Over-expressed copper/zinc superoxide dismutase localizes to mitochondria in neurons inhibiting the angiotensin II-mediated increase in mitochondrial superoxide

Angiotensin II (AngII) is the main effector peptide of the renin-angiotensin system (RAS), and contributes to the pathogenesis of cardiovascular disease by exerting its effects on an array of different cell types, including central neurons. AngII intra-neuronal signaling is mediated, at least in part, by reactive oxygen species, particularly superoxide (O2 (•-)). Recently, it has been discovered that mitochondria are a major subcellular source of AngII-induced O2 (•-). We have previously reported that over-expression of manganese superoxide dismutase (MnSOD), a mitochondrial matrix-localized O2 (•-) scavenging enzyme, inhibits AngII intra-neuronal signaling. Interestingly, over-expression of copper/zinc superoxide dismutase (CuZnSOD), which is believed to be primarily localized to the cytoplasm, similarly inhibits AngII intra-neuronal signaling and provides protection against AngII-mediated neurogenic hypertension. Herein, we tested the hypothesis that CuZnSOD over-expression in central neurons localizes to mitochondria and inhibits AngII intra-neuronal signaling by scavenging mitochondrial O2 (•-). Using a neuronal cell culture model (CATH.a neurons), we demonstrate that both endogenous and adenovirus-mediated over-expressed CuZnSOD (AdCuZnSOD) are present in mitochondria. Furthermore, we show that over-expression of CuZnSOD attenuates the AngII-mediated increase in mitochondrial O2 (•-) levels and the AngII-induced inhibition of neuronal potassium current. Taken together, these data clearly show that over-expressed CuZnSOD in neurons localizes in mitochondria, scavenges AngII-induced mitochondrial O2 (•-), and inhibits AngII intra-neuronal signaling

30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature

The mysteries of mammatus clouds: Observations and formation mechanisms

Mammatus clouds are an intriguing enigma of atmospheric fluid dynamics and cloud physics. Most commonly observed on the underside of cumulonimbus anvils, mammatus also occur on the underside of cirrus, cirrocumulus, altocumulus, altostratus, and stratocumulus, as well as in contrails from jet aircraft and pyrocumulus ash clouds from volcanic eruptions. Despite their aesthetic appearance, mammatus have been the subject of few quantitative research studies. Observations of mammatus have been obtained largely through serendipitous opportunities with a single observing system (e.g., aircraft penetrations, visual observations, lidar, radar) or tangential observations from field programs with other objectives. Theories describing mammatus remain untested, as adequate measurements for validation do not exist because of the small distance scales and short time scales of mammatus. Modeling studies of mammatus are virtually nonexistent. As a result, relatively little is known about the environment, formation mechanisms, properties, microphysics, and dynamics of mammatus. This paper presents a review of mammatus clouds that addresses these mysteries. Previous observations of mammatus and proposed formation mechanisms are discussed. These hypothesized mechanisms are anvil subsidence, subcloud evaporation/sublimation, melting, hydrometeor fallout, cloud-base detrainment instability, radiative effects, gravity waves, Kelvin-Helmholtz instability, Rayleigh-Taylor instability, and Rayleigh-Bénard-like convection. Other issues addressed in this paper include whether mammatus are composed of ice or liquid water hydrometeors, why mammatus are smooth, what controls the temporal and spatial scales and organization of individual mammatus lobes, and what are the properties of volcanic ash clouds that produce mammatus? The similarities and differences between mammatus, virga, stalactites, and reticular clouds are also discussed. Finally, because much still remains to be learned, research opportunities are described for using mammatus as a window into the microphysical, turbulent, and dynamical processes occurring on the underside of clouds. © 2006 American Meteorological Society

Prediction of the shear strength of reinforced masonry walls using a large experimental database and artificial neural networks

