814 research outputs found
Fourier methods for smooth distribution function estimation
In this paper we show how to use Fourier transform methods to analyze the
asymptotic behavior of kernel distribution function estimators. Exact
expressions for the mean integrated squared error in terms of the
characteristic function of the distribution and the Fourier transform of the
kernel are employed to obtain the limit value of the optimal bandwidth sequence
in its greatest generality. The assumptions in our results are mild enough so
that they are applicable when the kernel used in the estimator is a
superkernel, or even the sinc kernel, and this allows to extract some
interesting consequences, as the existence of a class of distributions for
which the kernel estimator achieves a first-order improvement in efficiency
over the empirical distribution function.Comment: 12 pages, 2 figure
A quantitative screen for metabolic enzyme structures reveals patterns of assembly across the yeast metabolic network.
Despite the proliferation of proteins that can form filaments or phase-separated condensates, it remains unclear how this behavior is distributed over biological networks. We have found that 60 of the 440 yeast metabolic enzymes robustly form structures, including 10 that assemble within mitochondria. Additionally, the ability to assemble is enriched at branch points on several metabolic pathways. The assembly of enzymes at the first branch point in de novo purine biosynthesis is coordinated, hierarchical, and based on their position within the pathway, while the enzymes at the second branch point are recruited to RNA stress granules. Consistent with distinct classes of structures being deployed at different control points in a pathway, we find that the first enzyme in the pathway, PRPP synthetase, forms evolutionarily conserved filaments that are sequestered in the nucleus in higher eukaryotes. These findings provide a roadmap for identifying additional conserved features of metabolic regulation by condensates/filaments
Development of a compact fluorescence spectroscopy sensor for non-invasive monitoring gut function
Monitoring gut permeability is currently either invasive, inaccurate or difficult to perform in infants. We present a compact fluorescence sensor that overcomes some of these limitations, paving the way for non-invasive gut permeability monitoring
A quantitative screen for metabolic enzyme structures reveals patterns of assembly across the yeast metabolic network
© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Noree, C., Begovich, K., Samilo, D., Broyer, R., Monfort, E., & Wilhelm, J. E. A quantitative screen for metabolic enzyme structures reveals patterns of assembly across the yeast metabolic network. Molecular Biology of the Cell, 30(21), (2019): 2721-2736, doi:10.1091/mbc.E19-04-0224.Despite the proliferation of proteins that can form filaments or phase-separated condensates, it remains unclear how this behavior is distributed over biological networks. We have found that 60 of the 440 yeast metabolic enzymes robustly form structures, including 10 that assemble within mitochondria. Additionally, the ability to assemble is enriched at branch points on several metabolic pathways. The assembly of enzymes at the first branch point in de novo purine biosynthesis is coordinated, hierarchical, and based on their position within the pathway, while the enzymes at the second branch point are recruited to RNA stress granules. Consistent with distinct classes of structures being deployed at different control points in a pathway, we find that the first enzyme in the pathway, PRPP synthetase, forms evolutionarily conserved filaments that are sequestered in the nucleus in higher eukaryotes. These findings provide a roadmap for identifying additional conserved features of metabolic regulation by condensates/filaments.We thank Douglass Forbes for comments on the manuscript, Susanne Rafelski for the gift of the pVTU-mito-dsRed plasmid, and Brian Zid for the gift of the pKT-mNeonGreen plasmid. Work at the Wilhelm lab was supported by a grant from the Hughes Collaborative Innovation Award program of the Howard Hughes Medical Institute and the James Wilhelm Memorial Fund. Kyle Begovich is a Howard Hughes Medical Institute Gilliam Fellow
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