High turnover in electro-oxidation of alcohols and ethers with a glassy carbon-supported phenanthroimidazole mediator.

Glassy carbon electrodes covalently modified with a phenanthroimidazole mediator promote electrochemical alcohol and ether oxidation: three orders of magnitude increase in TON, to ∼15 000 in each case, was observed compared with homogeneous mediated reactions. We propose the deactivation pathways in homogeneous solution are prevented by the immobilization: modified electrode reversibility is increased for a one-electron oxidation reaction. The modified electrodes were used to catalytically oxidize p-anisyl alcohol and 1-((benzyloxy)methyl)-4-methoxybenzene, selectively, to the corresponding benzaldehyde and benzyl ester, respectively

Readiness for Discharge in Parents of Hospitalized Children

Parental preparation for a child\u27s discharge from the hospital sets the stage for successful transitioning to care and recovery at home. In this study of 135 parents of hospitalized children, the quality of discharge teaching, particularly the nurses\u27 skills in “delivery” of parent teaching, was associated with increased parental readiness for discharge, which was associated with less coping difficulty during the first 3 weeks postdischarge. Parental coping difficulty was predictive of greater utilization of posthospitalization health services. These results validate the role of the skilled nurse as a teacher in promoting positive outcomes at discharge and beyond the hospitalization

Halogen Bonds Form the Basis for Selective P-TEFb Inhibition by DRB

SummaryCdk9, the kinase of the positive transcription elongation factor b, is required for processive transcription elongation by RNA polymerase II. Cdk9 inhibition contributes to the anticancer activity of many Cdk inhibitors under clinical investigation and hence there is interest in selective Cdk9 inhibitors. DRB (5,6-dichlorobenzimidazone-1-β-D-ribofuranoside) is a commonly used reagent for Cdk9 inhibition in cell biology studies. The crystal structures of Cdk9 and Cdk2 in complex with DRB reported here describe the molecular basis for the DRB selectivity toward Cdk9. The DRB chlorine atoms form halogen bonds that are specific for the Cdk9 kinase hinge region. Kinetic and thermodynamic experiments validate the structural findings and implicate the C-terminal residues of Cdk9 in contributing to the affinity for DRB. These results open the possibility to exploit halogen atoms in inhibitor design to specifically target Cdk9

Action of earthworms on flint burial – a return to Darwin’s estate

For thirty years, from the early 1840s, Charles Darwin documented the disappearance of flints in the grounds of Down House in Kent, at a location originally known as the “Stony Field”. This site (Great Pucklands Meadow - GPM) was visited in 2007 and an experiment set up in this ungrazed grassland. Locally-sourced flints (either large - 12 cm, or small – 5 cm dia.) were deposited at two densities within sixteen 1 m2 plots in a randomised factorial design. The area selected was distant from public access routes and remained unmown throughout the duration here reported. Fixed point photographs were taken at the outset to enable later photogrammetric analysis. After 6 years, the site was re-examined. The flints had generally been incorporated into the soil. Photographs were re-taken, proportion of buried flints recorded and measurements made of burial depth from a quarter of each plot. Results showed that large flints were more deeply incorporated than smaller (p=0.025), but more of the latter were below the soil surface. A controlled laboratory experiment was also conducted using Aporrectodea longa (the dominant earthworm species in GPM) to assess effects of casting in the absence of other biota. Results suggested that this species has a major influence on flint burial through surface casting. Combined with a long term, but small scale collection of A. longa casts from an area close to GPM, all results were consistent with those provided by Darwin and showed that rate of flint burial was within the range 0.21-0.96 cm y-1

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research Network Neuroimaging Study.

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing

In utero ultrafine particulate matter exposure causes offspring pulmonary immunosuppression.

Early life exposure to fine particulate matter (PM) in air is associated with infant respiratory disease and childhood asthma, but limited epidemiological data exist concerning the impacts of ultrafine particles (UFPs) on the etiology of childhood respiratory disease. Specifically, the role of UFPs in amplifying Th2- and/or Th17-driven inflammation (asthma promotion) or suppressing effector T cells (increased susceptibility to respiratory infection) remains unclear. Using a mouse model of in utero UFP exposure, we determined early immunological responses to house dust mite (HDM) allergen in offspring challenged from 0 to 4 wk of age. Two mice strains were exposed throughout gestation: C57BL/6 (sensitive to oxidative stress) and BALB/C (sensitive to allergen exposure). Offspring exposed to UFPs in utero exhibited reduced inflammatory response to HDM. Compared with filtered air (FA)-exposed/HDM-challenged mice, UFP-exposed offspring had lower white blood cell counts in bronchoalveolar lavage fluid and less pronounced peribronchiolar inflammation in both strains, albeit more apparent in C57BL/6 mice. In the C57BL/6 strain, offspring exposed in utero to FA and challenged with HDM exhibited a robust response in inflammatory cytokines IL-13 and Il-17. In contrast, this response was lost in offspring exposed in utero to UFPs. Circulating IL-10 was significantly up-regulated in C57BL/6 offspring exposed to UFPs, suggesting increased regulatory T cell expression and suppressed Th2/Th17 response. Our results reveal that in utero UFP exposure at a level close to the WHO recommended PM guideline suppresses an early immune response to HDM allergen, likely predisposing neonates to respiratory infection and altering long-term pulmonary health

