Three-dimensional structure of tropism-switching Bordetella bacteriophage.

Bacteriophage BPP-1, which infects Bordetella species, can switch its specificity by mutations to the ligand-binding surface of its major tropism-determinant protein, Mtd. This targeted mutagenesis results from the activity of a phage-encoded diversity-generating retroelement. Purified Mtd binds its receptor with low affinity, yet BPP-1 binding and infection of Bordettella cells are efficient because of high-avidity binding between phage-associated Mtd and its receptor. Here, using an integrative approach of three-dimensional (3D) structural analyses of the entire phage by cryo-electron tomography and single-prticle cryo-electron microscopy, we provide direct localization of Mtd in the phage and the structural basis of the high-avidity binding of the BPP-1 phage. Our structure shows that each BPP-1 particle has a T = 7 icosahedral head and an unusual tail apparatus consisting of a short central tail "hub," six short tail spikes, and six extended tail fibers. Subtomographic averaging of the tail fiber maps revealed a two-lobed globular structure at the distal end of each long tail fiber. Tomographic reconstructions of immuno-gold-labeled BPP-1 directly localized Mtd to these globular structures. Finally, our icosahedral reconstruction of the BPP-1 head at 7A resolution reveals an HK97-like major capsid protein stabilized by a smaller cementing protein. Our structure represents a unique bacteriophage reconstruction with its tail fibers and ligand-binding domains shown in relation to its tail apparatus. The localization of Mtd at the distal ends of the six tail fibers explains the high avidity binding of Mtd molecules to cell surfaces for initiation of infection.

Characterization of template switching and recombination during Moloney murine leukemia virus replication

Retroviruses uniquely co-package two copies of their genomic RNA within each virion. The two copies are used as templates for synthesis of the proviral DNA during the process of reverse transcription. Two template switches are required to complete retroviral DNA synthesis by the retroviral enzyme, reverse transcriptase. With two RNA genomes present in the virion, reverse transcriptase can make template switches utilizing only one of the RNA templates (intramolecular) or utilizing both RNA templates (intermolecular) during the process of reverse transcription. The results presented in this study show that during a single cycle of Moloney murine leukemia virus replication, both nonrecombinant and recombinant proviruses predominantly underwent intramolecular minus- and plus-strand transfers during the process of reverse transcription. This is the first study to examine the nature of the required template switches occurring during MLV replication and these results support the previous findings for SNV, and the hypothesis that the required template switches are ordered events. This study also determined rates for deletion and a rate of recombination for a single cycle of MLV replication. The rates reported here are comparable to the rates previously reported for both SNV and MLV. ^

The welfare state determinants of health: Implications of regimes and pathways

Background. Population health within and between nations is heavily influenced by political determinants, yet these determinants have received significantly less attention than socioeconomic factors in public health. It has been hypothesized that the welfare state, as a political variable, may play a particularly prominent role in affecting both health indicators and health disparities in developed countries. The research, however, provides conflicting evidence regarding the health impact of particular regimes over others and the mechanisms through which the welfare state can most significantly affect health.^ Objective. To perform a systematic review of the literature as a means of exploring what the current research indicates regarding the benefits or detriments of particular regimes styles and the pathways through which the welfare state can impact heath indicators and health disparities within developed countries.^ Methods. A thorough search of the EBSCO, Pubmed, Medline, Web of Science, and Scopus electronic databases was conducted and resulted in the identification of 15 studies that evaluated the association between welfare state regime and population health outcomes, and/or pathways through with the welfare state influences health. ^ Results. Social democratic countries tended to perform best when infant mortality rate (IMR) was the primary outcome of interest, whereas liberal countries performed strongly in relation to self perceived health. The results were mixed regarding welfare state effectiveness in mitigating health inequities, with Christian democratic countries performing as well as social democratic countries. In relation to welfare state pathways, public health spending and medical coverage were associated with positive health indicators. Redistributive impact of the welfare state was also consistently associated with better health outcomes while social security expenditures were not.^ Discussion/Conclusions. Studies consistently discovered a significant relationship between the welfare state and population health and/or health disparities, lending support to the hypothesis that the welfare state is, indeed, an important non-medical determinant of health. However, it is still fairly unclear which welfare state regime may be most protective for health, as results varied according to the measured health indicator. The research regarding welfare state pathways is particularly undeveloped, and does not provide much insight into the importance of in-kind service provision or cash transfers, or targeted or universal approaches to the welfare state. Suggestions to direct future research are provided.^