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zebrafish T cells

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https://www.readbyqxmd.com/read/27917506/comparative-in-vitro-toxicity-assessment-of-perfluorinated-carboxylic-acids
#1
Cecon T Mahapatra, Nur P Damayanti, Samuel C Guffey, Jennifer S Serafin, Joseph Irudayaraj, Maria S Sepúlveda
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27907103/tbx20-is-an-essential-regulator-of-embryonic-heart-growth-in-zebrafish
#2
Steffen Just, Linda Raphel, Ina M Berger, Anja Bühler, Mirjam Keßler, Wolfgang Rottbauer
The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein...
2016: PloS One
https://www.readbyqxmd.com/read/27902705/neuronal-ndrg4-is-essential-for-nodes-of-ranvier-organization-in-zebrafish
#3
Laura Fontenas, Flavia De Santis, Vincenzo Di Donato, Cindy Degerny, Béatrice Chambraud, Filippo Del Bene, Marcel Tawk
Axon ensheathment by specialized glial cells is an important process for fast propagation of action potentials. The rapid electrical conduction along myelinated axons is mainly due to its saltatory nature characterized by the accumulation of ion channels at the nodes of Ranvier. However, how these ion channels are transported and anchored along axons is not fully understood. We have identified N-myc downstream-regulated gene 4, ndrg4, as a novel factor that regulates sodium channel clustering in zebrafish. Analysis of chimeric larvae indicates that ndrg4 functions autonomously within neurons for sodium channel clustering at the nodes...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27880902/forward-genetic-screens-in-zebrafish-identify-pre-mrna-processing-pathways-regulating-early-t-cell-development
#4
Norimasa Iwanami, Katarzyna Sikora, Andreas S Richter, Maren Mönnich, Lucia Guerri, Cristian Soza-Ried, Divine-Fondzenyuy Lawir, Fernando Mateos, Isabell Hess, Connor P O'Meara, Michael Schorpp, Thomas Boehm
Lymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility of non-mammalian models to define the molecular basis of their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell development revealed several major genetic pathways. The identification of lineage-specific transcription factors and specific components of cytokine signaling and DNA replication and/or repair pathways known from studies of immunocompromised mammals provided an evolutionary cross-validation of the screen design...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27876801/ppfia1-drives-active-%C3%AE-5%C3%AE-1-integrin-recycling-and-controls-fibronectin-fibrillogenesis-and-vascular-morphogenesis
#5
Giulia Mana, Fabiana Clapero, Emiliano Panieri, Valentina Panero, Ralph T Böttcher, Hui-Yuan Tseng, Federico Saltarin, Elena Astanina, Katarzyna I Wolanska, Mark R Morgan, Martin J Humphries, Massimo M Santoro, Guido Serini, Donatella Valdembri
Basolateral polymerization of cellular fibronectin (FN) into a meshwork drives endothelial cell (EC) polarity and vascular remodelling. However, mechanisms coordinating α5β1 integrin-mediated extracellular FN endocytosis and exocytosis of newly synthesized FN remain elusive. Here we show that, on Rab21-elicited internalization, FN-bound/active α5β1 is recycled to the EC surface. We identify a pathway, comprising the regulators of post-Golgi carrier formation PI4KB and AP-1A, the small GTPase Rab11B, the surface tyrosine phosphatase receptor PTPRF and its adaptor PPFIA1, which we propose acts as a funnel combining FN secretion and recycling of active α5β1 integrin from the trans-Golgi network (TGN) to the EC surface, thus allowing FN fibrillogenesis...
November 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27866707/a-functional-variant-associated-with-atrial-fibrillation-regulates-pitx2c-expression-through-tfap2a
#6
Jiangchuan Ye, Nathan R Tucker, Lu-Chen Weng, Sebastian Clauss, Steven A Lubitz, Patrick T Ellinor
The most significantly associated genetic locus for atrial fibrillation (AF) is in chromosomal region 4q25, where four independent association signals have been identified. Although model-system studies suggest that altered PITX2c expression might underlie the association, the link between specific variants and the direction of effect on gene expression remains unknown for all four signals. In the present study, we analyzed the AF-associated region most proximal to PITX2 at 4q25. First, we identified candidate regulatory variants that might confer AF risk through a combination of mammalian conservation, DNase hypersensitivity, and histone modification from ENCODE and the Roadmap Epigenomics Project, as well as through in vivo analysis of enhancer activity in embryonic zebrafish...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27865929/g2-m-cell-cycle-arrest-on-ht-29-cancer-cells-and-toxicity-assessment-of-triphenylphosphanegold-i-carbonimidothioates-ph3pau-sc-or-nph-r-me-et-and-ipr-during-zebrafish-development
#7
Kah Kooi Ooi, Chien Ing Yeo, Theventhiran Mahandaran, Kok Pian Ang, Abdah Md Akim, Yoke-Kqueen Cheah, Hoi-Ling Seng, Edward R T Tiekink
Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death...
November 4, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27856326/expression-pattern-analysis-of-irf4-and-its-related-genes-revealed-the-functional-differentiation-of-irf4-paralogues-in-teleost
#8
Kete Ai, Kai Luo, Youshen Li, Wei Hu, Weihua Gao, Liu Fang, Guangming Tian, Guoliang Ruan, Qiaoqing Xu
In mammals, interferon regulatory factor 4 (IRF4) plays an important role in the process of development and differentiation of B cells, T cells and dendritic cells. It can regulate immune pathway through IRF5, MyD88, IL21, PGC1α, and NOD2. In the present study, we investigated the expression pattern of IRF4 paralogues and these related genes for the first time in teleosts. The results showed that these genes were all expressed predominantly in known immune tissues while IRF5 was also relatively highly expressed in muscle...
November 14, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27856309/hedgehog-signalling-acts-upstream-of-laminin-alpha1-transcription-in-the-zebrafish-paraxial-mesoderm
#9
Joseph Pickering, Vincent T Cunliffe, Freek Van Eeden, Anne-Gaëlle Borycki
Laminin-111 (α1β1γ1) is a member of the Laminin family of extra-cellular matrix proteins that comprises 16 members, components of basement membranes. Laminin-111, one of the first Laminin proteins synthesised during embryogenesis, is required for basement membrane deposition and has essential roles in tissue morphogenesis and patterning. Yet, the mechanisms controlling Laminin-111 expression are poorly understood. We generated a zebrafish transgenic reporter line that reproduces faithfully the expression pattern of lama1, the gene encoding Laminin α1, and we used this reporter line to investigate lama1 transcriptional regulation...
November 14, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27851892/the-sec-domain-protein-scfd1-facilitates-trafficking-of-ecm-components-during-chondrogenesis
#10
Ningning Hou, Yuxi Yang, Ian C Scott, Xin Lou
Chondrogenesis in the developing skeleton requires transformation of chondrocytes from a simple mesenchymal condensation to cells with a highly enriched extracellular matrix (ECM). This transition is in part accomplished by alterations in the chondrocyte protein transport machinery to cope with both the increased amount and large size of ECM components. In a zebrafish mutagenesis screen to identify genes essential for cartilage development, we uncovered a mutant that disrupts the gene encoding Sec1 family domain containing 1 (scfd1)...
