu, Liang-Peng Ma, Gui-Li Song, Yong Long, Han-Xiao Liu, Yang Liu, Jie Ping
Intrauterine growth retardation (IUGR) is a common obstetric complication lacking an optimal method for prenatal screening. DNA methylation profile in maternal blood holds significant promise for prenatal screening. Here, we aimed to screen out potential IUGR biomarkers in maternal blood from the perspective of DNA methylation. The IUGR rat model was established by prenatal maternal undernutrition. High-throughput bisulfite sequencing of genomic DNA methylation followed by functional clustering analysis for differentially methylated region (DMR)-associated genes demonstrated that genes regulating transcription had the most significantly changed DNA methylation status in maternal blood with IUGR...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220613/fully-automated-pipetting-sorting-system-for-different-morphological-phenotypes-of-zebrafish-embryos
#8
Helmut Breitwieser, Thomas Dickmeis, Marcel Vogt, Marco Ferg, Christian Pylatiuk
Systems biology methods, such as transcriptomics and metabolomics, require large numbers of small model organisms, such as zebrafish embryos. Manual separation of mutant embryos from wild-type embryos is a tedious and time-consuming task that is prone to errors, especially if there are variable phenotypes of a mutant. Here we describe a zebrafish embryo sorting system with two cameras and image processing based on template-matching algorithms. In order to evaluate the system, zebrafish rx3 mutants that lack eyes due to a patterning defect in brain development were separated from their wild-type siblings...
December 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/29217756/light-focusing-human-micro-lenses-derived-from-zebrafish-like-lens-cell-masses-model-lens-development-and-drug-induced-cataract-in-vitro
#9
Patricia Murphy, Md Humayun Kabir, Tarini Srivastava, Michele E Mason, Chitra Umala Dewi, Seakcheng Lim, Andrian Yang, Djordje Djordjevic, Murray C Killingsworth, Joshua W K Ho, David G Harman, Michael D O'Connor
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells...
December 7, 2017: Development
https://www.readbyqxmd.com/read/29216900/treatment-with-a-dna-methyltransferase-inhibitor-feminizes-zebrafish-and-induces-long-term-expression-changes-in-the-gonads
#10
Laia Ribas, Konstantinos Vanezis, Marco Antonio Imués, Francesc Piferrer
BACKGROUND: The role of epigenetic modifications such as DNA methylation during vertebrate sexual development is far from being clear. Using the zebrafish model, we tested the effects of one of the most common DNA methyltransferase (dnmt) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), which is approved for the treatment of acute myeloid leukaemia and is under active investigation for the treatment of solid tumours. Several dose-response experiments were carried out during two periods, including not only the very first days of development (0-6 days post-fertilization, dpf), as done in previous studies, but also, and as a novelty, the period of gonadal development (10-30 dpf)...
December 8, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29215726/sel1l-knockdown-negatively-influences-zebrafish-embryos-endothelium
#11
A Barbieri, S Carra, P De Blasio, F Cotelli, I Biunno
SEL1L (Suppressor/Enhancer of Lin-12-like) is a highly conserved gene associated with the Endoplasmic Reticulum-Associated Degradation (ERAD) pathway and involved in mediating the balance between stem cells self-renewal and differentiation of neural progenitors. It has been recently shown that SEL1L KO mice are embryonic lethal and display altered organogenesis. To better characterize the function of SEL1L in the early stages of embryonic development, we turned to the zebrafish model (D. rerio). After exploring sel1l expression by RT-PCR and in situ hybridization, we employed a morpholino-mediated down-regulation approach...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29215332/nodal-patterning-without-lefty-inhibitory-feedback-is-functional-but-fragile
#12
Katherine W Rogers, Nathan D Lord, James A Gagnon, Andrea Pauli, Steven Zimmerman, Deniz C Aksel, Deepak Reyon, Shengdar Q Tsai, J Keith Joung, Alexander F Schier
Developmental signaling pathways often activate their own inhibitors. Such inhibitory feedback has been suggested to restrict the spatial and temporal extent of signaling or mitigate signaling fluctuations, but these models are difficult to rigorously test. Here, we determine whether the ability of the mesendoderm inducer Nodal to activate its inhibitor Lefty is required for development. We find that zebrafish lefty mutants exhibit excess Nodal signaling and increased specification of mesendoderm, resulting in embryonic lethality...
December 7, 2017: ELife
https://www.readbyqxmd.com/read/29209275/lipid-uptake-metabolism-and-transport-in-the-larval-zebrafish
#13
REVIEW
Vanessa H Quinlivan, Steven A Farber
The developing zebrafish is a well-established model system for studies of energy metabolism, and is amenable to genetic, physiological, and biochemical approaches. For the first 5 days of life, nutrients are absorbed from its endogenous maternally deposited yolk. At 5 days post-fertilization, the yolk is exhausted and the larva has a functional digestive system including intestine, liver, gallbladder, pancreas, and intestinal microbiota. The transparency of the larval zebrafish, and the genetic and physiological similarity of its digestive system to that of mammals make it a promising system in which to address questions of energy homeostasis relevant to human health...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29209221/commentary-zebrafish-as-a-model-for-epilepsy-induced-cognitive-dysfunction-a-pharmacological-biochemical-and-behavioral-approach
#14
COMMENT
Avishek Amar
No abstract text is available yet for this article.
