Evaluation of In Vitro Virulence Characteristics of the Genus Pandoraea in Lung Epithelial Cells

Pandoraea species are emerging opportunistic pathogens capable of causing chronic lung infections in cystic fibrosis patients. This study examined the interactions of 17 Pandoraea isolates from the five identified species (Pandoraea apista, Pandoraea norimbergensis, Pandoraea pulmonicula, Pandoraea sputorum and Pandoraea pnomenusa) plus two Pandoraea genomospecies isolates with lung epithelial cells and their ability to form biofilms in vitro. Only three isolates showed an ability to invade A549 lung epithelial cells, and only one isolate was able to form biofilms. In contrast, all isolates triggered a pronounced pro-inflammatory response, with elevation of both interleukin (IL)-6 (two- to 19-fold) and IL-8 (10- to 50-fold) above that observed for a control strain of Escherichia coli. This property is likely to be a major factor in the pathogenesis of the genus

Accurately characterising the importance of wave-particle interactions in radiation belt dynamics: the pitfalls of statistical wave representations

Wave-particle interactions play a crucial role in energetic particle dynamics in the Earth's radiation belts. However the relative importance of different wave-modes in these dynamics is poorly understood. Typically this is assessed during geomagnetic storms using statistically averaged empirical wave models as a function of geomagnetic activity in advanced radiation belt simulations. However statistical averages poorly characterise extreme events such as geomagnetic storms in that storm-time ULF wave power is typically larger than that derived over a solar cycle and Kp is a poor proxy for storm-time wave power

Brainstem Raphe Pallidus and the Adjacent Area Contain a Novel Action Site in the Melanocortin Circuitry Regulating Energy Balance

The central melanocortin system plays a critical role in the regulation of energy balance in rodents and humans. The melanocortin signals in both the hypothalamus and brainstem contribute to this regulation. However, how the melanocortin signals of the hypothalamus interact with those intrinsic to the brainstem in the regulation of energy balance is poorly understood. The brainstem raphe pallidus (RPa) and adjacent areas contain melanocortin 4 receptor (MC4-R)-bearing neurons and sympathetic premotor neurons regulating thermogenesis. Here we report that α-melanocyte-stimulating hormone (α-MSH)-immunoreactive (IR) fibers are in close apposition to MC4-R neurons in the RPa. Retrograde tracing studies revealed a unique direct projection from hypothalamic proopiomelanocortin (POMC) neurons to the RPa and adjacent areas of the brainstem in mice and rats. Furthermore, microinjection of the MC3/4-R agonist MTII into the RPa area dose-dependently stimulated oxygen consumption and inhibited feeding, whereas microinjection of the antagonist, SHU9119, enhanced feeding. These data suggest a novel pathway of hypothalamic POMC neuronal efferents to brainstem RPa area MC4-R neurons in the melanocortin circuitry that contribute to coordinate regulation of energy balance

Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years.

OBJECTIVE: Maternal antenatal depression and anxiety are associated with increased risk of childhood behavioural and emotional problems in offspring; it remains unclear to what extent this is due to a maternal biological impact on foetal development. Here, we compare associations between maternal and paternal antenatal depression and anxiety with offspring anxiety disorders, thus controlling for some genetic and shared environmental factors. METHODS: We used data from the ALSPAC population cohort including measures of antenatal parental depression and anxiety. At 18 years, offspring completed the CIS-R interview, yielding diagnoses for anxiety disorders. Results were adjusted for confounding variables including parental postnatal depression and anxiety. RESULTS: Children of women with antenatal depression (18 weeks gestation), had an increased risk of anxiety disorders at 18 years of age (11.1% vs. 6.2%; adj. OR 1.75 (1.19, 2.58); p=0.01). Children of women with antenatal anxiety had increased risk of co-morbid anxiety and depression (adj. OR 1.39 (1.06, 1.82); p=0.02). No such associations were found with paternal antenatal depression or anxiety. LIMITATIONS: There was a high attrition rate from the original cohort to the CIS-R completion at 18 years postpartum. Parental mood was only assessed together at one time point during the antenatal period. CONCLUSIONS: The differences in the association between maternal and paternal mood during pregnancy and child outcomes supports the hypothesis that foetal programming may account, at least in part, for this association. We highlight the potential opportunity for preventative intervention by optimising antenatal mental health

Blocks of cyclotomic Hecke algebras and Khovanov-Lauda algebras

We construct an explicit isomorphism between blocks of cyclotomic Hecke algebras and (sign-modified) Khovanov-Lauda algebras in type A. These isomorphisms connect the categorification conjecture of Khovanov and Lauda to Ariki's categorification theorem. The Khovanov-Lauda algebras are naturally graded, which allows us to exhibit a non-trivial Z-grading on blocks of cyclotomic Hecke algebras, including symmetric groups in positive characteristic.Comment: 32 pages; minor changes to section

Physiological roles of pyruvate ferredoxin oxidoreductase and pyruvate formate-lyase in Thermoanaerobacterium saccharolyticum JW/SL-YS485

