Prevalence and Evolution of Core Photosystem II Genes in Marine Cyanobacterial Viruses and Their Hosts

Cyanophages (cyanobacterial viruses) are important agents of horizontal gene transfer among marine cyanobacteria, the numerically dominant photosynthetic organisms in the oceans. Some cyanophage genomes carry and express host-like photosynthesis genes, presumably to augment the host photosynthetic machinery during infection. To study the prevalence and evolutionary dynamics of this phenomenon, 33 cultured cyanophages of known family and host range and viral DNA from field samples were screened for the presence of two core photosystem reaction center genes, psbA and psbD. Combining this expanded dataset with published data for nine other cyanophages, we found that 88% of the phage genomes contain psbA, and 50% contain both psbA and psbD. The psbA gene was found in all myoviruses and Prochlorococcus podoviruses, but could not be amplified from Prochlorococcus siphoviruses or Synechococcus podoviruses. Nearly all of the phages that encoded both psbA and psbD had broad host ranges. We speculate that the presence or absence of psbA in a phage genome may be determined by the length of the latent period of infection. Whether it also carries psbD may reflect constraints on coupling of viral- and host-encoded PsbA–PsbD in the photosynthetic reaction center across divergent hosts. Phylogenetic clustering patterns of these genes from cultured phages suggest that whole genes have been transferred from host to phage in a discrete number of events over the course of evolution (four for psbA, and two for psbD), followed by horizontal and vertical transfer between cyanophages. Clustering patterns of psbA and psbD from Synechococcus cells were inconsistent with other molecular phylogenetic markers, suggesting genetic exchanges involving Synechococcus lineages. Signatures of intragenic recombination, detected within the cyanophage gene pool as well as between hosts and phages in both directions, support this hypothesis. The analysis of cyanophage psbA and psbD genes from field populations revealed significant sequence diversity, much of which is represented in our cultured isolates. Collectively, these findings show that photosynthesis genes are common in cyanophages and that significant genetic exchanges occur from host to phage, phage to host, and within the phage gene pool. This generates genetic diversity among the phage, which serves as a reservoir for their hosts, and in turn influences photosystem evolution

Three Prochlorococcus cyanophage genomes : signature features and ecological interpretations

© 2005 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in PLoS Biology 3 (2005): e144, doi:10.1371/journal.pbio.0030144.The oceanic cyanobacteria Prochlorococcus are globally important, ecologically diverse primary producers. It is thought that their viruses (phages) mediate population sizes and affect the evolutionary trajectories of their hosts. Here we present an analysis of genomes from three Prochlorococcus phages: a podovirus and two myoviruses. The morphology, overall genome features, and gene content of these phages suggest that they are quite similar to T7-like (P-SSP7) and T4-like (P-SSM2 and P-SSM4) phages. Using the existing phage taxonomic framework as a guideline, we examined genome sequences to establish ‘‘core’’ genes for each phage group. We found the podovirus contained 15 of 26 core T7-like genes and the two myoviruses contained 43 and 42 of 75 core T4-like genes. In addition to these core genes, each genome contains a significant number of ‘‘cyanobacterial’’ genes, i.e., genes with significant best BLAST hits to genes found in cyanobacteria. Some of these, we speculate, represent ‘‘signature’’ cyanophage genes. For example, all three phage genomes contain photosynthetic genes (psbA, hliP) that are thought to help maintain host photosynthetic activity during infection, as well as an aldolase family gene (talC) that could facilitate alternative routes of carbon metabolism during infection. The podovirus genome also contains an integrase gene (int) and other features that suggest it is capable of integrating into its host. If indeed it is, this would be unprecedented among cultured T7-like phages or marine cyanophages and would have significant evolutionary and ecological implications for phage and host. Further, both myoviruses contain phosphate-inducible genes (phoH and pstS) that are likely to be important for phage and host responses to phosphate stress, a commonly limiting nutrient in marine systems. Thus, these marine cyanophages appear to be variations of two well-known phages—T7 and T4—but contain genes that, if functional, reflect adaptations for infection of photosynthetic hosts in low-nutrient oceanic environments.This research was supported by the US DOE under grant numbers DEFG02– 99ER62814 and DE-FG02–02ER63445, and the National Science Foundation under grant number OCE-9820035 (to SWC)

Do computerised clinical decision support systems for prescribing change practice? A systematic review of the literature (1990-2007)

Computerised clinical decision support systems (CDSSs) are used widely to improve quality of care and patient outcomes. This systematic review evaluated the impact of CDSSs in targeting specific aspects of prescribing, namely initiating, monitoring and stopping therapy. We also examined the influence of clinical setting (institutional vs ambulatory care), system- or user-initiation of CDSS, multi-faceted vs stand alone CDSS interventions and clinical target on practice changes in line with the intent of the CDSS. We searched Medline, Embase and PsychINFO for publications from 1990-2007 detailing CDSS prescribing interventions. Pairs of independent reviewers extracted the key features and prescribing outcomes of methodologically adequate studies (experiments and strong quasi-experiments). 56 studies met our inclusion criteria, 38 addressing initiating, 23 monitoring and three stopping therapy. At the time of initiating therapy, CDSSs appear to be somewhat more effective after, rather than before, drug selection has occurred (7/12 versus 12/26 studies reporting statistically significant improvements in favour of CDSSs on = 50% of prescribing outcomes reported). CDSSs also appeared to be effective for monitoring therapy, particularly using laboratory test reminders (4/7 studies reporting significant improvements in favour of CDSSs on the majority of prescribing outcomes). None of the studies addressing stopping therapy demonstrated impacts in favour of CDSSs over comparators. The most consistently effective approaches used system-initiated advice to fine-tune existing therapy by making recommendations to improve patient safety, adjust the dose, duration or form of prescribed drugs or increase the laboratory testing rates for patients on long-term therapy. CDSSs appeared to perform better in institutional compared to ambulatory settings and when decision support was initiated automatically by the system as opposed to user initiation. CDSSs implemented with other strategies such as education were no more successful in improving prescribing than stand alone interventions. Cardiovascular disease was the most studied clinical target but few studies demonstrated significant improvements on the majority of prescribing outcomes. Our understanding of CDSS impacts on specific aspects of the prescribing process remains relatively limited. Future implementation should build on effective approaches including the use of system-initiated advice to address safety issues and improve the monitoring of therapy

Interventions designed to improve the quality and efficiency of medication use in managed care: A critical review of the literature – 2001–2007

<p>Abstract</p> <p>Background</p> <p>Managed care organizations use a variety of strategies to reduce the cost and improve the quality of medication use. The effectiveness of such policies is not well understood. The objective of this research was to update a previous systematic review of interventions, published between 1966 and 2001, to improve the quality and efficiency of medication use in the US managed care setting.</p> <p>Methods</p> <p>We searched MEDLINE and EMBASE for publications from July 2001 to January 2007 describing interventions targeting drug use conducted in the US managed care setting. We categorized studies by intervention type and adequacy of research design using commonly accepted criteria. We summarized the outcomes of well-controlled strategies and documented the significance and magnitude of effects for key study outcomes.</p> <p>Results</p> <p>We identified 164 papers published during the six-year period. Predominant strategies were: educational interventions (n = 20, including dissemination of educational materials, and group or one-to-one educational outreach); monitoring and feedback (n = 22, including audit/feedback and computerized monitoring); formulary interventions (n = 66, including tiered formulary and patient copayment); collaborative care involving pharmacists (n = 15); and disease management with pharmacotherapy as a primary focus (n = 41, including care for depression, asthma, and peptic ulcer disease). Overall, 51 studies met minimum criteria for methodological adequacy. Effective interventions included one-to-one academic detailing, computerized alerts and reminders, pharmacist-led collaborative care, and multifaceted disease management. Further, changes in formulary tier-design and related increases in copayments were associated with reductions in medication use and increased out-of-pocket spending by patients. The dissemination of educational materials alone had little or no impact, while the impact of group education was inconclusive.</p> <p>Conclusion</p> <p>There is good evidence for the effectiveness of several strategies in changing drug use in the managed care environment. However, little is known about the cost-effectiveness of these interventions. Computerized alerts showed promise in improving short-term outcomes but little is known about longer-term outcomes. Few well-designed, published studies have assessed the potential negative clinical effects of formulary-related interventions despite their widespread use. However, some evidence suggests increases in cost sharing reduce access to essential medicines for chronic illness.</p