Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the ...frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100-200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation.
Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite ...trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated dilation (
=0.29,
<0.00001). In young mice, 6 months of dietary supplementation with trimethylamine-N-oxide induced an aging-like impairment in carotid artery endothelium-dependent dilation to acetylcholine versus control feeding (peak dilation: 79±3% versus 95±3%,
<0.01). This impairment was accompanied by increased vascular nitrotyrosine, a marker of oxidative stress, and reversed by the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl. Trimethylamine-N-oxide supplementation also reduced activation of endothelial nitric oxide synthase and impaired nitric oxide-mediated dilation, as assessed with the nitric oxide synthase inhibitor L-NAME (N
-nitro-L-arginine methyl ester). Acute incubation of carotid arteries with trimethylamine-N-oxide recapitulated these events. Next, treatment with 3,3-dimethyl-1-butanol for 8 to 10 weeks to suppress trimethylamine-N-oxide selectively improved endothelium-dependent dilation in old mice to young levels (peak: 90±2%) by normalizing vascular superoxide production, restoring nitric oxide-mediated dilation, and ameliorating superoxide-related suppression of endothelium-dependent dilation. Lastly, among healthy middle-aged/older adults, higher plasma trimethylamine-N-oxide was associated with greater nitrotyrosine abundance in biopsied endothelial cells, and infusion of the antioxidant ascorbic acid restored flow-mediated dilation to young levels, indicating tonic oxidative stress-related suppression of endothelial function with higher circulating trimethylamine-N-oxide. Using multiple experimental approaches in mice and humans, we demonstrate a clear role of trimethylamine-N-oxide in promoting age-related endothelial dysfunction via oxidative stress, which may have implications for prevention of cardiovascular diseases.
Measuring the acidity of atmospheric aerosols is critical, as many key multiphase chemical reactions involving aerosols are highly pH-dependent. These reactions impact processes, such as secondary ...organic aerosol (SOA) formation, that impact climate and health. However, determining the pH of atmospheric particles, which have minute volumes (10–23–10–18 L), is an analytical challenge due to the nonconservative nature of the hydronium ion, particularly as most chemical aerosol measurements are made offline or under vacuum, where water can be lost and acid–base equilibria shifted. Because of these challenges, there have been no direct methods to probe atmospheric aerosol acidity, and pH has typically been determined by proxy/indirect methods, such as ion balance, or thermodynamic models. Herein, we present a novel and facile method for direct measurement of size-resolved aerosol acidity from pH 0 to 4.5 using quantitative colorimetric image processing of cellular phone images of (NH4)2SO4–H2SO4 aqueous aerosol particles impacted onto pH-indicator paper. A trend of increasing aerosol acidity with decreasing particle size was observed that is consistent with spectroscopic measurements of individual particle pH. These results indicate the potential for direct measurements of size-resolved atmospheric aerosol acidity, which is needed to improve fundamental understanding of pH-dependent atmospheric processes, such as SOA formation.
Comparative research on food web structure has revealed generalities in trophic organization, produced simple models, and allowed assessment of robustness to species loss. These studies have mostly ...focused on free-living species. Recent research has suggested that inclusion of parasites alters structure. We assess whether such changes in network structure result from unique roles and traits of parasites or from changes to diversity and complexity. We analyzed seven highly resolved food webs that include metazoan parasite data. Our analyses show that adding parasites usually increases link density and connectance (simple measures of complexity), particularly when including concomitant links (links from predators to parasites of their prey). However, we clarify prior claims that parasites "dominate" food web links. Although parasites can be involved in a majority of links, in most cases classic predation links outnumber classic parasitism links. Regarding network structure, observed changes in degree distributions, 14 commonly studied metrics, and link probabilities are consistent with scale-dependent changes in structure associated with changes in diversity and complexity. Parasite and free-living species thus have similar effects on these aspects of structure. However, two changes point to unique roles of parasites. First, adding parasites and concomitant links strongly alters the frequency of most motifs of interactions among three taxa, reflecting parasites' roles as resources for predators of their hosts, driven by trophic intimacy with their hosts. Second, compared to free-living consumers, many parasites' feeding niches appear broader and less contiguous, which may reflect complex life cycles and small body sizes. This study provides new insights about generic versus unique impacts of parasites on food web structure, extends the generality of food web theory, gives a more rigorous framework for assessing the impact of any species on trophic organization, identifies limitations of current food web models, and provides direction for future structural and dynamical models.
Recent experiments have produced mounting evidence of Majorana zero modes in nanowire-superconductor hybrids. Signatures of an expected topological phase transition accompanying the onset of these ...modes nevertheless remain elusive. We investigate a fundamental question concerning this issue: Do well-formed Majorana modes necessarily entail a sharp phase transition in these setups? Assuming reasonable parameters, we argue that finite-size effects can dramatically smooth this putative transition into a crossover, even in systems large enough to support well-localized Majorana modes. We propose overcoming such finite-size effects by examining the behavior of low-lying excited states through tunneling spectroscopy. In particular, the excited-state energies exhibit characteristic field and density dependence, and scaling with system size, that expose an approaching topological phase transition. We suggest several experiments for extracting the predicted behavior. As a useful byproduct, the protocols also allow one to measure the wire's spin-orbit coupling directly in its superconducting environment.
LocusZoom.js is a JavaScript library for creating interactive web-based visualizations of genetic association study results. It can display one or more traits in the context of relevant biological ...data (such as gene models and other genomic annotation), and allows interactive refinement of analysis models (by selecting linkage disequilibrium reference panels, identifying sets of likely causal variants, or comparisons to the GWAS catalog). It can be embedded in web pages to enable data sharing and exploration. Views can be customized and extended to display other data types such as phenome-wide association study (PheWAS) results, chromatin co-accessibility, or eQTL measurements. A new web upload service harmonizes datasets, adds annotations, and makes it easy to explore user-provided result sets.
LocusZoom.js is open-source software under a permissive MIT license. Code and documentation are available at: https://github.com/statgen/locuszoom/. Installable packages for all versions are also distributed via NPM. Additional features are provided as standalone libraries to promote reuse. Use with your own GWAS results at https://my.locuszoom.org/.
Supplementary data are available at Bioinformatics online.
The adoption of nutrient management practices can lead to win-win outcomes in terms of both improving productivity and reducing the environmental impact of farming. However, adoption of key practices ...remains below expectations globally. Few studies specifically focus on the adoption of nutrient management practices and the majority overlook psychological factors in their analysis. This study examines the factors which influence Irish farmers' intention to apply fertiliser on the basis of soil test results. An expanded version of the theory of planned behaviour is used as a framework for analysis. The influence of policy is also accounted for by this study which requires certain farmers in Ireland to adopt soil testing on a mandatory basis. The results for the national sample (n = 1009) show that attitudes, subjective norms (social pressure), perceived behavioural control (ease/difficulty) and perceived resources are significant and positively associated with farmers' intentions. In terms of the voluntary sample (n = 587), only attitude, perceived behavioural control and perceived resources are significantly and positively associated with farmers' intentions. Whereas, for the mandatory sample (n = 422), subjective norms, perceived behavioural control and perceived resources are significantly and correlated in a positive direction with intentions. A number of farm and farmer characteristics are also significantly associated with intentions. Policy recommendations are made based on these results.
•We examine factors influencing intentions to adopt nutrient management planning.•Policy plays a role in shaping which factors influence farmers' intentions.•Attitudes, norms, perceived control and resources positively influence intentions.•Dairy system, age, education and advisor also positively influence intentions.•Results are helpful in identifying factors influencing farmers' behaviour.
Key points
Age‐related arterial dysfunction, characterized by oxidative stress‐ and inflammation‐mediated endothelial dysfunction and arterial stiffening, is the primary risk factor for ...cardiovascular diseases.
To investigate whether age‐related changes in the gut microbiome may mediate arterial dysfunction, we suppressed gut microbiota in young and old mice with a cocktail of broad‐spectrum, poorly‐absorbed antibiotics in drinking water for 3–4 weeks.
In old mice, antibiotic treatment reversed endothelial dysfunction and arterial stiffening and attenuated vascular oxidative stress and inflammation.
To provide insight into age‐related changes in gut microbiota that may underlie these observations, we show that ageing altered the abundance of microbial taxa associated with gut dysbiosis and increased plasma levels of the adverse gut‐derived metabolite trimethylamine N‐oxide.
The results of the present study provide the first proof‐of‐concept evidence that the gut microbiome is an important mediator of age‐related arterial dysfunction and therefore may be a promising therapeutic target for preserving arterial function with ageing, thereby reducing the risk of cardiovascular diseases.
Oxidative stress‐mediated arterial dysfunction (e.g. endothelial dysfunction and large elastic artery stiffening) is the primary mechanism driving age‐related cardiovascular diseases. Accumulating evidence suggests the gut microbiome modulates host physiology because dysregulation (‘gut dysbiosis’) has systemic consequences, including promotion of oxidative stress. The present study aimed to determine whether the gut microbiome modulates arterial function with ageing. We measured arterial function in young and older mice after 3–4 weeks of treatment with broad‐spectrum, poorly‐absorbed antibiotics to suppress the gut microbiome. To identify potential mechanistic links between the gut microbiome and age‐related arterial dysfunction, we sequenced microbiota from young and older mice and measured plasma levels of the adverse gut‐derived metabolite trimethylamine N‐oxide (TMAO). In old mice, antibiotics reversed endothelial dysfunction area‐under‐the‐curve carotid artery dilatation to acetylcholine in young: 345 ± 16 AU vs. old control (OC): 220 ± 34 AU, P < 0.01; vs. old antibiotic‐treated (OA): 334 ± 15 AU; P < 0.01 vs. OC and arterial stiffening (aortic pulse wave velocity in young: 3.62 ± 0.15 m s−1 vs. OC: 4.43 ± 0.38 m s−1; vs. OA: 3.52 ± 0.35 m s−1; P = 0.03). These improvements were accompanied by lower oxidative stress and greater antioxidant enzyme expression. Ageing altered the abundance of gut microbial taxa associated with gut dysbiosis. Lastly, plasma TMAO was higher with ageing (young: 2.6 ± 0.4 μmol L−1 vs. OC: 7.2 ± 2.0 μmol L−1; P < 0.0001) and suppressed by antibiotic treatment (OA: 1.2 ± 0.2 μmol L−1; P < 0.0001 vs. OC). The results of the present study provide the first evidence for the gut microbiome being an important mediator of age‐related arterial dysfunction and oxidative stress and suggest that therapeutic strategies targeting gut microbiome health may hold promise for preserving arterial function and reducing cardiovascular risk with ageing in humans.
Key points
Age‐related arterial dysfunction, characterized by oxidative stress‐ and inflammation‐mediated endothelial dysfunction and arterial stiffening, is the primary risk factor for cardiovascular diseases.
To investigate whether age‐related changes in the gut microbiome may mediate arterial dysfunction, we suppressed gut microbiota in young and old mice with a cocktail of broad‐spectrum, poorly‐absorbed antibiotics in drinking water for 3–4 weeks.
In old mice, antibiotic treatment reversed endothelial dysfunction and arterial stiffening and attenuated vascular oxidative stress and inflammation.
To provide insight into age‐related changes in gut microbiota that may underlie these observations, we show that ageing altered the abundance of microbial taxa associated with gut dysbiosis and increased plasma levels of the adverse gut‐derived metabolite trimethylamine N‐oxide.
The results of the present study provide the first proof‐of‐concept evidence that the gut microbiome is an important mediator of age‐related arterial dysfunction and therefore may be a promising therapeutic target for preserving arterial function with ageing, thereby reducing the risk of cardiovascular diseases.
•TPB used to identify variables influencing farmers’ intentions to follow a NMP.•Attitude, perceived control and subjective norm positively influence intentions.•Subjective norm has a positive effect ...on attitude and perceived control.•Policy and trusted information sources play a role in determining perceptions.
Farmer decision making in relation to chemical fertiliser and manure use is of great concern to policy makers. Inefficient use can lead to both environmental pollution and financial losses to farmers. Following a nutrient management plan (NMP) can help to mitigate these impacts and improve farm incomes. As the use of NMPs remains below expectation globally, this study aims to provide insights into the drivers of farmers’ intentions to follow a NMP and to understand how behavioural change can be encouraged. An extended version of the theory of planned behaviour is adopted and structural equation modelling is used to analyse survey data collected from a sample of Irish farmers. Results show that intention to follow a NMP is primarily driven by perceived behavioural control (ease/difficulty) over following a NMP, followed by subjective norm (social pressure) and finally attitude (negative/positive evaluation) towards following a NMP. We also find that subjective norm is an important predictor of both attitude and perceived behavioural control. Furthermore, policies that require certain farmers to develop a NMP on a mandatory basis, plays a significant role in influencing famers’ attitude, subjective norm and perceived behavioural control. Finally, trust in technical sources of information (e.g. advisor and discussion group) is found to be a more influential determinant of farmers’ attitude, subjective norm and perceived behavioural control than trust in social information sources (e.g. family and the media). These results provide a comprehensive understanding of the variables driving farmers’ intentions to follow a NMP and highlight the importance of both socio-psychological and institutional variables in the analysis of farmer decision making.