This paper analyses the accuracy of a selection of expressions currently available to estimate the in-plane shear strength of reinforced masonry (RM) walls, including those presented in some international masonry codes. For this purpose, predictions of such expressions are compared with a set of xperimental results reported in the literature. The experimental database includes specimens built with ceramic bricks and concrete blocks tested in partially and fully grouted conditions, which typically present a shear failure mode. Based on the experimental data collected and using artificial neural networks (ANN), this paper presents alternative expressions to the different existing methods to predict the in-plane shear strength of RM walls. The wall aspect ratio, the axial pre-compression level on the wall, the compressive strength of masonry, as well as the amount and spacing of vertical and horizontal reinforcement throughout the wall are taken into consideration as the input parameters for the proposed expressions. The results obtained show that ANN-based proposals give good predictions and in general fit the experimental results better than other calculation methods.This work was supported by the Fondo Nacional de Ciencia y Tecnologia de Chile, (Fondecyt de Iniciacion) [grant number 11121161].Aguilar, V.; Sandoval, C.; Adam Martínez, JM.; Garzón-Roca, J.; Valdebenito, G. (2016). Prediction of the shear strength of reinforced masonry walls using a large experimental database and artificial neural networks. Structure and Infrastructure Engineering. 12(12):1661-1674. https://doi.org/10.1080/15732479.2016.1157824S16611674121

The Role of the Uncinate Margin in Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Survival Analysis

Introduction: Positive margins during pancreaticoduodenectomy for pancreatic cancer portend worse survival, but additional resection of the uncinate margin is typically unfeasible without major vascular reconstruction. The survival benefit of resecting additional neck or bile duct margins in the face of a positive uncinate is also unknown. We examined the impact of re-resection of these margins on survival. Methods: Patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy from 2006-2015. Pancreatic neck, bile duct, uncinate, and duodenal frozen section margins were assessed before and after resection of positive margins. Kaplan-Meier survival curves were compared with log-rank tests. Multivariable Cox regression was used to assess the effect of margin status on overall survival. Results: Among 508 patients identified, 388 (76.4%) underwent a pylorus-preserving procedure, 435 (85.6%) had T3 tumors, and 379 (74.6%) had nodal involvement. There were 21 instances where an uncinate margin was concurrently positive with a neck or bile duct margin; this additional neck or bile duct margin was resected in 13 cases (61.9%). Resection of additional margins when the uncinate was concurrently positive was not associated with improved survival (p=0.36). Median survival with and without positive uncinate margins was 13.8 vs. 19.7 months (p=0.04). A positive uncinate margin was associated with decreased survival independent of other margins and cancer stage (HR 1.28 [95% CI 1.00-1.65]). Conclusion: In patients with pancreatic adenocarcinoma, positive uncinate margins are associated with decreased overall survival; resection of additional margins at the neck and bile duct in those with a positive uncinate margin is not warranted

Density Matrix Renormalisation Group Approach to the Massive Schwinger Model

The massive Schwinger model is studied, using a density matrix renormalisation group approach to the staggered lattice Hamiltonian version of the model. Lattice sizes up to 256 sites are calculated, and the estimates in the continuum limit are almost two orders of magnitude more accurate than previous calculations. Coleman's picture of `half-asymptotic' particles at background field theta = pi is confirmed. The predicted phase transition at finite fermion mass (m/g) is accurately located, and demonstrated to belong in the 2D Ising universality class.Comment: 38 pages, 18 figures, submitted to PR

Low Dose Daily Iron Supplementation Improves Iron Status and Appetite but not Anemia, Whereas Quarterly Anthelminthic Treatment Improves Growth, Appetite and Anemia in Zanzibari Preschool Children.

