9 research outputs found

    Maternal distress in late pregnancy alters obstetric outcomes and the expression of genes important for placental glucocorticoid signalling

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    The experience of maternal distress in pregnancy is often linked with poorer obstetric outcomes for women as well as adverse outcomes for offspring. Alterations in placental glucocorticoid signalling and subsequent increased fetal exposure to cortisol have been suggested to underlie this relationship. In the current study, 121 pregnant women completed the Perceived Stress Scale, State Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale in the third trimester of pregnancy. Placental samples were collected after delivery. Maternal history of psychiatric illness and miscarriage were significant predictors of poorer mental health in pregnancy. Higher anxiety was associated with an increase in women delivering via elective Caesarean Section, and an increase in bottle-feeding. Birth temperature was mildly reduced among infants of women with high levels of depressive symptomology. Babies of mothers who scored high in all stress (cumulative distress) measures had reduced 5-min Apgar scores. High cumulative distress reduced the expression of placental HSD11B2 mRNA and increased the expression of placental NR3C1 mRNA. These data support a role for prenatal distress as a risk factor for altered obstetric outcomes. The alterations in placental gene expression support a role for altered placental glucocorticoid signalling in the relationship between maternal prenatal distress and adverse outcomes

    A small molecule activator of p300/CBP histone acetyltransferase promotes survival and neurite growth in a cellular model of Parkinson’s disease

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    Parkinson’s disease (PD) is a progressive neurodegenerative disease characterised by motor and non-motor symptoms, resulting from the degeneration of nigrostriatal dopaminergic neurons and peripheral autonomic neurons. Given the limited success of neurotrophic factors in clinical trials, there is a need to identify new small molecule drugs and drug targets to develop novel therapeutic strategies to protect all neurons that degenerate in PD. Epigenetic dysregulation has been implicated in neurodegenerative disorders, while targeting histone acetylation is a promising therapeutic avenue for PD. We and others have demonstrated that histone deacetylase inhibitors have neurotrophic effects in experimental models of PD. Activators of histone acetyltransferases (HAT) provide an alternative approach for the selective activation of gene expression, however little is known about the potential of HAT activators as drug therapies for PD. To explore this potential, the present study investigated the neurotrophic effects of CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), which is a potent small molecule activator of the histone acetyltransferase p300/CBP, in the SH-SY5Y neuronal cell line. We report that CTPB promoted the survival and neurite growth of the SH-SY5Y cells, and also protected these cells from cell death induced by the neurotoxin 6-hydroxydopamine. This study is the first to investigate the phenotypic effects of the HAT activator CTPB, and to demonstrate that p300/CBP HAT activation has neurotrophic effects in a cellular model of PD

    Romidepsin induces caspase-dependent cell death in human neuroblastoma cells

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    Neuroblastoma is the most common extracranial pediatric solid tumor, arising from the embryonic sympathoadrenal lineage of the neural crest, and is responsible for 15% of childhood cancer deaths. Although survival rates are good for some patients, those children diagnosed with high-risk neuroblastoma have survival rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge and the development of novel therapeutic strategies is essential. Given that there is widespread epigenetic dysregulation in neuroblastoma, epigenetic pharmacotherapy holds promise as a therapeutic approach. In recent years, histone deacetylase (HDAC) inhibitors, which cause selective activation of gene expression, have been shown to be potent chemotherapeutics for the treatment of a wide range of cancers. Here we examined the ability of the FDA-approved drug Romidepsin, a selective HDAC1/2 inhibitor, to act as a cytotoxic agent in neuroblastoma cells. Treatment with Romidepsin at concentrations in the low nanomolar range induced neuroblastoma cell death through caspase-dependent apoptosis. Romidepsin significantly increased histone acetylation, and significantly enhanced the cytotoxic effects of the cytotoxic agent 6-hydroxydopamine, which has been shown to induce cell death in neuroblastoma cells through increasing reactive oxygen species. Romidepsin was also more potent in MYCN-amplified neuroblastoma cells, which is an important prognostic marker of poor survival. This study has thus demonstrated that the FDA-approved chemotherapeutic drug Romidepsin has a potent caspase-dependent cytotoxic effect on neuroblastoma cells, whose effects enhance cell death induced by other cytotoxins, and suggests that Romidepsin may be a promising chemotherapeutic candidate for the treatment of neuroblastoma

    Broad-scale mapping of seafloor habitats in the north-east Atlantic using existing environmental data

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    If marine management policies and actions are to achieve long-term sustainable use and management of the marine environment and its resources, they need to be informed by data giving the spatial distribution of seafloor habitats over large areas. Broad-scale seafloor habitat mapping is an approachwhich has the benefit of producing maps covering large extents at a reasonable cost. This approach was first investigated by Roff et al. (2003), who, acknowledging that benthic communities are strongly influenced by the physical characteristics of the seafloor, proposed overlaying mapped physical variables using a geographic information system (GIS) to produce an integrated map of the physical characteristics of the seafloor. In Europe the method was adapted to the marine section of the EUNIS (European Nature Information System) classification of habitat types under the MESH project, andwas applied at an operational level in 2011 under the EUSeaMap project. The present study compiled GIS layers for fundamental physical parameters in the northeast Atlantic, including (i) bathymetry, (ii) substrate type, (iii) light penetration depth and (iv) exposure to near-seafloor currents andwave action. Based on analyses of biological occurrences, significant thresholds were fine-tuned for each of the abiotic layers and later used in multi-criteria raster algebra for the integration of the layers into a seafloor habitat map. The final result was a harmonised broad-scale seafloor habitat map with a 250 m pixel size covering four extensive areas, i.e. Ireland, the Bay of Biscay, the Iberian Peninsula and the Azores. The map provided the first comprehensive perception of habitat spatial distribution for the Iberian Peninsula and the Azores, and fed into the initiative for a pan- European map initiated by the EUSeaMap project for Baltic, North, Celtic and Mediterranean seas.info:eu-repo/semantics/publishedVersio

