Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia cenocepacia</it>, an opportunistic pathogen that causes lung infections in cystic fibrosis (CF) patients, is associated with rapid and usually fatal lung deterioration due to necrotizing pneumonia and sepsis, a condition known as cepacia syndrome. The key bacterial determinants associated with this poor clinical outcome in CF patients are not clear. In this study, the cytotoxicity and procoagulant activity of <it>B. cenocepacia </it>from the ET-12 lineage, that has been linked to the cepacia syndrome, and four clinical isolates recovered from CF patients with mild clinical courses were analysed in both <it>in vitro </it>and <it>in vivo </it>assays.</p> <p>Methods</p> <p><it>B. cenocepacia-</it>infected BEAS-2B epithelial respiratory cells were used to investigate the bacterial cytotoxicity assessed by the flow cytometric detection of cell staining with propidium iodide. Bacteria-induced procoagulant activity in cell cultures was assessed by a colorimetric assay and by the flow cytometric detection of tissue factor (TF)-bearing microparticles in cell culture supernatants. Bronchoalveolar lavage fluids (BALF) from intratracheally infected mice were assessed for bacterial proinflammatory and procoagulant activities as well as for bacterial cytotoxicity, by the detection of released lactate dehydrogenase.</p> <p>Results</p> <p>ET-12 was significantly more cytotoxic to cell cultures but clinical isolates Cl-2, Cl-3 and Cl-4 exhibited also a cytotoxic profile. ET-12 and CI-2 were similarly able to generate a TF-dependent procoagulant environment in cell culture supernatant and to enhance the release of TF-bearing microparticles from infected cells. In the <it>in vivo </it>assay, all bacterial isolates disseminated from the mice lungs, but Cl-2 and Cl-4 exhibited the highest rates of recovery from mice livers. Interestingly, Cl-2 and Cl-4, together with ET-12, exhibited the highest cytotoxicity. All bacteria were similarly capable of generating a procoagulant and inflammatory environment in animal lungs.</p> <p>Conclusion</p> <p><it>B. cenocepacia </it>were shown to exhibit cytotoxic and procoagulant activities potentially implicated in bacterial dissemination into the circulation and acute pulmonary decline detected in susceptible CF patients. Improved understanding of the mechanisms accounting for <it>B. cenocepacia</it>-induced clinical decline has the potential to indicate novel therapeutic strategies to be included in the care <it>B. cenocepacia</it>-infected patients.</p

Stringy effects in black hole decay

We compute the low energy decay rates of near-extremal three(four) charge black holes in five(four) dimensional N=4 string theory to sub-leading order in the large charge approximation. This involves studying stringy corrections to scattering amplitudes of a scalar field off a black hole. We adapt and use recently developed techniques to compute such amplitudes as near-horizon quantities. We then compare this with the corresponding calculation in the microscopic configuration carrying the same charges as the black hole. We find perfect agreement between the microscopic and macroscopic calculations; in the cases we study, the zero energy limit of the scattering cross section is equal to four times the Wald entropy of the black hole.Comment: 32 page

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Developing country consumers’ acceptance of biofortified foods: a synthesis

The success of biofortified staple crops depends on whether they are accepted and consumed by target populations. In the past 8 years, several studies were undertaken to understand consumers’ acceptance of foods made with biofortified staple crops. Consumer acceptance is measured in terms of their sensory evaluation and economic valuation of biofortified varieties vis-à-vis conventional ones. These studies apply expert sensory panel and hedonic trait analyses methods adopted from food sciences literature, as well as various preference elicitation methods (including experimental auctions, revealed choice experiments, and stated choice experiments) adopted from experimental economics literature. These studies also test the impact of various levers on consumers’ evaluation and valuation for biofortified foods. These levers include (i) nutrition information and the media through which such information is conveyed; (ii) the length and content of nutrition information; (iii) different branding options; (iv) the nature (national or international) of the branding/certification agency that is endorsing the biofortified staple food; and (v) the nature (national or international) of the agency that is delivering the biofortified staple food. This paper brings together evidence on consumer acceptance of biofortified crops on 5 crops across 7 countries in Africa, Asia and Latin America. The results of these studies are expected to aid in the development of biofortified crops that consumers like, as well as in the development of appropriate marketing and consumer awareness or information campaigns to encourage the switch in consumption from traditional staples to biofortified ones

Replication Fork Polarity Gradients Revealed by Megabase-Sized U-Shaped Replication Timing Domains in Human Cell Lines

In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome