Fusion protein of Δ27LFn and EFn has the potential as a novel anthrax toxin inhibitor

PA-binding domain of LF (LFn) or PA-binding domain of EF (EFn) is the anthrax protective antigen (PA) binding domain of anthrax lethal factor (LF) or edema factor (EF). Here we show the development of a novel anthrax toxin inhibitor, fusion protein of N-terminal 27 amino acids deletion of LFn (Δ27LFn) and EFn. In a cell model of intoxication, fusion protein of Δ27LFn and EFn (Δ27LFn-EFn) was a 62-fold more potent toxin inhibitor than LFn or EFn, and this increased activity corresponded to a 39-fold higher PA-binding affinity by Biacore analysis. More importantly, Δ27LFn-EFn could protect the highly susceptible Fischer 344 rats from anthrax lethal toxin challenge. This work suggested that Δ27LFn-EFn has the potential as a candidate therapeutic agent against anthrax.

Structured summary

MINT-7014735, MINT-7014747, MINT-7014761: PA63 (uniprotkb:P13423) and LF (uniprotkb:P15917) bind (MI:0407) by surface plasmon resonance (MI:0107)     

2008年中国植物科学若干领域重要研究进展

在国家各类重大研究计划的持续支持和推动下, 2008年中国植物科学研究继续快速发展, 中国科学家在植物科学各领域中取得了大量的原创性研究成果, 尤其是在水稻株型功能基因组、水稻开花控制和种子发育、生殖隔离机制以及转基因生态安全研究等方面取得了一系列重大进展, 受到了国内外的广泛关注。该文对2008年中国本土科学家在植物生命科学若干领域取得的重要研究进展进行概括性评述, 旨在全面追踪当前中国植物科学领域发展的最新前沿和热点事件, 并展现我国科学家所取得的杰出成就。     

Divergence of exonic splicing elements after gene duplication and the impact on gene structures

Background  

The origin of new genes and their contribution to functional novelty has been the subject of considerable interest. There has been much progress in understanding the mechanisms by which new genes originate. Here we examine a novel way that new gene structures could originate, namely through the evolution of new alternative splicing isoforms after gene duplication.     

SEPALLATA3: the 'glue' for MADS box transcription factor complex formation

Background  

Plant MADS box proteins play important roles in a plethora of developmental processes. In order to regulate specific sets of target genes, MADS box proteins dimerize and are thought to assemble into multimeric complexes. In this study a large-scale yeast three-hybrid screen is utilized to provide insight into the higher-order complex formation capacity of the Arabidopsis MADS box family. SEPALLATA3 (SEP3) has been shown to mediate complex formation and, therefore, special attention is paid to this factor in this study.     

Impact of Pyrolysis Treatment on Heavy Metals in Sediment

This paper describes a laboratory study that examined the effect of pyrolysis treatment on the behavior of Hg, Cr, Zn, Pb, Cu and Cd in a stream sediment. The influences of pyrolysis on the evaporation, sequential extraction and leaching behavior of these metals were investigated. Cr, Zn, Pb and Cu were retained quantitively in the solid residue at temperatures up to 800°C while mercury and cadmium were completely or partially evaporated. The metal form distribution in the sludge samples was determined by the sequential extraction procedure. The procedure revealed that as a consequence of pyrolysis, the metals were more strongly fixed in the treated sediment, as could be seen by the decrease with temperature of the first two sequential-extracted fractions and increase of the residue fraction. The leaching results showed that the quantities of the studied metals leached in the two pyrolysis samples were lower than those in the untreated sediment. The amounts of metals leached from the pyrolysis residues correlated significantly with the first extracted fraction (exchangeable fraction).     

Transgene Expression Is Associated with Copy Number and Cytomegalovirus Promoter Methylation in Transgenic Pigs

Transgenic animals have been used for years to study gene function, produce important proteins, and generate models for the study of human diseases. However, inheritance and expression instability of the transgene in transgenic animals is a major limitation. Copy number and promoter methylation are known to regulate gene expression, but no report has systematically examined their effect on transgene expression. In the study, we generated two transgenic pigs by somatic cell nuclear transfer (SCNT) that express green fluorescent protein (GFP) driven by cytomegalovirus (CMV). Absolute quantitative real-time PCR and bisulfite sequencing were performed to determine transgene copy number and promoter methylation level. The correlation of transgene expression with copy number and promoter methylation was analyzed in individual development, fibroblast cells, various tissues, and offspring of the transgenic pigs. Our results demonstrate that transgene expression is associated with copy number and CMV promoter methylation in transgenic pigs.     

Digestion of Raw and Roasted Almonds in Simulated Gastric Environment

Knowledge of digestion kinetics of solid foods in human stomach, as affected by food processing methods, is critical in establishing processing conditions at the manufacturing stage to achieve desirable release of nutrients in the gastrointestinal tract. The objective of this study was to investigate how roasting affected disintegration and solid release properties of almond in simulated gastric environment. In vitro trials were performed for raw and roasted almonds by using static soaking method and a model stomach system. The changes in sample weight, dry mass, and moisture during the trials were determined. Both compression and penetration tests were used to investigate the texture of almonds with a focus on the influence of absorption of gastric juice. Light microscopy and transmission electronic microscopy were used to study the change in microstructure of the raw and roasted almonds after simulated digestion. The results suggested that the slow disintegration rate and the high amount of swelling of the almonds in the stomach may contribute to their high satiety property. Roasting significantly improved the disintegration rates of almonds and increased loss of solids during simulated digestion, which is well correlated with the decrease in the rigidity of almond samples after absorbing gastric juice. Microstructure of digested almonds showed breakage and breach of cell walls due to acid hydrolysis. Intercellular and intracellular channels formed in almonds during roasting are important for penetration of gastric juice that may facilitate an effective digestion.     

Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention: Analyses from the Rakai Trials

Background

Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC.

Methods and Findings

HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43–0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51–0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30–0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (χ² p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15–0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19–1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49–1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0–38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI −1.2 to 77.1).

Conclusions

Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition.

NIH Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00425984","term_id":"NCT00425984"}}NCT00425984

Gates Foundation Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00124878","term_id":"NCT00124878"}}NCT00124878 Please see later in the article for the Editors'' Summary