    Mapping seabed habitats over large areas: prospects and limits

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    Since its inception, in 2009, EMODnet Seabed Habitats has brought together a European consortium of specialists in benthic ecology and seabed habitat mapping to develop a transnational broad-scale seabed habitat map, named EUSeaMap. EUSeaMap is the only pan-European cartographic product that provides a standardised trans-boundary overview of the spatial distribution of seabed habitats across Europe. As such, it has been extensively used in various applications such as Marine Protected Area evaluation or cumulative impact of stressors on habitats, and it is likely to be used again in the future in various marine ecosystem assessments. It is therefore important to continue to update it regularly when significant improvements to the data products that constitute its basis, i.e. the seabed substrate, bathymetry or environmental variables, are published. In addition to EUSeaMap, it would be desirable to provide stakeholders with products on the spatial distribution of targeted habitats/biotopes such as those of conservation interest (e.g. kelp forest, seagrass meadows, coral reefs). Some techniques, hereafter referred to as "SDMs", are acknowledged to be effective in mapping these habitats. We argue that a program that would use these techniques to map these key habitats/biotopes in European waters would be invaluable, but such a program can only be achieved if there is a significant improvement in the spatial resolution of environmental variables. An important message of this report is therefore that the EU should consider funding a project that would develop spatially explicit high-resolution (at least 500 m) data products on key variables (light availability, hydrodynamics, wave exposure, temperature, oxygenation, chlorophyll-a, phosphate, nitrate, etc.) that would spatially cover all European waters

    EUSeaMap 2019, A European broad-scale seabed habitat map, technical report

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    EUSeaMap 2019 is the third iteration of EUSeaMap. All versions have been produced as part of the EMODnet Seabed Habitats project, which is one of several thematic lots in EMODnet. The project has brought together a European consortium of specialists in benthic ecology and seabed habitat mapping. The partners first collaborated in EMODnet phase 1 (2009-2012) to deliver a prototype predictive seabed habitat map in four trial basins (Greater North Sea, Celtic Seas, Baltic, Western Mediterranean). This predictive model was named EUSeaMap (Cameron and Askew, 2011). In EMODnet Phase 2 (2012-2016), the consortium extended EUSeaMap coverage to all European regions (Populus et al, 2017). In the new version, the spatial coverage was extended further North in order to include the Barents Sea. The spatial detail was substantially improved. This was made possible by improvements to the physical predictor variables created by the other EMODnet lots which are the input data to the EUSeaMap model. A substantial revision of the map creation process has also been carried out in order to make it more reproducible. This document describes all these modifications which have led to the elaboration of EUSeaMap 2019

    EUSeaMap 2021. A European broad-scale seabed habitat map

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    EUSeaMap 2021 is the fifth iteration of EUSeaMap. All versions have been produced as part of the EMODnet Seabed Habitats project, which is one of several thematic lots in EMODnet. The project has brought together a European consortium of specialists in benthic ecology and seabed habitat mapping. The partners first collaborated in EMODnet phase 1 (2009-2012) to deliver a prototype predictive seabed habitat map in four trial basins (Greater North Sea, Celtic Seas, Baltic, Western Mediterranean). This predictive model was named EUSeaMap (Cameron and Askew, 2011). In EMODnet Phase 2 (2012-2016), the consortium extended EUSeaMap coverage to all European regions (Populus et al, 2017). In phase 3 (2017-2021), a first version (2019) extended the spatial coverage further North in order to include the Barents Sea, developed better environmental data were incorporated, and dramatically improved the spatial detail. The new version, developed in the period 2019-2021 and named 2021, is substantially evolved from the previous version as it accounts for new seabed substrate data published by EMODnet Geology in 2021, including in Denmark, Estonia, France, Ireland, Italy, Latvia, Norway and Spain, 2) is published in new classifications, including the new version of the marine section of EUNIS, named EUNIS 2019 and 3) addresses some issues identified in EUSeaMap 2019

    EUSeaMap 2023, A European broad-scale seabed habitat map, Technical Report

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    EUSeaMap 2023 is the sixth iteration of EUSeaMap. All versions have been produced as part of the EMODnet Seabed Habitats project, which is one of several thematic lots in EMODnet. The project has brought together a European consortium of specialists in benthic ecology and seabed habitat mapping. The partners first worked together in EMODnet Phase 1 (2009-2012) to develop a prototype predictive seabed habitat map in four test basins (Greater North Sea, Celtic Seas, Baltic Sea, Western Mediterranean). This predictive model was named EUSeaMap (Cameron and Askew, 2011). In EMODnet Phase 2 (2012-2016), the consortium extended the spatial coverage of EUSeaMap to all European regions (Populus el al., 2017). In Phase 3 (2017-2021), a first version (2019) extended the spatial coverage further north to include the Barents Sea, incorporated improved environmental data, and dramatically improved the spatial detail. In 2021 EUSeaMap was improved with new seabed substrate data and was published in new classifications, including the new version of the marine section of EUNIS, called EUNIS 2019. In this new version, called EUSeaMap 2023, EUSeaMap has been extended to the Caribbean Sea and the Caspian Sea. In Continental Europe, Macaronesia, Iceland and the Arctic, progress has been made in integrating new data on seabed substrate, bathymetry, wave energy and the probability of the occurrence of the halocline at the bottom of the Baltic Sea
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