669 research outputs found

    Zebrafish aplnra functions in epiboly

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

    The structure and function of vertebrate fibroblast growth factor receptor 1

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    The vertebrate fibroblast growth factor receptor 1 (FGFR1) is alternatively spliced generating multiple splice variants that are differentially expressed during embryo development and in the adult body. The restricted expression patterns of FGFR1 isoforms, together with differential expression and binding of specific ligands, leads to activation of common FGFR1 signal transduction pathways, but may result in distinctively different biological responses as a result of differences in cellular context. FGFR1 isoforms are also present in the nucleus in complex with various fibroblast growth factors where they function to regulate transcription of target genes.Casper Groth and Michael Lardell

    Mitochondrion to endoplasmic reticulum apposition length in zebrafish embryo spinal progenitors is unchanged in response to perturbations associated with Alzheimer’s disease

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    Published: June 21, 2017Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD). The length of mitochondrion-endoplasmic reticulum (M-ER) appositions is increased in Psen1-/-/Psen2-/- double knockout murine embryonic fibroblasts and in fibroblasts from AD-affected individuals. Development of an easily accessible, genetically manipulable, in vivo system for studying M-ER appositions would be valuable so we attempted to manipulate M-ER apposition length in zebrafish (Danio rerio) embryos. We injected fertilized zebrafish eggs with antisense morpholino oligonucleotides (MOs) that inhibit expression of zebrafish familial AD gene orthologues psen1 and psen2. Furthermore, we treated zebrafish embryos with DAPT (a highly specific Îł-secretase inhibitor) or with sodium azide (to mimic partially hypoxic conditions). We then analyzed M-ER apposition in an identified, presumably proliferative neural cell type using electron microscopy. Our analysis showed no significant differences in M-ER apposition lengths at 48 hours post fertilization (hpf) between psen1 & psen2 MO co-injected embryos, embryos treated with DAPT, or sodium azide, and control embryos. Instead, the distribution of M-ER apposition lengths into different length classes was close to identical. However, this indicates that it is feasible to reproducibly measure M-ER size distributions in zebrafish embryos. While our observations differ from those of murine and human studies, this may be due to differences in cellular differentiation and metabolic state, cell age, or species-specific responses. In particular, by focusing on a presumably proliferative embryonic cell type, we may have selected a cell heavily already reliant on anaerobic glycolysis and less responsive to factors affecting M-ER apposition. Future examination of more differentiated, more secretory cell types may reveal measurable responses of M-ER apposition to environmental and genetic manipulation.Morgan Newman, Lena Halter, Anne Lim, Michael Lardell

    The identity and distribution of neural cells expressing the mesodermal determinant spadetail

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    BACKGROUND: The spadetail (spt) gene of zebrafish is expressed in presomitic mesoderm and in neural cells previously suggested to be Rohon-Beard neurons. The mechanism(s) generating the apparently irregular rostrocaudal distribution of spt-expressing cells in the developing CNS is unknown. RESULTS: spt-expressing neural cells co-express huC, a marker of neurons. These cells also co-express the genes islet-1, -2 and -3 but not valentino. The islet-1 gene expression, irregular distribution and dorsolateral position of spt-expressing cells in the developing CNS are characteristic of dorsal longitudinal ascending (DoLA) interneurons. Shortly after their birth, these neurons extend processes rostrally into which spt mRNA is transported. At 24 hours post fertilisation(hpf), spt-expressing neurons occur most frequently at rostral levels caudal of the 5(th)-formed somite pair. There is no apparent bias in the number of spt-expressing cells on the left or right sides of embryos. Extended staining for spt-transcription reveals expression in the dorsocaudal cells of somites at the same dorsoventral level as the spt-expressing neurons. There is frequent juxtaposition of spt-expression in newly formed somites and in neurons. This suggests that both types of spt-expressing cell respond to a common positional cue or that neurons expressing spt are patterned irregularly by flanking somitic mesoderm. CONCLUSIONS: spt-expressing cells in the developing CNS appear to be DoLA interneurons. The irregular distribution of these cells along the rostrocaudal axis of the spinal cord may be due to "inefficient" patterning of neural spt expression by a signal(s) from flanking, regularly distributed somites also expressing spt

    Knowledge Translation in Action: An Evaluation of the Implementation of Customised Birthweight Centiles at One New Zealand District Health Board

