Genome-wide profiling of methylation identifies novel targets with aberrant hyper-methylation and reduced expression in low-risk myelodysplastic syndromes

Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.

Assessing the determinants of public confidence in the police: A case study of a post-conflict community in Northern Ireland

Drawing upon original survey research this article seeks to identify the generative processes that influence perceptions of the police in the context of an inner-city neighbourhood in Northern Ireland that has been affected by increases in crime and disorder in the aftermath of the peace process. Conceptually we draw upon recent research from England and Wales that outlines confidence in the police in terms of instrumental and expressive dimensions. We apply this framework and consider whether it provides a useful template for understanding the post-conflict dynamics of police-community relations in our study area. Contrary to much received wisdom our analysis suggests that instrumental concerns about crime and illegal activity are a more influential predictor of attitudes to the police than expressive concerns with disorder and anti-social behaviour. Consequently our discussion points to the variance in local and national survey data and questions the degree to which the latter can usefully inform our understanding of trends and developments in discrete micro-spaces. Our conclusion outlines the potential policy implications for state policing practice in deprived urban spaces.

Redispersion of Gold Supported on Oxides

Although many gold heterogeneous catalysts have been shown to exhibit significant activity and high selectivity for a wide range of reactions in both the liquid and gas phases, they are prone to irreversible deactivation. This is often associated with sintering or loss of the interaction of the gold with the support. Herein, we report on the use of methyl iodide as a method of dispersing gold nanoparticles supported on silica, titania, and alumina supports. In the case of titania- and alumina-based catalysts, the gold was transformed from nanometer particles into small clusters and some atomically dispersed gold. In contrast, although there was a drop in the gold particle size on the silica support following CH3I treatment, the size remained in the submicrometer range. The structural changes were correlated with changes in the selectivity and activity for ethanol dehydration and benzyl alcohol oxidation. From these observations, it is clear that this treatment provides a method by which deactivated gold catalysts can be reactivated via redispersion of the gold.

Local framings

Framings provide a way to construct Quillen functors from simplicial sets to any given model category. A more structured set- up studies stable frames giving Quillen functors from spectra to stable model categories. We will investigate how this is compatible with Bousfield localisation to gain insight into the deeper structure of the stable homotopy category. We further show how these techniques relate to rigidity questions and how they can be used to study algebraic model categories.

A tale of two chitons: Is habitat specialisation linked to distinct associated bacterial communities?

Although most chitons (Mollusca: Polyplacophora) are shallow-water molluscs, diverse species also occur in deep-sea habitats. We investigated the feeding strategies of two species, Leptochiton boucheti and Nierstraszella lineata, recovered on sunken wood sampled in the western Pacific, close to the Vanuatu Islands. The two species display distinctly different associations with bacterial partners. Leptochiton boucheti harbours Mollicutes in regions of its gut epithelium and has no abundant bacterium associated with its gill. Nierstraszella lineata displays no dense gut-associated bacteria, but harbours bacterial filaments attached to its gill epithelium, related to the Deltaproteobacteria symbionts found in gills of the wood-eating limpet Pectinodonta sp. Stable carbon and nitrogen isotope signatures and an absence of cellulolytic activity give evidence against a direct wood-feeding diet; both species are secondary consumers within the wood food web. We suggest that the distinct associations with bacterial partners are linked to niche specialisations of the two species. Nierstraszella lineata is in a taxonomic family restricted to sunken wood and is possibly adapted to more anoxic conditions thanks to its gill-associated bacteria. Leptochiton boucheti is phylogenetically more proximate to an ancestral form not specialised on wood and may itself be more of a generalist; this observation is congruent with its association with Mollicutes, a bacterial clade comprising gut-associated bacteria occurring in several metazoan phyla.

A new radiocarbon chronology of Baumkirchen, stratotype for the onset of the Upper Wurmian in the Alps

ABSTRACT

The start of the Upper Wurmian in the Alps was marked by massive fluvioglacial aggradation prior to the arrival of the Central Alpine glaciers. In 1984, the Subcommission on European Quaternary Stratigraphy defined the clay pit of Baumkirchen (in the foreland of the Inn Valley, Austria) as the stratotype for the Middle to Upper Wurmian boundary in the Alps. Key for the selection of this site was its radiocarbon chronology, which still ranks among the most important datasets of this time interval in the Alps. In this study we re-sampled all available original plant specimens and established an accelerator mass spectrometry chronology which supersedes the published 40-year-old chronology. The new data show a much smaller scatter and yielded slightly older conventional radiocarbon dates clustering at ca. 31 C-14 ka BP. When calibrated using INTCAL13 the new data suggest that the sampled interval of 653-681 m in the clay pit was deposited 34-36 cal ka BP. Using two new radiocarbon dates of bone fragments found in the fluvioglacial gravel above the banded clays allows us to constrain the timing of the marked change from lacustrine to fluvioglacial sedimentation to ca. 32-33 cal ka BP, which suggests a possible link to the Heinrich 3 event in the North Atlantic. Copyright (c) 2013 John Wiley & Sons, Ltd.

