Viruses transfer the antiviral second messenger cGAMP between cells.

Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development.

Exploring the economics of motorcycle helmet laws--implications for low and middle-income countries.

This paper reviews economic evaluations of motorcycle helmet interventions in preventing injuries. A comprehensive literature review focusing on the effectiveness of motorcycle helmet use, and on mandatory helmet laws and their enforcement was done. When helmet laws were lifted between 1976-80, 48 states within the U.S.A. experienced a cost of $342,047 per excess fatality of annual net savings. Helmet laws in the USA had a benefit-cost ratio of 1.33 to 5.07. Taiwan witnessed a 14% decline in motorcycle fatalities and a 22% reduction of head injury fatalities with the introduction of a helmet law. In Thailand, where 70-90% of all crashes involve motorcycle, after enforcement of a helmet law, helmet-use increased five-fold, the number of injured motorcyclists decreased by 33.5%, head injuries decreased by 41.4%, and deaths decreased by 20.8%. There is considerable evidence that mandatory helmet laws with enforcement alleviate the burden of traffic injuries greatly. For low and middle-income countries with high rates of motorcycle injuries, enforced, mandatory motorcycle helmet laws are potentially one of the most cost-effective interventions available.

MicroRNAs silence gene expression by repressing protein expression and/or by promoting mRNA decay.

microRNAs (miRNAs) represent a novel class of genome-encoded eukaryotic regulatory RNAs that silence gene expression posttranscriptionally. Although the proteins mediating miRNA biogenesis and function have been identified, the precise mechanism by which miRNAs regulate the expression of target mRNAs remains unclear. We summarize recent work from our laboratory demonstrating that miRNAs silence gene expression by at least two independent mechanisms: by repressing translation and/or by promoting mRNA degradation. In Drosophila, both mechanisms require Argonaute 1 (AGO1) and the P-body component GW182. Moreover, mRNA degradation by miRNAs is effected by the enzymes involved in general mRNA decay, including deadenylases and decapping enzymes, which also localize to P bodies. Our findings suggest a model for miRNA function in which AGO1 associates with miRNA targets through miRNA:mRNA base-pairing interactions. GW182 interacts with AGO1 and recruits deadenylases and decapping enzymes, leading to mRNA degradation. However, not all miRNA targets are degraded: Some stay in a translationally silent state, from which they may eventually be released. We propose that the final outcome of miRNA regulation (i.e., degradation vs. translational repression) is influenced by other RNA-binding proteins interacting with the targeted mRNA.

The economic dimensions of interpersonal violence

It strengthens the case for investing in prevention even further by highlighting the enormous economic costs of the consequences of interpersonal violence, and reviewing the limited but nonetheless striking evidence for the cost-effectiveness of preventionprogrammes. Document in pdf format; Acrobat Reader required.

Economic evaluation of Mectizan distribution.

The distribution of ivermectin has dramatically altered the nature of onchocerciasis control. Existing economic analyses of ivermectin distribution programmes show that these programmes have a highly beneficial impact. Most analyses have estimated the economic benefits in terms of increased labour productivity as a result of reductions in blindness, and in terms of additional land-availability because of a reduced transmission of the parasite. Economic evaluations of the Onchocerciasis Control Program (OPC) in West Africa have calculated a net present value - equivalent discounted benefits minus discounted costs - of $485 million for the programme over a 39-year period, using a conservative 10% rate to discount future health and productivity gains. The net present value for the African Program for Onchocerciasis Control (APOC) is calculated at 88 million US dollars over a 21-year time period, also using a 10% discount rate. Cost-effectiveness analyses of ivermectin distribution have found a cost of 14-30 US dollars per disability-adjusted life-year prevented - estimates comparable with other priority disease control programmes. However, the economic success of ivermectin distribution is sensitive to the fact that the drug itself has been donated free of charge. The market value of Merck's donations to the APOC for just 1 year considerably outweighs the benefits calculated for both the OPC and the APOC over the life of these projects. Pending the development of an effective macrofilaricide, the distribution of ivermectin will remain a public health priority into the foreseeable future.