Studies on the virome of the entomopathogenic fungus Beauveria bassiana reveal novel dsRNA elements and mild hypervirulence.

© 2017 Kotta-Loizou, Coutts. 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 author and source are credited. Kotta-Loizou I, Coutts RHA (2017) 'Studies on the Virome of the Entomopathogenic Fungus Beauveria bassiana Reveal Novel dsRNA Elements and Mild Hypervirulence', PLoS Pathogens, 13(1): e1006183. doi:10.1371/journal.ppat.1006183The entomopathogenic fungus Beauveria bassiana has a wide host range and is used as a biocontrol agent against arthropod pests. Mycoviruses have been described in phytopathogenic fungi while in entomopathogenic fungi their presence has been reported only rarely. Here we show that 21.3% of a collection of B. bassiana isolates sourced from worldwide locations, harbor dsRNA elements. Molecular characterization of these elements revealed the prevalence of mycoviruses belonging to the Partitiviridae and Totiviridae families, the smallest reported virus to date, belonging to the family Narnaviridae, and viruses unassigned to a family or genus. Of particular importance is the discovery of members of a newly proposed family Polymycoviridae in B. bassiana. Polymycoviruses, previously designated as tetramycoviruses, consist of four non-conventionally encapsidated capped dsRNAs. The presence of additional non-homologous genomic segments in B. bassiana polymycoviruses and other fungi illustrates the unprecedented dynamic nature of the viral genome. Finally, a comparison of virus-free and virus-infected isogenic lines derived from an exemplar B. bassiana isolate revealed a mild hypervirulent effect of mycoviruses on the growth of their host isolate and on its pathogenicity against the greater wax moth Galleria mellonella, highlighting for the first time the potential of mycoviruses as enhancers of biocontrol agents.Peer reviewedFinal Published versio

Key issues in the design of pay for performance programs

Pay for performance (P4P) is increasingly being used to stimulate healthcare providers to improve their performance. However, evidence on P4P effectiveness remains inconclusive. Flaws in program design may have contributed to this limited success. Based on a synthesis of relevant theoretical and empirical literature, this paper discusses key issues in P4P-program design. The analysis reveals that designing a fair and effective program is a complex undertaking. The following tentative conclusions are made: (1) performance is ideally defined broadly, provided that the set of measures remains comprehensible, (2) concerns that P4P encourages "selection" and "teaching to the test" should not be dismissed, (3) sophisticated risk adjustment is important, especially in outcome and resource use measures, (4) involving providers in program design is vital, (5) on balance, group incentives are preferred over individual incentives, (6) whether to use rewards or penalties is context-dependent, (7) payouts should be frequent and low-powered, (8) absolute targets are generally preferred over relative targets, (9) multiple targets are preferred over single targets, and (10) P4P should be a permanent component of provider compensation and is ideally "decoupled" form base payments. However, the design of P4P programs should be tailored to the specific setting of implementation, and empirical research is needed to confirm the conclusions

Chromosome microarray analysis as first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities

n this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors

Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial

Background: This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-conceptual health and risk behaviours, teen pregnancy and the resultant birth outcomes, early child health and maternal health. Methods and Design: Fifty-seven schools (86% of 66 eligible secondary schools) in Perth, Australia were recruited to the clustered (by school) randomised trial, with even randomisation to the intervention and control arms. Between 2003 and 2006, the VIP program was administered to 1,267 participants in the intervention schools, while 1,567 participants in the non-intervention schools received standard curriculum. Participants were all female and aged between 13-15 years upon recruitment. Pre and post-intervention questionnaires measured short-term impact and participants are now being followed through their teenage years via data linkage to hospital medical records, abortion clinics and education records. Participants who have a live birth are interviewed by face-to-face interview. Kaplan-Meier survival analysis and proportional hazards regression will test for differences in pregnancy, birth and abortion rates during the teenage years between the study arms.Discussion: This protocol paper provides a detailed overview of the trial design as well as initial results in the form of participant flow. The authors describe the intervention and its delivery within the natural school setting and discuss the practical issues in the conduct of the trial, including recruitment. The trial is pragmatic and will directly inform those who provide Infant Simulator based programs in school settings

FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection

<p>Abstract</p> <p>Background</p> <p>Feline immunodeficiency virus (FIV) is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment.</p> <p>Results</p> <p>In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells <it>ex vivo </it>as demonstrated by detectable FIV <it>gag </it>RNA and 2-long terminal repeat (LTR) circle junctions. Viral LTR and <it>gag </it>sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation.</p> <p>Conclusions</p> <p>Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of <it>in vivo </it>mechanisms of lentiviral latency.</p

Multiple determinants of lifespan memory differences

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss

Deletion of Glutamate Delta-1 Receptor in Mouse Leads to Aberrant Emotional and Social Behaviors

The delta family of ionotropic glutamate receptors consists of glutamate δ1 (GluD1) and glutamate δ2 (GluD2) receptors. While the role of GluD2 in the regulation of cerebellar physiology is well understood, the function of GluD1 in the central nervous system remains elusive. We demonstrate for the first time that deletion of GluD1 leads to abnormal emotional and social behaviors. We found that GluD1 knockout mice (GluD1 KO) were hyperactive, manifested lower anxiety-like behavior, depression-like behavior in a forced swim test and robust aggression in the resident-intruder test. Chronic lithium rescued the depression-like behavior in GluD1 KO. GluD1 KO mice also manifested deficits in social interaction. In the sociability test, GluD1 KO mice spent more time interacting with an inanimate object compared to a conspecific mouse. D-Cycloserine (DCS) administration was able to rescue social interaction deficits observed in GluD1 KO mice. At a molecular level synaptoneurosome preparations revealed lower GluA1 and GluA2 subunit expression in the prefrontal cortex and higher GluA1, GluK2 and PSD95 expression in the amygdala of GluD1 KO. Moreover, DCS normalized the lower GluA1 expression in prefrontal cortex of GluD1 KO. We propose that deletion of GluD1 leads to aberrant circuitry in prefrontal cortex and amygdala owing to its potential role in presynaptic differentiation and synapse formation. Furthermore, these findings are in agreement with the human genetic studies suggesting a strong association of GRID1 gene with several neuropsychiatric disorders including schizophrenia, bipolar disorder, autism spectrum disorders and major depressive disorder

Behavioral modeling of human choices reveals dissociable effects of physical effort and temporal delay on reward devaluation

There has been considerable interest from the fields of biology, economics, psychology, and ecology about how decision costs decrease the value of rewarding outcomes. For example, formal descriptions of how reward value changes with increasing temporal delays allow for quantifying individual decision preferences, as in animal species populating different habitats, or normal and clinical human populations. Strikingly, it remains largely unclear how humans evaluate rewards when these are tied to energetic costs, despite the surge of interest in the neural basis of effort-guided decision-making and the prevalence of disorders showing a diminished willingness to exert effort (e.g., depression). One common assumption is that effort discounts reward in a similar way to delay. Here we challenge this assumption by formally comparing competing hypotheses about effort and delay discounting. We used a design specifically optimized to compare discounting behavior for both effort and delay over a wide range of decision costs (Experiment 1). We then additionally characterized the profile of effort discounting free of model assumptions (Experiment 2). Contrary to previous reports, in both experiments effort costs devalued reward in a manner opposite to delay, with small devaluations for lower efforts, and progressively larger devaluations for higher effort-levels (concave shape). Bayesian model comparison confirmed that delay-choices were best predicted by a hyperbolic model, with the largest reward devaluations occurring at shorter delays. In contrast, an altogether different relationship was observed for effort-choices, which were best described by a model of inverse sigmoidal shape that is initially concave. Our results provide a novel characterization of human effort discounting behavior and its first dissociation from delay discounting. This enables accurate modelling of cost-benefit decisions, a prerequisite for the investigation of the neural underpinnings of effort-guided choice and for understanding the deficits in clinical disorders characterized by behavioral inactivity

Prospects for the development of probiotics and prebiotics for oral applications

There has been a paradigm shift towards an ecological and microbial community-based approach to understanding oral diseases. This has significant implications for approaches to therapy and has raised the possibility of developing novel strategies through manipulation of the resident oral microbiota and modulation of host immune responses. The increased popularity of using probiotic bacteria and/or prebiotic supplements to improve gastrointestinal health has prompted interest in the utility of this approach for oral applications. Evidence now suggests that probiotics may function not only by direct inhibition of, or enhanced competition with, pathogenic micro-organisms, but also by more subtle mechanisms including modulation of the mucosal immune system. Similarly, prebiotics could promote the growth of beneficial micro-organisms that comprise part of the resident microbiota. The evidence for the use of pro or prebiotics for the prevention of caries or periodontal diseases is reviewed, and issues that could arise from their use, as well as questions that still need to be answered, are raised. A complete understanding of the broad ecological changes induced in the mouth by probiotics or prebiotics will be essential to assess their long-term consequences for oral health and disease

Systematic review: Effects, design choices, and context of pay-for-performance in health care

<p>Abstract</p> <p>Background</p> <p>Pay-for-performance (P4P) is one of the primary tools used to support healthcare delivery reform. Substantial heterogeneity exists in the development and implementation of P4P in health care and its effects. This paper summarizes evidence, obtained from studies published between January 1990 and July 2009, concerning P4P effects, as well as evidence on the impact of design choices and contextual mediators on these effects. Effect domains include clinical effectiveness, access and equity, coordination and continuity, patient-centeredness, and cost-effectiveness.</p> <p>Methods</p> <p>The systematic review made use of electronic database searching, reference screening, forward citation tracking and expert consultation. The following databases were searched: Cochrane Library, EconLit, Embase, Medline, PsychINFO, and Web of Science. Studies that evaluate P4P effects in primary care or acute hospital care medicine were included. Papers concerning other target groups or settings, having no empirical evaluation design or not complying with the P4P definition were excluded. According to study design nine validated quality appraisal tools and reporting statements were applied. Data were extracted and summarized into evidence tables independently by two reviewers.</p> <p>Results</p> <p>One hundred twenty-eight evaluation studies provide a large body of evidence -to be interpreted with caution- concerning the effects of P4P on clinical effectiveness and equity of care. However, less evidence on the impact on coordination, continuity, patient-centeredness and cost-effectiveness was found. P4P effects can be judged to be encouraging or disappointing, depending on the primary mission of the P4P program: supporting minimal quality standards and/or boosting quality improvement. Moreover, the effects of P4P interventions varied according to design choices and characteristics of the context in which it was introduced.</p> <p>Future P4P programs should (1) select and define P4P targets on the basis of baseline room for improvement, (2) make use of process and (intermediary) outcome indicators as target measures, (3) involve stakeholders and communicate information about the programs thoroughly and directly, (4) implement a uniform P4P design across payers, (5) focus on both quality improvement and achievement, and (6) distribute incentives to the individual and/or team level.</p> <p>Conclusions</p> <p>P4P programs result in the full spectrum of possible effects for specific targets, from absent or negligible to strongly beneficial. Based on the evidence the review has provided further indications on how effect findings are likely to relate to P4P design choices and context. The provided best practice hypotheses should be tested in future research.</p