A unified approach to Performance Assessment (PA) of geological CO2 storage

AbstractPerformance Assessment (PA) evaluates the effectiveness of a specified system or sub-system relative to some criteria of interest to particular stakeholders. A flexible PA approach has been developed for geological CO2 storage, by which qualitative information, quantitative data, output from numerical models and expert judgments are combined within a decision-support framework. The methodology has been implemented in three software tools: (1) TESLA, which is used to construct decision trees, propagate evidence and record the logic underlying a decision; (2) an on-line database of Features, Events and Processes (FEPs) targeted at CO2 storage; and (3) QPAC-CO2, for modelling system performance

Differential Expression of Iron Acquisition Genes by Brucella melitensis and Brucella canis during Macrophage Infection

Brucella spp. cause chronic zoonotic disease often affecting individuals and animals in impoverished economic or public health conditions; however, these bacteria do not have obvious virulence factors. Restriction of iron availability to pathogens is an effective strategy of host defense. For brucellae, virulence depends on the ability to survive and replicate within the host cell where iron is an essential nutrient for the growth and survival of both mammalian and bacterial cells. Iron is a particularly scarce nutrient for bacteria with an intracellular lifestyle. Brucella melitensis and Brucella canis share ∼99% of their genomes but differ in intracellular lifestyles. To identify differences, gene transcription of these two pathogens was examined during infection of murine macrophages and compared to broth grown bacteria. Transcriptome analysis of B. melitensis and B. canis revealed differences of genes involved in iron transport. Gene transcription of the TonB, enterobactin, and ferric anguibactin transport systems was increased in B. canis but not B. melitensis during infection of macrophages. The data suggest differences in iron requirements that may contribute to differences observed in the lifestyles of these closely related pathogens. The initial importance of iron for B. canis but not for B. melitensis helps elucidate differing intracellular survival strategies for two closely related bacteria and provides insight for controlling these pathogens

Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis

<p>Abstract</p> <p>Background</p> <p><it>Tropheryma whipplei</it>, the agent of Whipple's disease, causes localised infections in the absence of histological digestive involvement. Our objective is to describe <it>T. whipplei </it>encephalitis.</p> <p>Methods</p> <p>We first diagnosed a patient presenting dementia and obesity whose brain biopsy and cerebrospinal fluid specimens contained <it>T. whipplei </it>DNA and who responded dramatically to antibiotic treatment. We subsequently tested cerebrospinal fluid specimens and brain biopsies sent to our laboratory using <it>T. whipplei </it>PCR assays. PAS-staining and <it>T. whipplei </it>immunohistochemistry were also performed on brain biopsies. Analysis was conducted for 824 cerebrospinal fluid specimens and 16 brain biopsies.</p> <p>Results</p> <p>We diagnosed seven patients with <it>T. whipplei </it>encephalitis who demonstrated no digestive involvement. Detailed clinical histories were available for 5 of them. Regular PCR that targeted a monocopy sequence, PAS-staining and immunohistochemistry were negative; however, several highly sensitive and specific PCR assays targeting a repeated sequence were positive. Cognitive impairments and ataxia were the most common neurologic manifestations. Weight gain was paradoxically observed for 2 patients. The patients' responses to the antibiotic treatment were dramatic and included weight loss in the obese patients.</p> <p>Conclusions</p> <p>We describe a new clinical condition in patients with dementia and obesity or ataxia linked to <it>T. whipplei </it>that may be cured with antibiotics.</p

Differential Function of Lip Residues in the Mechanism and Biology of an Anthrax Hemophore

To replicate in mammalian hosts, bacterial pathogens must acquire iron. The majority of iron is coordinated to the protoporphyrin ring of heme, which is further bound to hemoglobin. Pathogenic bacteria utilize secreted hemophores to acquire heme from heme sources such as hemoglobin. Bacillus anthracis, the causative agent of anthrax disease, secretes two hemophores, IsdX1 and IsdX2, to acquire heme from host hemoglobin and enhance bacterial replication in iron-starved environments. Both proteins contain NEAr-iron Transporter (NEAT) domains, a conserved protein module that functions in heme acquisition in Gram-positive pathogens. Here, we report the structure of IsdX1, the first of a Gram-positive hemophore, with and without bound heme. Overall, IsdX1 forms an immunoglobin-like fold that contains, similar to other NEAT proteins, a 310-helix near the heme-binding site. Because the mechanistic function of this helix in NEAT proteins is not yet defined, we focused on the contribution of this region to hemophore and NEAT protein activity, both biochemically and biologically in cultured cells. Site-directed mutagenesis of amino acids in and adjacent to the helix identified residues important for heme and hemoglobin association, with some mutations affecting both properties and other mutations affecting only heme stabilization. IsdX1 with mutations that reduced the ability to associate with hemoglobin and bind heme failed to restore the growth of a hemophore-deficient strain of B. anthracis on hemoglobin as the sole iron source. These data indicate that not only is the 310-helix important for NEAT protein biology, but also that the processes of hemoglobin and heme binding can be both separate as well as coupled, the latter function being necessary for maximal heme-scavenging activity. These studies enhance our understanding of NEAT domain and hemophore function and set the stage for structure-based inhibitor design to block NEAT domain interaction with upstream ligands

Sequestration and Scavenging of Iron in Infection

The proliferative capability of many invasive pathogens is limited by the bioavailability of iron. Pathogens have thus developed strategies to obtain iron from their host organisms. In turn, host defense strategies have evolved to sequester iron from invasive pathogens. This review explores the mechanisms employed by bacterial pathogens to gain access to host iron sources, the role of iron in bacterial virulence, and iron-related genes required for the establishment or maintenance of infection. Host defenses to limit iron availability for bacterial growth during the acute-phase response and the consequences of iron overload conditions on susceptibility to bacterial infection are also examined. The evidence summarized herein demonstrates the importance of iron bioavailability in influencing the risk of infection and the ability of the host to clear the pathogen

The differing perspectives of road users and service providers

A survey of almost 3000 people gathered evidence on people’s experiences of problems on Britain’s roads, their level of support for potential solutions, and on the different perspectives of transport professionals. An assessment was made of the steps required to reduce gaps between users’ expectations and their current experience. Questions raised by the findings include: the likelihood that current policy priorities are influenced by inaccurate assumptions about what the public would find acceptable; the potentially misleading impressions created by vicarious opinions; the need to re-weight survey responses to correct for differential response rates; and the role of public opinion, media pressure and professional judgement in the political decision-making process