902 research outputs found

    Learning Together: Modern Developments In Education Law

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    Panel Discussion from legal practitioners discussing the various challenges and processes of working in the field of education law

    Impact of RNA Editing on Functions of the Serotonin 2C Receptor in vivo

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    Transcripts encoding 5-HT2C receptors are modified posttranscriptionally by RNA editing, generating up to 24 protein isoforms. In recombinant cells, the fully edited isoform, 5-HT2C-VGV, exhibits blunted G-protein coupling and reduced constitutive activity. The present studies examine the signal transduction properties of 5-HT2C-VGV receptors in brain to determine the in vivo consequences of altered editing. Using mice solely expressing the 5-HT2C-VGV receptor (VGV/Y), we demonstrate reduced G-protein coupling efficiency and high-affinity agonist binding of brain 5-HT2C-VGV receptors. However, enhanced behavioral sensitivity to a 5-HT2C receptor agonist was also seen in mice expressing 5-HT2C-VGV receptors, an unexpected finding given the blunted G-protein coupling. In addition, mice expressing 5-HT2C-VGV receptors had greater sensitivity to a 5-HT2C inverse agonist/antagonist enhancement of dopamine turnover relative to wild-type mice. These behavioral and biochemical results are most likely explained by increases in 5-HT2C receptor binding sites in the brains of mice solely expressing 5-HT2C-VGV receptors. We conclude that 5-HT2C-VGV receptor signaling in brain is blunted, but this deficiency is masked by a marked increase in 5-HT2C receptor binding site density in mice solely expressing the VGV isoform. These findings suggest that RNA editing may regulate the density of 5-HT2C receptor binding sites in brain. We further caution that the pattern of 5-HT2C receptor RNA isoforms may not reflect the pattern of protein isoforms, and hence the inferred overall function of the receptor

    Spatial Analysis of Cirques from Three Regions of Iceland: Implications for Cirque Formation and Palaeoclimate

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    This study is a quantitative analysis of cirques in three regions of Iceland: Tröllaskagi, the East Fjords and Vestfirðir. Using Google Earth and the National Land Survey of Iceland Map Viewer, we identified 347 new cirques on Tröllaskagi and the East Fjords region, and combined these data with 100 cirques previously identified on Vestfirðir. We used ArcGIS to measure length, width, aspect, latitude and distance to coastline of each cirque. Palaeo‐equilibrium‐line altitudes (palaeo‐ELAs) of palaeo‐cirque glaciers were calculated using the altitude‐ratio method, cirque‐floor method and minimum‐point method. The mean palaeo‐ELA values in Tröllaskagi, the East Fjords and Vestfirðir are 788, 643 and 408 m a.s.l, respectively. Interpolation maps of palaeo‐ELAs demonstrate a positive relationship between palaeo‐ELA and distance to coastline. A positive relationship between palaeo‐ELA and latitude is observed on Vestfirðir, a negative relationship is observed on Tröllaskagi and no statistically significant relationship is present on the East Fjords. The modal orientation of cirques on Tröllaskagi and Vestfirðir is northeast, while orientation of cirques in the East Fjords is north. Palaeo‐wind reconstructions for the LGM show that modal aspect is aligned with the prevailing north‐northeast wind directions, although aspect measurements demonstrate wide dispersion. Cirque length is similar on Tröllaskagi and the East Fjords, but cirques are approximately 200 m shorter in Vestfirðir. Cirque widths are similar in all three regions. Comparisons with a global data set show that cirques in Iceland are smaller and more circular than cirques in other regions of the world. Similar to glaciers in Norway and Kamchatka, our results demonstrate that access to a moisture source is a key parameter in determining palaeo‐ELAs in Iceland. Temperatures interpreted from palaeo‐ELA depressions suggest that these cirques may have been glaciated as recently as the Little Ice Age

    Pediatric ergot alkaloid exposures reported to the California Poison Control System: 1997–2008

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    ContextThe risk of toxicity from exposure to ergot alkaloid-containing medications in children is uncertain. Due to the alarming historical experience with severe toxicity and the syndrome of ergotism from natural and synthetic ergot alkaloids, triage recommendations for pediatric exposures to medicinal agents containing ergot alkaloids may be inappropriate and inconsistent.ObjectivesThe goal of this study was to describe the clinical effects of unintentional ergot alkaloid exposures in children and to identify the need for hospitalization in these cases.MethodsThis was a retrospective cohort study of all pediatric (< 7 years old) ergot alkaloid exposures reported to the California Poison Control System (CPCS) from 1997 to 2008. Case narratives were reviewed and assessed for patient demographics, ergot alkaloid agent and dose, route of and reason for exposure, symptoms, therapy, hospitalization period, and final outcome.ResultsOf the 374 cases, 353 met the inclusion criteria. The median age was 24 months (Range: 7-72 months) with more than 99% oral route of exposure. The most frequent clinical effect was gastrointestinal distress (16%), followed by lethargy (5%). Two cases with significant vascular and CNS symptoms were identified, both with complete recovery. For symptomatic patients, all symptoms were there at time of initial presentation. The majority, 62%, of all patients were treated in the hospital setting. The median length of hospital stay was 4 h (Range: 1-36 h). Ergot exposures had a similar number of serious outcomes (moderate or worse effects) compared to all other pediatric poisonings reported to the CPCS during the study period (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.25-3.95), but were associated with a disproportionately higher number of hospitalizations (OR, 13.8; 95% CI, 11.1-17.1).ConclusionsPediatric ergot exposures were associated with few transient adverse effects but multiple hospitalizations. Rare cases of significant toxicity associated with methylergonovine exposures were found. Current poison control send-in protocols and emergency department (ED) guidelines should consider home management and short ED stays as opposed to lengthy critical care bed admissions

    Laminar-turbulent transition in Raman fiber lasers:a first passage statistics based analysis

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    Loss of coherence with increasing excitation amplitudes and spatial size modulation is a fundamental problem in designing Raman fiber lasers. While it is known that ramping up laser pump power increases the amplitude of stochastic excitations, such higher energy inputs can also lead to a transition from a linearly stable coherent laminar regime to a non-desirable disordered turbulent state. This report presents a new statistical methodology, based on first passage statistics, that classifies lasing regimes in Raman fiber lasers, thereby leading to a fast and highly accurate identification of a strong instability leading to a laminar-turbulent phase transition through a self-consistently defined order parameter. The results have been consistent across a wide range of pump power values, heralding a breakthrough in the non-invasive analysis of fiber laser dynamics

    An Arabidopsis flavonoid transporter is required for anther dehiscence and pollen development

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    FLOWER FLAVONOID TRANSPORTER (FFT) encodes a multidrug and toxin efflux family transporter in Arabidopsis thaliana. FFT (AtDTX35) is highly transcribed in floral tissues, the transcript being localized to epidermal guard cells, including those of the anthers, stigma, siliques and nectaries. Mutant analysis demonstrates that the absence of FFT transcript affects flavonoid levels in the plant and that the altered flavonoid metabolism has wide-ranging consequences. Root growth, seed development and germination, and pollen development, release and viability are all affected. Spectrometry of mutant versus wild-type flowers shows altered levels of a glycosylated flavonol whereas anthocyanin seems unlikely to be the substrate as previously speculated. Thus, as well as adding FFT to the incompletely described flavonoid transport network, it is found that correct reproductive development in Arabidopsis is perturbed when this particular transporter is missing

    Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

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    Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

    How to distinguish starbursts and quiescently star-forming galaxies: The `bimodal' submillimetre galaxy population as a case study

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    In recent work (arXiv:1101.0002) we have suggested that the high-redshift (z ~ 2-4) bright submillimetre galaxy (SMG) population is heterogeneous, with major mergers contributing both at early stages, where quiescently star-forming discs are blended into one submm source (`galaxy-pair SMGs'), and late stages, where mutual tidal torques drive gas inflows and cause strong starbursts. Here we combine hydrodynamic simulations of major mergers with 3-D dust radiative transfer calculations to determine observational diagnostics that can distinguish between quiescently star-forming SMGs and starburst SMGs via integrated data alone. We fit the far-IR SEDs of the simulated galaxies with the optically thin single-temperature modified blackbody, the full form of the single-temperature modified blackbody, and a power-law temperature-distribution model. The effective dust temperature, T_dust, and power-law index of the dust emissivity in the far-IR, \beta, derived can significantly depend on the fitting form used, and the intrinsic \beta\ of the dust is not recovered. However, for all forms used here, there is a T_dust above which almost all simulated galaxies are starbursts, so a T_dust cut is very effective at selecting starbursts. Simulated merger-induced starbursts also have higher L_IR/M_gas and L_IR/L_FUV than quiescently star-forming galaxies and lie above the star formation rate-stellar mass relation. These diagnostics can be used to test our claim that the SMG population is heterogeneous and to observationally determine what star formation mode dominates a given galaxy population. We comment on applicability of these diagnostics to ULIRGs that would not be selected as SMGs. These `hot-dust ULIRGs' are typically starburst galaxies lower in mass than SMGs, but they can also simply be SMGs observed from a different viewing angle.Comment: 21 pages, 11 figures. Accepted for publication in MNRAS. Minor changes to text but otherwise identical to v

    A Rapid New Assay to Detect RNA Editing Reveals Antipsychotic-Induced Changes in Serotonin-2C Transcripts

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    ABSTRACT We report the development of a new assay as an alternative to direct DNA sequencing to measure RNA-edited variation in tissue. The new assay has been validated and is accurate, cheaper, more rapid, and less labor-intensive than DNA sequencing. We also outline the statistical modeling required for analyses of the hierarchical, clustered RNA-editing data generated in these studies. Using the new technique, we analyzed the effects of long-term antipsychotic medication on serotonin-2C receptor (5-HT 2C R) RNA editing in rat brain. Our hypothesis that a drug with high affinity for 5-HT 2C R, such as clozapine, would alter its RNA-editing profile was not confirmed. Whereas haloperidol, a typical antipsychotic drug that is primarily a dopamine receptor antagonist, reduced 5-HT 2C VNV isoform frequency and the level of RNA editing at the D site, risperidone and not the prototype atypical antipsychotic drug clozapine increased the frequency of 5-HT 2C VNV and D-site editing. Our data emphasize that caution is required in the interpretation of RNA-editing data in studies of psychiatric disorders, because these studies usually include subjects who received long-term exposure to medication. This newly established method will facilitate high-throughput investigations of RNA editing in disease pathology and in the pharmacological activity of drugs. The revelation that the human genome comprises between 30,000 and 40,000 protein-coding genes was unexpected, because such few genes are unlikely to explain the functional diversity between humans and less complex organisms. These interspecies differences could arise from post-transcriptional processes such as RNA editing and alternative splicing, which allow a single gene to generate several protein variants. The current study focuses on RNA editing. The recent detection of 1637 potential new substrates for RNA editing Because of their relatively recent discovery, substrates of RNA editing have not been extensively characterized. Adenine-to-inosine RNA editing in mammalian brain has been identified in ionotropic receptors (such as the GluR2 subunit of the ␣-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor) and in the serotonin (5-HT)-2C receptor (R), which is coupled to GTP-binding protein. Discrepancies between genomic DNA and cDNA sequences led to the discovery of nucleotide changes caused by the activity of ADAR enzymes. In the fully edited 5-HT 2C R, three amino acid codons in the pre-mRNA are changed so that the sequence coding for IRNPI becomes VRGP
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