Iron deficiency and helminth infections are two common conditions of children in developing countries. The consequences of helminth infection in young children are not well described, and the efficacy of low dose iron supplementation is not well documented in malaria-endemic settings. A 12-mo randomized, placebo controlled, double-blind trial of 10 mg daily iron and/or mebendazole (500 mg) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6-71 mo with hemoglobin > 70 g/L at baseline. The trial was designed to examine treatment effects on growth, anemia and appetite in two age subgroups. Iron did not affect growth retardation, hemoglobin concentration or mild or moderate anemia (hemoglobin < 110 g/L or < 90 g/L, respectively), but iron significantly improved serum ferritin and erythrocyte protoporphyrin. Mebendazole significantly reduced wasting malnutrition. but only in children <30 mo old. The adjusted odds ratios (AORs) for mebendazole in this age group were 0.38 (95% CI: 0.16, 0.90) for weight-for-height less than -1 Z-score and 0.29 (0.09, 0.91) for small arm circumference. In children <24 mo old, mebendazole also reduced moderate anemia (AOR: 0.41, 0.18, 0.94). Both iron and mebendazole improved children's appetite, according to mothers' report. In this study, iron's effect on anemia was limited, likely constrained by infection, inflammation and perhaps other nutrient deficiencies. Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections. We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children, with deleterious effects on protein metabolism and erythropoiesis

Comparing the old and new generation SELDI-TOF MS: implications for serum protein profiling

<p>Abstract</p> <p>Background</p> <p>Although the PBS-IIc SELDI-TOF MS apparatus has been extensively used in the search for better biomarkers, issues have been raised concerning the semi-quantitative nature of the technique and its reproducibility. To overcome these limitations, a new SELDI-TOF MS instrument has been introduced: the PCS 4000 series. Changes in this apparatus compared to the older one are a.o. an increased dynamic range of the detector, an adjusted configuration of the detector sensitivity, a raster scan that ensures more complete desorption coverage and an improved detector attenuation mechanism. In the current study, we evaluated the performance of the old PBS-IIc and new PCS 4000 series generation SELDI-TOF MS apparatus.</p> <p>Methods</p> <p>To this end, two different sample sets were profiled after which the same ProteinChip arrays were analysed successively by both instruments. Generated spectra were analysed by the associated software packages. The performance of both instruments was evaluated by assessment of the number of peaks detected in the two sample sets, the biomarker potential and reproducibility of generated peak clusters, and the number of peaks detected following serum fractionation.</p> <p>Results</p> <p>We could not confirm the claimed improved performance of the new PCS 4000 instrument, as assessed by the number of peaks detected, the biomarker potential and the reproducibility. However, the PCS 4000 instrument did prove to be of superior performance in peak detection following profiling of serum fractions.</p> <p>Conclusion</p> <p>As serum fractionation facilitates detection of low abundant proteins through reduction of the dynamic range of serum proteins, it is now increasingly applied in the search for new potential biomarkers. Hence, although the new PCS 4000 instrument did not differ from the old PBS-IIc apparatus in the analysis of crude serum, its superior performance after serum fractionation does hold promise for improved biomarker detection and identification.</p

Transport of Canadian forest fire smoke over the UK as observed by lidar

Layers of aerosol at heights between 2 and 11&thinsp;km were observed with Raman lidars in the UK between 23 and 31 May 2016. A network of these lidars, supported by ceilometer observations, is used to map the extent of the aerosol and its optical properties. Space-borne lidar profiles show that the aerosol originated from forest fires over western Canada around 17 May, and indeed the aerosol properties – weak volume depolarisation ( &lt; 5&thinsp;%) and a lidar ratio at 355&thinsp;nm in the range 35–65&thinsp;sr – were consistent with long-range transport of forest fire smoke. The event was unusual in its persistence – the smoke plume was drawn into an atmospheric block that kept it above north-western Europe for 9 days. Lidar observations show how the smoke layers became optically thinner during this period, but the lidar ratio and aerosol depolarisation showed little change. The results demonstrate the value of a dense network of observations for tracking forest fire smoke, and show how the dispersion of smoke in the free troposphere leads to the emergence of discrete thin layers in the far field. They also show how atmospheric blocking can keep a smoke plume in the same geographic area for over a week.</p