Cell-type specific analysis of translating RNAs in developing flowers reveals new levels of control

Determining both the expression levels of mRNA and the regulation of its translation is important in understanding specialized cell functions. In this study, we describe both the expression profiles of cells within spatiotemporal domains of the Arabidopsis thaliana flower and the post-transcriptional regulation of these mRNAs, at nucleotide resolution. We express a tagged ribosomal protein under the promoters of three master regulators of flower development. By precipitating tagged polysomes, we isolated cell type specific mRNAs that are probably translating, and quantified those mRNAs through deep sequencing. Cell type comparisons identified known cell-specific transcripts and uncovered many new ones, from which we inferred cell type-specific hormone responses, promoter motifs and coexpressed cognate binding factor candidates, and splicing isoforms. By comparing translating mRNAs with steady-state overall transcripts, we found evidence for widespread post-transcriptional regulation at both the intron splicing and translational stages. Sequence analyses identified structural features associated with each step. Finally, we identified a new class of noncoding RNAs associated with polysomes. Findings from our profiling lead to new hypotheses in the understanding of flower development

Distinct sulfur saturation histories within the Palaeogene Magilligan Sill, Northern Ireland: Implications for Ni-Cu-PGE mineralisation in the North Atlantic Igneous Province

This is the author accepted manuscript. The final version is available from NRC Research Press via the DOI in this record.The ~60 m thick Magilligan Sill is part of the British Palaeogene Igneous Province in the North Atlantic. The sill comprises layers of dolerite and olivine gabbro, and it intrudes a thick sequence of Mesozoic mudstones and marls, which are locally baked at the sill margins. Since 2014, the sill has been an exploration target for orthomagmatic Ni-Cu-PGE sulfide mineralisation analogous to the Noril’sk-Talnakh intrusion in Russia. We present new petrological, geochemical and S-isotope data to assess the prospectivity of the sill and the underlying magmatic plumbing system. Most sulfides in the dolerite portions of the sill are < 50 μm in size and comprise only pyrite with PGE abundances below detection limit. In the olivine gabbros, > 150 μm size pentlandite, chalcopyrite and pyrrhotite grains contain < 4 ppm total PGE, 1 460 ppm Co and 88 ppm Ag. Pyrite from the dolerites have δ34S ranging from -10.0 to +3.4 ‰ and olivine gabbro sulfides range from -2.5 to -1.1 ‰, suggesting widespread crustal contamination. The S/Se ratios of sulfides in the dolerites and olivine gabbros range from 3 500 to 19 500 and from 1 970 to 3 710, respectively, indicating that the latter may have come from upstream in the magma plumbing system. The Magilligan Sill records multiple injections of mafic magma into an inflating sill package, each with distinct mechanisms towards S-saturation. Whilst the sulfide minerals in the sill do not constitute significant mineralisation themselves, detailed in-situ studies highlight a divergence in Ssaturation histories, and suggest that a larger volume of olivine gabbro sulfides at depth may be prospective

On the Emergence of Tremor in Prodromal Parkinson's Disease

Clinical, neuropathological and neuroimaging research suggests that pathological changes in Parkinson’s disease (PD) start many years before the emergence of motor signs. Since disease-modifying treatments are likely to be most effective when initiated early in the disease process, there has been significant interest in characterizing prodromal PD. Some people with PD describe autonomic symptoms at the time of diagnosis suggesting that autonomic dysfunction is a common feature of prodromal PD. Furthermore, subtle motor signs may be present and emerge prior to the time of diagnosis. We present a series of patients who, in the prodromal phase of PD, experienced the emergence of tremor initially only while yawning or straining at stool and discuss how early involvement of autonomic brainstem nuclei could lead to these previously unreported phenomena. The hypothalamic paraventricular nucleus (PVN) plays a central role in autonomic control including bowel/bladder function, cardiovascular homeostasis and yawning and innervates multiple brainstem nuclei involved in autonomic functions (including brainstem reticular formation, locus ceruleus, dorsal raphe nucleus and motor nucleus of the vagus). The PVN is affected in PD and evidence from related phenomena suggest that the PVN could increase tremor either by increasing downstream cholinergic activity on brainstem nuclei such as the reticular formation or by stimulating the locus ceruleus to activate the cerebellothalamocortical network via the ventrolateral nucleus of the thalamus. Aberrant cholinergic/noradrenergic transmission between these brainstem nuclei early in PD couldlead to tremor before the emergence of other parkinsonian signs, representing an early clinical clue to prodromal PD

