Proximity driven plastid-nucleus relationships are facilitated by tandem plastid-ER dynamics.

Peri-nuclear clustering (PNC) of chloroplasts has largely been described in senescent and pathogen- or ROS- stressed cells. Stromules, tubular plastid extensions are also observed under similar conditions. Coincident observations of PNC and stromules associate the two phenomena in facilitating retrograde signaling between chloroplasts and the nucleus. However, PNC incidence in non-stressed cells under normal growth and developmental conditions, when stromules are usually not observed, remains unclear. Using transgenic Arabidopsis expressing different organelle-targeted fluorescent proteins we show that PNC is a dynamic subcellular phenomenon that continues in the absence of light and is not dependent on stromule formation. PNC is facilitated by tandem plastid-ER dynamics created through membrane contact sites between the two organelles. While PNC increases upon ER-membrane expansion, some plastids may remain in the peri-nuclear region due to their localization in ER-lined nuclear indentions. Moreover, some PNC plastids may sporadically extend stromules into ER-lined nuclear grooves. Our findings strongly suggest that PNC is not an exclusive response to stress caused by pathogens, high light or exogenous-H2O2 treatment and does not require stromule formation. However, morphological and behavioural alterations in ER and concomitant changes in tandem, plastid-ER dynamics play a major role in facilitating the phenomenon.

Sweden SimSmoke: the effect of tobacco control policies on smoking and snus prevalence and attributable deaths.

BACKGROUND: This study examines the effect of past tobacco control policies and projects the effect of future policies on smoking and snus use prevalence and associated premature mortality in Sweden. METHODS: The established SimSmoke model was adapted with population, smoking rates and tobacco control policy data from Sweden. SimSmoke evaluates the effect of taxes, smoke-free air, mass media, marketing bans, warning labels, cessation treatment and youth access policies on smoking and snus prevalence and the number of deaths attributable to smoking and snus use by gender from 2010 to 2040. RESULTS: Sweden SimSmoke estimates that significant inroads to reducing smoking and snus prevalence and premature mortality can be achieved through tax increases, especially when combined with other policies. Smoking prevalence can be decreased by as much as 26% in the first few years, reaching a 37% reduction within 30 years. Without effective tobacco control policies, almost 54 500 lives will be lost in Sweden due to tobacco use by the year 2040. CONCLUSION: Besides presenting the benefits of a comprehensive tobacco control strategy, the model identifies gaps in surveillance and evaluation that can help better focus tobacco control policy in Sweden.

Elucidating the Subcellular Localization of GLRaV-3 Proteins Encoded by the Unique Gene Block in N. benthamiana Suggests Implications on Plant Host Suppression.

Grapevine leafroll-associated virus 3 (GLRaV-3) is a formidable threat to the stability of the global grape and wine industries. It is the primary etiological agent of grapevine leafroll disease (GLD) and significantly impairs vine health, fruit quality, and yield. GLRaV-3 is a member of the genus Ampelovirus, Closteroviridae family. Viral genes within the 3' proximal unique gene blocks (UGB) remain highly variable and poorly understood. The UGBs of Closteroviridae viruses include diverse open reading frames (ORFs) that have been shown to contribute to viral functions such as the suppression of the host RNA silencing defense response and systemic viral spread. This study investigates the role of GLRaV-3 ORF8, ORF9, and ORF10, which encode the proteins p21, p20A, and p20B, respectively. These genes represent largely unexplored facets of the GLRaV-3 genome. Here, we visualize the subcellular localization of wildtype and mutagenized GLRaV-3 ORFs 8, 9, and 10, transiently expressed in Nicotiana benthamiana. Our results indicate that p21 localizes to the cytosol, p20A associates with microtubules, and p20B is trafficked into the nucleus to carry out the suppression of host RNA silencing. The findings presented herein provide a foundation for future research aimed at the characterization of the functions of these ORFs. In the long run, it would also facilitate the development of innovative strategies to understand GLRaV-3, mitigate its spread, and impacts on grapevines and the global wine industry.

Germany SimSmoke: the effect of tobacco control policies on future smoking prevalence and smoking-attributable deaths in Germany.

INTRODUCTION: Although Germany has recently implemented some tobacco control policies, there is considerable scope to strengthen policies consistent with the MPOWER guidelines. This article describes the development of a simulation model projecting the effect of future tobacco control policies in Germany on smoking prevalence and associated premature mortality. METHODS: Germany SimSmoke-an adapted version of the SimSmoke simulation model of tobacco control policy-uses population, smoking rates, and policy data for Germany. It assesses, individually and in combination, the effect of seven types of policies: taxes, smoke-free air laws, mass media campaigns, advertising bans, warning labels, cessation treatment, and youth access policies. RESULTS: With a comprehensive set of policies, smoking prevalence within the first few years can be reduced by about 22.0% relative to the status quo and by 37.9% (40.5%) for males (females) in 30 years. By 2040, 39,548 deaths could be averted in that year alone. Without stronger policies, 700,000 additional smoking-attributable deaths (SADs) would occur in Germany over the next 30 years. CONCLUSIONS: The model indicates that the consequences of inaction are considerable; without the implementation of a stronger set of policies, smoking prevalence rates will remain relatively stable, and SADs among women will continue to rise over a 30-year horizon. Significant inroads into reducing smoking prevalence and premature mortality can be achieved through strengthening tobacco control policies in line with MPOWER recommendations.

The effect of tobacco control policies on smoking prevalence and smoking-attributable deaths in Ireland using the IrelandSS simulation model.

OBJECTIVES: This study estimates the relative contribution of policies implemented between 1998 and 2010 to reductions in smoking prevalence by 2010. It then models the impact of implementing stronger policies, relative to a scenario of inaction, on smoking prevalence and smoking-attributable mortality in Ireland. METHODS: IrelandSS is an adapted version of SimSmoke, a dynamic simulation model used to examine the effect of tobacco control policies on smoking prevalence, through initiation and cessation, and associated future premature mortality. RESULTS: Model predictions for smoking prevalence are reasonably close to those from surveys. As a result of tobacco control policies implemented between 1998 and 2010, there was a 22% relative reduction in smoking prevalence and 1716 fewer smoking-attributable deaths (SADs) by 2010 increasing to a 29% relative reduction in prevalence and 50 215 fewer SADs by 2040. With the introduction of stricter FCTC-compliant policies in 2011, the smoking prevalence can be decreased by as much as 13% initially, increasing to 28% by 30 years. With these stronger policies, a total of 24 768 SADs will be averted by 2040. CONCLUSIONS: Predictions from the IrelandSS model suggest that policies implemented between 1998 and 2010 have had considerable effect; however, appreciable reductions in smoking prevalence and SADs can still be achieved through increasing taxes, maintaining a high-intensity tobacco control media campaign, introducing graphic health warnings and improving smoking cessation services.

SimSmokeFinn: how far can tobacco control policies move Finland toward tobacco-free 2040 goals?

AIMS: Finland is the first country to stipulate in law that its aim is to end the use of tobacco products containing compounds that are toxic to humans and that create addiction. This paper describes the development of a simulation model examining the potential effect of tobacco control policies in Finland on smoking prevalence and associated future premature mortality. METHODS: The model is developed using the SimSmoke simulation model of tobacco control policy, previously developed for other nations. The model uses population, smoking rates, and tobacco control policy data for Finland. It assesses, individually, and in combination, the effect of seven types of policies: taxes, smoke-free air laws, mass media campaigns, advertising bans, warning labels, cessation treatment, and youth access policies. RESULTS: With a comprehensive set of policies, smoking prevalence can be decreased by as much as 15% in the first few years, increasing to 29% by 20 years and 34% by 30 years. By 2040, 1300 deaths can be averted in that year alone with the stronger set of policies. Without effective tobacco control policies, 23,000 additional lives will be lost due to smoking over all years through 2040. CONCLUSIONS: The model shows that significant inroads to reducing smoking prevalence and premature mortality can be achieved through tax increases, a high-intensity media campaign complete with programmes to encourage cessation, a comprehensive cessation treatment programme, stronger health warnings, and enforcement of youth access laws. Other policies will be needed to further reduce tobacco use.

