A big challenge in current systems biology research arises when different types of data must be accessed from separate sources and visualized using separate tools. The high cognitive load required to ...navigate such a workflow is detrimental to hypothesis generation. Accordingly, there is a need for a robust research platform that incorporates all data and provides integrated search, analysis, and visualization features through a single portal. Here, we present ePlant (http://bar.utoronto.ca/eplant), a visual analytic tool for exploring multiple levels of Arabidopsis thaliana data through a zoomable user interface. ePlant connects to several publicly available web services to download genome, proteome, interactome, transcriptome, and 3D molecular structure data for one or more genes or gene products of interest. Data are displayed with a set of visualization tools that are presented using a conceptual hierarchy from big to small, and many of the tools combine information from more than one data type. We describe the development of ePlant in this article and present several examples illustrating its integrative features for hypothesis generation. We also describe the process of deploying ePlant as an “app” on Araport. Building on readily available web services, the code for ePlant is freely available for any other biological species research.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Global warming will jeopardize the persistence and genetic diversity of many species. Assisted colonization, or the movement of species beyond their current range boundary, is a conservation strategy ...proposed for species with limited dispersal abilities or adaptive potential. However, species that rely on photoperiodic and thermal cues for development may experience conflicting signals if transported across latitudes. Relocating multiple, distinct populations may remedy this quandary by expanding genetic variation and promoting evolutionary responses in the receiving habitat – a strategy known as assisted gene flow. To better inform these policies, we planted seeds from latitudinally distinct populations of the annual legume, Chamaecrista fasciculata, in a potential future colonization site north of its current range boundary. Plants were exposed to ambient or elevated temperatures via infrared heating. We monitored several life history traits and estimated patterns of natural selection to determine the adaptive value of plastic responses. To assess the feasibility of assisted gene flow between phenologically distinct populations, we counted flowers each day and estimated the degree of temporal isolation between populations. Increased temperatures advanced each successive phenological trait more than the last, resulting in a compressed life cycle for all but the southern‐most population. Warming altered patterns of selection on flowering onset and vegetative biomass. Population performance was dependent on latitude of origin, with the northern‐most population performing best under ambient conditions and the southern‐most performing most poorly, even under elevated temperatures. Among‐population differences in flowering phenology limited the potential for genetic exchange among the northern‐ and southern‐most populations. All plastic responses to warming were neutral or adaptive; however, photoperiodic constraints will likely necessitate evolutionary responses for long‐term persistence, especially when involving populations from disparate latitudes. With strategic planning, our results suggest that assisted colonization and assisted gene flow may be feasible options for preservation.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In plants, the temporal pattern of floral displays, or display schedules, delimits an individual's mating opportunities. Thus, variation in the shape of display schedules can affect the degree of ...population synchrony and the strength of phenological assortative mating by flowering onset date. A good understanding of the mechanisms regulating the timing of flowering onset has been developed, but we know less about factors influencing subsequent patterns of floral display. We observed unusual multimodal display schedules in temperate populations of the annual legume Chamaecrista fasciculata. Here, we ask whether ‘flowering pulses’ are simultaneous among individuals and populations and explore potential underlying mechanisms and consequences of pulsed flowering. We monitored daily flower production for individual plants from genetically divergent populations during a series of field experiments that manipulated three potential influencers of display schedule shape: average daily temperature, pollinator availability and watering schedules. We measured floral longevity to isolate the contributions of flower retention and flower deployment to display schedules. We assessed relationships between flowering and environmental variables and compared estimates of population synchrony, individual synchrony and the strength of assortative mating with those of 29 unimodally flowering species from the area. We observed simultaneous flowering pulses in all experiments, with peaks aligned among individuals and populations despite variation in flowering onset and/or duration. Pulses were not the result of increases in average temperature, pollinator availability or variation in watering schedules. Seasonal fluctuations in temperature correlated with floral longevity and flower deployment, suggesting that the shape of display schedules may be plastic in response to fluctuations in temperature. Average population and individual synchrony differed only slightly from those of the species with unimodal schedules, while the average strength of assortative mating for flowering onset date was strongly reduced (0.21 in C. fasciculata vs. 0.35 for the 29 other species). Synthesis. Researchers should take caution in assuming that components of display schedules are genetically or developmentally correlated with flowering onset. Variation in the shape of display schedules can influence patterns of gene flow within or between populations, with potential effects on the strength of phenological assortative mating and subsequent responses to selection.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
High throughput sequencing has opened the doors for investigators to probe genetic variation present in large populations of organisms. In plants, the 1001 Genomes Project (1001genomes.org) is one ...such effort that sought to characterize the extant worldwide variation in Arabidopsis thaliana for future analyses to compare and draw upon. In my thesis I began the construction of a synthetic yeast pathway to test the effects of natural non-synonymous variants on the activation of the A. thaliana abscisic acid (ABA) signaling pathway in the hopes of characterizing variants that modulate pathway output. I constructed a series of expression cassettes to confirm the correct expression and localization of our ABA members and laid the groundwork for future members to continue constructing the pathway. Additionally, I created a web application called The Variant Viewer, for investigators to query the 1001 Genomes database and view variants in any A. thaliana gene.
Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do ...fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 µg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (H(T)PCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the H(T)PC range, whereas no effects were observed at plasma concentrations below the H(T)PCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
β-Amyloid (Aβ) peptides are thought to be critically involved in the etiology of Alzheimer's disease (AD). The aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required ...for the production of Aβ, and BACE1 inhibition is thus an attractive target for the treatment of AD. We show that verubecestat (MK-8931) is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of Aβ40, Aβ42, and sAPPβ (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys. Chronic treatment of rats and monkeys with verubecestat achieved exposures >40-fold higher than those being tested in clinical trials in AD patients yet did not elicit many of the adverse effects previously attributed to BACE inhibition, such as reduced nerve myelination, neurodegeneration, altered glucose homeostasis, or hepatotoxicity. Fur hypopigmentation was observed in rabbits and mice but not in monkeys. Single and multiple doses were generally well tolerated and produced reductions in Aβ40, Aβ42, and sAPPβ in the CSF of both healthy human subjects and AD patients. The human data were fit to an amyloid pathway model that provided insight into the Aβ pools affected by BACE1 inhibition and guided the choice of doses for subsequent clinical trials.
Marine fisheries and future ocean conflict Spijkers, Jessica; Morrison, Tiffany H; Blasiak, Robert ...
Fish and fisheries,
September 2018, Volume:
19, Issue:
5
Journal Article
Peer reviewed
Open access
Conflict over marine fishery resources is a growing security concern. Experts expect that global changes in our climate, food systems and oceans may spark or exacerbate resource conflicts. An initial ...scan of 803 relevant papers and subsequent intensive review of 31 fisheries conflict studies, focused on subnational and international conflicts, suggests that four substantial scientific gaps need addressing to improve our understanding of the nature and drivers of fisheries conflict. First, fisheries conflict and levels of conflict intensity are not precisely defined. Second, complex adaptive systems thinking is underutilized but has the potential to produce more realistic causal models of fishery conflict. Third, comparative large‐scale data and suitably integrative methodologies are lacking, underscoring the need for a standardized and comparable database of fisheries conflict cases to aid extrapolation beyond single case‐studies. Fourth, there is room for a more widespread application of higher order concepts and associated terminology. Importantly, the four gaps highlight the homogenized nature of current methodological and theoretical approaches to understanding fishery conflict, which potentially presents us with an oversimplified understanding of these conflicts. A more nuanced understanding of the complex and dynamic nature of fishery conflict and its causes is not only scientifically critical, but increasingly relevant for policymakers and practitioners in this turbulent world.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Summary Background A third of the 2·5 billion people worldwide without access to improved sanitation live in India, as do two-thirds of the 1·1 billion practising open defecation and a quarter of the ...1·5 million who die annually from diarrhoeal diseases. We aimed to assess the effectiveness of a rural sanitation intervention, within the context of the Government of India's Total Sanitation Campaign, to prevent diarrhoea, soil-transmitted helminth infection, and child malnutrition. Methods We did a cluster-randomised controlled trial between May 20, 2010, and Dec 22, 2013, in 100 rural villages in Odisha, India. Households within villages were eligible if they had a child younger than 4 years or a pregnant woman. Villages were randomly assigned (1:1), with a computer-generated sequence, to undergo latrine promotion and construction or to receive no intervention (control). Randomisation was stratified by administrative block to ensure an equal number of intervention and control villages in each block. Masking of participants was not possible because of the nature of the intervention. However, households were not told explicitly that the purpose of enrolment was to study the effect of a trial intervention, and the surveillance team was different from the intervention team. The primary endpoint was 7-day prevalence of reported diarrhoea in children younger than 5 years. We did intention-to-treat and per-protocol analyses. This trial is registered with ClinicalTrials.gov , number NCT01214785. Findings We randomly assigned 50 villages to the intervention group and 50 villages to the control group. There were 4586 households (24 969 individuals) in intervention villages and 4894 households (25 982 individuals) in control villages. The intervention increased mean village-level latrine coverage from 9% of households to 63%, compared with an increase from 8% to 12% in control villages. Health surveillance data were obtained from 1437 households with children younger than 5 years in the intervention group (1919 children younger than 5 years), and from 1465 households (1916 children younger than 5 years) in the control group. 7-day prevalence of reported diarrhoea in children younger than 5 years was 8·8% in the intervention group and 9·1% in the control group (period prevalence ratio 0·97, 95% CI 0·83–1·12). 162 participants died in the intervention group (11 children younger than 5 years) and 151 died in the control group (13 children younger than 5 years). Interpretation Increased latrine coverage is generally believed to be effective for reducing exposure to faecal pathogens and preventing disease; however, our results show that this outcome cannot be assumed. As efforts to improve sanitation are being undertaken worldwide, approaches should not only meet international coverage targets, but should also be implemented in a way that achieves uptake, reduces exposure, and delivers genuine health gains. Funding Bill & Melinda Gates Foundation, International Initiative for Impact Evaluation (3ie), and Department for International Development-backed SHARE Research Consortium at the London School of Hygiene & Tropical Medicine.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have used multiband imaging to investigate the nature of an extreme starburst environment in the nearby Lyman break galaxy analogue Haro 11 (ESO 350−IG038) by means of its stellar cluster ...population. The central starburst region has been observed in eight different high-resolution Hubble Space Telescope (HST) wavebands, sampling the stellar and gas components from UV to near-infrared. Photometric imaging of the galaxy was also carried out at 2.16 μm by NaCo AO instrument at the ESO Very Large Telescope. We constructed integrated spectral energy distributions (SEDs) for about 200 star clusters located in the active star-forming regions and compared them with single stellar population models (suitable for physical properties of very young cluster population) in order to derive ages, masses and extinctions of the star clusters. The cluster age distribution we recover confirms that the present starburst has lasted for 40 Myr, and shows a peak of cluster formation only 3.5 Myr old. With such an extremely young cluster population, Haro 11 represents a unique opportunity to investigate the youngest phase of the cluster formation process and evolution in starburst systems. We looked for possible relations between cluster ages, extinctions and masses. Extinction tends to diminish as a function of the cluster age, but the spread is large and reaches the highest dispersion for clusters in partial embedded phases (<5 Myr). A fraction of low-mass (below 104 M⊙), very young (1–3 Myr) clusters is missing, either because they are embedded in the parental molecular cloud and heavily extinguished, or because of blending with neighbouring clusters. The range of the cluster masses is wide; we observe that more than 30 per cent of the clusters have masses above 105 M⊙, qualifying them as super star clusters. Almost half of the cluster sample is affected by flux excesses at wavelengths >8000 Å which cannot be explained by simple stellar evolutionary models. Fitting SED models over all wavebands leads to systematic overestimates of cluster ages and incorrect masses for the stellar population supplying the light in these clusters. We show that the red excess affects also the HST F814W filter, which is typically used to constrain cluster physical properties. The clusters which show the red excess are younger than 40 Myr; we discuss possible physical explanations for the phenomenon. Finally, we estimate that Haro 11 has produced bound clusters at a rate almost a factor of 10 higher than the massive and regular spirals, like the Milky Way. The present cluster formation efficiency is ∼38 per cent of the galactic star formation rate.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