Electric Car Purchase Price as a Factor Determining Consumers’ Choice and their Views on Incentives in Europe

The deployment of zero-emission vehicles has the potential to drastically reduce air pollution and greenhouse gas emissions from road transport. The purpose of this study is to provide evidence on, and quantify the factors that influence, the European market for electric and fuel cell car technologies. The paper reports the results of a stated preference survey among 1,248 car owners in France, Germany, Italy, Poland, Spain and the United Kingdom. The variables that influence powertrain choice are quantified in a nested multinomial logit model. We find that the electric car purchase price continues to be a major deterrent to sales in the surveyed countries. The majority of the respondents considered government incentives as fundamental or important for considering an electric car purchase. Because of the differences in the socio-economic characteristics of consumers in each country, the effectiveness of government incentives may vary across Europe

Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool.

To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT)

Adverse drug reactions and off-label and unlicensed medicines in children: a nested case control study of inpatients in a pediatric hospital

Off-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs

Microarray-based gene set analysis: a comparison of current methods

BACKGROUND: The analysis of gene sets has become a popular topic in recent times, with researchers attempting to improve the interpretability and reproducibility of their microarray analyses through the inclusion of supplementary biological information. While a number of options for gene set analysis exist, no consensus has yet been reached regarding which methodology performs best, and under what conditions. The goal of this work was to examine the performance characteristics of a collection of existing gene set analysis methods, on both simulated and real microarray data sets. Of particular interest was the potential utility gained through the incorporation of inter-gene correlation into the analysis process. RESULTS: Each of six gene set analysis methods was applied to both simulated and publicly available microarray data sets. Overall, the various methodologies were all found to be better at detecting gene sets that moved from non-active (i.e., genes not expressed) to active states (or vice versa), rather than those that simply changed their level of activity. Methods which incorporate correlation structures were found to provide increased ability to detect altered gene sets in some settings. CONCLUSION: Based on the results obtained through the analysis of simulated data, it is clear that the performance of gene set analysis methods is strongly influenced by the features of the data set in question, and that methods which incorporate correlation structures into the analysis process tend to achieve better performance, relative to methods which rely on univariate test statistics

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children - a prospective observational cohort study of 6,601 admissions

Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors

Quantifying vertical mixing in estuaries

© 2008 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Environmental Fluid Mechanics 8 (2008): 495-509, doi:10.1007/s10652-008-9107-2.Estuarine turbulence is notable in that both the dissipation rate and the buoyancy frequency extend to much higher values than in other natural environments. The high dissipation rates lead to a distinct inertial subrange in the velocity and scalar spectra, which can be exploited for quantifying the turbulence quantities. However, high buoyancy frequencies lead to small Ozmidov scales, which require high sampling rates and small spatial aperture to resolve the turbulent fluxes. A set of observations in a highly stratified estuary demonstrate the effectiveness of a vessel-mounted turbulence array for resolving turbulent processes, and for relating the turbulence to the forcing by the Reynolds-averaged flow. The observations focus on the ebb, when most of the buoyancy flux occurs. Three stages of mixing are observed: (1) intermittent and localized but intense shear instability during the early ebb; (2) continuous and relatively homogeneous shear-induced mixing during the mid-ebb, and weakly stratified, boundary-layer mixing during the late ebb. The mixing efficiency as quantified by the flux Richardson number Rf was frequently observed to be higher than the canonical value of 0.15 from Osborn (J Phys Oceanogr 10:83–89, 1980). The high efficiency may be linked to the temporal–spatial evolution of shear instabilities.The funding for this research was obtained from ONR Grant N00014-06-1-0292 and NSF Grant OCE-0729547

Adaptive Filtering Enhances Information Transmission in Visual Cortex

Sensory neuroscience seeks to understand how the brain encodes natural environments. However, neural coding has largely been studied using simplified stimuli. In order to assess whether the brain's coding strategy depend on the stimulus ensemble, we apply a new information-theoretic method that allows unbiased calculation of neural filters (receptive fields) from responses to natural scenes or other complex signals with strong multipoint correlations. In the cat primary visual cortex we compare responses to natural inputs with those to noise inputs matched for luminance and contrast. We find that neural filters adaptively change with the input ensemble so as to increase the information carried by the neural response about the filtered stimulus. Adaptation affects the spatial frequency composition of the filter, enhancing sensitivity to under-represented frequencies in agreement with optimal encoding arguments. Adaptation occurs over 40 s to many minutes, longer than most previously reported forms of adaptation.Comment: 20 pages, 11 figures, includes supplementary informatio