Urban vertical air pollution gradient and dynamics investigated with low-cost sensors and large-eddy simulations

A network of five low-cost air pollution sensor (LCS) nodes was deployed vertically on the exterior of the H. C. Ørsted Institute at the University of Copenhagen, Denmark, to investigate the transport of pollution from the road below. All LCS nodes measured PM2.5, NO2, and O3 at 1-min time resolution, and one of them also measured noise. Traffic was monitored with a webcam, where traffic type and levels were derived using a machine-learning algorithm. We investigated how well traffic-related air pollution, noise, and real-time traffic counts serve as proxies for one another. The correlations between NO2, noise, and traffic count exhibited relatively low values when considering all the data. However, these correlations significantly increased under southwesterly wind direction and low wind speed, reaching R2 = 0.40 for NO2 and noise, R2 = 0.51 for NO2 and traffic volume, and R2 = 0.70 for noise and traffic volume. These results indicate a common source, namely traffic, for all three parameters. The five LCS nodes spanning 25 m vertically had extremely low intervariability with minimum R2-values of 0.98 for PM2.5, 0.89 for NO2, and 0.97 for O3. The system could not detect a vertical gradient in pollution levels. Large-eddy simulation model runs using the PALM model system generally supported the lack of gradient observed in measured observations. Under slightly unstable stratification, concentration remained relatively constant with height for southwesterly and southerly winds. Conversely, winds from the north, west, and northwest showed an increase in concentration with height. For other wind directions, the concentration decreased with height by approximately 40 % to 50 %, which is not as strong as for neutral stratification, attributed to enhanced vertical mixing under unstable stratification. Based on the measurements and modeling, we conclude that the vertical concentration profile is very sensitive to stratification, and under these conditions, the concentration outside the window of a fifth-floor office is almost the same as for an office on the ground floor

Experimental stylo accessions produce higher yields than commercial pasture legume varieties on light textured soils in southern Queensland.

Pasture legumes are the best long-term option to increase productivity of grass pastures for large areas of Australia, however there are no commercially available, summer-growing legume varieties that are well adapted to sandy and loamy textured soils in the frost prone sub-tropics. A recently completed eight-year project collected 40 accessions of legumes from old pasture evaluation trial sites that were sown more than 20 years ago, as well as two roadside locations. These accessions were compared to 10 commercial varieties and three previously shortlisted accessions across six trial sites (three districts and two soil types) in southern Queensland between 2016 – 2019, during drought years. The five highest yielding accessions of stylos were from two species (Stylosanthes scabra and S. seabrana) and had 39 – 67% higher yields than the best performing commercial variety when averaged across all trials. These accessions also had good disease tolerance and formed effective nodules with commercial rhizobia. The five highest yielding accessions have been shortlisted for release as new varieties due to their potential to significantly improve productivity for the grazing industries in the sub-tropics of Australia

Causes of Multiple Sclerosis: a functional genomics approach

Multiple Sclerosis (MS) is the most common disabling neurological disease affecting young adults in Western Society. To date, 55 strongly associated single nucleotide polymorphisms have been discovered. We now need to identify causal genes. While T-cells as targets for therapeutic intervention have rarely proven useful, there is strong clinical and in-vitro data identifying NK cell deficiencies in patients, and key roles for monocytes in myelin and axon destruction and autoantigen presentation. RNA extracted from magnetic bead sorted monocytes and NK cells, of healthy controls (HC) and untreated patients with relapsing remitting MS (RRMS), was labelled and hybridised to Affymetrix Human Gene 1.0 ST arrays. Expression values were standardized across chips using RMA and quantile normalization as implemented in GenePattern. Genes were ranked by expression difference significance by Mann Whitney U test and ANOVA. To date, we have analysed monocytes of 30 patients and 39 HC, and NK cells from 25 patients and 32 HC. Expression differences of those genes adjacent to MS associated risk SNPs lying between 110kb upstream and 40kb downstream of a candidate gene were considered. We have identified three genes worthy of further analysis on this basis: RGS1, HHEX and THEMIS. To test the relevance of these candidates to central nervous system (CNS) autoimmunity, we aim to mimic phenotypes associated with these expression quantitative trait loci (eQTL) in in-vitro cultures of purified NK cells and monocytes, and in-vivo in a mouse model of MS - experimental autoimmune encephalomyelitis (EAE)