Selective oxidative destruction of iron-sulfur clusters Ferricyanide oxidation of Azotobacter vinelandii ferredoxin I

AbstractThe destructive oxidation of aerobically isolated 7Fe Azotobacter vinelandii ferredoxin I [(7Fe)FdI] by Fe(CN)63− is examined using low-temperature magnetic circular dichroism (MCD) and EPR. The results demonstrate that oxidation of the [3Fe-3S] cluster occurs only after essentially complete destruction of the [4Fe-4S] cluster. It is therefore feasible by controlled Fe(CN)63− oxidation to obtain a partially metallated form of FdI, (3Fe)FdI, containing only a [3Fe-3S) cluster. The MCD and EPR data demonstrate that the [3Fe-3S] cluster in (3Fe)FdI is essentially identical in structure to that in the native protein

Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression

Traditional toxicological paradigms have relied on factors such as age, genotype, and disease status to explain variability in responsiveness to toxicant exposure; however, these are neither sufficient to faithfully identify differentially responsive individuals nor are they modifiable factors that can be leveraged to mitigate the exposure effects. Unlike these factors, the epigenome is dynamic and shaped by an individual’s environment. We sought to determine whether baseline levels of specific chromatin modifications correlated with the interindividual variability in their ozone (O3)-mediated induction in an air–liquid interface model using primary human bronchial epithelial cells from a panel of 11 donors. We characterized the relationship between the baseline abundance of 6 epigenetic markers with established roles as key regulators of gene expression—histone H3 lysine 4 trimethylation (H3K4me3), H3K27 acetylation (H3K27ac), pan-acetyl H4 (H4ac), histone H3K27 di/trimethylation (H3K27me2/3), unmodified H3, and 5-hydroxymethylcytosine (5-hmC)—and the variability in the O3-induced expression of IL-8, IL-6, COX2, and HMOX1. Baseline levels of H3K4me3, H3K27me2/3, and 5-hmC, but not H3K27ac, H4ac, and total H3, correlated with the interindividual variability in O3-mediated induction of HMOX1 and COX2. In contrast, none of the chromatin modifications that we examined correlated with the induction of IL-8 and IL-6. From these findings, we propose an “epigenetic seed and soil” model in which chromatin modification states between individuals differ in the relative abundance of specific modifications (the “soil”) that govern how receptive the gene is to toxicant-mediated cellular signals (the “seed”) and thus regulate the magnitude of exposure-related gene induction

Vector and Scalar Meson Resonances in K→πππK\rightarrow\pi\pi\pi Decays

Corrections to $K\rightarrow\pi\pi\pi$ induced by vector and scalar meson exchange are investigated within chiral perturbation theory.Comment: 15pages, Latex-file, TUM-T31-41/9

Trust in financial services: Retrospect and prospect

Fostering and maintaining high levels of trust in the financial services sector is seen as crucial because of the characteristics of many financial service and in order to promote consumer engagement in the sector. In this article, we report evidence from a body of work and other commentary to provide an insight into trends in consumer trust in the sector as a whole, in comparison with other organisations and how different types of financial services provider have performed relative to each other. We show that the financial services sector as a whole is trusted more than some comparator institutions, and that aggregate levels of trust in the sector have fluctuated a relatively small amount subsequent to the financial crisis. However, important differences between provider types are apparent and these differences have become more profound in the recent past. We provide suggestions as to how trust in the sector may be improved and provider an analysis of current initiatives to improve trust levels in the sector in general and in banking in particular

Dust Formation and Survival in Supernova Ejecta

The presence of dust at high redshift requires efficient condensation of grains in SN ejecta, in accordance with current theoretical models. Yet, observations of the few well studied SNe and SN remnants imply condensation efficiencies which are about two orders of magnitude smaller. Motivated by this tension, we have (i) revisited the model of Todini & Ferrara (2001) for dust formation in the ejecta of core collapse SNe and (ii) followed, for the first time, the evolution of newly condensed grains from the time of formation to their survival - through the passage of the reverse shock - in the SN remnant. We find that 0.1 - 0.6 M_sun of dust form in the ejecta of 12 - 40 M_sun stellar progenitors. Depending on the density of the surrounding ISM, between 2-20% of the initial dust mass survives the passage of the reverse shock, on time-scales of about 4-8 x 10^4 yr from the stellar explosion. Sputtering by the hot gas induces a shift of the dust size distribution towards smaller grains. The resulting dust extinction curve shows a good agreement with that derived by observations of a reddened QSO at z =6.2. Stochastic heating of small grains leads to a wide distribution of dust temperatures. This supports the idea that large amounts (~ 0.1 M_sun) of cold dust (T ~ 40K) can be present in SN remnants, without being in conflict with the observed IR emission.Comment: MNRAS accepte

