A Superoxide Dismutase C Mutant of Haemophilus ducreyi Is Virulent in Human Volunteers

Haemophilus ducreyi produces a periplasmic copper-zinc superoxide dismutase (Cu-Zn SOD), which is thought to protect the organism from exogenous reactive oxygen species generated by neutrophils during an inflammatory response. We had previously identified the gene, sodC, responsible for the production and secretion of Cu-Zn SOD and constructed an isogenic H. ducreyi strain with a mutation in the sodC gene (35000HP-sodC-cat). Compared to the parent, the mutant does not survive in the presence of exogenous superoxide (L. R. San Mateo, M. Hobbs, and T. H. Kawula, Mol. Microbiol. 27:391-404, 1998) and is impaired in the swine model of H. ducreyi infection (L. R. San Mateo, K. L. Toffer, P. E. Orndorff, and T. H. Kawula, Infect. Immun. 67:5345-5351, 1999). To test whether Cu-Zn SOD is important for bacterial survival in vivo, six human volunteers were experimentally infected with 35000HP and 35000HP-sodC-cat and observed for papule and pustule formation. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule formation rates were 75% (95% confidence intervals [CI], 43 to 95%) at 12 parent-inoculated sites and 67% (95% CI, 41 to 88%) at 18 mutant-inoculated sites (P = 0.47). There was no significant difference in levels of H. ducreyi recovery from mutant- and parent-inoculated biopsy sites. These results suggest that expression of Cu-Zn SOD does not play a major role in the survival of this pathogen in the initial stages of experimental infection of humans

Investigating the driving mechanisms of coronal mass ejections

The objective of this investigation was to first examine the kinematics of coronal mass ejections (CMEs) using EUV and coronagraph images, and then to make a comparison with theoretical models in the hope to identify the driving mechanisms of the CMEs. We have studied two CMEs which occurred on 2006 Dec. 17 (CME06) and 2007 Dec. 31 (CME07). The models studied in this work were catastrophe, breakout, and toroidal instability models. We found that after the eruption, the accelerations of both events exhibited a drop before increasing again. Our comparisons with the theories suggested that CME06 can be best described by a hybrid of the catastrophe and breakout models while CME07 is most consistent with the breakout model.Comment: 9 pages 7 figure

Period Integrals of CY and General Type Complete Intersections

We develop a global Poincar\'e residue formula to study period integrals of families of complex manifolds. For any compact complex manifold $X$ equipped with a linear system $V^*$ of generically smooth CY hypersurfaces, the formula expresses period integrals in terms of a canonical global meromorphic top form on $X$. Two important ingredients of our construction are the notion of a CY principal bundle, and a classification of such rank one bundles. We also generalize our construction to CY and general type complete intersections. When $X$ is an algebraic manifold having a sufficiently large automorphism group $G$ and $V^*$ is a linear representation of $G$, we construct a holonomic D-module that governs the period integrals. The construction is based in part on the theory of tautological systems we have developed in the paper \cite{LSY1}, joint with R. Song. The approach allows us to explicitly describe a Picard-Fuchs type system for complete intersection varieties of general types, as well as CY, in any Fano variety, and in a homogeneous space in particular. In addition, the approach provides a new perspective of old examples such as CY complete intersections in a toric variety or partial flag variety.Comment: An erratum is included to correct Theorem 3.12 (Uniqueness of CY structure

Mini-review on substrate & inoculum loadings for anaerobic co-digestion of food waste

Increasing production of food waste can lead to major environmental pollution if it is disposed without proper control in many countries. Food waste can be regarded as a resource rather than unwanted discard due to its high potential for resource recovery. Anaerobic digestion of food waste has shown promising potential for food waste treatment and valorisation by producing biogas as a renewable energy and digestate as fertiliser. Food waste has high biogas potential due to the presence of highly labile organic matter but this can lead to process instability. The process instability is often linked to the imbalance of process intermediates that affects the microbial community. Common parameters that are crucial for ensuring optimal metabolic activity of anaerobes includes temperature, pH, carbon-nitrogen ratio, organic loading rate, retention time and nutrient concentration. Co-digestion of food waste with other feedstocks are increasingly being practiced for better nutrient balance and reducing chances for rapid acidfication. The optimum conditions for the process has been shown to vary following different microbial inoculants and loadings of the respective substrates. This study aims to review only the effect of substrate and inoculum used during the AD of food waste, including the type of co-digested substrate, the mixing ratio, the microbial inoculant used and the substrate to inoculum ratio