November 13, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27835862/a-novel-mutation-in-nuclear-prelamin-a-recognition-factor-like-causes-diffuse-pulmonary-arteriovenous-malformations
#11
Hong-Zhou Liu, Chun-Xian Du, Jing Luo, Xue-Ping Qiu, Zu-Hua Li, Qi-Yong Lou, Zhan Yin, Fang Zheng
Two daughters in a Chinese consanguineous family were diagnosed as diffuse pulmonary arteriovenous malformations (PAVMs) and screened using whole exome sequencing (WES) and copy number variations (CNVs) chips. Though no mutation was found in the established causative genes of capillary malformation-AVMs (CM-AVMs) or PAVMs, Ser161Ile (hg19 NM_022493 c.482G>T) mutation in nuclear prelamin A recognition factor-like (NARFL) was identified. Ser161Ile mutation in NARFL conservation region was predicted to be deleterious and absent in 500 population controls and Exome Aggregation Consortium (ExAC) Database...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834222/polarized-cortical-tension-drives-zebrafish-epiboly-movements
#12
Amayra Hernández-Vega, María Marsal, Philippe-Alexandre Pouille, Sébastien Tosi, Julien Colombelli, Tomás Luque, Daniel Navajas, Ignacio Pagonabarraga, Enrique Martín-Blanco
The principles underlying the biomechanics of morphogenesis are largely unknown. Epiboly is an essential embryonic event in which three tissues coordinate to direct the expansion of the blastoderm. How and where forces are generated during epiboly, and how these are globally coupled remains elusive. Here we developed a method, hydrodynamic regression (HR), to infer 3D pressure fields, mechanical power, and cortical surface tension profiles. HR is based on velocity measurements retrieved from 2D+T microscopy and their hydrodynamic modeling...
November 9, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27831568/arqiv-hts-a-versatile-whole-organism-screening-platform-enabling-in-vivo-drug-discovery-at-high-throughput-rates
#13
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/27827822/ndrg1b-and-fam49ab-modulate-the-pten-pathway-to-control-t-cell-lymphopoiesis-in-the-zebrafish
#14
Roman A Li, David Traver, Thomas Matthes, Julien Y Bertrand
During hematopoiesis, the balance between proliferation, differentiation and apoptosis is tightly regulated in order to maintain homeostasis. Failure in these processes can ultimately lead to uncontrolled proliferation and leukemia. Phosphatase and tensin homolog (PTEN) is one of the molecular pathways involved in this balance. By opposing PI3-Kinases, PTEN inhibits proliferation and promotes differentiation, and is thus considered a tumor suppressor. Indeed, PTEN is frequently mutated in many cancers, including leukemias...
November 8, 2016: Blood
https://www.readbyqxmd.com/read/27810924/single-cell-imaging-of-normal-and-malignant-cell-engraftment-into-optically-clear-prkdc-null-scid-zebrafish
#15
John C Moore, Qin Tang, Nora Torres Yordán, Finola E Moore, Elaine G Garcia, Riadh Lobbardi, Ashwin Ramakrishnan, Dieuwke L Marvin, Anthony Anselmo, Ruslan I Sadreyev, David M Langenau
Cell transplantation into immunodeficient mice has revolutionized our understanding of regeneration, stem cell self-renewal, and cancer; yet models for direct imaging of engrafted cells has been limited. Here, we characterize zebrafish with mutations in recombination activating gene 2 (rag2), DNA-dependent protein kinase (prkdc), and janus kinase 3 (jak3). Histology, RNA sequencing, and single-cell transcriptional profiling of blood showed that rag2 hypomorphic mutant zebrafish lack T cells, whereas prkdc deficiency results in loss of mature T and B cells and jak3 in T and putative Natural Killer cells...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27805568/hand2-inhibits-kidney-specification-while-promoting-vein-formation-within-the-posterior-mesoderm
#16
Elliot A Perens, Zayra V Garavito-Aguilar, Gina P Guio-Vega, Karen T Peña, Yocheved L Schindler, Deborah Yelon
Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM...
November 2, 2016: ELife
https://www.readbyqxmd.com/read/27792790/phactr1-is-a-genetic-susceptibility-locus-for-fibromuscular-dysplasia-supporting-its-complex-genetic-pattern-of-inheritance
#17
Soto Romuald Kiando, Nathan R Tucker, Luis-Jaime Castro-Vega, Alexander Katz, Valentina D'Escamard, Cyrielle Tréard, Daniel Fraher, Juliette Albuisson, Daniella Kadian-Dodov, Zi Ye, Erin Austin, Min-Lee Yang, Kristina Hunker, Cristina Barlassina, Daniele Cusi, Pilar Galan, Jean-Philippe Empana, Xavier Jouven, Anne-Paule Gimenez-Roqueplo, Patrick Bruneval, Esther Soo Hyun Kim, Jeffrey W Olin, Heather L Gornik, Michel Azizi, Pierre-François Plouin, Patrick T Ellinor, Iftikhar J Kullo, David J Milan, Santhi K Ganesh, Pierre Boutouyrie, Jason C Kovacic, Xavier Jeunemaitre, Nabila Bouatia-Naji
Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We analyzed ~26K common variants (MAF>0.05) generated by exome-chip arrays in 249 FMD patients and 689 controls. We replicated 13 loci (P<10-4) in 402 cases and 2,537 controls and confirmed an association between FMD and a variant in the phosphatase and actin regulator 1 gene (PHACTR1)...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27789622/ligament-versus-bone-cell-identity-in-the-zebrafish-hyoid-skeleton-is-regulated-by-mef2ca
#18
James T Nichols, Bernardo Blanco-Sánchez, Elliott P Brooks, Raghuveer Parthasarathy, John Dowd, Arul Subramanian, Gregory Nachtrab, Kenneth D Poss, Thomas F Schilling, Charles B Kimmel
Heightened phenotypic variation among mutant animals is a well-known, but poorly understood phenomenon. One hypothetical mechanism accounting for mutant phenotypic variation is progenitor cells variably choosing between two alternative fates during development. Zebrafish mef2ca(b1086) mutants develop tremendously variable ectopic bone in their hyoid craniofacial skeleton. Here, we report evidence that a key component of this phenotype is variable fate switching from ligament to bone. We discover that a 'track' of tissue prone to become bone cells is a previously undescribed ligament...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27764198/comparative-analysis-of-membrane-vesicles-from-three-piscirickettsia-salmonis-isolates-reveals-differences-in-vesicle-characteristics
#19
Julia I Tandberg, Leidy X Lagos, Petter Langlete, Eva Berger, Anne-Lise Rishovd, Norbert Roos, Deepa Varkey, Ian T Paulsen, Hanne C Winther-Larsen
Membrane vesicles (MVs) are spherical particles naturally released from the membrane of Gram-negative bacteria. Bacterial MV production is associated with a range of phenotypes including biofilm formation, horizontal gene transfer, toxin delivery, modulation of host immune responses and virulence. This study reports comparative profiling of MVs from bacterial strains isolated from three widely disperse geographical areas. Mass spectrometry identified 119, 159 and 142 proteins in MVs from three different strains of Piscirickettsia salmonis isolated from salmonids in Chile (LF-89), Norway (NVI 5692) and Canada (NVI 5892), respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27745833/variants-in-the-oxidoreductase-pyroxd1-cause-early-onset-myopathy-with-internalized-nuclei-and-myofibrillar-disorganization
#20
Gina L O'Grady, Heather A Best, Tamar E Sztal, Vanessa Schartner, Myriam Sanjuan-Vazquez, Sandra Donkervoort, Osorio Abath Neto, Roger Bryan Sutton, Biljana Ilkovski, Norma Beatriz Romero, Tanya Stojkovic, Jahannaz Dastgir, Leigh B Waddell, Anne Boland, Ying Hu, Caitlin Williams, Avnika A Ruparelia, Thierry Maisonobe, Anthony J Peduto, Stephen W Reddel, Monkol Lek, Taru Tukiainen, Beryl B Cummings, Himanshu Joshi, Juliette Nectoux, Susan Brammah, Jean-François Deleuze, Viola Oorschot Ing, Georg Ramm, Didem Ardicli, Kristen J Nowak, Beril Talim, Haluk Topaloglu, Nigel G Laing, Kathryn N North, Daniel G MacArthur, Sylvie Friant, Nigel F Clarke, Robert J Bryson-Richardson, Carsten G Bönnemann, Jocelyn Laporte, Sandra T Cooper
This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase...
November 3, 2016: American Journal of Human Genetics
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