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    Identifying small for gestational age (SGA) and large for gestational age (LGA) babies is important, because these babies may be at increased risk of hypoglycaemia at birth. It is proposed that customised birthweight centiles (CBWC) can more accurately identify these babies by taking into account several physiological variables of the pregnancy affecting birthweight. These variables are: maternal height and booking weight, ethnicity, parity, the baby's gender and gestation. CBWC for a New Zealand (NZ) population were developed by McCowan, Stewart, Francis and Gardosi (2004), and can be downloaded for free from www.gestation.net. Using CBWC is not in common practice in NZ, even though its use was discussed in a 2007 Health and Disability Commissioner report in relation to neonatal hypoglycaemia. The setting for the study was a NZ District Health Board (DHB) that calculates a CBWC for each birth. The research question asked how the evidence behind CBWC was put into practice and what outcomes resulted from translating this knowledge into action. This was a mixed methods evaluation which included interviews, focus groups, an audit and document analysis. The knowledge-to-action (KTA) framework (Straus, Tetroe, & Graham, 2009) was used as a theoretical template to describe the implementation process that occurred. The results revealed that maternity care providers were initially challenged by the evidence. But over time, guideline compliance improved as practitioners experienced the benefit of using CBWC in practice. All agreed that the CBWC calculator was user-friendly. However, the audit demonstrated it was easy to make a mistake or manipulate results when using the calculator. CBWC can help identify babies at risk of hypoglycaemia who otherwise would have been missed. But it is unknown what difference it had made in improving neonatal morbidity and mortality, due to insufficient data. But anecdotally, stakeholders felt it had made a difference. The findings demonstrated that knowledge translation is a complex process which is difficult to capture within a one-dimensional framework. However, using such a framework can identify what stages are needed to complete an implementation process

    Association between the detection of alcohol, illicit drugs and/or psychotropic medications/ opioids in patients admitted due to trauma and trauma recidivism: A cohort study

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    To quantify the association between the presence and type of drug detected and trauma recidivism in a cohort of patients admitted due to trauma. The incidence rate of TR was 10.94 cases per 100 patient-years in the group of patients negative for substances and 27.99 per 100 patient-years in positive patients. The survival curves show very significant differences in cumulative recurrence-free survival between the groups (Log Rank: p<0.001). Both the aHRR and the aIRR estimates show an increased risk of re-injury due to alcohol consumption (aIRR: 2.33 (1.72±3.15), p<0.001), cannabis use (aIRR: 1.87 (1.09±3.20), p = 0.022) and polydrug use (aIRR: 2.34 (1.80±3.04), p<0.001). The presence of alcohol and/or illicit drugs in these patients doubles the risk of trauma recidivismThis work was supported by the Dirección General de Tráfico, Spain [grant number: 0100DGT22389

    Propuesta metodolĂłgica para la instalaciĂłn de museos submarinos cerca de la costa

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    En el presente proyecto fin de carrera se ha procedido a analizar el proceso de instalación de arrecifes artificiales cerca de la costa y a valorar los efectos que pueda causar en ella. Concretamente, se ha orientado hacia el estudio de aquellos que fomentan la práctica de actividades tales como el submarinismo, centrando la atención en los museos submarinos. Se ha desarrollado una metodología para su instalación en la cual se han tenido en cuenta las existentes, ampliadas en aquellos aspectos que se han considerado puntos débiles. Posteriormente dicha metodología se ha aplicado a un caso real que ha servido para evaluar las afecciones que este tipo de instalaciones puede causar sobre la morfodinámica de la costa. Se ha verificado que su impacto es mínimo, y que igualmente su diseño en planta tiene poca influencia.Proyecto Fin de Carrera de la Univ. de Granada, Grupo de Dinámica de Flujos Ambientales (TEP209

    The protein tyrosine phosphatase Pez regulates TGFβ, epithelial–mesenchymal transition, and organ development

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    Epithelial–mesenchymal transition (EMT), crucial during embryogenesis for new tissue and organ formation, is also considered to be a prerequisite to cancer metastasis. We report here that the protein tyrosine phosphatase Pez is expressed transiently in discrete locations in developing brain, heart, pharyngeal arches, and somites in zebrafish embryos. We also find that Pez knock-down results in defects in these organs, indicating a crucial role in organogenesis. Overexpression of Pez in epithelial MDCK cells causes EMT, with a drastic change in cell morphology and function that is accompanied by changes in gene expression typical of EMT. Transfection of Pez induced TGFβ signaling, critical in developmental EMT with a likely role also in oncogenic EMT. In zebrafish, TGFβ3 is co- expressed with Pez in a number of tissues and its expression was lost from these tissues when Pez expression was knocked down. Together, our data suggest Pez plays a crucial role in organogenesis by inducing TGFβ and EMT

    The influence of heavy goods vehicle traffic on accidents on different types of Spanish interurban roads

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    This paper illustrates a methodology developed to analyze the influence of traffic conditions, i.e. volume and composition on accidents on different types of interurban roads in Spain, by applying negative binomial models. The annual average daily traffic was identified as the most important variable, followed by the percentage of heavy goods vehicles, and different covariate patterns were found for each road type. The analysis of hypothetical scenarios of the reduction of heavy goods vehicles in two of the most representative freight transportation corridors, combined with hypotheses of total daily traffic mean intensity variation, produced by the existence or absence of induced traffic gives rise to several scenarios. In all cases a reduction in the total number of accidents would occur as a result of the drop in the number of heavy goods transport vehicles, However the higher traffic intensity, resulting of the induction of other vehicular traffic, reduces the effects on the number of accidents on single carriageway road segments compared with high capacity roads, due to the increase in exposure. This type of analysis provides objective elements for evaluating policies that encourage modal shifts and road safety enhancements
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