Smoking characteristics of Polish immigrants in Dublin.

BACKGROUND: This study examined two main hypotheses: a) Polish immigrants' smoking estimates are greater than their Irish counterparts (b) Polish immigrants purchasing cigarettes from Poland smoke "heavier" (>/= 20 cigarettes a day) when compared to those purchasing cigarettes from Ireland. The study also set out to identify significant predictors of 'current' smoking (some days and everyday) among the Polish immigrants. METHODS: Dublin residents of Polish origin (n = 1,545) completed a previously validated Polish questionnaire in response to an advertisement in a local Polish lifestyle magazine over 5 weekends (July-August, 2007). The Office of Tobacco Control telephone-based monthly survey data were analyzed for the Irish population in Dublin for the same period (n = 484). RESULTS: Age-sex adjusted smoking estimates were: 47.6% (95% Confidence Interval [CI]: 47.3%; 48.0%) among the Poles and 27.8% (95% CI: 27.2%; 28.4%) among the general Irish population (p < 0.001). Of the 57% of smokers (n = 345/606) who purchased cigarettes solely from Poland and the 33% (n = 198/606) who purchased only from Ireland, 42.6% (n = 147/345) and 41.4% (n = 82/198) were "heavy" smokers, respectively (p = 0.79). Employment (Odds Ratio [OR]: 2.89; 95% CI: 1.25-6.69), lower education (OR: 3.76; 95%CI: 2.46-5.74), and a longer stay in Ireland (>24 months) were significant predictors of current smoking among the Poles. An objective validation of the self-reported smoking history of a randomly selected sub-sample immigrant group, using expired carbon monoxide (CO) measurements, showed a highly significant correlation coefficient (r = 0.64) of expired CO levels with the reported number of cigarettes consumed (p < 0.0001). CONCLUSION: Polish immigrants' smoking estimates are higher than their Irish counterparts, and particularly if employed, with only primary-level education, and are overseas >2 years.

The benefits from complying with the framework convention on tobacco control: a SimSmoke analysis of 15 European nations.

INTRODUCTION: This article compares the predicted impact of tobacco tax increases alone and as part of a comprehensive tobacco control strategy on smoking prevalence and smoking-attributable deaths (SADs) across 15 European countries. METHODS: Country-specific population, smoking prevalence and policy data with modified parameter values have been applied to the previously validated SimSmoke model for 10 high-income and 5 middle-income European nations. The impact of past and potential future policies is modelled. RESULTS: Models generally validated well across the 15 countries, and showed the impact of past policies. Without stronger future policies, 44 million lives would be lost due to smoking across the 15 study countries between 2011 and 2040, but effective policies could avert 7.7 million of those premature deaths. CONCLUSIONS: Results suggest that past policies have been effective in reducing smoking rates, but there is also a strong potential for future policies consistent with the Framework Convention on Tobacco Control. When specific taxes are increased to 70% of retail price, strong smoke-free air laws, youth access laws and marketing restrictions are enforced, stronger health warnings are implemented, and cessation treatment and media campaigns are supported, smoking prevalence and SADs will fall substantially in European countries.

The efficacy of different models of smoke-free laws in reducing exposure to second-hand smoke: a multi-country comparison.

Exposure to second-hand tobacco smoke is a serious public health concern and while all EU Member States have enacted some form of regulation aimed at limiting exposure, the scope of these regulations vary widely and many countries have failed to enact comprehensive legislation creating smoke-free workplaces and indoor public places. To gauge the effectiveness of different smoke-free models we compared fine particles from second-hand smoke in hospitality venues before and after the implementation of smoking bans in France, Greece, Ireland, Italy, Portugal, Turkey, and Scotland. Data on PM2.5 fine particle concentration levels were recorded in 338 hospitality venues across these countries before and after the implementation of smoke-free legislation. Changes in mean PM2.5 concentrations during the period from pre- to post-legislation were then compared across countries. While a reduction in PM2.5 was observed in all countries, those who had enacted and enforced more fully comprehensive smoke-free legislation experienced the greatest reduction in second-hand tobacco smoke. Comprehensive smoke-free laws are more effective than partial laws in reducing exposure to second-hand tobacco smoke. Also, any law, regardless of scope must be actively enforced in order to have the desired impact. There is continued need for surveillance of smoke-free efforts in all countries.

