Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations

BACKGROUND: The thymidine kinase (tk) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1. METHODS: A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol) within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases. RESULTS: Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAA(r)5 exhibited a 2–4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed signficant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA stucture. CONCLUSIONS: This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a) mutations may be modulated by other viral polypeptides cooperating with Pol, and (b) the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2

Social Media, Professional Media, and Mobilization in Contemporary Britain:Explaining the Strengths and Weaknesses of the Citizens’ Movement 38 Degrees

This article was published in the journal Political Studies [SAGE © The Author(s)] and the definitive version is available at: https://doi.org/10.1177/0032321716631350Digital media continue to reshape political activism in unexpected ways. Within a period of a few years, the internet-enabled UK citizens’ movement 38 Degrees has amassed a membership of 3 million and now sits alongside similar entities such as America’s MoveOn, Australia’s GetUp! and the transnational movement Avaaz. In this article, we contribute to current thinking about digital media and mobilisation by addressing some of the limitations of existing research on these movements and on digital activism more generally. We show how 38 Degrees’ digital network repertoires coexist interdependently with its strategy of gaining professional news media coverage. We explain how the oscillations between choreographic leadership and member influence and between digital media horizontalism and elite media-centric work constitute the space of interdependencies in which 38 Degrees acts. These delicately balanced relations can quickly dissolve and be replaced by simpler relations of dependence on professional media. Yet despite its fragility, we theorise about how 38 Degrees may boost individuals’ political efficacy, irrespective of the outcome of individual campaigns. Our conceptual framework can be used to guide research on similar movements

Dissemination and implementation of an educational tool for veterans on complementary and alternative medicine: a case study

Background Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean–Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. Methods In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. Findings We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. Interpretation Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support

From the animal house to the field : are there consistent individual differences in immunological profile in wild populations of field voles (Microtus agrestis)?

Inbred mouse strains, living in simple laboratory environments far removed from nature, have been shown to vary consistently in their immune response. However, wildlife populations are typically outbreeding and face a multiplicity of challenges, parasitological and otherwise. In this study we seek evidence of consistent difference in immunological profile amongst individuals in the wild. We apply a novel method in this context, using longitudinal (repeated capture) data from natural populations of field voles, Microtus agrestis, on a range of life history and infection metrics, and on gene expression levels. We focus on three immune genes, IFN-γ, Gata3, and IL-10, representing respectively the Th1, Th2 and regulatory elements of the immune response. Our results show that there was clear evidence of consistent differences between individuals in their typical level of expression of at least one immune gene, and at most all three immune genes, after other measured sources of variation had been taken into account. Furthermore, individuals that responded to changing circumstances by increasing expression levels of Gata3 had a correlated increase in expression levels of IFN-γ. Our work stresses the importance of acknowledging immunological variation amongst individuals in studies of parasitological and infectious disease risk in wildlife populations

Why do adult women in Vietnam take iron tablets?

BACKGROUND: Conducting iron supplementation programs has been a major strategy to reduce iron deficiency anemia in pregnancy. However, only a few countries have reported improvements in the anemia rate at a national level. The strategies used for control of nutrition problems need regular review to maintain and improve their effectiveness. The objective of this study was to analyze the factors in compliance with taking iron tablets, where daily doses of iron (60 mg) and folic acid (400 μg) were distributed in rural Vietnamese communes. METHODS: A cross sectional survey was conducted in Nghe An province, Vietnam in January, 2003. The study population was adult women aged less than 35 years who delivered babies between August 1(st )2001 and December 1(st )2002 (n = 205), of which 159 took part in the study. Data for the study were collected from a series of workshops with community leaders, focus group discussions with community members and a questionnaire survey. RESULTS: Improvements in the rate of anemia was not given a high priority as one of the commune's needs, but the participants still made efforts to continue taking iron tablets. Two major factors motivated the participants to continue taking iron tablets; their experience of fewer spells of dizziness (50%), and their concern for the health of their newborn baby (54%). When examining the reasons for taking iron tablets for at least 5–9 months, the most important factor was identified as 'a frequent supply of iron tablets' (OR = 11.93, 95% CI: 4.33–32.85). CONCLUSION: The study found that multiple poor environmental risk factors discouraged women from taking iron tablets continuously. The availability (frequent supply) of iron tablets was the most effective way to help adult women to continue taking iron tablets

Multi-Locus Phylogeographic and Population Genetic Analysis of Anolis carolinensis: Historical Demography of a Genomic Model Species

The green anole (Anolis carolinensis) has been widely used as an animal model in physiology and neurobiology but has recently emerged as an important genomic model. The recent sequencing of its genome has shed new light on the evolution of vertebrate genomes and on the process that govern species diversification. Surprisingly, the patterns of genetic diversity within natural populations of this widespread and abundant North American lizard remain relatively unknown. In the present study, we use 10 novel nuclear DNA sequence loci (N = 62 to 152) and one mitochondrial locus (N = 226) to delimit green anole populations and infer their historical demography. We uncovered four evolutionarily distinct and geographically restricted lineages of green anoles using phylogenetics, Bayesian clustering, and genetic distance methods. Molecular dating indicates that these lineages last shared a common ancestor ∼2 million years ago. Summary statistics and analysis of the frequency distributions of DNA polymorphisms strongly suggest range-wide expansions in population size. Using Bayesian Skyline Plots, we inferred the timing of population size expansions, which differ across lineages, and found evidence for a relatively recent and rapid westward expansion of green anoles across the Gulf Coastal Plain during the mid-Pleistocene. One surprising result is that the distribution of genetic diversity is not consistent with a latitudinal shift caused by climatic oscillations as is observed for many co-distributed taxa. This suggests that the most recent Pleistocene glacial cycles had a limited impact on the geographic distribution of the green anole at the northern limits of its range

