The shape of health to come: prospective study of the determinants of 30-year health trajectories in the Alameda County Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57268/1/Kaplan GA et al The shape of health to come prospective study of the determinants of 30 year health trajectories in the Alameda County Study.pd

Effects of potential additives to promote seal swelling on the thermal stability of synthetic jet fuels

Synthetic fuels derived from the Fischer-Tropsch (F-T) process using natural gas or coal-derived synthesis gas as feedstocks can be used for powering of ground vehicles, aircraft and ships. Because of their chemical and physical properties, F-T fuels will probably require additives in order to meet specifications with respect to lubricity and seal swell capability for use in ground and air vehicles. These additives can include oxygenates and compounds containing other heteroatoms that may adversely affect thermal stability. In order to understand what additives will be the most beneficial, a comprehensive experimental and computational study of conventional and additized fuels has been undertaken. The experimental approach includes analysis of the trace oxygenate and nitrogen-containing compounds present in conventional petroleum-derived fuels and trying to relate their presence (or absence) to changes in the desired properties of the fuels. This paper describes the results of efforts to test the thermal stability of synthetic fuels and surrogate fuels containing single-component additives that have been identified in earlier research as the best potential additives for promoting seal swelling in synthetic fuels, as well as mixtures of synthetic and petroleum-derived fuels

Plasmonics-enhanced metal–organic framework nanoporous films for highly sensitive near-infrared absorption

Combined plasmonic nanocrystals and metal–organic framework thin-films are fabricated for sensing gases in the near-infrared range. This nanocomposite thin-film shows a highly sensitive response in near-infrared absorption, which is attributed to preconcentration of gas molecules in metal–organic framework pores causing close proximity to the electromagnetic fields at the plasmonic nanocrystal surface

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Positive selection inhibits gene mobilization and transfer in soil bacterial communities

Horizontal gene transfer (HGT) between bacterial lineages is a fundamental evolutionary process that accelerates adaptation. Sequence analyses show that conjugative plasmids are principal agents of HGT in natural communities. However, we lack understanding of how the ecology of bacterial communities and their environments affect the dynamics of plasmid-mediated gene mobilization and transfer. Here we show, in simple experimental soil bacterial communities containing a conjugative mercury resistance plasmid, the repeated, independent mobilization of transposon-borne genes from chromosome to plasmid, plasmid to chromosome and, in the absence of mercury selection, interspecific gene transfers from the chromosome of one species to the other via the plasmid. By reducing conjugation, positive selection for plasmid-encoded traits, like mercury resistance, can consequently inhibit HGT. Our results suggest that interspecific plasmid-mediated gene mobilization is most likely to occur in environments where plasmids are infectious, parasitic elements rather than those where plasmids are positively selected, beneficial elements

Multi-host environments select for host-generalist conjugative plasmids

BACKGROUND: Conjugative plasmids play an important role in bacterial evolution by transferring ecologically important genes within and between species. A key limit on interspecific horizontal gene transfer is plasmid host range. Here, we experimentally test the effect of single and multi-host environments on the host-range evolution of a large conjugative mercury resistance plasmid, pQBR57. Specifically, pQBR57 was conjugated between strains of a single host species, either P. fluorescens or P. putida, or alternating between P. fluorescens and P. putida. Crucially, the bacterial hosts were not permitted to evolve allowing us to observe plasmid evolutionary responses in isolation. RESULTS: In all treatments plasmids evolved higher conjugation rates over time. Plasmids evolved in single-host environments adapted to their host bacterial species becoming less costly, but in the case of P. fluorescens-adapted plasmids, became costlier in P. putida, suggesting an evolutionary trade-off. When evolved in the multi-host environment plasmids adapted to P. fluorescens without a higher cost in P. putida. CONCLUSION: Whereas evolution in a single-host environment selected for host-specialist plasmids due to a fitness trade-off, this trade-off could be circumvented in the multi-host environment, leading to the evolution of host-generalist plasmids

Adaptive modulation of antibiotic resistance through intragenomic coevolution

Bacteria gain antibiotic resistance genes by horizontal acquisition of mobile genetic elements (MGEs) from other lineages. Newly acquired MGEs are often poorly adapted causing intragenomic conflicts; these are resolved by either compensatory adaptation - of the chromosome or the MGE - or reciprocal coadaptation. The footprints of such intragenomic coevolution are present in bacterial genomes, suggesting an important role promoting genomic integration of horizontally acquired genes, but direct experimental evidence of the process is limited. Here we show adaptive modulation of tetracycline resistance via intragenomic coevolution between Escherichia coli and the multidrug resistant plasmid RK2. Tetracycline treatments, including monotherapy or combination therapies with ampicillin, favoured de novo chromosomal resistance mutations coupled with mutations on RK2 impairing the plasmid-encoded tetracycline efflux pump. These mutations together provided increased tetracycline resistance at reduced cost. Additionally, the chromosomal resistance mutations conferred cross-resistance to chloramphenicol. Reciprocal coadaptation was not observed under ampicillin-only or no antibiotic selection. Intragenomic coevolution can create genomes comprising multiple replicons that together provide high-level, low-cost resistance, but the resulting co-dependence may limit the spread of coadapted MGEs to other lineages

Efficiency of Purine Utilization by Helicobacter pylori: Roles for Adenosine Deaminase and a NupC Homolog

The ability to synthesize and salvage purines is crucial for colonization by a variety of human bacterial pathogens. Helicobacter pylori colonizes the gastric epithelium of humans, yet its specific purine requirements are poorly understood, and the transport mechanisms underlying purine uptake remain unknown. Using a fully defined synthetic growth medium, we determined that H. pylori 26695 possesses a complete salvage pathway that allows for growth on any biological purine nucleobase or nucleoside with the exception of xanthosine. Doubling times in this medium varied between 7 and 14 hours depending on the purine source, with hypoxanthine, inosine and adenosine representing the purines utilized most efficiently for growth. The ability to grow on adenine or adenosine was studied using enzyme assays, revealing deamination of adenosine but not adenine by H. pylori 26695 cell lysates. Using mutant analysis we show that a strain lacking the gene encoding a NupC homolog (HP1180) was growth-retarded in a defined medium supplemented with certain purines. This strain was attenuated for uptake of radiolabeled adenosine, guanosine, and inosine, showing a role for this transporter in uptake of purine nucleosides. Deletion of the GMP biosynthesis gene guaA had no discernible effect on mouse stomach colonization, in contrast to findings in numerous bacterial pathogens. In this study we define a more comprehensive model for purine acquisition and salvage in H. pylori that includes purine uptake by a NupC homolog and catabolism of adenosine via adenosine deaminase