Crystal structure of sTALL-1 reveals a virus-like assembly of TNF family ligands

TALL-1/BAFF/BLyS was recently identified as a member of the tumor necrosis factor (TNF) ligand family. The crystal structure of the functional soluble TALL-1 (sTALL-1) has been determined at 3.0 A. sTALL-1 forms a virus-like assembly with 200 A diameter in the crystals, containing 60 sTALL-1 monomers. The cluster formation is mediated by a "flap" region of the sTALL-1 monomer. The virus-like assembly was also detected in solution using gel filtration and electron microscopy. Deletion of the flap region disrupted the formation of the virus-like assembly. The mutant sTALL-1 still bound its receptor but could not activate NF-kappaB and did not stimulate B lymphocyte proliferation. Finally, we found the virus-like cluster of sTALL-1 exists in physiological condition. We propose that this virus-like assembly of sTALL-1 is the functional unit for TALL-1 in vivo.     

Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

Introduction

Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches.

Methods

A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions.

Results

The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology.

Conclusion

When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers.     

Pea aphid symbiont relationships established by analysis of 16S rRNAs

The pea aphid (Acyrthosiphon pisum Harris) harbors two morphologically distinct procaryotic intracellular symbionts. The genes for the 16S rRNA from these symbionts have been cloned and sequenced. Comparisons with sequences of 16S rRNAs from selected procaryotes indicate that the two symbionts are evolutionarily distinct from each other and are members of the gamma-3 subdivision of the class Proteobacteria. One of the symbionts is a member of the family Enterobacteriaceae, while the other constitutes a lineage distinct from these organisms. Both symbionts appear to have only one copy of their rRNA operon.     

In Vivo Neutralization of α-Cobratoxin with High-Affinity Llama Single-Domain Antibodies (VHHs) and a VHH-Fc Antibody

Small recombinant antibody fragments (e.g. scFvs and V_HHs), which are highly tissue permeable, are being investigated for antivenom production as conventional antivenoms consisting of IgG or F(ab’)₂ antibody fragments do not effectively neutralize venom toxins located in deep tissues. However, antivenoms composed entirely of small antibody fragments may have poor therapeutic efficacy due to their short serum half-lives. To increase serum persistence and maintain tissue penetration, we prepared low and high molecular mass antivenom antibodies. Four llama V_HHs were isolated from an immune V_HH-displayed phage library and were shown to have high affinity, in the low nM range, for α-cobratoxin (α–Cbtx), the most lethal component of Naja kaouthia venom. Subsequently, our highest affinity V_HH (C2) was fused to a human Fc fragment to create a V_HH2-Fc antibody that would offer prolonged serum persistence. After in planta (Nicotiana benthamiana) expression and purification, we show that our V_HH2-Fc antibody retained high affinity binding to α–Cbtx. Mouse α–Cbtx challenge studies showed that our highest affinity V_HHs (C2 and C20) and the V_HH2-Fc antibody effectively neutralized lethality induced by α–Cbtx at an antibody:toxin molar ratio as low as ca. 0.75×:1. Further research towards the development of an antivenom therapeutic involving these anti-α-Cbtx V_HHs and V_HH2-Fc antibody molecules should involve testing them as a combination, to determine whether they maintain tissue penetration capability and low immunogenicity, and whether they exhibit improved serum persistence and therapeutic efficacy.     

Does doping with aluminum alter the effects of ZnO nanoparticles on the metabolism of soil pseudomonads?

Doping of ZnO nanoparticles (NPs) is being used to increase their commercialization in the optical and semiconductor fields. This paper addresses whether doping with Al alters how ZnO NPs at nonlethal levels modifies the metabolism of soil-borne pseudomonads which are beneficial in performing bioremediation or promoting plant growth. The differences in X-ray diffraction (XRD) patterns, observed between commercial ZnO and Al-doped ZnO NPs indicated the aluminum was present as Al NPs. Both particles aggregated in the bacterial growth medium and formed colloids of different surface charges. They had similar effects on bacterial metabolism: rapid, dose-dependent loss in light output indicative of temporary toxicity in a biosensor constructed in Pseudomonas putida KT2440; increased production of a fluorescent pyoverdine-type siderophore, and decreased levels of indole acetic acid and phenazines in Pseudomonas chlororaphis O6. Solubilization of Zn and Al from the NPs contributed to these responses to different extents. These findings indicate that Al-doping of the ZnO NPs did not reduce the ability of the NPs to alter bacterial metabolism in ways that could influence performance of the pseudomonads in their soil environment.     

NEW TAXONOMIC CRITERIA IN THE CLASSIFICATION OF CHLOROCOCCUM SPECIES. I. PIGMENTATION12

Eighteen isolates of Chlorococcum were incubated under defined culture conditions for 6-7 weeks. At that time, isolates were separated into green, yellow-green, orange, or red color groups according to the color of the cultures. Total chlorophyll, carotenoid concentration, and percentage of carotenoids in relation to total pigment content were measured for each species. Individual carotenoids of each isolate were identified and quantified. Each color group had pigment characteristics which were distinctive. Other studies on Chlorococcum are discussed in relation to this work. It is proposed that pigmentation of old cultures be used as the first criterion for distinguishing species of Chlorococcum.