Leading Learning Networks in Education

This study is one of the main outcomes of Leading Learning by Networking, an Erasmus+ project. It concerns the management of learning networks in schools with regard to the mission of these networks in the context of growing diversity. The text consists of three main parts. The opening chapter is of theoretical study, dealing with the term Professional learning networks and various factors that facilitate this form of collaboration in schools. Attention is also paid to the role of headteachers in the creation of and support for learning networks. The second part is a summary of the results of a qualitative research, which was carried out by means of interviews, aimed at recognition of some aspects of networking in selected schools in the partner countries. Part three describes a range of data obtained from a questionnaire survey on headteachers’ needs and experience in the management of learning networks

The Relative Importance of Clinical, Economic, Patient Values and Feasibility Criteria in Cancer Drug Reimbursement in Canada:A Revealed Preferences Analysis of Recommendations of the Pan-Canadian Oncology Drug Review 2011–2017

Background: Most Canadian provinces and territories rely on the pan-Canadian Oncology Drug Review (pCODR) to provide recommendations regarding public reimbursement of cancer drugs. The pCODR review process considers four dimensions of value—clinical benefit, economic evaluation, patient-based values and adoption feasibility—but they do not define weights for individual decision criteria or an acceptable threshold for any of the criteria. Given this implicit review process, it is of interest to understand which factors appear to carry the most weight in pCODR recommendations using a revealed preferences approach. Methods: Using publicly available decision summaries (n = 91) describing submissions and resulting recommendations 2011–2017, we extracted ten attributes that characterized each submission. Using logistic regression, we identified statistically significant attributes and estimated their relative impact in final recommendations. Results: Clinical aspects appear to carry the greatest weight in the decision to reject or not reject, along with aspects of patient value (treatments with no alternatives were less likely to be rejected). Cost effectiveness does not appear to play a role in the initial decision to reject or not reject but is critical in full versus conditional approvals. There is evidence of a maximum acceptable threshold of around $Can140,000 per quality-adjusted life-year (QALY) gained. Conclusion: A set of factors driving pCODR recommendations is identifiable, supporting the consistency of the review process. However, the implicit nature of the review process and the difficulty of extracting and interpreting some of the attribute levels used in the analysis suggests that the process may still lack full transparency

AKARI and BLAST Observations of the Cassiopeia A Supernova Remnant and Surrounding Interstellar Medium

We use new large area far infrared maps ranging from 65 - 500 microns obtained with the AKARI and the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) missions to characterize the dust emission toward the Cassiopeia A supernova remnant (SNR). Using the AKARI high resolution data we find a new "tepid" dust grain population at a temperature of ~35K and with an estimated mass of 0.06 solar masses. This component is confined to the central area of the SNR and may represent newly-formed dust in the unshocked supernova ejecta. While the mass of tepid dust that we measure is insufficient by itself to account for the dust observed at high redshift, it does constitute an additional dust population to contribute to those previously reported. We fit our maps at 65, 90, 140, 250, 350, and 500 microns to obtain maps of the column density and temperature of "cold" dust (near 16 K) distributed throughout the region. The large column density of cold dust associated with clouds seen in molecular emission extends continuously from the surrounding interstellar medium to project on the SNR, where the foreground component of the clouds is also detectable through optical, X-ray, and molecular extinction. At the resolution available here, there is no morphological signature to isolate any cold dust associated only with the SNR from this confusing interstellar emission. Our fit also recovers the previously detected "hot" dust in the remnant, with characteristic temperature 100 K.Comment: Accepted for publication in the Astrophysical Journal. Maps and related data are available at http://blastexperiment.info

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

Herschel-ATLAS: Multi-wavelength SEDs and physical properties of 250 micron-selected galaxies at z < 0.5

We present a pan-chromatic analysis of an unprecedented sample of 1402 250 micron-selected galaxies at z < 0.5 (mean z = 0.24) from the Herschel-ATLAS survey. We complement our Herschel 100-500 micron data with UV-K-band photometry from the Galaxy And Mass Assembly (GAMA) survey and apply the MAGPHYS energy-balance technique to produce pan-chromatic SEDs for a representative sample of 250 micron selected galaxies spanning the most recent 5 Gyr of cosmic history. We derive estimates of physical parameters, including star formation rates, stellar masses, dust masses and infrared luminosities. The typical H-ATLAS galaxy at z < 0.5 has a far-infrared luminosity in the range 10^10 - 10^12 Lsolar (SFR: 1-50 Msolar/yr) thus is broadly representative of normal star forming galaxies over this redshift range. We show that 250 micron-selected galaxies contain a larger mass of dust at a given infra-red luminosity or star formation rate than previous samples selected at 60 micron from IRAS. We derive typical SEDs for H-ATLAS galaxies, and show that the emergent SED shape is most sensitive to specific star formation rate. The optical-UV SEDs also become more reddened due to dust at higher redshifts. Our template SEDs are significantly cooler than existing infra-red templates. They may therefore be most appropriate for inferring total IR luminosities from moderate redshift submillimetre selected samples and for inclusion in models of the lower redshift submillimetre galaxy populations.Comment: 26 pages, 24 figures, Accepted by MNRA