Exchange of nutrients and oxygen across the sediment-water interface below a Sparus aurata marine fish farm in the north-western Mediterranean Sea

Purpose: This study analyzes the effects of aquaculture activities in open seawater in the north-western coastal waters of the Mediterranean Sea. It is the first of its kind to be based on benthic flux data gathered in situ below fish farms for this particular area. Materials and methods: Samples were collected on four sampling campaigns over a 1-year cycle under a Sparus aurata fish farm facility where benthic fluxes were measured in situ using light and dark benthic chambers. Bottom water and sediment samples were also collected. Data were compared to those for a nearby control station. Results and discussion: Significant differences were found (ANOVA, p < 0. 05) between concentrations of organic matter (OM), total phosphorus and redox potentials in sediments located under the cages and those of the control station. The consumption of dissolved oxygen (DO) by sediment and positive ammonium (NH4 +) fluxes was stimulated by OM content, with correlations of r = -0. 60 (p < 0. 01) and r = 0. 70 (p < 0. 01), respectively. The OM content of sediments was found to be consistently higher under the cages than at the control station, with the highest value (1. 8 ± 0. 7 %) under the cages observed during the early summer; values of DO and NH4 + fluxes were -64 ± 17 and 12. 7 ± 1. 0 mmol m-2 day-1, respectively. PO4 3- fluxes were consistently higher in the fish farm sediments (between 0. 58 and 0. 98 mmol m-2 day-1) than those observed at the control station. Nitrate (NO3 -) fluxes were found to be consistently negative due to denitrification occurring in the sediments and were related to the concentration of NO3 - in bottom waters (r = 0. 92, p < 0. 01). Si fluxes were shown to be associated with water temperature (r = 0. 59, p < 0. 05). Conclusions: The results imply that sediments located below cages accumulate organic matter originating from aquaculture activities, especially during summer months when this activity increases. Sediments undergo biogeochemical changes that mainly affect fluxes of DO, NH4 + and soluble reactive phosphorus, although these do not seem to have a significant impact on the quality of the water column due to the hydrodynamic characteristics of the area. © 2012 Springer-Verlag.We would like to thank the Caja del Mediterraneo for a predoctoral fellowship fund for this research and Antonio Asuncion Acuigroup Maremar manager for the facilities and support in conducting the study. The translation of this paper was funded by the Universidad Politecnica de Valencia, Spain. We are grateful for the valuable comments of the anonymous reviewers on previous versions of the manuscript.Morata Higón, T.; Sospedra, J.; Falco Giaccaglia, SL.; Rodilla Alama, M. (2012). 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Reviewing, indicating, and counting books for modern research evaluation systems

In this chapter, we focus on the specialists who have helped to improve the conditions for book assessments in research evaluation exercises, with empirically based data and insights supporting their greater integration. Our review highlights the research carried out by four types of expert communities, referred to as the monitors, the subject classifiers, the indexers and the indicator constructionists. Many challenges lie ahead for scholars affiliated with these communities, particularly the latter three. By acknowledging their unique, yet interrelated roles, we show where the greatest potential is for both quantitative and qualitative indicator advancements in book-inclusive evaluation systems.Comment: Forthcoming in Glanzel, W., Moed, H.F., Schmoch U., Thelwall, M. (2018). Springer Handbook of Science and Technology Indicators. Springer Some corrections made in subsection 'Publisher prestige or quality

Characterisation of paediatric brain tumours by their MRS metabolite profiles.

1 H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours

Advances in understanding and treating ADHD

Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability

Acute exposure to a high-fat diet in juvenile male rats disrupts hippocampal-dependent memory and plasticity through glucocorticoids

The limbic circuit is still undergoing maturation during juvenility and adolescence, explaining why environmental and metabolic challenges during these developmental periods can have specific adverse effects on cognitive functions. We have previously shown that long-term exposure (8-12 weeks) to high-fat diet (HFD) during adolescence (from weaning to adulthood), but not at adulthood, was associated with altered amygdala and hippocampal functions. Moreover, these HFD effects were normalized by treatment with glucocorticoid receptor (GR) antagonists. Here, we examined in male rats whether acute exposure (7-9 days) to HFD during juvenility [from postnatal day (PND) 21 to PND 28-30] or adulthood (from PND 60 to PND 67-69) is sufficient to affect hippocampal functions and whether it is also dependent on GRs activation. Juvenile HFD abolished both hippocampal synaptic plasticity, assessed through in vivo long-term potentiation (LTP) in CA1, and long-term hippocampal-dependent memory, using object location memory (OLM). No effect of HFD was observed in short-term OLM suggesting a specific effect on consolidation process. In contrast, adult HFD enhanced in vivo LTP and OLM. Systemic application of GR antagonist alleviated HFD-induced LTP and OLM impairments in juveniles. These results suggest that acute exposure to HFD during juvenility is sufficient to impair hippocampal functions in a GR-dependent manner. Interestingly, this effect depends on the developmental period studied as acute exposure to HFD at adulthood did not impair, but rather enhanced, hippocampal functions

Some environmental factors influencing phytoplankton in the Southern Ocean around South Georgia

Data on phytoplankton and zooplankton biomass, and physical and chemical variables, are combined with a published multivariate description of diatom species composition to interpret variation within an area around South Georgia surveyed during an austral summer. Large-scale species distributions could be equated to the different water masses which reflected the interaction of the Antarctic Circumpolar Current with the island and the Scotia Ridge. Small-scale factors were found to act at an interstation scale and imposed local variation on the biogeographic pattern. Nutrient depletion could be related to phytoplankton biomass but no single inorganic nutrient of those measured (NO 3 −N, PO 4 −P and silica) could be identified as important. The ratio Si:P appeared to be more important as an ecological factor. The impact of grazing by krill and other zooplankton could only be resolved as differences in phytoplankton biomass and phaeopigment content. Diatom species composition showed a relation to local krill abundance very different from that suggested by published studies, but could be explained as the effect of earlier grazing outside the study area. The effects of vertical mixing could not account for interstation differences as pycnocline depth was uniformly greater than euphotic depth, and vertical stability very low. Some comparison was made with data collected in 1926–31 by the Discovery Investigations. Significant differences in the distribution of certain taxa such as Chaetoceros criophilum and C. socialis were traced to major differences in hydrology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46983/1/300_2004_Article_BF00443379.pd

P2X<inf>7</inf> receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages

The P2X7R is highly expressed on the macrophage cell surface, and activation of infected cells by extracellular ATP has been shown to kill intracellular bacteria and parasites. Furthermore, single nucleotide polymorphisms that decrease receptor function reduce the ability of human macrophages to kill Mycobacterium tuberculosis and are associated with extrapulmonary tuberculosis. In this study, we show that macrophages from people with the 1513C (rs3751143, NM-002562.4:c.1487A>C) loss-of-function P2X 7R single nucleotide polymorphism are less effective in killing intracellular Toxoplasma gondii after exposure to ATP compared with macrophages from people with the 1513A wild-type allele. Supporting a P2X 7R-specific effect on T. gondii, macrophages from P2X7R knockout mice (P2X7R-/-) are unable to kill T. gondii as effectively as macrophages from wild-type mice. We show that P2X 7R-mediated T. gondii killing occurs in parallel with host cell apoptosis and is independent of NO production. Copyright © 2010 by The American Association of Immunologists, Inc

A five-gene hedgehog signature developed as a patient preselection tool for hedgehog inhibitor therapy in medulloblastoma

Purpose:&nbsp;Distinct molecular subgroups of medulloblastoma (MB), including hedgehog (Hh) pathway-activated disease, have been reported. We identified and clinically validated a five-gene Hh signature assay that can be used to preselect patients with Hh pathway-activated MB. Experimental Design: Genes characteristic of the Hh MB subgroup were identified through published bioinformatic analyses. Thirty-two genes shown to be differentially expressed in fresh frozen and formalin-fixed paraffin-embedded tumor samples and reproducibly analyzed by RT-PCR were measured in matched samples. These data formed the basis for building a multi-gene logistic regression model derived through elastic net methods from which the five-gene Hh signature emerged after multiple iterations. Based on signature gene expression levels, the model computed a propensity score to determine Hh activation using a threshold set a priori. The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed. Results: Five differentially expressed genes in MB (GLI1, SPHK1, SHROOM2, PDLIM3, and OTX2) were found to associate with Hh pathway activation status. In an independent validation study, Hh activation status of 25 MB samples showed 100% concordance between the five-gene signature and Affymetrix profiling. Further, in MB samples from 50 patients treated with sonidegib, all six patients who responded were found to have Hh-activated tumors. Three patients with Hh-activated tumors had stable or progressive disease. No patients with Hh-nonactivated tumors responded. Conclusions: This five-gene Hh signature can robustly identify Hh-activated MB and may be used to preselect patients who might benefit from sonidegib treatment.</div

A Cell-Based MAPK Reporter Assay Reveals Synergistic MAPK Pathway Activity Suppression by MAPK Inhibitor Combination in BRAF-Driven Pediatric Low-Grade Glioma Cells

Pilocytic astrocytomas (PAs) as well as other pediatric low-grade gliomas (pLGGs) exhibit genetic events leading to aberrant activation of the MAPK pathway. The most common alterations are KIAA1549:BRAF fusions, BRAFV600E and NF1 mutations. Novel drugs targeting the MAPK pathway (MAPKi) are prime candidates for the treatment of these single-pathway diseases. We aimed to develop an assay suitable for pre-clinical testing of MAPKi in pLGGs with the goal to identify novel MAPK pathway suppressing synergistic drug combinations. A reporter plasmid (pDIPZ) with a MAPK-responsive ELK-1-binding element driving the expression of destabilized firefly luciferase was generated and packaged using a lentiviral vector system. Pediatric glioma cell lines with a BRAF fusion (DKFZ-BT66) and a BRAFV600E mutation (BT-40) background, respectively, were stably transfected. Modulation of the MAPK pathway activity by MAPKi was measured using the luciferase reporter and validated by detection of phosphorylated protein levels. A screen of a MAPKi library was performed and synergy of selected combinations was calculated. Screening of a MAPKi library revealed MEK inhibitors as the class inhibiting the pathway with the lowest IC50s, followed by ERK and next-generation RAF inhibitors. Combination treatments with different MAPKi classes showed synergistic effects in BRAF fusion as well as BRAFV600E mutation backgrounds. We here report a novel reporter assay for medium- to high-throughput pre-clinical drug testing in pLGG cell lines. The assay confirmed MEK, ERK and next-generation RAF inhibitors as potential treatment approaches for KIAA1549:BRAF and BRAFV600E mutated pLGGs. In addition, the assay revealed that combination treatments synergistically suppressed MAPK pathway activity