Ovarian vein thrombosis in a polytrauma patient

A young mother presented to a Major Trauma Centre (MTC) following a road traffic collision. Her admission computed tomography (CT) traumagram demonstrated liver and renal lacerations, spinal and pelvic fractures with no abnormalities of the ovarian veins. Her inpatient course was uncomplicated other than a sustained, isolated raised c-reactive protein (CRP). CT abdomen one week after injury demonstrated stable solid organ injuries and the additional, unexpected finding of a right ovarian vein thrombosis (OVT). A pragmatic approach was taken towards the management of the OVT given the haemorrhagic risk from her traumatic injuries. A multi-disciplinary, consultant-led plan was made to slowly increase enoxaparin to a therapeutic dose under close surveillance and to then switch to warfarin following an outpatient consultation with a consultant haematologist. A magnetic resonance venogram was performed after 3 months of anticoagulation and this demonstrated complete resolution of the OVT and normal appearances of the ovary

The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cells

Activated mast cells are a major source of the eicosanoids PGD(2) and leukotriene C(4) (LTC(4)), which contribute to allergic responses. These eicosanoids are produced following the ERK1/2-dependent activation of cytosolic phospholipase A(2), thus liberating arachidonic acid, which is subsequently metabolized by the actions of 5-lipoxygenase and cyclooxygenase to form LTC(4) and PGD(2), respectively. These pathways also generate reactive oxygen species (ROS), which have been proposed to contribute to FcepsilonRI-mediated signaling in mast cells. In this study, we demonstrate that, in addition to ERK1/2-dependent pathways, ERK1/2-independent pathways also regulate FcepsilonRI-mediated eicosanoid and ROS production in mast cells. A role for the Tec kinase Btk in the ERK1/2-independent regulatory pathway was revealed by the significantly attenuated FcepsilonRI-dependent PGD(2), LTC(4), and ROS production in bone marrow-derived mast cells of Btk(-/-) mice. The FcepsilonRI-dependent activation of Btk and eicosanoid and ROS generation in bone marrow-derived mast cells and human mast cells were similarly blocked by the PI3K inhibitors, Wortmannin and LY294002, indicating that Btk-regulated eicosanoid and ROS production occurs downstream of PI3K. In contrast to ERK1/2, the PI3K/Btk pathway does not regulate cytosolic phospholipase A(2) phosphorylation but rather appears to regulate the generation of ROS, LTC(4), and PGD(2) by contributing to the necessary Ca(2+) signal for the production of these molecules. These data demonstrate that strategies to decrease mast cell production of ROS and eicosanoids would have to target both ERK1/2- and PI3K/Btk-dependent pathways

Antigen and Thapsigargin Promote Influx of Ca2+ in Rat Basophilic RBL-2H3 Cells by Ostensibly Similar Mechanisms That Allow Filling of Inositol 1,4,5-Trisphosphate-Sensitive and Mitochondrial Ca2+ Stores

In single, Fura 2-loaded RBL-2H3 cells, antigen and thapsigargin depleted the same intracellular pool of Ca2+ in the absence of external Ca2+; provision of external Ca2+ induced immediate increases in levels of free Ca2+ ([Ca2+](i)). These increases were dependent on the presence of external Ca2+ and, presumably, on influx of Ca2+ across the cell membrane. Both stimulants enhanced intracellular accumulation of 45Ca2+ through ostensibly similar mechanisms because accumulation was blocked to similar extents by various multivalent cations or by depolarization with K+. Because thapsigargin blocked reuptake of Ca2+ into inositol 1,4,5-trisphosphate sensitive stores, uptake occurred independently of the refilling of these stores. Uptake was dependent instead on sequestration of 45Ca2+ in a pool of high capacity that was insensitive to thapsigargin, caffeine, GTP and inositol 1,4,5-trisphosphate but sensitive to ionomycin and mitochondrial inhibitors. The existence of an inositol 1,4,5-trisphosphate-insensitive pool was also apparent in permeabilized cells; at 0.1 μM [Ca2+](i), uptake of 45Ca2+ was largely confined (\u3e 80%) to the inositol 1,4,5-trisphosphate-sensitive pool, but at 2 μM [Ca2+](i) uptake was largely (\u3e 60%) into the inositol 1,4,5-trisphosphate-insensitive pool. Provision of mitochondrial inhibitors along with thapsigargin to block uptake into both pools, did not impair the thapsigargin-induced increase in [Ca2+](i) or influx of Ca2+, as indicated by changes in Fura 2 fluorescence, but did block the intracellular accumulation of 45Ca2+. The studies illustrate the utility of simultaneous measurements of [Ca2+](i) and 45Ca2+ uptake for a full accounting of Ca2+ homoeostasis as exemplified by the ability to distinguish between influx and mitochondrial uptake of Ca2+

