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    Designer Sinorhizobium meliloti strains and multi-functional vectors enable direct inter-kingdom DNA transfer
    (Public Library of Science, 2019-06-17) Brumwell, Stephanie L.; MacLeod, Michael R.; Huang, Tony; Cochrane, Ryan R.; Meaney, Rebecca S.; Zamani, Maryam; Matysiakiewicz, Ola; Dan, Kaitlyn N.; Janakirama, Preetam; Edgell, David R.; Charles, Trevor C.; Finan, Turlough M.; Karas, Bogumil J.
    Storage, manipulation and delivery of DNA fragments is crucial for synthetic biology applications, subsequently allowing organisms of interest to be engineered with genes or pathways to produce desirable phenotypes such as disease or drought resistance in plants, or for synthesis of a specific chemical product. However, DNA with high G+C content can be unstable in many host organisms including Saccharomyces cerevisiae. Here, we report the development of Sinorhizobium meliloti, a nitrogen-fixing plant symbioticα-Proteobacterium, as a novel host that can store DNA, and mobilize DNA to E. coli, S. cerevisiae, and the eukaryotic microalgae Phaeodactylum tricornutum. To achieve this, we deleted the hsdR restriction-system in multiple reduced genome strains of S. meliloti that enable DNA transformation with up to 1.4 x 105 and 2.1 x 103 CFU μg-1 of DNA efficiency using electroporation and a newly developed polyethylene glycol transformation method, respectively. Multi-host and multi-functional shuttle vectors (MHS) were constructed and stably propagated in S. meliloti, E. coli, S. cerevisiae, and P. tricornutum. We also developed protocols and demonstrated direct transfer of these MHS vectors via conjugation from S. meliloti to E. coli, S. cerevisiae, and P. tricornutum. The development of S. meliloti as a new host for inter-kingdom DNA transfer will be invaluable for synthetic biology research and applications, including the installation and study of genes and biosynthetic pathways into organisms of interest in industry and agriculture.
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    Statistical methods for classification of 5hmC levels based on the Illumina Inifinium HumanMethylation450 (450k) array data, under the paired bisulfite (BS) and oxidative bisulfite (oxBS) treatment
    (Public Library of Science, 2019-06-13) Slynko, Alla; Benner, Axel
    Hydroxymethylcytosine (5hmC) methylation is a well-known epigenetic mark that is involved in gene regulation and may impact genome stability. To investigate a possible role of 5hmC in cancer development and progression, one must be able to detect and quantify its level first. In this paper, we address the issue of 5hmC detection at a single base resolution, starting with consideration of the well-established 5hmC measure Δβ and, in particular, with an analysis of its properties, both analytically and empirically. Then we propose several alternative hydroxymethylation measures and compare their properties with those of Δβ. In the absence of a gold standard, the (pairwise) resemblance of those 5hmC measures to Δβ is characterized by means of a similarity analysis and relative accuracy analysis. All results are illustrated on matched healthy and cancer tissue data sets as derived by means of bisulfite (BS) and oxidative bisulfite converting (oxBS) procedures.
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    High rates of health care utilization in pediatric multiple sclerosis: A Canadian population-based study
    (Public Library of Science, 2019-06-11) Marrie, Ruth Ann; O'Mahony, Julia; Maxwell, Colleen J.; Ling, Vicki; Yeh, E. Ann; Arnold, Douglas L.; Bar-Or, Amit; Banwell, Brenda
    We aimed to compare health care utilization of children with pediatric-onset multiple sclerosis to that of age, sex and geographically-matched children without multiple sclerosis. Using population-based administrative data from Ontario, Canada for the period 2003–2014, we applied a validated case definition to identify persons aged ≤18 years with multiple sclerosis. We identified up to 5 children without multiple sclerosis matched on sex, age, and region of residence. In each cohort, we determined annual rates of any hospitalization and physician services use. Using general linear models we compared utilization rates adjusting for age, sex, region, socioeconomic status and year. Subsequently, we limited the analysis to incident cases of multiple sclerosis and their matches, and compared rates of utilization in the year of multiple sclerosis diagnosis, and the three years thereafter. We identified 659 youth with multiple sclerosis (428 incident cases), and 3,294 matched controls. Two-thirds of both cohorts were female. After adjustment for sociodemographic factors and year, the multiple sclerosis cohort was more likely to be hospitalized than the matched cohort (odds ratio 15.2; 95%CI: 12.0, 19.1), and had higher rates of ambulatory physician visits (rate ratio 4.58; 95%CI: 4.26, 4.92). The odds of hospitalization (odds ratio 40.1; 95%CI: 27.1, 59.5) and physician visits (rate ratio 5.14; 95%CI: 4.63, 5.71) were markedly elevated in the year of MS diagnosis, declining thereafter but remaining elevated versus the matched cohort. Children with multiple sclerosis have substantially elevated rates of health care utilization as compared to matched children without multiple sclerosis, over calendar time and throughout the early disease course.
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    Charting pathways to climate change mitigation in a coupled socio-climate model
    (Public Library of Science, 2019-06-06) Bury, Thomas M.; Bauch, Chris T.; Anand, Madhur
    Geophysical models of climate change are becoming increasingly sophisticated, yet less effort is devoted to modelling the human systems causing climate change and how the two systems are coupled. Here, we develop a simple socio-climate model by coupling an Earth system model to a social dynamics model. We treat social processes endogenously—emerging from rules governing how individuals learn socially and how social norms develop—as well as being influenced by climate change and mitigation costs. Our goal is to gain qualitative insights into scenarios of potential socio-climate dynamics and to illustrate how such models can generate new research questions. We find that the social learning rate is strongly influential, to the point that variation of its value within empirically plausible ranges changes the peak global temperature anomaly by more than 1°C. Conversely, social norms reinforce majority behaviour and therefore may not provide help when we most need it because they suppress the early spread of mitigative behaviour. Finally, exploring the model’s parameter space for mitigation cost and social learning suggests optimal intervention pathways for climate change mitigation. We find that prioritising an increase in social learning as a first step, followed by a reduction in mitigation costs provides the most efficient route to a reduced peak temperature anomaly. We conclude that socio-climate models should be included in the ensemble of models used to project climate change.
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    A local optimization framework for addressing conservation conflicts in mosaic ecosystems
    (Public Library of Science, 2019-05-31) Nowack, Shane; Bauch, Chris T.; Anand, Madhur
    An effective strategy to resolve conservation conflicts on lands outside of nature reserves is to consider the spatial arrangement of agricultural and native vegetation parcels such that the ecological value of the landscape is improved without reducing the amount of land used for agricultural production. Global optimization methods have been used to identify the best spatial arrangement of land parcels for a given project goal, but these methods are not designed to provide pathways to reach the optimum from the initial landscape. Here we describe how local search algorithms can be used to develop land parcel rearrangement pathways to obtain a landscape that sustains greater species richness than the initial landscape without changing the amount of land used for agricultural production. To demonstrate how the local optimization framework can be applied, an ecological setting based on a forest-grassland mosaic ecosystem in Rio Grande do Sul, Brazil was constructed. Plant samples collected from this region were used to construct species area curves. Multiple locally optimal solutions that improved the modeled species richness of the landscape almost to globally optimal levels were identified. To support the results, the algorithm was also applied to a 306,250 ha forest-grassland region of Rio Grande do Sul. The case study results suggested that conservation polices solely based on landowners satisfying a legal reserve percentage on their property should be revised to consider landscape-level connectivity. Providing multiple possible solutions for landscape configurations using local optimization methods may improve managerial flexibility for decision-makers, compared to global optimization approaches providing a single solution. Furthermore, the algorithm details the parcel exchange pathways that are required to reach the optimal land state. We conclude that local and global optimization approaches can be used in combination to improve land use decision-making for conservation, in mosaic ecosystems as well as other terrestrial ecosystems