Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1,2,3,4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction

Adult Repellency and Larvicidal Activity of Five Plant Essential Oils Against Mosquitoes

The larvicidal activity and repellency of 5 plant essential oils—thyme oil, catnip oil, amyris oil, eucalyptus oil, and cinnamon oil—were tested against 3 mosquito species: Aedes albopictus, Ae. aegypti, and Culex pipiens pallens. Larvicidal activity of these essentials oils was evaluated in the laboratory against 4th instars of each of the 3 mosquito species, and amyris oil demonstrated the greatest inhibitory effect with LC50 values in 24 h of 58 µg/ml (LC90  =  72 µg/ml) for Ae. aegypti, 78 µg/ml (LC90  =  130 µg/ml) for Ae. albopictus, and 77 µg/ml (LC90  =  123 µg/ml) for Cx. p. pallens. The topical repellency of these selected essential oils and deet against laboratory-reared female blood-starved Ae. albopictus was examined. Catnip oil seemed to be the most effective and provided 6-h protection at both concentrations tested (23 and 468 µg/cm2). Thyme oil had the highest effectiveness in repelling this species, but the repellency duration was only 2 h. The applications using these natural product essential oils in mosquito control are discussed

Epstein–Barr virus BRLF1 inhibits transcription of IRF3 and IRF7 and suppresses induction of interferon-β

Activation of interferon regulatory factors (IRFs) 3 and 7 is essential for the induction of Type I interferons (IFN) and innate antiviral responses, and herpesviruses have evolved mechanisms to evade such responses. We previously reported that Epstein-Barr Virus BZLF1, an immediate-early (IE) protein, inhibits the function of IRF7, but the role of BRLF1, the other IE transactivator, in IRF regulation has not been examined. We now show that BRLF1 expression decreased induction of IFN-β, and reduced expression of IRF3 and IRF7; effects were dependent on N- and C-terminal regions of BRLF1 and its nuclear localization signal. Endogenous IRF3 and IRF7 RNA and protein levels were also decreased during cytolytic EBV infection. Finally, production of IFN-β was decreased during lytic EBV infection and was associated with increased susceptibility to superinfection with Sendai virus. These data suggest a new role for BRLF1 in the ability of to evade host innate immune responses

Epstein–Barr virus BRLF1 inhibits transcription of IRF3 and IRF7 and suppresses induction of interferon-β

Activation of interferon regulatory factors (IRFs) 3 and 7 is essential for the induction of Type I interferons (IFN) and innate antiviral responses, and herpesviruses have evolved mechanisms to evade such responses. We previously reported that Epstein-Barr Virus BZLF1, an immediate-early (IE) protein, inhibits the function of IRF7, but the role of BRLF1, the other IE transactivator, in IRF regulation has not been examined. We now show that BRLF1 expression decreased induction of IFN-β, and reduced expression of IRF3 and IRF7; effects were dependent on N- and C-terminal regions of BRLF1 and its nuclear localization signal. Endogenous IRF3 and IRF7 RNA and protein levels were also decreased during cytolytic EBV infection. Finally, production of IFN-β was decreased during lytic EBV infection and was associated with increased susceptibility to superinfection with Sendai virus. These data suggest a new role for BRLF1 in the ability of to evade host innate immune responses

Restoring native forest understory: The influence of ferns and light in a hawaiian experiment

Ecological restoration is an increasingly important component of sustainable land management. We explore potential facilitative relationships for enhancing the cost-effectiveness of restoring native forest understory, focusing on two factors: (1) overstory shade and (2) possible facilitation by a fern (Dryopteris wallichiana), one of few native colonists of pasture in our montane Hawai\u27i study system. We planted 720 understory tree seedlings and over 4000 seeds of six species under six planting treatments: a full factorial combination of low, medium and high light, situating plantings in either the presence or absence of a mature fern. After three years, 75% of outplanted seedlings survived. Seedling survivorship was significantly higher in the presence of a fern (79% vs. 71% without a fern) and in medium and low light conditions (81% vs. 64% in high light). Relative height was highest at low to medium light levels. After 2.2 years, 2.8% of the planted seeds germinated. We observed no significant differences in seed germination relative to light level or fern presence. Analyzing several approaches, we found nursery germination of seeds followed by outplanting ca. 20% less costly than direct seeding in the field. This study opens new questions about facilitation mechanisms that have the potential to increase the extent and effectiveness of restoration efforts. © 2013 by the authors

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups