Papers by Claudia Dominguez
Memorias Do Instituto Oswaldo Cruz, 2005
This study was conducted to compare among the most recent generation of five screening tests lice... more This study was conducted to compare among the most recent generation of five screening tests licensed in Argentina, in order to evaluate which of the tests has the best sensitivity for detection of antibodies against hepatitis C virus (HCV). The tests analyzed were: Detect-HCV (3.0) Biochem ImmunoSystems, Canada; Hepatitis C EIA Wiener Lab., Argentina; Equipar HCV Ab, Italy; Murex HCV 4.0, UK and Serodia-HCV particles agglutination test, Japan. The results obtained showed high discrepancy between the different kits used and show that some of the tests assessed have a low sensitivity for anti-HCV detection in both chronic infections and early seroconversion, and indicate that among the commercially available kits in Argentina, Murex HCV 4.0 (UK) and Serodia-HCV particles agglutination test (Japan) have the best sensitivity for HCV screening. Although the sensitivity of the assays is the first parameter to be considered for blood screening, more studies should be carried out to assess the specificity of such assays.
Development, 2008
Mutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Gold... more Mutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Goldberg-Shprintzen syndrome (GSS) in humans. The cellular function of KBP and the basis of the symptoms of GSS, however, remain unclear. Here, we report the identification and characterization of a zebrafish kbp mutant. We show that kbp is required for axonal outgrowth and maintenance. In vivo time-lapse analysis of neuronal development shows that the speed of early axonal outgrowth is reduced in both the peripheral and central nervous systems in kbp mutants. Ultrastructural studies reveal that kbp mutants have disruption to axonal microtubules during outgrowth. These results together suggest that kbp is an important regulator of the microtubule dynamics that drive the forward propulsion of axons. At later stages, we observe that many affected axons degenerate. Ultrastructural analyses at these stages demonstrate mislocalization of axonal mitochondria and a reduction in axonal number in the peripheral, central and enteric nervous systems. We propose that kbp is an important regulator of axonal development and that axonal cytoskeletal defects underlie the nervous system defects in GSS.
Science, 2009
The myelin sheath allows axons to conduct action potentials rapidly in the vertebrate nervous sys... more The myelin sheath allows axons to conduct action potentials rapidly in the vertebrate nervous system. Axonal signals activate expression of specific transcription factors, including Oct6 and Krox20, that initiate myelination in Schwann cells. Elevation of cyclic adenosine monophosphate (cAMP) can mimic axonal contact in vitro, but the mechanisms that regulate cAMP levels in vivo are unknown. Using mutational analysis in zebrafish, we found that the G protein-coupled receptor Gpr126 is required autonomously in Schwann cells for myelination. In gpr126 mutants, Schwann cells failed to express oct6 and krox20 and were arrested at the promyelinating stage. Elevation of cAMP in gpr126 mutants, but not krox20 mutants, could restore myelination. We propose that Gpr126 drives the differentiation of promyelinating Schwann cells by elevating cAMP levels, thereby triggering Oct6 expression and myelination.
Developmental Biology, 2006
The myelin sheath insulates axons in the vertebrate nervous system, allowing rapid propagation of... more The myelin sheath insulates axons in the vertebrate nervous system, allowing rapid propagation of action potentials via saltatory conduction. Specialized glial cells, termed Schwann cells in the PNS and oligodendrocytes in the CNS, wrap axons to form myelin, a compacted, multilayered sheath comprising specific proteins and lipids. Disruption of myelinated axons causes human diseases, including multiple sclerosis and Charcot-Marie-Tooth peripheral neuropathies. Despite the progress in identifying human disease genes and other mutations disrupting glial development and myelination, many important unanswered questions remain about the mechanisms that coordinate the development of myelinated axons. To address these questions, we began a genetic dissection of myelination in zebrafish. Here we report a genetic screen that identified 13 mutations, which define 10 genes, disrupting the development of myelinated axons. We present the initial characterization of seven of these mutations, defining six different genes, along with additional characterization of mutations that we have described previously. The different mutations affect the PNS, the CNS, or both, and phenotypic analyses indicate that the genes affect a wide range of steps in glial development, from fate specification through terminal differentiation. The analysis of these mutations will advance our understanding of myelination, and the mutants will serve as models of human diseases of myelin.
Este manual aborda y ejercita la construcción de tablas de vida horizontales o dinámicas y tablas... more Este manual aborda y ejercita la construcción de tablas de vida horizontales o dinámicas y tablas de vida verticales o estáticas, y se definen y realizan ejercicios sobre estadísticos y parámetros poblacionales, con el apoyo de planillas de cálculo específicas. Para estudiar los modelos de crecimiento exponencial y logístico se plantean actividades de simulación de crecimiento y fluctuación de abundancia de poblaciones. Se aplican herramientas como el cálculo de elasticidad para el manejo de poblaciones. Un breve desarrollo teórico de conceptos y ejercitaciones sirve de introducción a los modelos clásicos de competencia interespecífica y de depredadorpresa de Lotka-Volterra, seguido de actividades de simulación de crecimiento y fluctuación de abundancia de poblaciones. Luego continúa con problemas relacionados con el principio de exclusión competitiva, usando como herramienta un programa de simulación. Se define para cada una de las especies que compiten el tipo de recursos que explotan, la tasa de consumo, la asignación de energía para supervivencia y para reproducción y se plantea como desafío verificar la predicción que se deriva de la hipótesis de exclusión competitiva.
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Papers by Claudia Dominguez