Differential Influence of Clonal Integration on Morphological and Growth Responses to Light in Two Invasive Herbs

Background and aims: In contrast to seeds, high sensitivity of vegetative fragments to unfavourable environments may limit the expansion of clonal invasive plants. However, clonal integration promotes the establishment of propagules in less suitable habitats and may facilitate the expansion of clonal invaders into intact native communities. Here, we examine the influence of clonal integration on the morphology and growth of ramets in two invasive plants, Alternanthera philoxeroides and Phyla canescens, under varying light conditions. Methods: In a greenhouse experiment, branches, connected ramets and severed ramets of the same mother plant were exposed under full sun and 85 % shade and their morphological and growth responses were assessed. Key results: The influence of clonal integration on the light reaction norm (connection6light interaction) of daughter ramets was species-specific. For A. philoxeroides, clonal integration evened out the light response (total biomass, leaf mass per area, and stem number, diameter and length) displayed in severed ramets, but these connection6light interactions were largely absent for P. canescens. Nevertheless, for both species, clonal integration overwhelmed light effect in promoting the growth of juvenile ramets during early development. Also, vertical growth, as an apparent shade acclimation response, was more prevalent in severed ramets than in connected ramets. Finally, unrooted branches displayed smaller organ size and slower growth than connected ramets, but the pattern of light reaction was similar, suggesting mothe

Decision to take osteoporosis medication in patients who have had a fracture and are 'high' risk for future fracture: A qualitative study

Abstract Background Patients' values and preferences are fundamental tenets of evidence-based practice, yet current osteoporosis (OP) clinical guidelines pay little attention to these issues in therapeutic decision making. This may be in part due to the fact that few studies have examined the factors that influence the initial decision to take OP medication. The purpose of our study was to examine patients' experiences with the decision to take OP medication after they sustained a fracture. Methods A phenomenological qualitative study was conducted with outpatients identified in a university teaching hospital fracture clinic OP program. Individuals aged 65+ who had sustained a fragility fracture within 5 years, were 'high risk' for future fracture, and were prescribed OP medication were eligible. Analysis of interview data was guided by Giorgi's methodology. Results 21 patients (6 males, 15 females) aged 65-88 years participated. All participants had low bone mass; 9 had OP. Fourteen patients were taking a bisphosphonate while 7 patients were taking no OP medications. For 12 participants, the decision to take OP medication occurred at the time of prescription and involved minimal contemplation (10/12 were on medication). These patients made their decision because they liked/trusted their health care provider. However, 4/10 participants in this group indicated their OP medication-taking status might change. For the remaining 9 patients, the decision was more difficult (4/9 were on medication). These patients were unconvinced by their health care provider, engaged in risk-benefit analyses using other information sources, and were concerned about side effects; 7/9 patients indicated that their OP medication-taking status might change at a later date. Conclusions Almost half of our older patients who had sustained a fracture found the decision to take OP medication a difficult one. In general, the decision was not considered permanent. Health care providers should be aware of their potential role in patients' decisions and monitor patients' decisions over time

Physical activity and optimal self-rated health of adults with and without diabetes

<p>Abstract</p> <p>Background</p> <p>Regular physical activity can improve people's overall health and contribute to both primary and secondary prevention of many chronic diseases and conditions including diabetes. The aim of this study was to examine the association between levels of physical activity and optimal self-rated health (SRH) of U.S. adults with and without diabetes in all 50 states and territories of the Unites States.</p> <p>Methods</p> <p>We estimated the prevalence of optimal SRH by diabetes status of 430,912 adults aged 18 years and older who participated in the 2007 state-based survey of the Behavioral Risk Factor Surveillance System (BRFSS). Prevalence ratios were produced with multivariate Cox regression models using levels of physical activity as a predictor and status of optimal SRH as an outcome variable while controlling for sociodemographic and behavioral health risk factors.</p> <p>Results</p> <p>The prevalence of reporting optimal SRH was 53.3%, 52.2%, and 86.2% for adults with type 1 diabetes, type 2 diabetes, and without diabetes, respectively. Also in the aforementioned order, adults who reported being active had an increased likelihood of 81%, 32%, and 18% for reporting optimal SRH, when compared with adults who reported being inactive.</p> <p>Conclusions</p> <p>Regular physical activity of adults, particularly adults with diabetes, is associated with optimal SRH. The findings of this study underscore the importance of advising and motivating adults with diabetes so that physical activity can be integrated into their lifestyle for diabetes care. Additionally, a population-based effort to promote physical activity in communities may benefit adults in general by improving their overall health and well-being.</p