Background: Thermoanaerobacter saccharolyticum is a thermophilic microorganism that has been engineered to produce ethanol at high titer (30–70 g/L) and greater than 90 % theoretical yield. However, few genes involved in pyruvate to ethanol production pathway have been unambiguously identified. In T. saccharolyticum, the products of six putative pfor gene clusters and one pfl gene may be responsible for the conversion of pyruvate to acetyl-CoA. To gain insights into the physiological roles of PFOR and PFL, we studied the effect of deletions of several genes thought to encode these activities. Results: It was found that pyruvate ferredoxin oxidoreductase enzyme (PFOR) is encoded by the pforA gene and plays a key role in pyruvate dissimilation. We further demonstrated that pyruvate formate-lyase activity (PFL) is encoded by the pfl gene. Although the pfl gene is normally expressed at low levels, it is crucial for biosynthesis in T. saccharolyticum. In pforA deletion strains, pfl expression increased and was able to partially compensate for the loss of PFOR activity. Deletion of both pforA and pfl resulted in a strain that required acetate and formate for growth and produced lactate as the primary fermentation product, achieving 88 % theoretical lactate yield. Conclusion: PFOR encoded by Tsac_0046 and PFL encoded by Tsac_0628 are only two routes for converting pyruvate to acetyl-CoA in T. saccharolyticum. The physiological role of PFOR is pyruvate dissimilation, whereas that of PFL is supplying C1 units for biosynthesis

A framework for understanding and quantifying the loss and acceleration of relativistic electrons in the outer radiation belt during geomagnetic storms

We present detailed analysis of the global relativistic electron dynamics as measured by total radiation belt content (RBC) during coronal mass ejection (CME) and corotating interaction region (CIR)‐driven geomagnetic storms. Recent work has demonstrated that the response of the outer radiation belt is consistent and repeatable during geomagnetic storms. Here we build on this work to show that radiation belt dynamics can be divided into two sequential phases, which have different solar wind dependencies and which when analyzed separately reveal that the radiation belt responds more predictably than if the overall storm response is analyzed as a whole. In terms of RBC, in every storm we analyzed, a phase dominated by loss is followed by a phase dominated by acceleration. Analysis of the RBC during each of these phases demonstrates that they both respond coherently to solar wind and magnetospheric driving. However, the response is independent of whether the storm response is associated with either a CME or CIR. Our analysis shows that during the initial phase, radiation belt loss is organized by the location of the magnetopause and the strength of Dst and ultralow frequency wave power. During the second phase, radiation belt enhancements are well organized by the amplitude of ultralow frequency waves, the auroral electroject index, and solar wind energy input. Overall, our results demonstrate that storm time dynamics of the RBC is repeatable and well characterized by solar wind and geomagnetic driving, albeit with different dependencies during the two phases of a storm

Modelling extreme rain accumulation with an application to the 2011 Lake Champlain flood

A simple strategy is proposed to model total accumulation in non-overlapping clusters of extreme values from a stationary series of daily precipitation. Assuming that each cluster contains at least one value above a high threshold, the cluster sum S is expressed as the ratio S=M/P of the cluster maximum M and a random scaling factor P (0, 1]. The joint distribution for the pair (M, P) is then specified by coupling marginal distributions for M and P with a copula. Although the excess distribution of M is well approximated by a generalized Pareto distribution, it is argued that, conditionally on P<1, a scaled beta distribution may already be sufficiently rich to capture the behaviour of P . An appropriate copula for the pair (M, P) can also be selected by standard rank-based techniques.This approach is used to analyse rainfall data from Burlington, Vermont, and to estimate the return period of the spring 2011 precipitation accumulation which was a key factor in that year’s devastating flood in the RichelieuValley Basin in Qu´ebec, Canada

ULF wave derived radiation belt radial diffusion coefficients

Waves in the ultra-low-frequency (ULF) band have frequencies which can be drift resonant with electrons in the outer radiation belt, suggesting the potential for strong interactions and enhanced radial diffusion. Previous radial diffusion coefficient models such as those presented by Brautigam and Albert (2000) have typically used semiempirical representations for both the ULF wave’s electric and magnetic field power spectral densities (PSD) in space in the magnetic equatorial plane. In contrast, here we use ground- and space-based observations of ULF wave power to characterize the electric and magnetic diffusion coefficients. Expressions for the electric field power spectral densities are derived from ground-based magnetometer measurements of the magnetic field PSD, and in situ AMPTE and GOES spacecraft measurements are used to derive expressions for the compressional magnetic field PSD as functions of Kp, solar wind speed, and L-shell. Magnetic PSD results measured on the ground are mapped along the field line to give the electric field PSD in the equatorial plane assuming a guided Alfvén wave solution and a thin sheet ionosphere. The ULF wave PSDs are then used to derive a set of new ULF-wave driven diffusion coefficients. These new diffusion coefficients are compared to estimates of the electric and magnetic field diffusion coefficients made by Brautigam and Albert (2000) and Brautigam et al. (2005). Significantly, our results, derived explicitly from ULF wave observations, indicate that electric field diffusion is much more important than magnetic field diffusion in the transport and energization of the radiation belt electrons

Imaging in Vascular Access

This review examines four imaging modalities; ultrasound (US), digital subtraction angiography (DSA), magnetic resonance imaging (MRI) and computed tomography (CT), that have common or potential applications in vascular access (VA). The four modalities are reviewed under their primary uses, techniques, advantages and disadvantages, and future directions that are specific to VA. Currently, US is the most commonly used modality in VA because it is cheaper (relative to other modalities), accessible, non-ionising, and does not require the use of contrast agents. DSA is predominantly only performed when an intervention is indicated. MRI is limited by its cost and the time required for image acquisition that mainly confines it to the realm of research where high resolution is required. CT’s short acquisition times and high resolution make it useful as a problem-solving tool in complex cases, although accessibility can be an issue. All four imaging modalities have advantages and disadvantages that limit their use in this particular patient cohort. Current imaging in VA comprises an integrated approach with each modality providing particular uses dependent on their capabilities. MRI and CT, which currently have limited use, may have increasingly important future roles in complex cases where detailed analysis is required