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29209178/a-three-layer-network-model-of-direction-selective-circuits-in-the-optic-tectum
#15
Fatima Abbas, Marcus A Triplett, Geoffrey J Goodhill, Martin P Meyer
The circuit mechanisms that give rise to direction selectivity in the retina have been studied extensively but how direction selectivity is established in retinorecipient areas of the brain is less well understood. Using functional imaging in larval zebrafish we examine how the direction of motion is encoded by populations of neurons at three layers of the optic tectum; retinal ganglion cell axons (RGCs), a layer of superficial inhibitory interneurons (SINs), and periventricular neurons (PVNs), which constitute the majority of neurons in the tectum...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/29208761/priming-of-innate-antimycobacterial-immunity-by-heat-killed-listeria-monocytogenes-induces-sterilizing-response-in-the-adult-zebrafish-tuberculosis-model
#16
Hanna Luukinen, Milka Marjut Hammarén, Leena-Maija Vanha-Aho, Aleksandra Svorjova, Laura Kantanen, Sampsa Järvinen, Bruno Vincent Luukinen, Eric Dufour, Mika Rämet, Vesa Pekka Hytönen, Mataleena Parikka
Mycobacterium tuberculosis remains one of the most problematic infectious agents due to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. Host-directed therapies aiming at optimal modulation of immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. In this study, we have established a zebrafish-Mycobacterium marinum natural host-pathogen model system to study induced protective immune responses in mycobacterial infection...
November 30, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29207953/genomic-signature-of-highland-adaptation-in-fish-a-case-study-in-tibetan-schizothoracinae-species
#17
Chao Tong, Fei Tian, Kai Zhao
BACKGROUND: Genome-wide studies on highland adaptation mechanism in terrestrial animal have been widely reported with few available for aquatic animals. Tibetan Schizothoracinae species are ideal model systems to study speciation and adaptation of fish. The Schizothoracine fish, Gymnocypris przewalskii ganzihonensis had underwent the ecological niche shift from salt water to freshwater, and also experienced a recent split from Gymnocypris przewalskii przewalskii. In addition, G. p. ganzihonensis inhabited harsh aquatic environment including low temperature and hypoxia as well as other Schizothoracinae species, its genetic mechanism of highland adaptation have yet to be determined...
December 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29207258/macrophage-dependent-cytoplasmic-transfer-during-melanoma-invasion-in%C3%A2-vivo
#18
Minna Roh-Johnson, Arish N Shah, Jason A Stonick, Kumud R Poudel, Julia Kargl, Grace H Yang, Julie di Martino, Rafael E Hernandez, Charles E Gast, Luai R Zarour, Susumu Antoku, A McGarry Houghton, Jose Javier Bravo-Cordero, Melissa H Wong, John Condeelis, Cecilia B Moens
Interactions between tumor cells and tumor-associated macrophages play critical roles in the initiation of tumor cell motility. To capture the cellular interactions of the tumor microenvironment with high-resolution imaging, we directly visualized tumor cells and their interactions with macrophages in zebrafish. Live imaging in zebrafish revealed that macrophages are dynamic, yet maintain sustained contact with tumor cells. In addition, the recruitment of macrophages to tumor cells promotes tumor cell dissemination...
December 4, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29204646/a-novel-zebrafish-model-for-studying-metastatic-behavior-of-human-conjunctival-melanoma-cells
#19
Michele C Madigan
No abstract text is available yet for this article.
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29204645/evaluation-of-fli-gfp-casper-zebrafish-embryos-as-a-model-for-human-conjunctival-melanoma
#20
Kelly Cristine de Sousa Pontes, Arwin Groenewoud, Jinfeng Cao, Livia Maria Silva Ataide, Ewa Snaar-Jagalska, Martine J Jager
Purpose: Conjunctival melanoma (CM) is a rare malignant disease that can lead to recurrences and metastases. There is a lack of effective treatments for the metastases, and we set out to develop a new animal model to test potential therapies. Zebrafish are being used as a model for many diseases, and our goal was to test whether this animal could be used to study CM. Methods: Three human CM cell lines (CRMM-1 and CM2005.1, which both harbor a B-RAF mutation, and CRMM-2, which has an N-RAS mutation) were injected into the yolk sac, around the eye, and into the duct of Cuvier of transgenic (fli:GFP) Casper zebrafish embryos...
December 1, 2017: Investigative Ophthalmology & Visual Science
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