652 research outputs found

    Bacterial microevolution and the Pangenome

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    The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history

    Mechanical behaviour and rupture of normal and pathological human ascending aortic wall

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    The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart

    Accelerated discovery of two crystal structure types in a complex inorganic phase field

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    The discovery of new materials is hampered by the lack of efficient approaches to the exploration of both the large number of possible elemental compositions for such materials, and of the candidate structures at each composition1. For example, the discovery of inorganic extended solid structures has relied on knowledge of crystal chemistry coupled with time-consuming materials synthesis with systematically varied elemental ratios2,3. Computational methods have been developed to guide synthesis by predicting structures at specific compositions4,5,6 and predicting compositions for known crystal structures7,8, with notable successes9,10. However, the challenge of finding qualitatively new, experimentally realizable compounds, with crystal structures where the unit cell and the atom positions within it differ from known structures, remains for compositionally complex systems. Many valuable properties arise from substitution into known crystal structures, but materials discovery using this approach alone risks both missing best-in-class performance and attempting design with incomplete knowledge8,11. Here we report the experimental discovery of two structure types by computational identification of the region of a complex inorganic phase field that contains them. This is achieved by computing probe structures that capture the chemical and structural diversity of the system and whose energies can be ranked against combinations of currently known materials. Subsequent experimental exploration of the lowest-energy regions of the computed phase diagram affords two materials with previously unreported crystal structures featuring unusual structural motifs. This approach will accelerate the systematic discovery of new materials in complex compositional spaces by efficiently guiding synthesis and enhancing the predictive power of the computational tools through expansion of the knowledge base underpinning them

    Validation and Clinical Application of a First Order Step Response Equation for Nitrogen Clearance During FRC Measurement

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    OBJECTIVE: To derive a difference equation based on mass conservation and on alveolar tidal volumes for the calculation of Functional Residual Capacity. Derive an equation for the FRC from the difference equation. Furthermore, to derive and validate a step response equation as a solution of the difference equation within the framework of digital signal processing where the FRC is known a priori. METHODS: A difference equation for the calculation of Functional Residual Capacity is derived and solved as step response of a first order system. The step response equation calculates endtidal fractions of nitrogen during multiple breath nitrogen clearance. The step response equation contains the eigenvalue defined as the ratio of FRC to the sum of FRC and alveolar tidal ventilation. Agreement of calculated nitrogen fractions with measured fractions is demonstrated with data from a metabolic lung model, measurements from patients in positive pressure ventilation and volunteers breathing spontaneously. Examples of eigenvalue are given and compared between diseased and healthy lungs and between ventilatory settings. RESULTS: Comparison of calculated and measured fractions of endtidal nitrogen demonstrates a high degree of agreement in terms of regression and bias and limits of agreement (precision) in Bland & Altman analysis. Examples illustrate the use of the eigenvalue as a possible discriminator between disease states. CONCLUSION: The first order step response equation reliably calculates endtidal fractions of nitrogen during washout based on a Functional Residual Capacity. The eigenvalue may be a clinically valuable index alone or in conjunction with other indices in the analysis of respiratory states and may aid in the setting of the ventilator

    Balanced gene losses, duplications and intensive rearrangements led to an unusual regularly sized genome in Arbutus unedo chloroplasts

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    Completely sequenced plastomes provide a valuable source of information about the duplication, loss, and transfer events of chloroplast genes and phylogenetic data for resolving relationships among major groups of plants. Moreover, they can also be useful for exploiting chloroplast genetic engineering technology. Ericales account for approximately six per cent of eudicot diversity with 11,545 species from which only three complete plastome sequences are currently available. With the aim of increasing the number of ericalean complete plastome sequences, and to open new perspectives in understanding Mediterranean plant adaptations, a genomic study on the basis of the complete chloroplast genome sequencing of Arbutus unedo and an updated phylogenomic analysis of Asteridae was implemented. The chloroplast genome of A. unedo shows extensive rearrangements but a medium size (150,897 nt) in comparison to most of angiosperms. A number of remarkable distinct features characterize the plastome of A. unedo: five-fold dismissing of the SSC region in relation to most angiosperms; complete loss or pseudogenization of a number of essential genes; duplication of the ndhH-D operon and its location within the two IRs; presence of large tandem repeats located near highly re-arranged regions and pseudogenes. All these features outline the primary evolutionary split between Ericaceae and other ericalean families. The newly sequenced plastome of A. unedo with the available asterid sequences allowed the resolution of some uncertainties in previous phylogenies of Asteridae

    A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus

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    The bacterium Myxococcus xanthus glides through soil in search of prey microbes, but when food sources run out, cells cooperatively construct and sporulate within multicellular fruiting bodies. M. xanthus strains isolated from a 16 × 16-cm-scale patch of soil were previously shown to have diversified into many distinct compatibility types that are distinguished by the failure of swarming colonies to merge upon encounter. We sequenced the genomes of 22 isolates from this population belonging to the two most frequently occurring multilocus sequence type (MLST) clades to trace patterns of incipient genomic divergence, specifically related to social divergence. Although homologous recombination occurs frequently within the two MLST clades, we find an almost complete absence of recombination events between them. As the two clades are very closely related and live in sympatry, either ecological or genetic barriers must reduce genetic exchange between them. We find that the rate of change in the accessory genome is greater than the rate of amino-acid substitution in the core genome. We identify a large genomic tract that consistently differs between isolates that do not freely merge and therefore is a candidate region for harbouring gene(s) responsible for self/non-self discrimination

    The influence of early aging on eye movements during motor simulation

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    Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging

    Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

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    We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z0.03z\sim 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z0.6z\sim 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

    progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement

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    Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.We describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux). We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence.The multiple genome alignments generated by our software provide a platform for comparative genomic and population genomic studies. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve

    Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

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    We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z0.03z\sim 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z0.6z\sim 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July
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