Regulation of Reactive Oxygen Species and the Antioxidant Protein DJ-1 in Mastocytosis

Neoplastic accumulation of mast cells in systemic mastocytosis (SM) associates with activating mutations in the receptor tyrosine kinase KIT. Constitutive activation of tyrosine kinase oncogenes has been linked to imbalances in oxidant/antioxidant mechanisms in other myeloproliferative disorders. However, the impact of KIT mutations on the redox status in SM and the potential therapeutic implications are not well understood. Here, we examined the regulation of reactive oxygen species (ROS) and of the antioxidant protein DJ-1 (PARK-7), which increases with cancer progression and acts to lessen oxidative damage to malignant cells, in relationship with SM severity. ROS levels were increased in both indolent (ISM) and aggressive variants of the disease (ASM). However, while DJ-1 levels were reduced in ISM with lower mast cell burden, they rose in ISM with higher mast cell burden and were significantly elevated in patients with ASM. Studies on mast cell lines revealed that activating KIT mutations induced constant ROS production and consequent DJ-1 oxidation and degradation that could explain the reduced levels of DJ-1 in the ISM population, while IL-6, a cytokine that increases with disease severity, caused a counteracting transcriptional induction of DJ-1 which would protect malignant mast cells from oxidative damage. A mouse model of mastocytosis recapitulated the biphasic changes in DJ-1 and the escalating IL-6, ROS and DJ-1 levels as mast cells accumulate, findings which were reversed with anti-IL-6 receptor blocking antibody. Our findings provide evidence of increased ROS and a biphasic regulation of the antioxidant DJ-1 in variants of SM and implicate IL-6 in DJ-1 induction and expansion of mast cells with KIT mutations. We propose consideration of IL-6 blockade as a potential adjunctive therapy in the treatment of patients with advanced mastocytosis, as it would reduce DJ-1 levels making mutation-positive mast cells vulnerable to oxidative damage

Radar backscatter measurements from Arctic sea ice during the fall freeze-up

Radar backscatter measurements from sea ice during the fall freeze-up were performed by the United States Coast Guard Icebreaker Polar Star as a part of the International Arctic Ocean Expedition (IAOE'91) from Aug. to Sep. 1991. The U.S. portion of the experiment took place on board the Polar Star and was referred to as TRAPOLEX '91 (Transpolar expedition) by some investigators. Before prematurely aborting its mission because of mechanical failure of her port shaft, the Polar Star reached 84 deg 57 min N latitude at 35 deg E longitude. The ship was in the ice (greater than 50 percent coverage) from 14 Aug. until 3 Sep. and was operational for all but 6 days due to two instances of mechanical problems with the port shaft. The second was fatal to the ship's participation in the expedition. During the expedition, radar backscatter was measured at C-band under a variety of conditions. These included measurements from young ice types as well as from multiyear and first-/second-year sea ice during the fall freeze-up. The sea ice types were determined by measurement of the ice properties at several of the stations and by visual inspection on others. Radar backscatter measurements were performed over a large portion of the ship's transit into the Arctic ice pack. These were accompanied by in situ sea ice property characterization by the U.S. Army Cold Regions Research and Engineering Laboratory (CRREL) at several stations and, when snow was present, its properties were documented by The Microwave Group, Ottawa River (MWG)

