Assessing Malaria Vaccine Efficacy

After many years of silence, eradication of malaria is, once again, one of the top priorities on the agenda of many international health and development agencies. To meet this idealistic goal, a combination of control tools is needed. From this armentarium, a malaria vaccine is central to prevent infection and/or disease. However, numerous malaria vaccine candidates have shown limited efficacy in Phase II and III studies. One reason for these failures has been that the assessment of efficacy in the context of malaria has been difficult to standardize. In this article, we have reviewed and discussed the different ways to assess the outcome of a malaria vaccination

The Salmonella SPI2 Effector SseI Mediates Long-Term Systemic Infection by Modulating Host Cell Migration

Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically for long periods of time despite the presence of a robust immune response. Chronically infected hosts are asymptomatic and transmit disease to naïve hosts via fecal shedding of bacteria, thereby serving as a critical reservoir for disease. We show that the bacterial effector protein SseI (also called SrfH), which is translocated into host cells by the Salmonella Pathogenicity Island 2 (SPI2) type III secretion system (T3SS), is required for Salmonella typhimurium to maintain a long-term chronic systemic infection in mice. SseI inhibits normal cell migration of primary macrophages and dendritic cells (DC) in vitro, and such inhibition requires the host factor IQ motif containing GTPase activating protein 1 (IQGAP1), an important regulator of cell migration. SseI binds directly to IQGAP1 and co-localizes with this factor at the cell periphery. The C-terminal domain of SseI is similar to PMT/ToxA, a bacterial toxin that contains a cysteine residue (C1165) that is critical for activity. Mutation of the corresponding residue in SseI (C178A) eliminates SseI function in vitro and in vivo, but not binding to IQGAP1. In addition, infection with wild-type (WT) S. typhimurium suppressed DC migration to the spleen in vivo in an SseI-dependent manner. Correspondingly, examination of spleens from mice infected with WT S. typhimurium revealed fewer DC and CD4+ T lymphocytes compared to mice infected with ΔsseI S. typhimurium. Taken together, our results demonstrate that SseI inhibits normal host cell migration, which ultimately counteracts the ability of the host to clear systemic bacteria

New catalysts for polymerization of substituted acetylenes

The investigation of electroactive polymers and other functional materials has become one of the most important areas of research in polymer and materials science during past two decades. Polyacetylenes, the most important and promising conducting polymers and gas permeable materials, have attracted much interest. The exploration for high efficient and easy manipulatable catalysts for polymerization of acetylenes is of extremely importance in views of both theoretical aspects and practical applications. Quite a few organotransition metal compounds have been reported as effective catalysts for the polymerization of acetylenes. polyacetylenes of high molecular weights with good yields have been obtained (1,2). However, most of the catalysts are air- and moisture-sensitive and must be handled in dry and inert atmospheres. Additionally, Lewis acids or cocatalysts are necessary and UV irradiation should be applied to create the active initiating species. In order to overcome the drawbacks of the previous catalyst systems, we have recently succeeded in developing efficient air-stable catalysts for polymerizing acetylenes. The catalysts can be handled in air. No additional Lewis acids, cocatalysts or UV irradiation are necessary. Polyacetylenes of high molecular weights are obtained in good yields. The Polyacetylenes show high thermal stability

Synthesis and Properties of Hyperbranched Polyferrocenylenesilynes

Organometallic polymers consisting of three-dimensionally alternating ferrocene and silyne units are synthesized in high yields by a one-pot procedure of coupling reactions. The hyperbranched polymers are electronically conjugated, with their absorption spectra extending into the infrared region. The polymers ceramize when pyrolyzed, with higher temperatures favoring the formation of ceramics with larger metallic nanoclusters. The ceramics containing iron silicide nanocrystals exhibit outstanding soft ferromagnetisms with excellent magnetic susceptibilities and practically nil hysteresis losses

Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis

Intracellular bacterial pathogens Francisella novicida and the Live Vaccine Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome, which leads to the activation of caspase-1 and the processing and secretion of active IL-1β, IL-18 and pyroptosis. Previous studies have reported that F. novicida and LVS mutants in specific genes (e.g. FTT0584, mviN and ripA) induce elevated inflammasome activation and hypercytotoxicity in host cells, leading to the proposal that F. novicida and LVS may have proteins that actively modulate inflammasome activation. However, there has been no direct evidence of such inflammasome evasion mechanisms. Here, we demonstrate for the first time that the above mutants, along with a wide range of F. novicida hypercytotoxic mutants that are deficient for membrane-associated proteins (ΔFTT0584, ΔmviN, ΔripA, ΔfopA and ΔFTN1217) or deficient for genes involved in O-antigen or LPS biosynthesis (ΔwbtA and ΔlpxH) lyse more intracellularly, thus activating increased levels of AIM2-dependent pyroptosis and other innate immune signalling pathways. This suggests that an inflammasome-specific evasion mechanism may not be present in F. novicida and LVS. Furthermore, future studies may need to consider increased bacterial lysis as a possible cause of elevated stimulation of multiple innate immune pathways when the protein composition or surface carbohydrates of the bacterial membrane is altered