The road to smoke-free legislation in Ireland.

AIM: To describe the process through which Ireland changed its policies towards smoking in work-places and distil lessons for others implementing or extending smoke-free laws. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: This analysis is informed by a review of secondary sources including a commissioned media analysis, documentary analysis and key informant interviews with policy actors who provide insight into the process of smoke-free policy development. The policy analysis techniques used include the development of a time-line for policy reform, stakeholder analysis, policy mapping techniques, impact analysis through use of secondary data and a review process. The policy analysis triangle, which highlights the importance of examining policy content, context, actors and processes, will be used as an analytical framework. FINDINGS: The importance of the political, economic, social and cultural context emerged clearly. The interaction of the context with the policy process both in identification of need for policy and its formulation demonstrated the opportunity for advocates to exert influence at all points of the process. The campaign to support the legislation had the following characteristics: a sustained consistent simple health message, sustained political leadership/commitment, a strong coalition between the Health Alliance, the Office of Tobacco Control and the Department of Health and Children, with cross-party political support and trade union support. The public and the media support clearly defined the benefit of deliberate and consistent planning and organization of a communication strategy. CONCLUSIONS: The Irish smoke-free legislation was a success as a policy initiative because of timing, dedication, planning, implementation and the existence of strong leadership and a powerful convinced credible political champion.

Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study.

BACKGROUND: The increasing demand for platelet products, and concern over the transfusion-associated risks of alloimmunisation and infections, have motivated a search for improved methods aimed at keeping exposure to donor antigens to a minimum. Transfusion of thrombopoietin-derived autologous platelets might provide an alternative strategy. We aimed to compare the safety and efficacy of this strategy with that of transfusion with fresh allogeneic platelets in patients with severe chemotherapy-induced thrombocytopenia. METHODS: 20 patients with gynaecological malignancies were treated with two doses of 1.2 microg/kg recombinant human thrombopoietin. From day 12, we aimed to collect 50 units of platelets from these patients by plateletpheresis. Harvested platelets were cryopreserved in ThromboSol and 2% dimethyl sulfoxide (DMSO) for use in subsequent autologous transfusions. Patients then received carboplatin for up to six cycles. Patients were randomly assigned to group A (n=10), which received allogeneic fresh platelets at the first instance of severe thrombocytopenia (platelet count <15,000/microL) and then autologous cryopreserved platelets at the next, or to group B (n=10), which received first autologous and then allogeneic platelets. In subsequent cycles, all patients received autologous platelets while available. The primary endpoint was platelet count increment corrected for the number of platelets transfused and the patients' body-surface area. Analysis was by intention to treat. FINDINGS: Treatment with recombinant human thrombopoietin significantly increased platelet count (median 2.3-fold [range 1.5-3.3], p<0.0001) in all but one patient in group A. The median number of platelets collected per patient was 53 units (14-66) in two collections (one to three). There was no significant difference in the corrected platelet count increments (CCIs) between the 19 paired transfusions of cryopreserved autologous platelets and fresh allogeneic platelets (median 1-h CCI 15.7 vs 19.8, p=0.398; median 24-h CCI 13.0 vs 18.1, p=0.398). 14 of the 19 patients had a good response (1-h CCI >7.5) to their first transfusion of allogeneic platelets. By contrast, all patients had a good response to their first transfusion of autologous platelets (p=0.063). Moreover, no significant decrease in the CCIs (p=0.405) was seen over six cycles after autologous platelet transfusions (n=63). No transfusion reactions or any serious adverse event was recorded during autologous platelet transfusions. INTERPRETATION: Recombinant human thrombopoietin facilitated collection of multiple units of platelets, which could be cryopreserved and reinfused to counteract severe thrombocytopenia during multicycle chemotherapy. Transfusion of autologous cryopreserved platelets derived from recombinant human thrombopoietin can provide a viable strategy to minimise the risks of allogeneic platelet transfusions and provide a long-lasting supply of platelet support.