Plans to eradicate invasive mammals on an island inhabited by humans and domestic animals (Corvo, Azores, Portugal)

Oppel, S., Beaven, B.M., Bolton, M., Bodey, T.W., Geraldes, P., Oliveira, N., Hervias, S., Henriques, A., Silva, C

Future challenges of coastal landfills exacerbated by sea level rise

In England and Wales, there are at least 1700 coastal landfills in the coastal flood plain and at least 60 threatened by erosion, illustrating a global problem. These landfills are a major issue in shoreline management planning (SMP) which aims to manage the risks associated with flooding and coastal erosion. Where landfills exist, "hold the line" (requiring the building or upgrading of artificial defences to maintain the current shoreline) is often selected as the preferred SMP option, although government funding is not available at present. To investigate these issues in detail, three case-study landfills are used to examine the risks of future flooding and erosion together with potential mitigation options. These cases represent a contrasting range of coastal landfill settings. The study includes consideration of sea-level rise and climate change which exacerbates risks of erosion and flooding of landfills. It is fundamental to recognise that the release of solid waste in coastal zones is a problem with a geological timescale and these problems will not go away if ignored. Future erosion and release of solid waste is found to be more of a threat than flooding and leachate release from landfills. However, while leachate release can be assessed, there is presently a lack of methods to assess the risks from the release of solid waste. Hence, a lack of science constrains the design of remediation options

COLECCIÓN CARIDAD RODRÍGUEZ PÉREZ-GALDÓS [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Global Peak in Atmospheric Radiocarbon Provides a Potential Definition for the Onset of the Anthropocene Epoch in 1965.

Anthropogenic activity is now recognised as having profoundly and permanently altered the Earth system, suggesting we have entered a human-dominated geological epoch, the 'Anthropocene'. To formally define the onset of the Anthropocene, a synchronous global signature within geological-forming materials is required. Here we report a series of precisely-dated tree-ring records from Campbell Island (Southern Ocean) that capture peak atmospheric radiocarbon (14C) resulting from Northern Hemisphere-dominated thermonuclear bomb tests during the 1950s and 1960s. The only alien tree on the island, a Sitka spruce (Picea sitchensis), allows us to seasonally-resolve Southern Hemisphere atmospheric 14C, demonstrating the 'bomb peak' in this remote and pristine location occurred in the last-quarter of 1965 (October-December), coincident with the broader changes associated with the post-World War II 'Great Acceleration' in industrial capacity and consumption. Our findings provide a precisely-resolved potential Global Stratotype Section and Point (GSSP) or 'golden spike', marking the onset of the Anthropocene Epoch

Circular dichroism spectroscopic detection of ligand binding induced subdomain IB specific structural adjustment of human serum albumin

This work demonstrates for the first time that binding of various compounds within subdomain IB of human serum albumin (HSA) provokes characteristic changes in the near-UV circular dichroism (CD) spectrum of the protein. It can be inferred from the spectroscopic features of difference ellipticity signals and from CD displacement experiments that tyrosine residues located in subdomain IB are the source of the observed spectral alterations. It is proposed that inclusion of some ligand molecules (bile acids, dehydroepiandrosterone sulfate, steroidal terpenes, fatty acids, ibuprofen, and gemfibrozil) into the pocket of subdomain IB disrupts the Tyr138?Tyr161 interhelical π?π stacking interaction, which is reflected in the CD spectrum. This phenomenon can be utilized for the CD detection of subdomain IB specific binding of endo- as well as exogenous agents and to study the drug binding associated local conformational adaptation of the HSA molecule