An insight into curcumin-based photosensitization as a promising and green food preservation technology

Consumer awareness on the side effects of chemical preservatives has increased the demand for natural preservation technologies. An efficient and sustainable alternative to current conventional preservation techniques should guarantee food safety and retain its quality with minimal side effects. Photosensitization, utilizing light and a natural photosensitizer, has been postulated as a viable and green alternative to the current conventional preservation techniques. The potential of curcumin as a natural photosensitizer is reviewed in this paper as a practical guide to develop a safe and effective decontamination tool for industrial use. The fundamentals of the photosensitization mechanism are discussed, with the main emphasis on the natural photosensitizer, curcumin, and its application to inactivate microorganisms as well as to enhance the shelf life of foods. Photosensitization has shown promising results in inactivating a wide spectrum of microorganisms with no reported microbial resistance due to its particular lethal mode of targeting nucleic acids. Curcumin as a natural photosensitizer has recently been investigated and demonstrated efficacy in decontamination and delaying spoilage. Moreover, studies have shown the beneficial impact of an appropriate encapsulation technique to enhance the cellular uptake of photosensitizers, and therefore, the phototoxicity. Further studies relating to improved delivery of natural photosensitizers with inherent poor solubility should be conducted. Also, detailed studies on various food products are warranted to better understand the impact of encapsulation on curcumin photophysical properties, photo-driven release mechanism, and nutritional and organoleptic properties of treated foods

Reactive oxygen species regulate context-dependent inhibition of NFAT5 target genes

The activation of nuclear factor of activated T cells 5(NFAT5), a well-known osmoprotective factor, can be induced by isotonic stimuli, such as activated Toll-like receptors (TLRs). It is unclear, however, how NFAT5 discriminates between isotonic and hypertonic stimuli. In this study we identified a novel context-dependent suppression of NFAT5 target gene expression in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) or a high salt (NaCl) concentration. Although LPS and NaCl both used NFAT5 as a core transcription factor, these stimuli mutually inhibited distinct sets of NFAT5 targets within the cells. Although reactive oxygen species (ROS) are essential for this inhibition, the source of ROS differed depending on the context: mitochondria for high salt and xanthine oxidase for TLRs. Specifically, the high salt-induced suppression of interleukin-6 (IL-6) production was mediated through the ROS-induced inhibition of NFAT5 binding to the IL-6 promoter. The context-dependent inhibition of NFAT5 target gene expression was also confirmed in mouse spleen and kidney tissues that were cotreated with LPS and high salt. Taken together, our data suggest that ROS function as molecular sensors to discriminate between TLR ligation and osmotic stimuli in RAW 264.7 macrophages, directing NFAT5 activity toward proinflammatory or hypertonic responses in a context-dependent manner.open3

Bim Nuclear Translocation and Inactivation by Viral Interferon Regulatory Factor

Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of the host cell. Human herpesvirus 8 (HHV-8) uses several strategies to block the host's innate antiviral defenses via interference with interferon and apoptotic signaling. Contributors include the four viral interferon regulatory factors (vIRFs 1–4), which function in dominant negative fashion to block cellular IRF activities in addition to targeting IRF signaling-induced proteins such as p53 and inhibiting other inducers of apoptosis such as TGFβ receptor-activated Smad transcription factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim was identified in transfected cells, by both immunofluorescence assay and western analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim was detected in nuclei of lytically infected endothelial cells. In vitro co-precipitation assays using purified vIRF-1 and Bim revealed direct interaction between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion and point mutagenesis. Generation and experimental utilization of Bim-refractory vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically, in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking of the interaction with cell-permeable peptide corresponding to the Bim-binding region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro-replication activity. To our knowledge, this is the first report of an IRF protein that interacts with a Bcl-2 family member and of nuclear sequestration of Bim or any other member of the family as a means of inactivation. The data presented reveal a novel mechanism utilized by a virus to control replication-induced apoptosis and suggest that inhibitory targeting of vIRF-1:Bim interaction may provide an effective antiviral strategy