Failed filament eruption inside a coronal mass ejection in active region 11121

Aims. We study the formation and evolution of a failed filament eruption observed in NOAA active region 11121 near the southeast
limb on November 6, 2010.
Methods. We used a time series of SDO/AIA 304, 171, 131, 193, 335, and 94 Å images, SDO/HMI magnetograms, as well as ROSA
and ISOON Hα images to study the erupting active region.
Results. We identify coronal loop arcades associated with a quadrupolar magnetic configuration, and show that the expansion and
cancellation of the central loop arcade system over the filament is followed by the eruption of the filament. The erupting filament
reveals a clear helical twist and develops the same sign of writhe in the form of inverse γ-shape.
Conclusions. The observations support the “magnetic breakout” process in which the eruption is triggered by quadrupolar reconnection
in the corona. We propose that the formation mechanism of the inverse γ-shape flux rope is the magnetohydrodynamic helical
kink instability. The eruption has failed because of the large-scale, closed, overlying magnetic loop arcade that encloses the active
region

Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs () across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of  from imputed SNPs (5.1× enrichment; p = 3.7 × 10⁻¹⁷) and 38% (SE = 4%) of  from genotyped SNPs (1.6× enrichment, p = 1.0 × 10⁻⁴). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of  despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease.

Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children: An observational cohort study

Background: Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department.

Methods: For this observational cohort study of diagnostic accuracy, children aged 0-13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid).

Findings: Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72-96], specificity 100% [97-100], positive predictive value 100% [85-100]; negative predictive value 98% [93-99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13-infinity] and negative likelihood ratio 0·11 [0·04-0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min-1 h 32 min).

Interpretation: Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful.

Assessment of the Activity of Photocatalytic Paint Using a Simple Smart Ink Designed for High Activity Surfaces

The use of an acid violet 7 (AV7) smart ink to assess the activity of photocatalytic paint is demonstrated. A linear correlation is established between the change in oxidized dye concentration, as measured by diffuse reflectance, and the change in the green component of the RGB color values, obtained using a portable hand-held scanner, suggesting that such tests can be monitored easily using an inexpensive piece of hand-held office equipment, as opposed to an expensive lab-based instrument, such as a diffuse reflectance UV/vis spectrophotometer. The bleaching of the AV7 follows first order kinetics, at a rate that is linearly dependent upon the UVA irradiance (0.30–3.26 mW cm–2). A comparison of relative rate of bleaching of the AV7 ink with the relative rate of removal of NOx, as determined using the ISO test (ISO 22197-1:2007), established a linear relationship between the two sets of results and the relevance of this correlation is discussed briefly.

Atmospheric cold plasma process for vegetable leaf decontamination: A feasibility study on radicchio (red chicory, Cichorium intybus L.)

Cold plasma is an emerging non-thermal processing technology that could be used for large scale leaf decontamination as an alternative to chlorine washing. In this study the effect of an atmospheric cold plasma apparatus (air DBD, 15 kV) on the safety, antioxidant activity and quality of radicchio (red chicory, Cichorium intybus L.) was investigated after 15 and 30 min of treatment (in afterglow at 70 mm from the discharge, at 22 °C and 60% of RH) and during storage. Escherichia coli O157:H7 inoculated on radicchio leaves was significantly reduced after 15 min cold plasma treatment (-1.35 log MPN/cm²). However, a 30 min plasma treatment was necessary to achieve a significant reduction of Listeria monocytogenes counts (-2.2 log CFU/cm²). Immediately after cold plasma treatment, no significant effects emerged in terms of antioxidant activity assessed by the ABTS and ORAC assay and external appearance of the radicchio leaves. Significant changes between treated and untreated radicchio leaves are quality defects based on the cold plasma treatment. Atmospheric cold plasma appears to be a promising processing technology for the decontamination of leafy vegetables although some criticalities, that emerged during storage, need to be considered in future studies.

Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in Type 1 diabetes

Our objective is to define differences in circulating lipoprotein subclasses between intensive vs. conventional management of Type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). Nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of five (interquartile range: four, six) years following randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSP between treatment groups. Standard total-, LDL- and HDL-cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSP showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, p=0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, p=0.007), total IDL/LDL (mean: 1000 vs. 1053 nmol/l, p=0.01), and small HDL (mean: 17.3 vs. 18.6 μmol/l, p<0.0001), the latter accounting for reduced total HDL (mean: 33.8 vs. 34.8 μmol/l, p=0.01). In conclusion, intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications.

Waiting time for cataract surgery and its influence on patient attitudes.

PURPOSE:

To characterize willingness to pay for private operations and preferred waiting time among patients awaiting cataract surgery in Hong Kong.

METHODS:

This was a cross-sectional survey. Subjects randomly selected from cataract surgical waiting lists in Hong Kong (n = 467) underwent a telephone interview based on a structured, validated questionnaire. Data were collected on private insurance coverage, preferred waiting time, amount willing to pay for surgery, and self-reported visual function and health status.

RESULTS:

Among 300 subjects completing the interview, 144 (48.2%) were 76 years of age or older, 177 (59%) were women, and mean time waiting for surgery was 17 +/- 15 months. Among 220 subjects (73.3%) willing to pay anything for surgery, the mean amount was US$552 +/- 443. With adjustment for age, education, and monthly household income, subjects willing to pay anything were less willing to wait 12 months for surgery (OR = 4.34; P = 0.002), more likely to know someone having had cataract surgery (OR = 2.20; P = 0.03), and more likely to use their own savings to pay for the surgery (OR = 2.21; P = 0.04). Subjects considering private cataract surgery, knowing people who have had cataract surgery, using nongovernment sources to pay for surgery, and having lower visual function were willing to pay more.

CONCLUSIONS:

Many patients wait significant periods for cataract surgery in Hong Kong, and are willing to pay substantial amounts for private operations. These results may have implications for other countries with cataract waiting lists.